This long review covers everything in the
lecture lessons, inclass assignments, and the pre-lessons. It is mostly my long notes where I discuss
topics in complete sentences. To review the text, please review the
chapter summaries, to review the homework, please look over your
homework reading and assignment. Material in homeworks 3 will be on the
final. For the text and the homework, the objectives provide you with the
topics to know.
stuff we may have skipped, if so, you do not need to review it.
Host defense part I
- Be able to differentiate between non-specific and specific
- Be able to give examples of nonspecific defenses, (both
mechanical and chemical defenses).
- Be familiar with the various kinds of blood cells and their
- Understand the process of inflammation and what chemicals and
cells play a role in inflammation.
- Be able to describe interferons and their role in host
- Be able to list the effects of complement activation.
Nonspecific & Specific Defenses
Last time we learned about disease, what causes it, how virulence
factors allow the
pathogen to establish itself and grow in a host
Today, we will learn about host defenses and how they protect the
The body has a number of defenses against pathogens. These
defenses fall into two
- Nonspecific defenses are defenses that protect against
any pathogen, regardless of the organism.
- Usually, this pertains to the host, such as an intact skin
and phagocytes that act against many potential
- Yet, as we discussed last time, the normal microbiota also
is a nonspecific defense, keeping pathogens out by
competition in a situation called microbial antagonism.
The normal microbiota can consume nutrients
needed by a pathogen, change the environment making it
unfavorable for the pathogen (such as changing the pH),
compete for space, and improve the health of the host so
that it can resist the pathogen better (such as intestinal
microbiota providing vitamins).
- Specific defenses protect against specific pathogens.
Specific defenses involve specialized cells of the immune system
called lymphocytes and the production of antibodies. We
will talk more about these in our next lesson.
- Together, these defenses make up the three
lines of defense. Let's watch an introductory
video on this.
- Table of Nonspecific & Specific Defenses (Similar
to Table 15.5):
Similar to Table 15.5: Nonspecific & Specific
|First line of defense
|2nd line of defense
|3rd line of defense
||phagocytic white blood cells
||Specialized lymphocytes:B and T cells
|mucous membranes & secretions
||inflammation & fever
Fig. 15.1: The Skin
- We have already talked about the skin as a barrier to
infection. Some of the reasons skin is a barrier to infection
- the outer layer is relatively dry and is dead, acting as a mechanical
- secretions from sweat glands inhibit growth (high in salt;
contains lysozyme which breaks down cell walls by attacking
peptidoglycan's sugar links and antimicrobial peptides,
mechanism not well understood)
- sebum (se-bum) from oil glands is a chemical barrier, coats
skin/hair w/ oil, sebum w/ the normal flora, lowers the pH
- Mucous Membranes line the body cavities
that are open to the exterior and act as a mechanical barrier
- They have secretions (mucus,
antimicrobial peptides) that act as nonspecific mechanical and
chemical barriers to infection.
- Certain mucous membranes have
specialized defenses -trachea have cilia.
- They have two
layers, an outer epithelium and an inner connective
- The thin living epithelial layer
provides a less efficient barrier than the skin, with the
respiratory and reproductive systems being common entry sites
The Respiratory System and its Defenses:
- nose hairs that filter out dust and microbes
- mucous that traps many microbes (mechanical barrier)
- mucous that contains antimicrobial
peptides and antibodies (chemical barriers)
- the ciliary escalator (ciliated cells which propel microbes up
toward the mouth)
- when you cough and swallow, gastric juice kills many bacteria
and inactivates many toxins (chemical barrier).
Other Defenses and Barriers:
- A mechanical barrier to infection includes the flow of urine
through the urinary system which sweeps bacteria out.
- Blood contains transferrins, proteins which bind iron. By
reducing the amount of available iron these chemical barriers
inhibit the growth of bacteria in the blood.
- Tears, saliva, and nasal mucus contain lysosyme (an enzyme
that degrades peptidoglycan).
- Tears are a mechanical barrier that wash the eyes upon
- Gastric juices contain digestive enzymes and acids.
So the various systems of the body have mechanical and chemical
barriers which serve as
a first line of defense against infection.
They are nonspecific in that they defend against many different
The Second Line of Defense
- The second line of defense is still nonspecific.
- It involves phagocytic white blood cells (WBC), inflammation,
and certain antimicrobial substances (interferon and
- All of these WBC and RBC originate from the same stem cell in
the adult bone marrow (video).
- Fig. 15.4
- Early in the lab, you looked at blood smears. You should
have noted that the red blood cells lacked nuclei. You should
also have noted that the cells with odd shaped blue-stained
nuclei were the white blood cells or leukocytes.
- During many infections the numbers of leukocytes are increased
though some diseases cause a decrease in leukocytes.
- Leukocytes (WBC) are divided into categories based on
their morphology and staining characteristics.
Granulocytes are WBC with visible granules in their
15.5). They include:
- basophils (ba'-so-fils)
stain blue-purple with the stain methylene blue. Basophils
release substances such as histamine (his'-tah-men) which
are important in inflammation and allergic responses.
- Eosinophils (e-o-sin'-o-phils)
are motile phagocytic cells. They stain red with the acidic dye
eosin. The numbers of eosinophils rise during allergic reactions
and also during helminth infections. They can attach to
parasitic worms and will secrete peroxide ions which kill the
- Neutrophils (noo'-tro-fils)
stain pale purple with a mixture of acidic and basic stains.
Note the lobed nuclei. Neutrophils are also called
polymorphonuclear leukocytes or PMNs. Neutrophils are motile and
phagocytic. They, eosinophils, and monocytes can squeeze through
capillaries and get into tissues where they'll destroy
microorganisms. Are 60-70% of all WBC.
- So, basophils, neutrophils and eosinophils are granulocytes.
Neutrophils and eosinophils are motile phagocytes.
Agranulocytes are WBC w/o visible cytoplasmic granules.
- Monocyte/Macrophages -The last motile phagocyte of the
blood is a monocyte. Some monocytes leave circulation and wander
around in body tissues where they mature into wandering
- Other macrophages, fixed macrophages, are found fixed in a
certain tissue or organ and sometimes have other
- Fixed macrophages are found in the lung, liver, nervous
system, bronchial tubes, lymph nodes, spleen, bone marrow,
and in the peritoneal cavity which surrounds abdominal
- Monocytes/macrophages are very important phagocytic
- Lymphocytes are the smallest WBC w/ a nucleus that
almost fills the cytoplasm. They are the second most common WBC
- Also occur in lymph nodes, tonsils, spleen, thymus, bone
marrow, appendix and small intestine.
- Lymphocytes are involved in specific immunity (the 3rd
line of defense).
- We'll talk about
lymphocytes in the lesson on immunity. W/ a light
microscope only, you cannot distinguish B from T-cells.
Phagocytosis by neutrophils, eosinophils and
mono/macrophages occur in
five phases ( Fig.
- Attraction -the phagocyte is attracted to the
microbe. This is called chemotaxis.
Compounds produced by the microorganism and damaged host cells
attract the phagocytes. Compliment proteins and cytokines secreted from
leukocytes can also attract phagocytes to an infection
site. We'll discuss these later.
- Adherence -the phagocyte must then adhere to
the microbe . If a microbe is first coated by an opsonin
protein, the phagocyte more readily adheres to it. The
coating of microbes with opsonin (op'-so-nin or
op'-saw-nin) proteins (antibodies and certain complement
proteins) is called opsonization.
- Ingestion -The phagocyte ingests
the microbe, surrounding it by a sac called a phagosome.
- Digestion or killing. Phagosomes fuse with lysosomes
containing lysozyme and ~30 enzymes which hydrolyze the
macromolecules of the microorganism. Lysosomes contain
lactic acids (pH ~ 4), hydrogen peroxide, superoxide radicals,
and hydroxyl radicals to destroy microbes. The residual body is
the indigested material left from the process.
- Elimination, the residual body (the digested phagosome)
moves to the plamsa membrane and is discharged outside the cell
What happens to the free radicles? Cells have enzymes to
neutralize them. You'll study catalase in the lab 2H2O2
--> H2O + O2.
- A few pathogens manage to live inside cells including
phagocytes. For example, Chlamydia (kla-mid-e-a), Mycobacterium
tuberculosis, and malarial parasites. These microbes
prevent the fusion phagosome and lysosome and keep the pH of the
phagosome too high for the digestive enzymes to work.
- A few leukocytes can kill pathogens extracellularly
w/o phagocytosis. They bind to and secrete toxins onto the
pathogen. This is the normal mode of action when
eosinophiles attack helminths and when natural killer
lymphocytes attack cancer or virally infected cells.
- Inflammation is a localized nonspecific response to tissue
damage that may be caused by heat, chemicals mechanical damage,
as well as by microbial infection.
- When used against infection, it is a process to confine the
agent of injury, destroy the agent, and repair the damaged
- The symptoms of inflammation include: redness, pain, heat, and
- We will follow the process of inflammation in a puncture
- When cells are damaged, they release inflammatory chemicals
such as bradykinin, histamine, kinins, prostaglandins
(pros-ta-glan'-dinz) and leukotrienes (loo-ko-tri'-enz).
- Histimine increases the vasodilatation and permeability
of blood vessels, increasing the flow of blood and plasma fluids
to the area. Both processes make it easier for WBC to
arrive at the site of injury as well as deliver antimicrobial
chemicals to the area, but they also result in swelling and
- Figs. 15.15,
- Kinins, leukotrienes and prostaglandins intensify the effects
of bradykinin and histamine and help to attract WBC to the
- Blood clotting proteins are delivered to the wound as the
capillaries become more permeable. Clots can keep microbes
from moving to other areas of the body.
- Pus may form at the wound as host cells die and fluids and
bacteria and phagocytes accumulate in a walled off cavity or
- Inside of an hour neutrophils are attracted to the site.
- Phagocytes stick to the endothelial lining of the vessels in a
process called margination. During emigration,
they squeeze between the endothelial cells in a couple of
minutes. Then they begin to destroy the invading microorganisms.
- Moncytes follow the neutrophils into the area. Once moncocytes
get into tissue they are called macrophages (wandering
- Neutrophils appear at the beginning of the inflammation and
macrophages dominate at the end. Macrophages are bigger and more
phagocytic than neutrophils. They can phagocytize tissue which
has been destroyed in addition to the invading organisms.
- The neutrophils and macrophages will eventually die and be
part of the pus at a wound. Pus either oozes at the
surface of the skin or is gradually absorbed by the body. With
time, the damaged tissue is repaired with the process of repair
actually starting during inflammation.
15.14 (15.17 older eds.) reviews inflammation of a
puncture wound. Bauman is a little out of date, steps 2
& 3 are not exactly correct.
- During the course of an infection, the frequency & number
of WBC change in the blood. Clinicians monitor both the
total white blood cell count and the count of the various types
of WBC as an indication of infection and of the phase of the
- Fever is another non-specific host response to
infection (see Fig. 15.18).
- Fever may inhibit the growth of some microorganisms,
intensifies some host defenses, and speeds repair
processes. Research has shown that when a fever is allowed
to run its course, the illness is over sooner.
- Some clinicians refrain from using fever-reducing drugs unless
the fever is too high or too long; others say the benefits are
too slight to endure its symptoms.
We've talked about phagocytes, inflammation and fever as
secondary lines of defense.
Two other secondary lines of defense include:
Interferon & complement.
- are proteins that are active against a variety of different
kinds of viruses. There are three kinds of interferon: alpha,
beta and gamma.
- Alpha and beta interferons are made by cells infected by
- Gamma interferon is made by lymphocytes to activate
macrophages and will not be further discussed.
- The production of new viruses in an infected cell induces the
production of interferon which is secreted and reacts with the
membrane of neighboring cells.
- This induces the neighboring cells to produce antiviral
proteins (which are otherwise untranscribed). So when new
viruses are released by the infected cell the neighboring cells
are equipped with antiviral proteins (AVPs) which inhibit the
replication of the virus.
- Antiviral proteins shut down protein synthesis & degrade
RNA in the neighboring cells upon viral infection. The
original infected cell likely dies.
- Fig. 15.11
Complement is an important set of proteins which are
found in the blood or serum.
- Complement activation occurs as a cascade. The products of one
reaction will cause another reaction to occur, resulting in the
activation of a cascade of several complement components.
- There are nine complement proteins, named c1-c9, some of which
can be cleaved into smaller active fragments.
- Once complement components are activated they have many
effects. These affects include:
- an increase of blood vessel permeability
- chemotactic attraction of phagocytes to the site.
- opsonization - one complement protein can coat microbes
making them more likely to be phagocytized by a WBC.
- cytolysis - once activated
some complement proteins will bind to pathogens and form
holes in its membrane, killing the pathogen. Gram-
cells w/ their exposed outer membrane and parasites w/o a
cell wall are particularly vulnerable.
- The activation of complement mainly occurs by two paths (Fig. 15.10):
- The classical pathway,
- The alternative pathway.
- In the classical pathway, antibodies bind to a
- Compliment then binds to the antibodies and begins the
complement cascade, resulting in holes in the microbe's
- This pathway involves specific host defenses (antibodies)
& nonspecific defenses (complement) against the pathogen.
- The alternative pathway involves nonspecific defenses
only. Lipid A and other molecules of pathogenic cells
interacts with factors in the blood (factors B, D & P) to
activate certain compliment proteins. Compliment cascade
then occurs forming membrane holes and killing the cell.
The Compliment Cascade
- Just to give you an overview for how the cascade
- Purple font below, understand the concepts, do not memorize
it, I'll provide the figure on an exam, but you must explain it.
- When antibodies bind
to the surface of a pathogen, C1 (the first complement
component) can bind to the antibody IgM or two IgG's.
(We'll discuss antibodies in the next lesson.)
- C1, when it is bound
to antibodies, will cleave C2 and C4 into fragments.
- One fragment from C2
(C2a) and one from C4 (C4b) combine and this molecule can
cleave C3 into C3a & C3b.
- C3a increases blood
vessel permeability. C3b coats microbes in opsonization
(signaling WBC to attack).
- C3b also combines w/
C2b & C4a to cleave C5 into C5a and C5b.
- C5a attracts
phagocytes to a site of injury.
- C5b initiate a series
of complement reactions which generate a protein complex that
forms a hole
in the plasma membrane. This is known as the compliment
cascade. The result is that the cell dies.
- So, the complement
cascade can be activated by either specific or nonspecific
responses. In the next lesson, we will talk more about the
production of antibodies and their role in specific host
Host Defenses II
- Be able to compare and contrast
humoral and cell-mediated immunity.
- Be able to list the results of
- Be able to describe the structures
of the various kinds of antibody molecules as well as their
- Understand how immunity can be
artificially, as well as naturally, acquired.
Differentiate between active and passive immunity.
- Be able to describe the types of
T-cells and their functions.
- Know the difference between
T-dependent and T-independent antigens.
- Last time we covered about nonspecific types of resistance to
infections, discussing the mechanical and chemical factors that
serve as a first line of defense (such as those associated with
the skin), and the 2nd line of defense including: the different
white blood cells.
- Today we'll look at specific resistance or the third line of
defense, or the host's immune response.
- This resistance depends on specialized lymphocytes (the B
& T) cells and the Lymphatic System
(especially the lymph nodes), the thymus, the spleen, the bone
marrow, the tonsils, appendix, and Peyer's patches in the
- Recall from an earlier class that the Lymphatic
System is a system of lymph vessels and nodes that
collect fluids that seep out of the circulatory system.
The collected lymph is filtered for infective organisms in the
lymph nodes before it is added back to the blood.
- Specific resistance is acquired, meaning
that it is learned, and it acts against a specific part of a
molecule. For example, when you are exposed to a new
virus, you can have no specific resistance to it. You
may mount a nonspecific defense and you may acquire a specific
- The things that cause you to mount a
specific immune response against them are called Antigens.
The nature of antigens: Fig. 16.1
- Most antigens are a protein or large polysccharide molecule
though it can be others.
- Lipids and nucleic acids are usually not very antigenic unless
combined with protein or polysaccaride.
- Certain molecules are "more antigenic" -that is the invoke a
stronger immune response than others.
- Most antigens have a molecular weight of 10,000 or greater
(water is 18, penicillin is 302).
- Small molecules can become an antigen if they are bound to a
bigger carrier molecule, such as a molecule in blood. (By the way, this is what happens when you
become allergic to penicillin.)
- Molecules of invading
microbes can serve as antigens, including molecules of
capsules, cells walls, flagella, toxins, and the coats of
- Each antigen molecule may have a number of antigenic
determinants. An antigenic determinant is also known as an
epitope and is exactly what the immune response is acting
- This immune response is performed by a lymphocyte.
Lymphocytes of Specific Host Defenses
- Fig. 15.5:
Recall that Lymphocytes are one kind of WBC.
- Recall that lymphocytes are the second most common WBC in
blood and that they are mostly a nucleus.
- There are various subtypes of lymphocytes, but only two main
types, B and T cells.
- (Actually, we ... discussed a 3rd type of lymphocytes, Natural
Killer (NK) cells that kill nonspecifically and extracellularly
like eosinophils. They target cancer cells and virally
- B cells and T cells originate as stem cells in
adult bone marrow or in the fetal liver &
- Immature T cells migrate to the thymus, a
gland near your heart.
- In the thymus, immature T-cell lymphocytes divide rapidly. But
only those with the ability to recognize foreign antigens
- After 2-3 days, mature T-cells emerge from the thymus and
migrate to a lymphoid tissue such as the lymph nodes or the
spleen or to the blood.
- T-cells are involved in the cell-mediated arm of
the immune system. It is called cell-mediated because its
immune response is all from cells.
- There are several types of T-cells. Some act against specific
foreign organisms or tissues and lyse them. Other T-cells help
regulate the activity of other immune system cells such as
macrophages & B-cells.
- Cell-mediated immunity is most effective against bacteria and
viruses located WITHIN host cells. It also acts against fungi,
protozoa, and helminths.
- Cell mediated immunity is responsible for the rejection of
foreign tissue in a transplant and is an important factor in the
body's response against cancer.
- B-cells also arise from stem cells in the bone marrow.
They mature in the bone marrow and migrate to lymphoid tissue or
to the blood.
- B-cells have antigen receptors on their cell surfaces, called
B-cell receptors or (BCR).
- Each B-cell contains ~500,000 copies of
1 receptor capable of binding 1 antigenic determinate, but as
there are 1X109 B-cells each w/ a different
receptor, we all have a B-cell that can react to nearly all
Selection Animation. (next three are in animation)
- When a B cell is is exposed to the
specific antigen it has receptors for, it will divide and
differentiate into a clone of many cells called plasma
cells. This process is called clonal selection.
- It is the plasma cells that make
antibodies which are proteins directed against the specific
antigen that activated the original B cell.
- A few B-cells differentiate instead into
long-lived memory cells. These cells are
responsible for the rapid response to a later infection.
- Antibodies are secreted from the plasma
cell and are found in extracellular fluids such as blood,
plasma, lymph and mucus.
- B-cells are part of the humoral (fluids) arm
of the immune system. It is called humoral because antibodies
are secreted into fluids, blood, lymph, mucus. The humoral
arm defends primarily against agents which are circulating
freely in body fluids, such as bacterial toxins and circulating
The Results of Antibody Binding
- When an antibody binds to an antigen it is mostly tagging the
foreign molecule or cell for destruction by phagocytes or
removal from the blood. The antibody usually does not damage the
antigen directly itself.
16.6: When antibodies bind to antigens any of the
following may occur:
- neutralization - By binding to a toxin an antibody
molecule may block the active site of the toxin, effectively
neutralizing the toxin. Antibodies can also bind to viruses and
bacteria and block their ability to adhere to cells.
- opsonization - antibodies can also bind to and coat the
bacteria. The antibody serves as an opsonin, enhancing
phagocytosis by signaling the phagocyte to attack here.
(Earlier, we talked about complement C3b serving as an opsonin).
One end of the antibody can bind to the pathogen while the other
end binds to a phagocyte.
- agglutination - an antibody molecule can bind to two
molecules or cells simultaneously. This can cause the cells or
antigenic molecules to aggregate or clump. Agglutination
enhances phagocytosis, reduces the number of infectious units to
be dealt with, hinders a pathogen from spreading, and
precipitates the antigen from the blood speeding its removal by
- complement activation - as was discussed earlier, the
binding of antibody to an antigen can allow one of the
complement proteins (C1) to bind to the antibody complex,
activating the complement protein and resulting in complement
cascade. Complement cascade is a chain reaction complement
proteins forming a hole in a pathogenic cell, lysing the
cell. The antibody is not lysing the cell directly, it
requires the activation of complement.
- inflammation - remember that one of the actions of
complement is to attract phagocytes to the area and increase
blood vessel permeability. By binding to antigen,
antibodies provide a spot for complement to bind and then
promote inflammation at the site.
- antibody-dependent cell mediated cytotoxicity - in
this process the target organism is coated with antibodies to
signal its destruction by a nonspecific immune cell. The
nonspecific cells are natural killer cells (a kind of
lymphocyte), macrophages, neutrophils and eosinophils. When the
target cell is coated with antibodies, nonspecific immune cells
can bind to the pathogen and secrete substances that lyse the
- killing by oxidation
-recently it was discovered that antibodies can catalyze the
production of oxidizing molecules which may kill bacteria
16.5, a simple antibody is shown.
- The molecule itself is shaped like a Y though it can bend.
- It consists of 4 polypeptide chains, 2 heavy and 2 light.
- Each antibody molecule has two binding sites (top of the Y)
which will interact with a specific antigenic determinant. The
two antigen binding sites are identical and are called the Fab
or variable region.
- Complement and phagocytes bind at the other end (called Fc or
- The structure of antibody molecules: Fig.
- - an antibody is often drawn as a
"Y." The molecule itself is shaped like a Y (although it is
flexible and can take on a T shape). It is composed of two
longer heavy chains. which are held together by disulfide
bridges. At the ends of the Y's arms each heavy chain is bound
to a light chain,also by disulfide bridges. So each molecule
is two heavy chains and two light chains. At the ends of the Y
both the light chains and the heavy chains have a variable
region. The structure of the variable region reflects the
antigen to which the antibody will bind. Antigen binds to the
ends of these variable regions (two antigenic determiniants
bind per molecule).
- The lower part of the Y is the constant region. There are five
different types of constant regions, which accounts for each of
the five classes of antibodies or immunoglobulin
molecules. The lower part of the Y is also
called the Fc region (c for constant). As we have seen,
sometimes the Fc region can bind to white blood cells or to
- The five types of immunoglobulin (Ig) are defined by
the amino acid sequence of the constant region.
IgG - is a monomer that is the most abundant Ig type in
blood and is small
enough to leave the blood and enter tissues. It enhances
phagocytosis when bound to
antigens, it neutralizes toxins and viruses, it protects against
bacteria by triggering
the complement system, it crosses the placenta and protects the
fetus. In short it
can do everything against an antigen.
IgM - a pentamer of five Y's held together via a J-chain.
It is especially
involved in agglutination reactions (it has ten places for
binding!) and in enhancing
phagocytosis. It can do most things IgG can do except that it it
too large to leave the
blood and cross the placenta. IgM is the first
antibody produced on initial
exposure to an antigen. A few days into the infection IgG is
produced instead. If a second
exposure takes place IgM levels rise some but the abundance of
antibody that's produced is
IgA - is both a monomer and a dimer and is most common in
mucus and secretions
like saliva, tears and breast milk. The secretory form is a dimer,
serum IgA is a monomer.
Prevents attachment of pathogens to mucosal surfaces, important in
respiratory infections. Its presence in colostrum helps protect
IgE - is a monomer that attaches to mast cells and
basophils (ba'-so-phils) to
release histamine causing inflammation. It is involved in allergic
reactions. When an
antigen such as pollen attaches to the IgE on a mast cell or
basophil, the cell releases
histamine and other chemicals. This may be a protective response
especially in the
response to parasitic worms as it attracts phagocytic cells. Yet,
it is a problem in
IgD is a monomer and the B cell receptor, BCR. It is
found on the surface
of B cells. Each BCR is specific for only one antigenic
determinant and each B cell is
covered with ~500,000 identical BCRs. When Antigen binds to a BCR
clonal selection occurs
to that B cell. Note, some BCR's are also IgM. You
should realize that the IgD
which initially binds to an antigen later becomes the IgM which
will bind to the same
antigen that later becomes the IgG which binds to the same
antigen. The same B-cell
makes all these antibodies types, though at different times.
(Note: everything in red font will not be on Midterm2.
The exact cutoff point may be sooner than this and will
be discussed in class.)
Immunity can be acquired
naturally or artificially and can be active or passive
|Natural -you get the
Antigen naturally (you get the flu)
||Active -you get immunity
yourself (you make Ab)
|Artificial -you get Antigen
fr/ a health care provider
(you get a flu shot)
|Passive -you get immunity
(the doctor gives you antibodies)
- Naturally acquired active
immunity comes from an infection and is lifelong for
some diseases, like measles and chicken pox. In these cases
antigens enter the body and the body produces antibodies and
- Naturally acquired passive
immunity is when antibodies pass from a mother to her
fetus via the placenta. As we've discussed, IgG crosses the
placenta and will confer passive immunity to the fetus. IgA is
found in breast milk and helps to confer immunity to the
- Artificially acquired active
immunity is provided by vaccination. In response to
vaccines the body produces antibodies and specialized
- Artificially acquired
passive immunity is when antibodies (not antigens) are
administered. These antibodies come from a person who is
already immune to the disease. Some of you may have received
gamma globulin shots before traveling. Gamma globulin with a
high titer of antibody against certain antigens is available.
High titer means a higher concentration of a specific
antibody. An example is the tetanus immune globulin which is
given when a person may have been exposed to tetanus. So,
passively administered antibodies are sometimes used to treat
diseases. This kind of immunity is short-lived because
antibodies are degraded by the recipient.
Cell mediated immunity
- As we discussed, it is mediated
by T-cells. T cells are similar to B-cells in that:
- react specifically with
only one antigenic determinant. Yet, Ag do not
bind to T-cells, macrophages & other
antigen-presenting cells bring the antigen to the T-cell.
- undergo clonal selection,
where they divide and differentiate on exposure to a
specific antigen. T-cells have T-cell receptors (TCRs)
which specifically bind certain antigens.
- generate memory T-cells
(allows immunity against future exposure of the antigen)
- Cell-mediated immunity is
directed against endogenous antigens, that is antigens
associated with host cells like viral antigens or the novel
antigens on cancer cells.
- Types of T cells can be
distinguished based on characteristic cell surface
molecules. T cells are divided into cytotoxic T cells
and helper T cells.
Cytotoxic T cells (TC)
target cells on
contact. Tc cells are particularly effective against viruses
and bacteria inside
host cells. Tc video.
- Once a cytotoxic T cell is
bound to a cell it will either form a pore in the membrane of
the target cell using perforin proteins causing the cell to
lyse or it will induce the target cell to undergo apoptosis (ah-pop-to-sis,
programmed cell death).
- Fig. 16.17???
Helper T cells (TH)
produce cytokines. Upon exposure to an antigen by an Antigen
(mainly macrophages and their kin), they differentiate into
type1 and type 2 helper T
Type 1 helper T-cells
produce cytokines that activate and stimulate the
proliferation of cytotoxic T
Stimulated cytotoxic T cells proliferate and attack
infected cells. Remember that
cytotoxic T-cells contain multiple copies of one T-cell receptor
on its surface that can
bind to only one antigenic determinant so that cell mediated
responses are specific.
Type 2 helper T-cells make
cytokines that further expand a clone of B-cells and activate
them in the production of
Types of Antigens
- Which arm of the immune system
gets activated depends on the type of Antigen. There are
- T-dependent antigen are
a certain kind of antigen that require the assistance of
helper T cells to ensure the production large amounts of
antibody. These antigens are mainly proteins found on viruses,
bacteria, foreign red blood cells, as well as small antigens
needing a carrier molecule. Both arms of the immune
system get activated.
- T-independent antigens can
stimulate B cells directly without the help of T-cells. These
antigens are usually composed of repeating subunits such as
polysaccharide or lipopolysaccarides such as those found on
bacterial capsules or cell walls. (Fig
16.12) (TC cells still need TH
cell stimulation in order to mount a T-cell response.
T-cells generally always need helper T-cells, so only the
humoral arm is activated here.)
CD 4 vs CD 8
- Another way in which T-cells
are classified is based on the cell's surface molecules.
- CD 4 cells have the surface
molecule CD 4 and are primarily on helper T cells.
- CD 8 molecules are on cytotoxic
- HIV attaches to cells by the CD
4 molecule and AIDS patients show a decrease in their CD 4
cells. Clearly a reduction of T helper
cells will influence the effectiveness of both arms of
the immune system.
Lesson 10: Immunization and
- Except for grafts, ch 18 will be covered, some sections only
- Ch 17, only covering immunization p. 494-502 (3rd ed. 490-498,
2nd ed. 485-493, 1st edition, 487-495)
- Be able to name the different types of vaccines and list their
advantages and weaknesses.
- Be able to relate how B and T-cells work from an earlier
lesson to how vaccines work.
- Be able to list the 4 types of hypersensitivities, whether
they are B or T-cell cell mediated, and be able to give an
- Be able to discuss how autoimmune diseases come about.
- Be able to discuss how which autoimmune diseases get what
- Edward Jenner performed the first immunization against
- He used another virus (cowpox) to immunize people against
- No one understood why his vaccine worked, but it was because
the two viruses were related enough so that when our bodies
reacted to cowpox, the B and T-cells would also react to
- The next vaccine was not produced for nearly 100 years by
Louis Pasteur whose experiments finally illuminated the
principles for making further vaccines.
Immunity and Vaccines
- As discussed in a previous lesson, immunity can come about in
- passive immunity -where serum or antibodies are injected
into a person to make them immediately resistant to the
antigen. Passive immunity may also come from a mother
to her child.
- active immunity -where an antigen (called a vaccine) is
administered and the patient responds to the antigen and
creates memory cells so that the patient will respond
vigorously to the antigen in the future.
- There are 3 types of vaccines:
- Attenuated live vaccines
- Inactivated (killed) vaccines
- Toxoid vaccines
Attenuated live vaccines
- The virulence of the virus or pathogen has been removed or
reduced so that it no longer causes disease.
- In reality, they may cause mild disease and they are living
organisms, so that mutation back to virulence will happen at an
extremely low frequency (oral polio: 1 case per 2 million).
- They invoke both strong T and B cell responses, require one or
few doses, and immunity is usually lifelong.
- They are live organisms so that they can spread from the
vaccinated individual to their susceptible neighbors, providing
herd immunity (protecting the herd).
- Examples, the attenuated oral polio vaccine (Sabin), cowpox,
Inactivated (killed) vaccines
- The virus or pathogen has been killed, or only molecules or
fragments of the organism are used.
- Several booster doses are required, immunity is usually long,
but not lifelong.
- Only a humoral response is made, no T-cell response.
- Examples, inactivated polio (Salk) shots, flu shots, rabies
- The vaccine is intended not to fight the pathogen, but rather
the toxin that the pathogen makes. These vaccines use
modified toxins that are not toxic but stimulate an immune
- Examples, tetanus and diphtheria vaccines.
- Immune responses are not strong or long lasting, so they
require several boosters during childhood and reinoculations
every 10 years.
- Only a humoral response is made, no T-cell response occurs.
- Vaccines use the immune system to
prevent disease, but the immune
system can also cause disease.
- A Hypersensitivity/allergy is a
disorder of the immune system.
- Hypersensitivity refers to a
response to an antigen that is beyond what can be considered
normal, can be too much or at the wrong time or both.
- They can be either B-cell or T-cell mediated
- B-cell are responsible for 3 of the 4 types of
hypersensitivities (named Types I, II, III)
- B-cell hypersensitivities most are relatively rapid immune
responses, w/i minutes
- T-cell hypersensitivities
- Responsible for Type IV hypersensitivity
- take longer, usually 24-72 hours.
Types of hypersensitivitis:
Type I: Anaphalactic
- First exposure to antigen sensitizes your system to the
- B-cells get stimulated to produce
antibodies, including IgE
- IgE coats Mast Cells and Basophiles, they are now primed
- Second Exposure of Antigen
- Antigen binds to IgE on Mast cells/Basophiles
- These cells dump out histamine/heparin/other inflammatory
- Get a rapid inflammatory response
- if local, not usually a problem, is an allergy
- if systemic, can be life threatening
- bronchial smooth muscles contract, blood vessels can
swell, may close the airway
- Epinephrine may be used to relax the muscles
Type II: Cytotoxic
- host is exposed to something (usually cells) that carry an
- antibodies are produced against the antigen
- host destroys the antigen usually w/ compliment, but may
- is responsible for many autoimmune diseases, destroying RBC
upon mismatched blood transfusion, Rh incompatibility between
mother and fetus.
- Unlike other B-cell mediated hypersensitivities, this one
takes time, 5-12 hrs..
- Rh is an example, Fig
- Rh+ antigen is a surface molecule on RBC of some humans and
- Rh- individuals do not have the molecule
- The placenta normally keeps fetal RBC out of the mother, but
during later pregnancy, abortions, or childbirth, fetal blood
often spills into the mother (20-50% cases). This can be
dangerous for a second Rh+ fetus in a Rh- mother.
Medication can now solve this problem.
Type III: Immune Complex Hypersensitivity
- often mediated by IgG but can be other antibodies.
- in an infection, IgG binds to a small antigen forming a
complex that is small enough to circulate and avoid being
- (IgM complexes and aggregation/agglutinations are much larger
and less likely to do this.)
- these IgG complexes get wedged in small places, capillaries,
- The complexes attracts complement, phagocytes, interleukins,
and other inflammatory agents,
- the inflammation damages your tissue.
- Examples, hypersensitivity pneumonitis (noo-mōn-ī'tus) caused
by dust or mold breathed into the lungs, which have IgA, more
often called: farmer's lungs, pigeon breeder's lungs, and
Type IV: Cell-Mediated Hypersensitivity
- mediated by T-cells, no antibodies involved
- generally takes 24-72 hours, more time need for Tc to act and
- antigen usually crosses the skin or mucosa from outside, such
as w/ poison ivy
- antigen can also be from a tissue or organ transplant
- regardless of it origin, the antigen stimulates Tc cells
- Tc cells kill cells with the antigen and call in other
inflammatory factors including WBC
- This causes cell and tissue damage w/ pus often accumulating.
- Example, the pus and reaction of poison
Review of Types of Hypersensitivity
Type I (anaphylactic)
to mast cells or basophiles causing release of histamine
shock from drug or insect bite, hay fever, asthma
IgM bind to target cell, complement is activated, cell
antigen form complexes that cause inflammation
- the immune
systems creates B and T cells that react to many antigens
- normally in
early childhood, the body prunes cells that react to antigens
of the self
- if the immune
system does produce antibodies or Tc cells that react to the
self, it is an autoimmune disease
- most develop
with no predisposing factor, though viral infections may play
a role in some cases
- more likely to
occur in older individuals and in woman
preponderance of woman is thought to involve pregnancy, where
fetal antigens cross the placenta. Curiously, cells from
the fetus may move into the mother and possibly cause
autoimmunity, but cells from the mother may also move into the
daughter and possibly cause autoimmunity. Mom's female
cells are less likely to live in sons.
There are many
autoimmune disease of two types:
- Single Tissue
hemolytic anemia -make antibodies against their own RBC
attack on islets of Langerhans results in type I diabetes
disease -antibodies bind to pituitary which over
stimulates its stimulating the thyroid to produce thyroid
sclerosis (MS) is caused by Tc cells destroying myelin
sheaths of neurons.
(systemic lupus erythematosus) -Tc and antibodies produced
against many types of antigens on the patients
cells. Autoantibodies against DNA form immune
complex which lodge in and damage the kidneys.
arthritis -patients make antibodies against collagen,
causing inflammation in the joints. With each
recurrence the damage gets worse, eventually destroying
Congenital Immunodeficiency Diseases
- inherited defects have been found in all the bodies lines of
defense, they include:
- phagocytes that are unable to kill ingested bacteria (chronic
- most common are defects in the ability to produce one type of
- IgA deficiency - most common, children have multiple
respiratory and gastrointestinal infections
- IgG or IgM defiency -more likely to have bacterial infections
- severe B cell deficiency (Bruton-type agammaglobulinemia)
-mostly boys who cannot make any antibodies, usually have
recurrent bacterial infections. They are usually ok w/
viral and eukaryotic infections. Until relatively
recently, these patients did not survive into adulthood.
- T-cell deficiencies (DiGeorge anomaly) -children lack a thymus
and have no T-cells. Children are resistant to most
bacteria, but usually die before reaching adulthood from viral
- Severe combined immunodeficiency disease (Bubble Boy Disease)
-children are born without B or T-cells.
- Genetic engineering of people has begun. Some of these
children with immune disorders have been genetically
engineered to the specifications
desired by their parents!
Lesson 11: Viruses
- Be able to list the characteristics of viruses.
- Be able to describe the structural components
of animal and bacterial viruses.
- Be able to compare and contrast a lytic vs a
lysogenic life cycle;
- Be able to compare and contrast latent,
budding, and lytic cycles of animal viruses.
- Be able to discuss how a latent and budding
virus effects the process of disease.
- Be able to compare and contrast bacterial and
animal viruses with regard to their interaction with host.
- Be able to list the variation among viruses
with respect to nucleic acid content.
- Be able to discuss prions and viroids.
- Realize that this is just an introduction,
virology is a huge field.
- They are obligate intracellular parasites;
- have few or no enzymes for metabolism
- cannot manufacture protein, ATP, nucleic acid,
or anything on their own;
- multiply inside living cells by using the
machinery of the host cell.
- They cause the host to make viral proteins that
surround the viral nucleic acid;
- together, viral proteins and a molecule of
viral nucleic acid makeup naked viruses.
- Some viruses also have an outer membrane called
- Two Types of viruses: Naked and Enveloped
- There are viruses to every kingdom; we'll only
study bacterial and animal viruses.
- Are they alive? It depends on who you
Viruses have different components to their structure,
- if you remember back to the first homework,
most bacteria are ~1000nm in diameter.
- Most viruses are a bit smaller than 100nm in
diameter, or < 1/10 the size of bacteria.
- A RBC
is ~10,000nm, E. coli: 3000 X 1000nm,
bacteriophage T4 is 225 x 50nm.
- Lots of variation in the size & shape of
- Ebola virus is almost as big as the smallest
bacteria (intracellular), ~400nm. Poliovirus is one of
the smallest at ~30nm.
- Morphology includes whether they're enveloped
- Viral Components (Fig.
(what you find in viruses)
- Nucleic acid: an innermost molecule, can
be DNA or RNA but not both.
- depending on the viral family, can be
double stranded (dsRNA or dsDNA)
- or single stranded (ssRNA or ssDNA)
- ssRNA can be (+) strand (that is can be
read by ribosomes as mRNA)
- or (-) strand (cannot be read by
ribosomes, complimenatry to mRNA).
- Capsid: is a protein coat surrounding
the nucleic acid.
- Envelope: around the capsid in some
viruses, called enveloped
viruses, Fig 13.7.
- May aid in the attachment to a host cell.
- The host range of a virus depends on its
ability to bind to a cell.
- Most viruses are specific
and only infect certain host species or even specific
- This specificity is because
certain viral surface proteins or glycoproteins only bind
to certain receptors on the surface of host cells.
- You might recall that I
mentioned that HIV binds to cells containing the the CD4
receptor that is mainly found on helper T-cells.
- Spikes: molecules which protrude from
the viral surface of enveloped viruses, they are involved in
- Enzymes: some viruses
have one or a few enzymes; active only in a host cell.
- So, viruses vary quite a bit in their size,
shape, whether they are enveloped or not, if they have spikes,
if their genome is DNA or RNA, and if the genome is single or
- Much of this variation is used to classify
viruses including their:
- type of nucleic acid
- whether it is single or double stranded
- presence or absence of envelope
- their shape
- Viruses are referred to by their common English
names instead of using Latin genus and species names.
- They also are not classified into
superkingdoms, kingdoms, phylums, and classes, though a few
- They are generally only grouped into families,
genera, species, and strains.
- They are classified by the kingdom they infect,
for example animal and bacterial viruses.
- Viruses that grow in
bacteria (eubacteria) are called bacteriophages or
- This is T4, one of the most studied
- Note the tail fibers (which allow it to attach
to host cells), the tail sheath, and the capsid (head) of the
virus that contains the nucleic acid.
- Bacteriophage Lambda looks the same as
T4 except that it lacks tail fibers.
- Bacteriophages often have tail structures used
in attachment that are lacking in animal viruses.
Lytic Life Cycle
- Viruses have differnt ways of living called
- The first life cycle we will dicsuss is the Lytic Life Cycle.
- Discussing bacteriophages T4 and Lambda, but
similar for other lytic viruses.
- See Fig. 13.8 for T4, Fig. 13.11 for Lambda, and the outline for a video of the lytic life cycle.
- Infecting viruses stay on the outside of
- They attach and inject nucleic acid into the
cell. The sheath contracts almost like a syringe to make this
- Viral DNA directs the degradation of the host
chromosome, taking control of the cell.
- Viral DNA directs the cell to synthesize viral
- The components are assembled into virions (vī-rē-ons, or vir-ē-ons).
- The host cell lyses to release the virions,
which may then infect new cells, contiuing the lytic life
- It's possible to follow the lytic cycle over
time, see Fig.
- Burst time - time from attachment to release of
- Burst size - number of new virions released per
cell. These released viruses can than
infect neighboring host cells.
Viral Life Cycles
- In the lytic life cycle, bacteriophage
DNA stays separate from the host's
chromosome and lysis the host cell.
- Some bacterial and animal
viruses only have a lytic life cycle (i.e., T4).
- But, other viruses have other life cycles:
- lysogeny (some bacteriophages,
- budding or persistent infections
(some animal viruses, HIV)
- latency (some animal viruses,
- Some viruses have more than one life cycle;
Lambda has both lytic and lysogenic life cycles, and HIV has
both latency and budding.
- Bacteriophage Lambda has both a
lytic life cycle and a lysogenic cycle, see the outline for a video.
- In its lysogenic cycle, the viral DNA
integrates into the chromosome of the cell.
- This inserted viral DNA is called a prophage.
The viral genes responsible for the lytic cycle are repressed
by a viral protein of the lysogenic life cycle.
- The only time the prophage
replicates is when the chromosome replicates during cell
- The lysogenic bacteria live and reproduce
- For reasons that are
not well understood, occasionally the prophage DNA is exised
from the host's chromosome.
- When this happens, the virus shifts to the
lytic life cycle. Phage is assembled and the cell breaks
open releasing the virions.
Bacteriophages and Human Health
- Bacteriophages do not infect animals, but they
can affect human health in other ways.
- Prophages may give the host bacteria new
- Lysogenic bacteriophages can encode toxins,
capsules, and other virulence factors that may affect the
pathogenicity of their host bacteria.
- Recall, we discussed Corynebacteria
produces Diptheria toxin only when it is infected by a
lysogenic phage carrying the appropriate gene.
- Also, remember our lession on recombinant DNA
that sometimes bits of the host cell DNA are stuffed into the
viral capsids instead of viral DNA. Such a virion then
injects bacterial DNA into another bacterium in the process of
- Transduction is one way that bacteria can pick
up new phenotypes that may affect human health, such as genes
for antibiotic resistance.
- In the 1920's and 30's,
bacteriophages were actually given as therapy for patients
with bacterial infections, but this was discontinued in 40's
because it was not very successful and antibiotics became
- Today, lytic bacteriophages are
sometimes used to treat multidrug resistant bacterial
Budding and Persistent
- Some animal viruses integrate into
the host cell's DNA in a process similar to lysogeny
but we will call this a budding or persistent
- Unlike lysogenic bacteriophages, these animal
viruses become permanently a part of the host cell's
- The integrated viral DNA is called a provirus
and it can synthesize viral particles which bud out of a
cell's membrane without causing cell lysis.
- When budding
out of the cell, ER, or nuclear membrane, the virus takes a
part of the membrane with them; this how enveloped
viruses obtain their envelope.
- Some naked viruses
(lack an envelope) leave the cell by exocytosis w/o
causing cell lysis.
- Both these viruses usually
cause Persistent Infections and do not kill the cell
or degrade its DNA; cell killing is usually due to the
host's immune system.
- Sometimes, these viruses
become latent instead of replicating.
Animal Virus Latency
- Some animal viruses enter into latency, where
they can become dormant for long periods without replicating
or causing disease.
- Some latent animal viruses integrate into the
host chromosome, but others do not (recall that lysogenic
bactriophages always integrate).
- Chickenpox (Varicella-Zoster) is a virus that
can become latent. About 15% of people who had chickenpox
can develop shingles years later. The virus goes
latent in nerve cells.
- Another example is the herpes simplex virus-1
that causes cold
sores. The virus goes latent until your immune
system is weakened, such as when you have a cold. Then
cold sores break out often in the same spot as before.
- Animal viruses differ from bacterial viruses
in several respects.
- Table 13.4 illustrates these differences. (Only
show, you do not need to memorize these differences).
- Many bacteriophages have tails used in
attachment, animal viruses do not.
- Animal viruses use proteins in their spikes,
capsid, or envelope to attach.
- They also differ in viral penetration into
the cell, uncoating, site of synthesis, assembly, and
- Note that bacteriophages must replicate in
the cytoplasm, but animal viruses might not.
- Most DNA animal virus replicate in the
nucleus whereas most animal RNA viruses replicate in the
- RNA retroviruses such as HIV are one
exception, they replicate in the nucleus.
- HIV is a retrovirus.
- These viruses are special because they carry
the enzyme reverse transcriptase.
- Reverse transcriptase makes DNA from
retroviral RNA (or mRNA in a lab, it also will make the DNA
- (See Fig. 25.19, I drew it out to simplify
- This DNA then integrates into the host cell's
DNA where it may lay latent or it may be transcribed.
- Once transcribed, this RNA can be used as
both the viral genome and as mRNA to encode for viral capsid
- Viral RNA is packaged into the capsids to
- The virions then bud out and acquire their
envelope from the cell membrane.
- Prions are not viruses or cells,
nearly all the evidence is that they are infectious proteins.
- The initial work was done on a neurological
disease in sheep called scrapies, a disease sheep farmers having been
living with for centuries.
- Apparently, there are two forms of a certain
protein, PrP, a normal form and a prion form, see Fig.
13.21. The PrP protein is found in neural cells, especially brain cells.
- It is thought that the presence of the prion
form (the one that causes disease) makes the normal protein fold into the prion form. The
nerve cell then makes more normal PrP because it is too low in the cell and it needs it to function.
The normal protein is converted
into prion PrP by the prion form, and the cycle continues, so that the prion form builds up in the cell.
- The prion form causes problems for the cell and characteristic plaques are found in the
brains of humans and animals with prion diseases. The plaques
look like a sponge - hence the name "spongiform."
- In the 1990s, there was an epidemic of a
prion disease in British cattle. It's called Bovine
spongiform encephalopathy (in-sef-a-lop-a-thē) or
Mad Cow Disease.
- It is not known to spread from person to
person, but prion diseases are thought to spread among
animals, or animal to animal.
- The British had little use for cow brains, no one wanted to buy them.
So they fed their cows grain enriched
with ground up cow brains, so that the brains would not go to waste.
This allowed Mad Cow disease to quickly spread and it soon
became an epidemic.
- Shortly thereafter, a higher incidence of human (~175) and cat (~150)
prion disease was seen in Britain. The cat disease is called Feline spongiform encephalopathy,
the human disease is called Creutzfeldt-Jakob disease after the first families it was seen in. Both
domestic and zoological cats (tigers, lions, etc.) became ill. Oddly, dogs appeared to be resistant as none
got prion disease symptoms though they were eating food similar to domestic cats.
- Although unproven, it is thought that the
affected people and cats became diseased from eating prion infected beef. With the zoological cats,
it is known that they ate cows having Mad Cow symptoms that had been donated to the zoos.
Mad cow disease in the lab appears to infect all mammals tested, but in Britain, only people and
cats became ill.
- In Britain, feed regulations were put in
place and most of the cattle were incinerated so that the prion disease epidemic appears to be over.
- Viroids are not viruses, they are infectious
RNA molecules that infect plants. (Infectious RNA
molecules are also known to infect fungi but not
- They are like viruses without the protein
capsids. Meaning, a viroid RNA infects a plant cell, it uses the
cell's machinery to make more viroid RNA. The replicated viroid RNA leaves
the cell to infect more cells, and the cycle continues.
- Viroids cause several diseases in plants,
- Infections can be caused by
more than bacteria; viruses, prions, and viroids.
- Review of viral shapes video.
- Review of
viruses, click on the many links.
- Lastly, Prions in
more detail than you need to know.
Lesson 12: Pathogenic Viruses
- Be able to discuss why treating viruses has
not been very successful.
- Know that there are different viral families
among the DNA and RNA viruses.
- Be able to name and briefly describe some of
the common viral infections of man.
- Be able to list what family a virus
belongs to and what type of nucleic acid it has.
Viruses and Disease:
- There are many viruses that cause human
- We will only discuss some of them
- Because they are obligate intracellular
parasites, treating viruses has been elusive.
Anti-viral therapies have to get through the cell to get to
the virus and they cannot do much damage to the host's cells
w/o adversely affecting the host.
- Realize that there is not, has never been,
and for the foreseeable future there will not be any
antiviral therapy that can cure a viral disease.
- Prevention is possible by using vaccines, but
with our current medical knowledge a cure is not possible
for any viral disease!
- Are dsDNA virus with an envelope.
- Smallpox has played important roles in the
history of civilization, immunization, microbiology, and in
the history of medicine.
- Recall that we discussed that Edward Jenner
created the first vaccine against smallpox by using the
related cowpox virus.
- Smallpox was in 1980 the first and only
disease that has ever been eradicated from the
- Smallpox is now an extinct virus except for
stocks of it held by the CDC, a few labs, and the U.S. and
Russian army researchers.
- There were two strains of smallpox
- variola (ver-ē-ō'-la or ve-rī'-ō-la)
major -severe, mortality rate of 20+%
- variola minor -less severe, mortality
- Both strains produced high fevers (up to 107oF),
prostration, and pox
lesions that left severe scars.
Other Pox Viruses
- There are a number of other
viruses in the pox family that humans can get, such as cowpox
and monkeypox, but there is only one, molluscum
contagiosum that is a human virus.
- The later is not a severe
disease and is most commonly spread by contact among children
or sexually active adolescents.
Herpes Family of Viruses:
- dsDNA virus with an envelope.
- I discussed two members of the family last
time, so I'll only discuss the family and their new names
||Disease and notes
|Human herpesvirus 1
||herpes simplex virus-1
||cold sores, whitlow
|Human herpesvirus 2
||herpes simplex virus-2
lesions, whitlow, neonatal
|Human herpesvirus 3
|Human herpesvirus 4
||Epstein-Barr Virus, EBV
mono, Burkitt's lymphoma, etc. (~90%)
|Human herpesvirus 5
||most asymptomatic but may be severe in
fetuses, newborns and immunocompromised (US ~50, some 90%)
|Human herpesvirus 6
||causes illness and a skin
rash in children, may play role in MS, ~100%
|Human herpesvirus 7
||causes illness and a skin rash in children
usually a short time later than HHV 6.
|Human herpesvirus 8
sarcoma, a blood vessel cancer seen in the skin
(very low %)
The Family Papillomavirus
- dsDNA naked virus.
- Papillomaviruses cause benign growths called
warts on skin or mucous membranes.
- 40 varieties of papillomavirus cause warts in
- They are transmitted by direct contact or by
fomites because they are naked viruses, they are more stable
outside a host.
- The incubation time till obvious infection is
usually 3-4 months.
warts on the fingers especially common in boys.
warts on the sole of the feet are common among
- Flat warts are found on the trunk, face, elbow or knee and are not discussed in the early editions of Bauman.
warts are the most common sexually transmitted
- Genital warts increase your and your
partner's risk of many forms of cancer, and in females that
give a normal birth, it increases the risk that the child
will get cancer of the larynx.
- are dsDNA naked viruses.
- Around 30 different adenoviruses cause the cold.
- Also can cause eye infections called pinkeye
and diarrhea in children.
- (+) strand ssRNA naked viruses.
- > 100 varieties of picornaviruses cause colds
(rhinoviruses) making a vaccine impractical.
- Highly contagious, a single virion can cause
- Are respiratory infections, but the
most common means of transmission is hand to hand contact
with subsequent inoculation of the eyes by the hand.
- Antisepsis of the hands and disinfection of
surfaces is the best way to prevent their spread.
- Several varieties of picornaviruses are
transmitted by the fecal-oral route (enteroviruses)
- Polio, which we discussed earlier
- After Latin
America eradicated polio, the
U.N. began trying for some time now to make polio the
second disease eradicated
from the world, but it has been less successful in
war-torn and unstable regions.
- and Coxsackie A and B viruses
- Some varieties of Coxsackie A cause oral
lesions similar to herpes simplex.
- Other varieties of Coxsackie A cause colds
that are transmitted fecal to oral.
- One variety of Coxsackie A causes hand-foot-and-mouth
- A variety of Coxsackie B causes myocardial
& pericardial infections resembling a heart attack.
- Some Coxsackie B viruses infect the pancreas
and may cause diabetes as was discussed in a previous
- Other picornaviruses (not rhinoviruses nor
- Hepatitis A that is transmitted fecal to
- In summary, you probably noted that this
family of viruses is very diverse.
Families Togaviridae and Flaviviridae
(Togaviruses and Flaviviruses)
- Are (+)ss RNA viruses that are enveloped.
- Most are transmitted by arthropod vectors
(mosquitoes, ticks, flies, etc.).
- The vectors and the animals they bite are
reservoirs of disease.
- These viruses can have very broad host ranges
- Most cause mild flu-like symptoms 3-7 days
- Virus enters the blood so that biting
arthropods can become infected, but this is not persistent
- Occasionally, virus is spread to other
tissues which can cause severe disease.
- Eastern equine encephalitis
- Western equine encephalitis
- Venezuelan equine encephalitis
- West Nile virus (severe cases cause
- Dengue fever
- Yellow fever
- Yellow fever is the most severe disease, w/ a
mortality rate up to 20%. It was in the US. before
mosquito control and the development of a vaccine eradicated
- As recent as 2005, there was an outbreak of dengue fever in Texas which has the mosquito vector.
- The Zika virus is a Flaviviridae that is being spread by mosquitoes in Florida and Costa Rico. Recently, there is a pandemic of Zika virus disease as the virus has greatly expanded its geographic range. It causes microcephaly in newborns and can spread from males to females during sex and from mother to fetus in the womb.
or the German measles is caused by a togavirus, but it is
transmitted by the respiratory route, not by arthropod
- Is usually not serious, especially in kids,
though adults may develop encephalitis or orchitis.
- It can cause severe birth defects when a
pregnant mother becomes infected. Before the vaccine,
it was the leading cause of birth defects.
- The fact that Birth defects have stayed the same since WWII
despite the Rubella vaccine should be an Ecological warning to
- is caused by a flavivirus, but is not
transmitted by arthropods vectors, but by needles, blood,
- usually is asymptomatic but may lead to
severe liver damage. Is the leading cause of liver disease in USA.
- Are (+)ss RNA viruses that are
- Second most common cause of Colds, behind
rhinoviruses & ahead of adenoviruses.
- Are (-) strand ssRNA viruses containing an
- The paramyxo viruses include many childhood
- The measles
- one of the more contagious and serious
- diagnosed especially against rubella
(German measles) from Koplik's
- vaccine in combination w/ measles and
- Croup (kroop) and parainfluenza
- strain 4 is associated w/ mild upper
- strains 1 & 2 cause Croup, a severe
lower respiratory infection w/ inflammation that may
restrict the airway and causes a "seal bark".
- Are well known to you even if you have never
heard of orthomyxoviruses.
- Are (-) strand ssRNA viruses containing an
- In one winter, ~half the world's population
became infected and ~50 million people died from these
- In was the swine
flu pandemic of 1918-1919 that touched everywhere except
for Australia, they set up a quarantine.
- Influenza or the flu is caused by two species
of orthomyxoviruses, called types A and B.
- Can infect and grow in a variety of species,
including pigs and birds.
- The envelope has spikes containing
hemagglutinin (HA) or neuraminidase (NA).
- HA and NA are important in attachment and entry
into the host cell and are the major antigens on the virus.
- The flu genome is highly
changeable, especially for HA and NA.
- Mutations allow the HA and NA genes to change
slightly. This is called antigenic drift of the
- When two differing viruses exchange genes, this
may make major changes in the virus, and this is called antigenic
- Because of antigenic drift, flu shots are good
for only ~ 3 years.
- When antigenic shift occurs, people's immune
systems have no immunity to the new virus and epidemics
usually occur. This happens about every 10 yrs.
- Unlike other viruses, inside of one envelope,
there are 8 capsids each with different RNA molecules.
- The genome is split into 8
RNA pieces and each piece is put into a capsid, 8
capsids to one envelope.
- This unusual packaging helps the virus exchange
- There are many viruses that cause disease,
including 7 families of DNA
Viruses and 15 families of RNA
- In this and in previous lessons I have only
discussed a few of the more common viruses.
- They are all intracellular parasites, none have
a cure, many can be prevented by vaccination.
Lesson 13: Pathogenic Gram+ Bacteria
- Be able to discuss disease progression in
- Be able to discuss why evolution matters when
treating a disease.
- Be able to name and describe staphyloccoccal
- Be able to list the virulence factors
- A number of bacteria species
cause disease. Today, we'll discuss a few fr/ ch 19.
Recall that the cell walls of this
bacillus have lots of mycolic (mī-kol’ic)
acid, a long lipid chain of 60-90 carbons, giving Mycobacterium
- a slow growth rate
- protection from lysis upon phagocytosis by macrophages
- growth w/i WBC
- resistance to drying, can survive for months
- resistance to detergents, many antibiotics, and to Gram
- acid fast staining properties
- ~75 species known but only 3 or 4 (dependind on your edition
of the text) cause disease in man:
- M. tuberculosis
- M. leprae
(lep’rē or lep’rī),
- M. avium-intacellulare (ā’vē-um
- Cause the diseases of tuberculosis, leprosy,
and opportunistic infections in AIDS patients, respectively.
- Causes tuberculosis (TB) if the cord factor (a
virulence factor) is present.
- The chord factor causes daughter cells to remain attached to
each other in parallel alignment and is toxic to cells (Fig.
- It is a master at evading host defenses; disease progresses
- Infection can start anywhere, but most start in the lungs as
a respiratory infection.
- Mycobacterium attracts macrophages which engulf the
bacteria in phagosomes, but the bacteria prevent fusion of the
lysosome and phagosome.
- When the bacilli grow inside the phagosomes, they eventually
kill the macrophage, releasing bacteria and attracting more
macrophages to the area. The cycle repeats as the
released bacteria are phagocytized by other
- The large numbers of infiltrating macrophages begin to form
at the site of infection.
- Other cells encase the tubercle in collagen. After a
few weeks many of the macrophages in the tubercle die
releasing bacilli and forming a caseous
center. You are looking at a caseous substance here.
- The disease may remain dormant at this stage for decades.
- Most of the time, the immune system is able to stop disease
progression but is unable to rid the body of Mycobacteria as
the macrophages and tubercle hide the infection from an immune
- Such patients are carriers with a dormant disease.
- Sometimes, the immune system is able to break the stalemate
and kill all the Mycobacterium forming
calcified lesions on X rays.
- Sometimes, the bacterium is able to break the stalemate by
rupturing the tubercle and reestablishing an active
- If macrophages carrying the pathogen enter the blood or
lymph, the disease may spread throughout the body and is
called disseminated TB.
- Tuberculosis was once known as consumption, because
in a disseminated infection, the patient suffers weight loss,
coughing up blood, and a loss of vigor, as the bacteria grows
throughout the body.
tuberculosis is not very virulent, only ~5% of
infected people develop disease.
- Yet, for those that develop disseminated TB, the mortality
rate if left untreated is quite high.
Diagnosis and Treatment
Incidence and Risk Factors
- In the US, ~2,000 new cases/yr and ~2000
- Worldwide ~3 million die each year making it a leading infectious
killer in the world.
- Risk factors:
- patients with lowered immunity are at greatest
- diabetes, poor nutrition, stress, crowded living
conditions, drug and alcohol abuse, and smoking also
increase the risk.
Why Does Evolution Matter Video
- Staph are cocci that grow in clusters like grapes.
- Two species commonly cause staph infections:
epidermidis is part of your skin biota.
- It is an
opportunistic pathogen when introduced into the body by a puncture
or other wound,
- or in an
- Is a true
- It is often
found in nasal passages, the hands, and moist skin folds,
but can survive on skin.
- In culture, S.
aureus produces golden yellow colonies ("aur" means
- It is easily
transmitted between individuals by direct contact or by
fomites, such as when it is transmitted among athletes or
- The bacterium
has three features that make it virulent (Veer-you-lent).
to evade phagocytosis
- The surface of S.
aureus has a protein named protein A that
binds to the Fc portion of IgG, inactivating the antibody in
- inhibit its
acting as an opsonin (thereby slowing phagocytosis)
- inhibit its
compliment binding and attack against the bacteria.
- Most S.
aureus cells have coagulase
bound to its surfaces, an enzyme that causes
clotting around the bacteria.
- Clotting walls the bacteria
off, but also hides it from the immune system.
- When the
bacteria are few, it protects them until
their numbers grow, whereupon they dissolve the clot and
may overwhelm the immune system.
- The bacteria
also secrete a polysaccharide slime layer (or a capsule).
inhibits chemotaxis and phagocytosis by WBC
- (and aids
bacterial attachment to medical devices).
- S. aureus
produces a number of enzymes that increase its virulence
- Secreted coagulase
(unbound) that aids in forming a clot around the
that dissolves the fibrin threads in a blood clot. The bacteria
secrete the kinase when nutrients and space in the clot
become limiting so that it can spread to a new location.
or hī-al-your-ron-i-dās) that
breaks down the matrix between cells and basement membranes,
allowing the bacteria to spread.
(β)-lactamase (penicillinase) to inactivate
Toxins of S.
- S. aureus
produces a number of proteins that are toxins including:
- Five cytolytic
toxins: α,β,Γ,Δ, and leukocidin
(luke-a-sie-din) that lyse cells providing some
protection against phagocytosis. Leukocidin is
especially protective because it lyses white blood cells.
- 2 Exfoliative
toxins that dissolve desmosomes, which hold adjoining
epidermal cells together, causing the patient’s skin to
slough (sluff) off.
toxin causing Toxic shock syndrome.
- 5 Enterotoxins
(designated A-E) that cause food poisoning.
- S. aureus
food poisoning is one of the more common food borne
- It is really an
intoxication and not a food poisoning
because disease is caused by ingesting the enterotoxin
and not the bacteria itself.
aureus is quite resistant to drying, high
osmostic pressure and heat lamps. (In the lab
Staph grew on 7.5% salt in MSA plates.)
- The enterotoxin
is even more stable, surviving up to 30 minutes of boiling.
- Once the toxin
is formed, it is NOT destroyed if the food is reheated, even
though the bacteria die.
- It grows
well in foods like custards, cream pies, potato salad, processed meat,
and ham. (Many of these have high osmotic pressure from
sugar or salt that prevent other bacteria
- A typical
outbreak of Staphylococcal food poisoning goes something
- The food is
cooked, killing off bacteria that might out
- A worker
contaminates the food with his/her hands.
- The food
sits at room temperature or large masses of food cool
- Enough Staph
grows to release the toxins which are subsequently eaten
as the food has no unusual taste or appearance.
- Since it is
a preformed toxin, there is no waiting
for organisms to grow before you get sick.
does not last long as the toxins are cleared from the
usually appear in one to six hours and usually last 24
hours or less.
- S. aureus can
cause several skin diseases.
- is a reddening
of the skin that may spread over the entire body.
- It is caused by
Exfoliative toxin released by S. aureus growing
on the skin.
- As the condition
worsens, large blisters form that contain clear fluids but no
bacteria or WBC.
(No bacteria are present because the toxin causes it, not
- Within two days,
the skin epidermis peels off in sheets as if dipped in
- Serious secondary
infection may occur in denuded areas.
- is a skin
disease particularly of children.
- Patches on the
face/limbs form pyogenic (pus-filled)
vesicles that eventually crust over.
- The pus contains
bacteria and WBC differentiating it from scalded skin
80% of cases are caused by S. aureus, the rest by streptoccocci.
Boils and Carbuncles
infection of a hair follicle where the base becomes swollen
and puss filled.
- When this occurs
in an eyelid, it is called a sty.
folliculitis spreads deeper into the skin, it is called a boil
or furuncle (fyū-rung-kl).
- Furuncles are a
more painful and larger disease.
- When several
boils coalesce, they form a carbuncle
that invades deeper and causes fever and chills.
- If it invades
further, it spreads and becomes a systemic disease.
Diseases of S.
- Toxic Shock
Syndrome is usually caused by a localized infection of staph
cells that produce the systemic Toxic-shock-syndrome toxin.
- The infection is often a single wound or an abraded vagina,
but is fatal in ~5% of patients due to the toxin.
The toxin causes blood pressure to fall such that vital
organs (brain/heart) receive too little oxygen, red
skin that peels in sheets, and fever.
The syndrome occurs in both males and females, but in 1980,
there was an epidemic among women.
- Super-absorbent tampons were sold in that year and S. aureus grew very
well in them if they were left in place for prolonged periods.
- The removal of super-absorbent tampons and the reduction in
tampon absorbency largely returned the incidence of disease to
levels seen before 1980.
- Fig 19.22 reviews TB infection.
- The 9 staph infections include:
- S. epidermidis -puncture wounds
- S. aureus -toxic shock syndrome,
bacteremia, folliculitis, boils,
carbuncles, impetigo, scalded skin syndrome,
and enterotoxicosis (food poisoning).
- Good news: removing assigned reading ch 22,
pathogenic fungi, from the exam.
- Assigned reading of Ch. 19, but not covering
much of the chapter
- Know things like the families of bacteria and
the diseases they cause.
- Streptococci group A :
strep throat (pharynigitis), scarlet fever, impetigo
(most are staph), toxic shock syndrome (most are staph),
necrotizing fasciitis (flesh-eating strep), rheumatic
- Streptococci group B:
neonatal diseases, normal biota of lower Gi and lower
- Streptococci group viridans: normal
biota of mouth, throat, Gi and genitourinary
tracts. Cause cavities, and as an opportunistic
may cause bacteremia, meniningitis, and endocarditis.
- Streptococci pneumoniae: pneumonia,
sinusitis, otitis (ear), bacteremia,
meniningitis, and endocarditis.
- Enterococcus: normal biota
of GI, may cause nosocomial infections and endocarditis.
- Bacillus anthracis causes
gastrointestinal, cutaneous, or lung disease
- Clostridium species cause:
food poisoning, gas gangrene, explosive diarrhea,
pseudomembranous colitis, botulism, and tetanus.
- Listeria monocytogenes: severe
opportunistic infections in
pregnant women, newborns, elderly, and
- Corynebacterium diphtheriae
- Propionibacterium acnes
-acne, nosocomial infections fr/ medical devices.
- Nocardia and actinomyces - opportunistic infections.
from ch 20
- Endotoxin is present in all true Gram-, due to lipid A
in the outer membrane of the cell wall.
- Endotoxin symptoms: fever, vasodilation,
shock, and disseminated intravascular coagulation
(disseminated blood clots)
Enterics (family Enterobacteriaceae
- Large family, ~250 species, many are
opportunistic, some are pure pathogens.
- They are everywhere and cause a large
percentage of nosocomial
- They are coccobacilli or bacilli.
- We use their antigens to distinguish between
strains and species, including:
- a core polysaccharide that all have, so its
called the common antigen
- the "O polysaccharide" that varies by
- lipid A (which can cause serious disease)
- some species also have K and H antigens
- i.e, E. coli O157:H7 has antigens O157 &
H7 & is a potentially deadly strain.
- Enterics are
split into 3 groups:
- true pathogens
- Coliforms are opportunistic rods, found
everywhere, especially in the gut.
- Most follow the fecal-oral route of
transmission, including contaminated hands, food, and drink.
- E. coli is the most important
coliform causing a number of diseases.
- Strains containing the antigens O157, O111,
H8, and H7 are virulent.
- E. coli causes bacteremia
(bak-tēr-rēm'-mē-a), urinary tract infections, neonatal
meningitis, and gastroenteritis.
- Gastroenteritis is the most common disease,
prevalent in children in third world countries and is often
associated w/ a toxin. Symptoms include watery
diarrhea, cramps, nausea, and vomiting.
- Most of the urinary tract infections are in
women in the U.S. In nearly 1/3 in their lifetime, it
will spread up to the bladder once. If it spreads to
the kidneys, it is a serious disease involving fever, pain,
profuse perspiration, and vomiting.
- E. coli O157:H7 can cause bloody
diarrhea, colitis, kidney disorder, urinary tract and blood
infections which can be fatal. Most cases have been
associated w/ the consumption of undercooked beef or
unpasteurized milk or juice.
- Klebsiella pneumoniae (kleb-sē-el'a
nū-mō'nē-ē) causes pneumonia,
bacteremia, meningitis, wound and urinary tract infections.
- Serratia, Enterobacter, Hafnia, and
Citrobacter are all opportunistic pathogens.
- The noncoliforms are opportunistic pathogens,
mostly involving catheters.
- Proteus mirabilis (prō'tē-us
mi-ra'bi-lis) has the unusual property of
swarming and is the most common opportunistic pathogen in this group.
- Nearly half of all long term catheter
patients develop Proteus infections.
True Enteric Pathogens
- Three genera: Salmonella, Shigella, and
- Except for Yersinia,
most follow the fecal oral route of transmission.
- causes salmonellosis (nonbloody diarrhea,
fever, headache, muscle pain, nausea, vomiting, abdominal
- causes typhoid fever (gastroenteritis,
increasing fever, headache, muscle pains, malaise, appetite
loss for a week or more).
- Typhoid fever is a more sever and longer
lasting than salmonellosis.
- Some patients are asymptomatic carriers;
Typhoid Mary was the most famous.
- Shigella (shi-gel-la):
- cause severe dysentery called shigellosis (shi-gel-lō'sis)
having abdominal cramps, fever, diarrhea, and
- Survives stomach acids and colonizes the
- It uses host actin fibers to
propel itself into neighboring cells to avoid the immune
- Is easily killed by phagocytes.
- Depending on the strain, the mortality can be
as high as 20%.
enterocolitica and pseudotuberculosis follow
the fecal to oral route of transmission.
pestis is transmitted either by flea
bites or by respiration of aerosols.
pestis has two forms of the disease:
- bubonic plague
- when spread by starving fleas (infection
blocks their esophagus, so they jump around and bite a
lot), the infection causes painful swelling in the lymph
nodes called buboes
(bū'-bōs), giving it its name.
- if it gets in the blood, it becomes
disseminated and may grow widely.
- If it grows subcutaneously, it kills
tissue inviting secondary infection by Clostridium
causing gangrene. The dark color of the dead skin
gives it its second name, the "Black Death."
- pneumonic plague
- When it grows in the lungs, either from
dissemination of the blood or by respiratory infection
it is called pneumonic plague.
- This form develops rapidly, it starts
with a fever, malaise and pulmonary distress follow w/i
a day. It is fatal if not treated rapidly.
- Pneumonic plague can spread from person
to person, but is unlikely because it grows deep in the
lungs. The most likely culprit is this guy!
- Three members of this family are human pathogens that generally spread by
biting or blood sucking animals.
- As far as is known, the members of this
family only cause serious disease in man.
- The text is a little out of date when it says
it does not cause disease in animals, it causes gum disease
- Bartonella are bacilli that have
fastidious growth requirements.
- The most serious disease, bartonellosis,
is a species spread by flies in S. America. Its
symptoms include fever, severe anemia (it grows in and kills
RBC), headache, skin infections and is often fatal.
- Another species is spread by human lice and
causes trench fever (also called 5-day fever), which
was common in the trenches of WWI.
- (A picture of head lice, a case of trench
fever, and soldiers removing lice during WWI.)
- Cultural connection: trench fever helped
inspire JRR Tolkien!
- A third species, Bartonella henselae
(hen-sel-ē) is much more common, ~22,000 children in the
US/yr become infected. Children and immune suppressed
individuals are at greater risk, but others can get it.
- It has never been successfully cultured in
- The symptoms include prolonged fever,
malaise, swelling at the site of infection and the local
lymph nodes (see figure below).
- If untreated, disease often lasts for several
months and occasionally worsens into a serious infection.
- This and most Bartonella diseases can be
treated with antibiotics, but for unknown reasons, the
diseases often relapse.
- The cause of this last Bartonella
disease is the bite or scratch of this guy.
- Its name: cat scratch fever.
- Pseudomonas are
ubiquitous Gram- bacilli that are not particular about
their growth environment.
- They have been found growing in most moist
environments including mop water.
- Pseudomonas aeruginosa is a
species with many virulence factors:
- fimbriae and adhesins for attaching to
- a capsule for attaching and blocking
- the endotoxin Lipid A,
- exotoxins A and S (an exoenzyme) that inhibit
protein synthesis in eukaryotic cells,
- the enzyme elastase that degrades elastic
fibers, complement proteins, IgA and IgG,
- the blue-green pigment pyocyanin
that forms oxygen radicles that damage host tissue.
- It rarely makes healthy people sick
partly because it needs to breach the skin or mucous
- Yet, once it does, it can
cause opportunistic infections in compromised
patients nearly anywhere, such as respiratory, urinary
tract, and ear infections.
- It is very common in burn patients (2 out of 3 burn patients get it), it
thrives in the warm moist environment of a burn.
Such skin infections often have a blue-green pus.
Fibrosis and Biofilms
- P. aeruginosa infections in the lungs
of cystic fibrosis patients are common, can be life threatening.
This inherited disorder provides a suitable
environment for its growth, namely the thick mucus in the lungs.
- Chest thumping clears the mucus, allowing the patient to
breath better and removing a food supply for P. aeruginosa.
- The bacteria grow and feed on the mucus, which irritates the lungs
stimulating the lungs to produce more mucous. This allows more Pseudomonas
to grow in the lungs, irritating the lungs further which stimulates the production of more
mucus. This positive feedback loop exacerbates the patient's condition
and if not corrected leads to death.
- CF patients need to have chest thumping to stay healthy. Yet, the
first gene therapy trials have begun (inserting the corrective gene into some cells
of a cystic fibrosis patient). Early results show some improvement but did not bring
the patients to a normal level.
- You should understand how the culture of teenagers
aided researchers into getting volunteers for the gene therapy trials. :)
- This is not a simple infection. The
bacteria form a biofilm and thereby
become less susceptible to antibiotics compared to
free-living bacteria (see p. 170, 4th ed., 173, 3rd ed.,
174, 2nd ed., 177, 1st ed).
- Biofilms are microcolonies of bacteria
surrounded by a gooey extracellular matrix secreted by the
- The bacteria are able to sense the presence
and density of neighboring bacteria (quorum sensing), if the
density is sufficient, the bacteria then turn on genes to
form the biofilm.
Biofilms have a number of
properties that aid bacterial survival.
- Channels through the biofilm provide for the
diffusion of nutrients and waste removal.
- Oxygen and nutrient concentrations vary
within the biofilm causing the cells to be at differing
- Cells buried within the biofilm may be
dormant, allowing them to survive concentrations of
antibiotics and disinfectants that kill free-living
- Once the antimicrobial is removed, the
dormant cells can reestablish the biofilm.
- The biofilm layers tend to protect the inner
cells from antiseptics, such as bleach. Bleach kills
the outer cells, but may be inactivated before reaching the
- Biofilms also have a mechanism for generating
novel phenotypes, such as resistance to hydrogen
peroxide. They can turn on bacterial genes that are
not normally expressed or are able to manufacture larger
quantities of certain enzymes so that they are more
resistant to some antimicrobial agents.
- Biofilms contribute to diseases caused by
organisms other than Pseudomonas.
Legionnaire's disease, periodontal disease, and some ear
infections are just a few examples.
- The Center for Disease Control (CDC) estimates that biofilms account for
about two-thirds of all bacterial infections in man.
Other Gram- Bacteria from ch 20
- Assigned reading, but not covering
much of the chapter
- Know things like the families of
bacteria and the diseases they cause as in the
- Understand the Case Studies done in class (or
Homework) Similar will be on final.
Lesson 15: Other Bacteria from ch 21
- Assigned the reading, but not covering most
of ch. 21.
- For the reading, know the
families of bacteria and the
diseases they cause.
- See the chapter summary
- Note: the 4th ed. of the text moved
fr/ ch21 to ch20, I am covering it now.
- The first Bergey's Manual of Sytematic
Bacteriology divided prokaryotes into four divisions
based on their
cell walls: the Archaea, Gram positives, Gram
negatives, and Mycoplasmas.
- As we have discussed, when we look at the
Archaea are now considered a separate domain and
Mycoplasmas are considered closely related to Gram
- The mycoplasma are unusual in that they
wall-less bacteria. They also lack an electron transport
chain and the Krebs cycles. They can survive
without them because they are parasites.
- Because they do not have cell walls they
tend to be highly pleomorphic
(they have lots of different shapes). Sometimes they
look like fungi
("myco" means fungus).
- Mycoplasma are now grouped with the Gram
(even though they stain Gram negative).
- They are the smallest free-living cells,
ranging from 0.1-0.8 micrometers.
They can survive without a cell wall
because they colonize osmotically protected areas, such the mucous
membranes in the respiratory and genitourinary systems.
They are parasitic on animals and plants.
Mycoplasma pneumoniae (my-koh-plaz˘-mah
- causes "walking pneumonia."
- Attachment causes the cilia to stop
as more mycoplasma colonize the area, the epithelial
- Mucous builds up which irritates the
tract and allows other bacteria to colonize the area.
- Early symptoms include sore throat,
fever and malaise (mah-layz˘)
which are not
typical of other forms of pneumonia.
- Later symptoms include fluid in the lungs
persistent but unproductive cough that attempts to clear
- Pneumonia may last for several weeks, but
usually not severe enough to require
hospitalization. Some are
- Nasal secretions spread the mycoplasma
people in close contact.
- Walking pneumonia can occur throughout
which contrasts to other seasonal forms of pneumonia
(such as Streptococcus
- Ureaplasma (yū-rē-a-plaz'ma)
a genus w/i Mycoplasmas.
- They lack a cell wall as do Mycoplasmas and
similar in most respects.
- Ureaplasma can hydrolyze urea into ammonia;
- Ureaplasma urealyticum (yū-rē-a-plaz'ma
two species of
mycoplasmas often colonize the genitourinary tract of
humans and are STD's. They spread
easily as a STD.
- About 70% of
have Ureaplasma urealyticum.
hominis (hom-in-is) and M.
the other two STD; M. hominis infects
~15% of sexually
- Most patients do not know they are
infected, are asymptomatic; yet, the infection weakens the
body's defenses, puts holes in
the epithelial barrier, & increases the chance of a
secondary infection by something else.
- An infection may spread up the urethra to
the bladder, and from the bladder to either the kidneys or
- M. genitalium and U.
urealyticum may cause inflammation of the urethra.
- M. hominis may cause inflammation of
kidneys, pelvic inflammatory disease, and postpartum fever
- Pelvic inflammatory disease includes
of organs in
the pelvic cavity, fever and abdominal pain and occurs
women. (It spreads up the female reproductive
- Rickettsias are very small Gram- obligate
intracellular parasites that live in the cytoplasm of cells.
They are all transmitted by biting or blood
- Rickettsia rickettsii is the only member we
Rickettsia rickettsii (rik-kett˘-see-ah
rik-kett˘-see-ee or see-i)
causes Rocky Mountain Spotted Fever.
It was discovered in the
Rocky Mountains but is
more common elsewhere.
- It is transmitted by ticks between rodents
and humans. Bacteria is transmitted from the mother
tick to her eggs, and from male ticks to females during mating.
- The bacteria are inactive until the tick
feeds on blood for several hours, so prompt removal of ticks is protective.
Symptoms include a
spotted rash, malaise, fever, muscle pain, vomiting, and encephalitis.
- Death occurs in ~5% of treated cases and is much
higher in untreated cases.
- The spots and much of the disease's
symptoms come from the bacteria damaging the blood vessels so that they leak,
resulting in low blood pressure. This can be fatal to vital organs.
- Because treatment has to begin before the damage is done, quick treatment
with tetracycline or chloramphenicol is required. (I will not ask what drug is used to treat the disease.)
- Prevention is by using tick repellents and
promptly removing ticks.
- are Gram- tightly coiled bacteria that
- Recall from your reading of cell walls
early in the term that
spirochetes have a flagella inside of an axial
filament that wraps
around the outer membrane of the cell wall.
- As the endoflagella moves, it causes the
filament to rotate around the cell, causing the cell to
have a unique
- Parasitic spirochetes may use this movement
burrow through tissues. Syphilis is
believed to do this.
Treponema pallidum pallidum (trep-ō-nē'ma
species has several strains or subspecies, hence the
strain or subspecies causes syphilis, a STD.
other subspecies are not STD, are transmitted mostly by
contact, and this can occur
- The other strains of Teponema
cause disease primarily among
impoverished children in third world countries.
are their natural host, they cannot be cultured in cell
free media despite years of effort.
- Though syphilis, can be transmitted
by contact, it is largely transmitted by
sexual contact, usually during the
can spread from blood products and from
mother to fetus but not by fomites.
is w/ of penicillin G (primary/secondary), but it
must be extensive to have
any effect on tertiary syphilis.
has 4 stages:
syphilis -a small painless (and itchless) lesion
called a chancre
10-21 days following exposure.
are often unobserved in women.
are extremely infectious and remain for 3-6 weeks
up to 1/3 of the cases in healthy individuals, the
host can rid itself
of disease at this stage.
however, the bacteria invade the bloodstream,
spread, and develop later stages of
syphilis is a disseminated disease.
The pathogen has spread throughout the body.
include sore throat, mild fever, malaise, muscle
pain, and a widespread
rash is painless and itchless, can last for months,
and is extremely
- (Yes, you can get the disease by
touching the rash or chancre, though it is spread
primarily by sex.)
Latent Phase begins when the rash goes
away. The patient is asymptomatic.
disease is clinically inactive and may remain so for
are present but at lower numbers; a
mother may transmit it to her fetus causing birth
Syphilis -around 1/3 of the originally infected
patients enter this
tertiary syphilis, the immune system reacts
violently against the
pathogen, resulting in severe complications that may
affect any tissue
vary widely and may include dementia, blindness,
failure, and lesions called
gummas (gum'az), which are rubbery, painful,
- The immune system is causing far
more problem than the disease.
Other Treponema pallidums
3 diseases primarily among impoverished children in the
poverty/malnourishment may result in skin or mucous
allowing the eubacteria entry.
the diseases spread by direct contact among children.
is unusual in that it can spread by fomites.
is spread mainly by contaminated eating utensils, so
lesions increase in number and severity, usually
remaining around the
late stages skin, nasal or oral gummas form.
- Pinta and
spread by contact with
infected skin, usually during play.
pinta and yaws have unsightly skin lesions filled
time, the lesions enlarge into destructive lesions