Microbiology – Specific Immunity & Immunizations

 

I.  INTRODUCTION TO SPECIFIC IMMUNITY

 

            A.  The specific immune system protects us from SPECIFIC NONSELF

            organisms & substances.

                        1.  It is an induced response (it must be taught which things to

                        attack).

                        2.  Acquired immune responses are highly antigen-specific.

a.  The adaptive defenses recognize and destroy the specific

                                    antigen that initiated the response.

                        3.  Once the host has responded to a specific antigen, the memory

                        response to subsequent exposure to the same antigen is more

                        rapid and effective, thereby quickly eliminating that antigen.

                        4.  The specific immune system is signaled to respond by

                        macrophages and dendritic cells of the nonspecific immune

                        system.

                                    a.  These phagocytic cells are called __________________

                                    _______________________________________________.

b.  They engulf antigens and present fragments of these

antigens on their surfaces where they can be recognized by

T cells.

                        5.  Specific immune responses involve two sets of lymphocytes.

a.  Lymphocytes originate from stem cells in the bone

marrow.

                                    b.  B cells become immunocompetent in the bone marrow

                                    and produce an antibody (or immunoglobulin) response

                                                1)  This is known as humoral or _________________

                                                __________________________ immunity.

                                                2)  Activated B cells (called plasma cells) secrete

                                                antibodies into the body’s “humors” or fluids.  The

                                                antibodies are what attack the pathogens.

                                                3)  It works mainly against antigens dissolved in body

                                                fluids (e.g. toxins) and extracellular pathogens,

                                                primarily bacteria, that multiply in body fluids but

                                                rarely enter body cells.

                                    c.  T cells become immunocomptent in the thymus and

                                    produce a cellular immune response.

                                                1)  This is known as the ______________________

______________________________ immunity.

                                                2)  The living T cells directly attack pathogens

                                                3)  Cell-mediated immunity is particularly effective

                                                against…

a)  intracellular pathogens, such as fungi,

parasites, and viruses

b)  some cancer cells

c)  foreign tissue transplants.

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

                                    cells.

                                    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

            response). 

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

antigens. 

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

            vaccine

                        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

catch smallpox. 

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

cows). 

5)  Milkmaids who had caught cowpox never caught

smallpox.

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

                                                children. 

3.  They passed on their superior immune system to

their children. 

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

                                    includes…

                                                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.

                        1.  ___________________________________________________

                        immunity – Individuals suffer from a natural infection of a pathogen

                        & become immune to that pathogen upon recovery (e.g.

                        chickenpox).

                        2.  ___________________________________________________

                        immunity – Individuals are actively vaccinated with an antigen that

                        confers immunity.

                        3.  ___________________________________________________

                        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.

                        4.  ___________________________________________________

                        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 \        

                        pathogens.

                                    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

antibodies.

 

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

                                    5 years.

 

            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

            three forms.

                        1.  ___________________________________________________

                        – 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

normal circumstances. 

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.

2.  ___________________________________________________

– 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

vaccines)

3.  ___________________________________________________

– 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

                        some risks. 

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

reactions.

 

            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

                                    dangerous world. 

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 disease the U.S. is “free” of. 

d.  In these cases your only real protection is vaccination.

 

 

IV.  The underlying universal principle of the immune system deals with

recognizing self from nonself (foreign)

 

A.  This recognition is based upon the principle of

_________________________________ binding

                        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

its lifetime?

                        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

                                    your lifetime?

                                    b.  Your immune system needs to kill all pathogens it is

                                    exposed to and at the same time spare all of your normal

                                    body cells.

                        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

                                                body.

                                                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 _________________________________

_________________________________________ (MHC).

                        1)  Your lymphocytes won’t attack cells presenting

                        your unique MHC unless they are also presenting

                        nonself proteins.

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

                                                these cells.

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

                                                virus.

                                    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

                                    T cells).

                                    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

                        immune system. 

2)  These healthy cells will then be attacked by the

immune system. 

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

                                    transplant.

 

V.  ACTIVATION, PROLIFERATION AND DIFFERENTIATION OF T CELLS

AND B CELLS

 

            A.  __________________________ - for an immune response to occur, B

            and T cells must recognize that a foreign antigen is present.

                        1.  B cells can recognize and bind to antigens in extracellular fluid

                        without aid from other cells.

                                    a.  Although they can become activated independently, they

                                    require co-stimulation from other cells of the immune system

                                    to begin dividing (proliferating).

                        2.  T cells, however, can only recognize fragments of antigenic

                        proteins that first have been processed and presented in

                        association with MHC self-antigens.

                        3.  Processing of Exogenous Antigens - antigens formed outside

                        the body

                                    a.  Antigen-presenting cells (a.k.a. APCs, recall that these

                                    are cells of the nonspecific immune system) process

                                    exogenous antigens and present them together with MHC

                                    class II molecules to T cells.

                                    b.  These distress signals are then recognized by CD4-

                                    bearing T cells (Helper T cells) .

                        4.  Endogenous Antigens  - antigens that were synthesized in a

                        body cell (e.g., viral proteins from virus-infected cells)

                                    a.  Most cells of the body can process and present

                                    endogenous antigens together with MHC class I molecules

                                    to T cells.

                                    b.  These distress signals are then recognized by CD8-

                                    bearing T cells (Cytotoxic T cells).

 

            B.  Proliferation and Differentiation of B cells

                        1.  Millions of immunocompetent, but naive, B cells await activation.

                        2.  When an antigen binds to an antigen-receptor on the few

                        specific B cells that recognize that particular antigen, those B cells

                        are activated.

                                    a.  The antigen-receptor is chemically similar to the

                                    antibodies that will eventually be secreted by the progeny of

                                    that B cell.

                                    b.  Activated B cells become antigen-presenting cells.

                                                1)  Some antigen is taken into the cell, processed,

                                                and then presented, together with MHC II molecules,

                                                on the cell surface.

                                                2)  __________________________ recognize this

                                                signal and deliver the

                                                __________________________ needed for B cell

                                                proliferation and differentiation.

                        3.  Upon co-stimulation from Helper T cells, the B cells proliferation

                        through ______________________________________________.

a.  Clonal selection is the process of the few activated B

cells (those select cells that could bind with that specific

antigen) growing and multiplying to form an army of cells that

are capable of recognizing the same antigen (they are

clones of the B cells that produced them).

                        4.  Most clones develop into __________________________.

                                    a.  Plasma cells are the antibody-secreting cells of the

                                    humoral response

                        5.  The clones that do not become plasma cells develop into

                        __________________________.

 

            C.  Proliferation and Differentiation of T cells

                        1.  T cells await activation by the presentation of the specific

                        antigen they can bind to, but the recognition mechanism for this

                        antigen is different from B cells

                                    a.  T cells must accomplish a double recognition process:

                                    they must recognize both self (an MHC protein of a body

                                    cell) and nonself (antigen) at the same time.

                                    b.  T cell activation

                                                1)  Step 1:  A T cell must bind to another body cell

                                                presenting both MHC molecules (self proteins) and

                                                foreign antigens.

                                                2)  Step 2:  The T cell must recognize one or more co-

                                                stimulatory signals.

                                    c.  Co-stimulatory signals include…

                                                1)  Cytokines such as interleukin

                                                2)  Pairs of plasma membrane molecules, one on the

                                                surface of the T cell and a second on the surface of

                                                an APC.

                        2.  Once activated, a T cell enlarges and proliferates to form a

                        clone of cells that differentiate and perform functions according to

                        their T cell class.

                        3.  T cell classes include (remember that these cells can only be

                        differentiated based on surface markers)…

                                    a.  CD8-bearing T cells (a.k.a. _________________ T cells)

                                    b.  CD4-bearing T cells (a.k.a. _________________ T cells)

                                    c.  Suppressor T cells

                                    d.  Memory T cells

                                    e.  Gamma delta T cells (found in the intestine and more

                                    similar to NK cells than other T cells)

                                    f.  There are many other classes of T cells that have been

                                    and continue to be discovered.

 

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

antibody.

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

clones. 

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

II). 

                        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

                        APC. 

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

unique antigen. 

                        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.

 

VII.  ANTIBODY-MEDIATED IMMUNITY (a.k.a. Humoral Immunity)

 

            A.  Antibodies (a.k.a. immunoglobulins) are proteins secreted by plasma

            cells that are capable of binding with the antigen that caused their

            production.

1.  Recall that B cells are activated by the presence of the specific

antigen they can bind to.

2.  Activated B cells proliferate and differentiate. 

3.  Most of the cloned B cells become plasma cells that secret

specific antibodies that target the specific antigen that activated

them.

           

            B.  The structure of antibodies

                        1.  The basic antibody structure consists of four looping polypeptide

                        chains linked together by disulfide bonds.

2.  Antibodies have two heavy and two light polypeptide chains that

bind antigen in a close complementary fit.

 

http://www.slic2.wsu.edu:82/hurlbert/micro101/images/imm51.gif
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

recombination.

                                    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

                        ineffective (nontoxic). 

a.  Such neutralized toxins are called toxoids & can be used

as vaccines. 

b.  Specific antibody injections (called antitoxins) to specific

toxins are given in suspected cases tetanus or botulism

poisoning.

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

undone.

                        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

                                    viruses.

c.  It is the only class of immunoglobulins that can cross

the placenta.

                        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

surfaces.

                        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

                        and basophils.

a.  Reaction of cell-bound IgE helps to protect against some

multicellular parasites

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

molecules    

            a.  Recall that MHC class II molecules are found on antigen-

            presenting cells.

            b.  These cells include macrophages, dendritic cells, and B

            cells.

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

                        molecules.

                                    a.  Recall that all body cells (except RBC) have MHC class I

                                    molecules.

                                    b.  These cells would present foreign antigens when they

                                    were infected with an internal parasite (e.g. a virus) or are

                                    cancerous.

                        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

primary response.

2.  IgM production is the same, but there is a rapid rise in IgG.

 

 

Remembered Response (2524 bytes)

 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

vaccinations.