Microbiology – Specific Immunity & Immunizations
4) T cells have antibody-like receptors on their cell
surfaces that specifically bind to foreign antigens in
exactly the same way that antibodies do.
5) T cells have other receptors on their surfaces that
identify other cells within the body with which they are
designed to interact.
6) T cells act as the hit-men of the immune system.
Once a foreign cell is pointed out to these “killer cells”
they gang up on it and kill it
II. SOME VOCABULARY
A. __________________________ - anything that elicits the formation of
a specific immune response.
1. Antigens are large molecules (macromolecules, such as
proteins and polysaccharides) that contain many surface epitopes.
2. Antigens are usually foreign to the host, and react specifically
with antibodies and immune cells.
a. Most antigens are __________________________ that
can induce the production of specific antibodies or immune
b. __________________________ are small molecules that
cannot induce antibody formation unless complexed with
large carrier molecules.
1) The hapten alone can react specifically with the
antibodies or immune cells produced in response to
the hapten-carrier complex.
B. __________________________ – The particular unique chemical
groups on a molecule that are atingenic (that elicit a specific immune
1. In the case of proteins, these are sequences of only 10 to 25 aa.
C. __________________________ (Immunoglobins) – a special group of
soluble proteins that are produced in response to foreign antigens.
1. Antibodies are produced by special B cells called
2. They have unique binding sites (produced through genetic
recombination) on them which recognize & bind to the epitopes of
3. The antibody binding sites are highly specific.
D. ____________________________________________________ –
this can best be described as genetic immunity or immunity that an
organism is born with.
1. The nonspecific immune system is part of our innate immunity.
2. Innate immunity may apply to the vast majority of the members
of a species (species immunity), OR it can apply only to a
certain subgroup within a species down to a few individuals.
a. example of species immunity – Jenner – 1796 – smallpox
1) Prior to 1796, almost every European had caught
smallpox. The virus was occasionally fatal & left
Europeans with lifelong scars.
2) Jenner noticed that milkmaids seemed never to
3) Upon investigation, he found that cows suffer from
a similar disease called cowpox that humans are
normally insusceptible to.
4) However, milkmaids usually caught a mild case of
cowpox (they would get pox on their hands) from their
intimate contact with the disease (milking infected
5) Milkmaids who had caught cowpox never caught
6) Jenner intentionally exposed a young boy to
cowpox. After the boy recovered from the infection,
he exposed the boy to smallpox. The boy didn’t
develop a case of smallpox.
7) This was the world’s first vaccine.
8) Humans have a species immunity to cowpox &
Cows have a species immunity to smallpox.
b. Example of innate immunity is a subgroup of a species
1. Europeans had a tradition of exposure to smallpox.
Anyone who was especially susceptible to smallpox
died in childhood & didn’t leave children behind.
2. Those whose immune system provided some
protection from the smallpox virus survived to have
3. They passed on their superior immune system to
4. Unfortunately, Native Americans didn’t have this
tradition of exposure to smallpox. The arrival of
European explorers (& smallpox) was DEVASTATING
to native populations.
c. Further examples of innate immunity among subgroups
a. Northern Europeans appear to be more resistant
to tuberculosis than are most Africans.
b. Africans are innately resistant to a variety of
African diseases (such as malaria) to which
Europeans are highly susceptible.
3. Because of genetic variation within every species, there are
some individuals who are statistically more resistant to some
diseases, and more susceptible to other diseases.
a. Many factors (diet, stress, etc.) could explain why some
people “rarely” get colds or the flu.
b. However, one factor is that certain combinations of genes
render some people more resistant to the common cold
viruses, whereas others are very susceptible.
E. Acquired or Adaptive Immunity – immunity against specific antigens
that one acquires in one of two ways; actively or passively.
immunity – Individuals suffer from a natural infection of a pathogen
& become immune to that pathogen upon recovery (e.g.
immunity – Individuals are actively vaccinated with an antigen that
immunity – Individuals receive antibodies from their mother by a
natural process, such as in breast milk or in-utero transfer of
antibodies from mother to fetus.
a. In both of these circumstances, the infant is only resistant
to whatever the mother is resistant to.
immunity – Individuals are injected with POOLED serum (fluid part
of the blood excluding fibrinogen that forms clots) from immune
individuals that contain antibodies against a large number of \
a. In humans, a fraction of blood serum, _______________
________________________, that is highly enriched in
antibodies is injected into individuals that have been
exposed to certain pathogens
1) e.g. a nurse that has suffered a needle stick
wound & has therefore likely been exposed to
hepatitis & potentially worse diseases.
b. The gamma globulin is obtained from pooled sera from
many individuals & thus contains a broad spectrum of
III. Length of Immunity and Vaccinations
A. Passive acquired immunity is short-lived as the antibodies eventually
die off or are themselves removed from the body as foreign protein.
1. A person receiving the passive dose has not been exposed to
the antigens that caused the production of the antibodies.
2. Therefore, the person does not produce their own antibodies.
3. Thus, the immunity is transient.
4. Babies typically have destroyed all of the maternal antibodies by
6 weeks after birth.
B. The active forms of immunity are generally long-lived, particularly in
the case of recovery from a clinical infection. Sometimes this immunity is
life long (e.g. chickenpox), but in other cases it is not.
1. We once thought vaccinations induced life long immunity.
Unfortunately, this is turning out not to be the case.
2. There is a very effective vaccine against tetanus, but every year
hundreds of people who have been vaccinated against this
bacterium die because they have not gotten their booster shots.
a. When I was young, they recommended getting a tetanus
booster every 10 years. Now, the recommendation is every
C. What are vaccines? A __________________________ is a
preparation of living or inactivated microorganisms or viruses or their
components used to induce active immunity. Currently, vaccines come in
– these are mutants of microbes that have lost the ability, either
naturally or by treatment in the laboratory, to produce the
dangerous, clinical disease (these are avirulent strains). (e.g. the
polio vaccine virus)
a. Attenuated agents are antigenic and can replicate, but
are modified to be incapable of causing disease under
b. A vaccination consists of infecting you with a living
microbe which then produces a limited infection.
c. Because these attenuated strains are weak, the immune
system of normal healthy people quickly kill & eliminate them
from the body.
d. During this process the infection elicits a vigorous
immune response that protects the host from infection by the
related virulent, disease-producing form of the pathogen.
c. Live vaccines produce the best immunization because
they closely imitate the real thing.
– These vaccines consist of growing up cultures of the virulent,
disease-producing microbial strains & killing them in such a way
that they retain their ability to stimulate the body to produce an
immunological response to the live form. (e.g. anthrax & rabies
– These vaccines consists of substances isolated from the virulent
strains, such as polysaccharide material or protein components.
a. No whole organisms, living or dead, are present in these
vaccines. (e.g. the toxins in diphtheria, tetanus, & botulinum
and the polysaccharide from virulent pneumococci)
D. Are vaccines safe to use? It is never possible to prove that any
medical treatment is totally safe for all people under every set of
conditions. There is always some degree of risk, just as driving your car
to work always carries a degree of risk.
1. The live vaccines present the highest risk. A mutation may
occur that reverts the avirulent strain to virulence or that a particular
individual will be susceptible to the avirulent strain.
a. This happened with the smallpox vaccine when an
occasional person, usually a child, developed a severe, often
fatal, disease caused by the smallpox vaccine.)
2. Killed vaccines have had safety problems when the lethal
treatment failed to kill 100% of the microbes.
a. If you over-treat the microbe to be certain that all the
organisms are dead you can destroy the immunizing
components & make the vaccine ineffective.
3. The use of chemical components of pathogens also carries
a. Some people will react violently to these substances,
usually in an allergic reaction, & they can be
seriously harmed or even killed as a result.
b. The DPT vaccine combination has caused such
E. Should we bother to immunize ourselves & our children?
1. This is a decision that each individual must make for themselves
& their children, but it should be an informed decision.
a. Modern vaccines are about as safe as anything in this
b. Everyone who drives or is driven on the highways is in far
more danger of harm than they are being vaccinated.
2. Routine childhood immunizations have prevented millions of
cases of disease and many deaths during the past decades.
3. Universal immunization is essential to eradicate some diseases
and to preserve herd immunity against others.
a. Many parents are choosing not to immunize their children
because it “hurts” the child or due to religious objections.
b. This has led to an upsurge in the cases of childhood
diseases that had become rare due to universal childhood
vaccinations (such as pertussis or whooping cough).
c. This ever-growing pool of unvaccinated children poses a
future medical crisis.
4. Diseases are always present & they do not recognize borders.
a. We are so intimately connected with the rest of the world
today that diseases can appear from anywhere.
b. The strawberries or lettuce you just purchased at the
supermarket yesterday may have come from a country with
far less sanitation than we practice.
c. The person you sit by on the bus/subway may be a recent
immigrant or traveler coming from another country that is
rife with a
d. In these cases your only real protection is vaccination.
1. The principle of molecular recognition – ligand/receptor binding
involves interaction of antigens & antibodies.
a. These biological molecules interact by recognizing &
binding with one another in a highly specific manner.
b. Pairs of molecules that interact in this way are called
receptors or binding sites and ligands, respectively.
c. Specific regions of atoms (molecular domains) on a
receptor molecule have the characteristic of binding or
attaching (docking) specifically to unique molecular domains
on specific ligands.
2. The specific immune response involves interaction and chemical
binding of antigens & antibodies.
a. Recall that antigens are anything that the specific
immune system responds to.
b. Antigens are able to stimulate the proliferation of the
relatively few, specific lymphocytes (both T and B cells) that
are capable of binding to them.
1) Many of the activated B cells will become plasma
cells, producing antibodies.
2) These antibodies will bind with the specific antigen
that stimulated their production.
c. Antigens are further able to interact with the lymphocytes
they activated and the antibodies they produced.
3. Often, antigens are proteins on viral, bacterial, and cell surfaces.
a. Specific portions of antigen molecules, called antigenic
determinants, or epitopes, trigger immune responses.
B. How does a multicellular organism design a system for discriminating
self from the millions of nonself substances in the environment throughout
1. Remember that you are a unique gene pool of ONE (unless you
have an identical twin)
a. How does your immune system know what cold and flu
viruses, bacteria, parasites, etc. it will have to respond to in
b. Your immune system needs to kill all pathogens it is
exposed to and at the same time spare all of your normal
2. The immune response depends upon the process of
to solve this problem.
a. T and B cells are randomly produced by recombining a
limited set of genes.
1) Imagine a deck of 52 cards. The cards are
numbered from ace to king & have only four suites.
This is a relatively limited amount of information, but
when you shuffle the cards, think of the millions of
different combinations you can come up with.
b. In utero, the baby literally produces millions of random T
& B cells through genetic recombination (“shuffling”).
1) Embryonic cells contain a few hundred gene
segments that are shuffled and combined to form all
of the different T and B cells that are found in the
2) It is estimated that more than 100 million different
T and B cells can be produced in this manner.
c. Any T or B cell that reacts to self cells are destroyed.
d. This leaves the baby with millions of random T & B cells
that don’t respond to self & that might, just by chance,
respond to a foreign antigen presented to the immune
system sometime during a lifetime.
3. How does the body recognize self?
a. All self cells present self proteins on their cell surfaces
known as _________________________________
1) Your lymphocytes won’t attack cells presenting
your unique MHC unless they are also presenting
a) A self cell may suffer a mutation that
causes it to present a foreign (nonself) protein.
i) This often occurs in spontaneously
arising cancerous cells.
ii) Every year, we develop, on average,
two cancers that might grow
into tumors. Cancers are relatively rare
because our immune system destroys
iii) This demonstrates how efficient our
immune system is at what is called
b) A self cell would also present a nonself protein if it
were infected with an internal parasite such as a
b. There are actually two classes of MHC
1) MHC __________________________ molecules
are found on almost all human cells (excluding RBC).
a) Cells expressing MHC Class I molecules
are recognized by CD8-bearing T cells
(Cytotoxic T cells).
2) MHC __________________________ molecules
are expressed only on antigen-presenting cells
a) These cells include phagocytic cells
(macrophages, dendritic cells, etc.) and B cells.
b) Cells expressing MHC Class II molecules
are recognized by CD4-bearing T cells (Helper
c. Would the specific immune system ever attack normal
self cells? The answer is yes.
1) Unfortunately, healthy cells will sometimes
present, at some point in our lifetime, a surface
protein that was previously hidden from the
2) These healthy cells will then be attacked by the
3) This is how autoimmune diseases develop.
4) Autoimmune diseases are FAR more common in
women than in men. (This might be explained by
escaped fetal cells.)
d. The success of a proposed organ or tissue transplant
depends on histocompatibility. Tissue typing
(histocompatibility testing) is done before any organ
VI. The Current Theory of Antibody Formation
A. During fetal development the body randomly produces millions of T
and B cells, each of which produces only a single epitope binding
1. The B cells that produce self antibodies (antibodies against self
antigens) are destroyed.
2. This leaves millions of lines or clones of B cells that produce
random antibodies that might, just by chance, respond to a foreign
epitope from pathogen you are exposed to in the future.
B. We are going to imagine that the immune system has, for the first time
ever, been exposed to a bacterial pathogen, presenting antigen #3,425.
1. This particular foreign epitope (from bacterial pathogen # 3,425)
is processed by phagocytic cells of the nonspecific defense system
(the antigen-presenting cells).
a. This sets off a sequential series (cascade) of events
that activates a small population of the randomly-produced
B/T cells that happen (by chance) to have on their
surface receptor # 3,425 which binds to antigen # 3,425.
2. This activation triggers a rapid proliferation of that particular B
(and T) cell population (# 3,425), producing a large number of
3. These # 3,425 B cell clones differentiate into plasma cells which
are antibody-producing factories that spew out prodigious quantities
of ONE antibody # 3,425, that binds to the specific antigen-epitope
# 3,425 that stimulated it.
4. Antibody #3,425 floods through the fluids of the host and
wherever it binds to its epitope, it marks it for attack & destruction
by the appropriate cells & associated components of the immune
system (complement & PMNs etc.)
C. The special role of Helper T cells
1. A macrophage (or other antigen presenting cell) engulfs a virus
or bacteria & breaks down their proteins.
a. Antigenic fragments of these proteins are presented on
the surface of the macrophage (complexed with MHC Class
2. The few Helper T cells which contain receptors on their surface
that recognize the particular presented foreign antigen interact with
the unique MHC Class II -foreign antigen complex presented by the
a. This interaction triggers a series of events that activates
the Helper T cell.
3. The activated Helper T cells are stimulated to proliferate.
4. The activated Helper T cells interact physically (via
ligand/receptor interactions) with only those rare B cells
that make antibody that recognizes the same antigen molecules
that have activated the Helper T cell.
a. During this interaction the Helper T cells and B cells
recognize each other by their common recognition of the
4. The interaction between the Helper T cells and B cells
stimulates the Helper T cells to produce cytokines.
a. These cytokines stimulate the appropriate B cells to
proliferate & to differentiate into antibody-producing
plasma cells that produce the antibodies that bind the
antigen that the Helper T cell originally reacted to.
5. Cytokines produced by activated Helper T cells also activate
macrophages resulting in killing of intracellular organisms.
6. Therefore, the Helper T cell acts as a MASTER CONTROL
CELL of the immune system.
a. It is required for both the humoral (antibody) and cellular
immune systems to function.
b. When the Helper T cells are not present, the host’s fate is
sealed because the correct B cells will not proliferate & the
correct antibody will not be produced.
2. Antibodies have two heavy and two light polypeptide chains that
bind antigen in a close complementary fit.
The IgG molecule. IgG is composed of two protein subunits, a
LIGHT (blue) and a HEAVY CHAIN (orange) named according to
their relative sizes. The various chains are bonded together to form
the IgG molecule with disulfide bonds (S-S bonds).
3. Antibody monomers have a Y shape with an antigen-binding
(Fab) site (the variable part of the antibody) at the end of each arm
of the Y.
a. The Fab site is produced through genetic recombination.
b. The aa sequences in the variable regions are
DIFFERENT for each unique antibody produced by a clone
of plasma cells.
c. There are 2 equivalent binding sites for an antibody’s
specific epitope (at the end of each arm of the Y). Thus, a
single antibody can bind to two antigens.
4. The tail of the Y is the Fc region. This region is constant in all
antibodies of that class. It is not produced through genetic
a. The Fc part of the molecule accounts for many of the
biological functions of the antibody, unique to each class.
C. Types of Antibody Reactions – Upon exposure to an antigen, specific
antibodies floods through the host’s body fluids and wherever it binds to its
epitope it marks it for attack & destruction by the appropriate cells &
associated components of the immune system (complement, PMNs, etc.)
1. __________________________ – when the antigen is a soluble
toxin, the binding of an antibody to it will usually render the toxin
a. Such neutralized toxins are called toxoids & can be used
b. Specific antibody injections (called antitoxins) to specific
toxins are given in suspected cases tetanus or botulism
c. The antitoxin circulates through the body & binds &
neutralizes any toxin it contacts, preventing further damage.
However, the damage that has already occurred cannot be
2. __________________________ – Soluble antigens can be
precipitated from the body fluids in the presence of its antibody.
a. Antigen-antibody networks form & get heavy and large
enough to settle out of solution.
3. __________________________ – When the antigen is a large
particle, like a whole bacterium or RBC, the addition of its antibody
will cause cross-links to form between antibodies and antigens on
different cells, causing clumping.
4. __________________________ – Enhanced phagocytosis,
usually caused by coating of the particle to be ingested with either
antibody or complement components.
5. __________________________________________ – When
antibodies attach to antigens on foreign cells, the antibodies act as
fingers that point out the cell for destruction by complement.
a. Complement proteins bind to antibodies attached to
antigens on the target cell and produce holes in the cell’s
membrane, resulting in cell lysis and death.
D. There are 5 Immunoglobulin Classes
1. ___________ is the most common antibody and does most of
the humoral immune work.
a. IgG is a monomer.
b. IgG can cause opsonization, agglutination, precipitation,
complement fixation, and neutralization of toxins and
c. It is the only class of immunoglobulins that can cross
2. ___________, usually a pentamer, is the first class of
immunoglobulins produced during an immune response.
a. IgM is very efficient in agglutination, precipitation,
opsonization and complement activation.
3. ___________ is abundant as a dimer in secretions.
a. IgA prevents infection by inhibiting adherence of
organisms to host cells.
b. It is important in protecting mucous membrane
4. ___________ is a monomer found on B cell surfaces, where it
is a membrane receptor for the specific antigen it recognizes.
5. ___________ is a monomer that binds strongly to mast cells
a. Reaction of cell-bound IgE helps to protect against some
b. IgE contributes significantly to many allergic reactions.
VIII. CELL-MEDIATED IMMUNITY
A. _________________________________ (CD4-bearing T cells)
1. Recognize antigen fragments associated with MHC class II
a. Recall that MHC class II molecules are found on antigen-
b. These cells include macrophages, dendritic cells, and B
2. Activated Helper T cells secrete several cytokines.
a. The most important cytokine is ____________________.
b. Interleukin-2 acts as a co-stimulator for the proliferation of
other helper T cells, cytotoxic T cells, and B cells that are
bound to antigens.
c. Helper T cells also produce cytokines that activate
macrophages resulting in killing of intracellular organisms
3. Without helper T cells there is no adaptive immune
response because the helper T cells direct or help complete
the activation of all other immune cells.
B. _________________________________ (a.k.a. CD8-bearing T cells
or Killer T cells)
1. Recognize antigen fragments associated with MHC class I
a. Recall that all body cells (except RBC) have MHC class I
b. These cells would present foreign antigens when they
were infected with an internal parasite (e.g. a virus) or are
2. Cytotoxic T cells fight foreign invaders by killing the target cell
(the cell that bears the foreign antigen that stimulated its activation
and/or proliferation) without damaging the cytotoxic T cell itself
a. One killing mechanism uses ______________________
to cause cytolysis of the target cell.
b. The second mechanism uses ______________________
to activate damaging enzymes within the target cell.
3. Immunological surveillance is carried out by cytotoxic T cells.
a. Cytotoxic T cells recognize tumor antigens and destroy
the tumor cell.
b. They also can recognize proteins in transplanted organs
as foreign and mount a graft rejection.
C. Memory T cells are long-lived T cells that are programmed to
recognize the original invading antigen, allowing initiation of a much
swifter reaction should the pathogen invade the body at a later date.
D. Suppressor T cells release cytokines that suppress the activity of
both B cells and other types of T cells.
IX. IMMUNOLOGICAL MEMORY
A. Immunological memory is due to the presence of long-lived antibodies
and very long-lived lymphocytes that arise during proliferation and
differentiation of antigen-stimulated B and T cells.
1. Immunization against certain microbes is possible because
memory B cells and memory T cells remain after the primary
response to an antigen.
B. The primary immune response occurs on first exposure to a
particular antigen with a lag time of about 3–6 days.
1. It results in a slow rise in first IgM and later IgG antibodies.
C. The secondary immune response provides protection should the
same microbe enter the body again. The secondary response if faster,
more prolonged, and more effective.
1. There is rapid proliferation of memory cells, resulting in a far
greater antibody titer (amount of antibody in serum) than during a
2. IgM production is the same, but there is a rapid rise in IgG.
The response to an antigen (Ag) in terms of specific antibody production
over time. Initially the levels of each unique antibody are extremely low, however
as soon as the stimulation events occur and the plasma cell clone begins
producing antibodies the TITER (concentration or quantity/volume) of a unique
antibody begins to rise. It takes about 2 weeks for the Ab level to peak. Once the
foreign antigen is removed, antibody production slowly returns to a low level,
however MEMORY B CELLS remain in the system. When the original antigen
again appears in the host these memory cells respond rapidly and produce even
higher levels of antibodies. This "REMEMBERING RESPONSE" is why we
remain immune to many diseases for a long time. The secondary exposure to the
antigen may be natural or it may be artificial in the case of BOOSTER