Chapter 17
Specific Defenses of the Host
Immune Response
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Specific Resistance
offers third line of defense, effective against particular pathogens
Immunity involves a specific defensive response to an invasion by
foreign organisms or foreign substances
ANTIGENS are organisms or substances (typically foreign – though
occasionally your own) that provoke an immune response
the immune response involves antibodies and/or specialized
lymphocytes
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Antigen vs Antibody
Don’t let these similar words be confusing!
Antigen – any substance recognized as foreign by your immune
system, which provokes an immune response.
Antibody – an immune system protein produced to combat foreign
antigens
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Antigens as Invaders
What sort of things may serve as antigens?
Immune response may be triggered by a number of invading organisms
or substances:
pathogenic bacteria, viruses, fungi, protozoa, or helminths
foreign materials such as pollen, insect venom, or transplanted tissue
cancerous body cells can also be targeted (but immune system is not
effective against them once a solid tumor is established)
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Types of Acquired Immunity
Acquired immunity: the protection an animal develops against certain
types of microbes or foreign substances. This develops over the
lifetime of the individual
Four kinds of acquired immunity:
Naturally acquired active immunity
Naturally acquired passive immunity
Artificially acquired active immunity
Artificially acquired passive immunity
More on these shortly…
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Naturally Acquired
Active Immunity
Active - obtained when exposed to antigens in the course of daily life
lifelong immunity to some diseases, such as measles or chickenpox
for others, only short term (a few years), as in the case of some
intestinal disease
subclinical infections (produce no noticeable signs of illness) can also
give immunity
In all of these your immune system recognizes the antigen and designs
a specific antibody to recognize that particular antigen
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Naturally Acquired
Passive Immunity
Passive - involves the natural transfer of antibodies from a mother to
her infant
transplacental transfer occurs across the placenta: infant is temporarily
immune to certain disease if antibodies passed from the mother (who
was immune to the disease)
certain antibodies are also passed in the first breast secretions called
colostrum
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Artificially Acquired
Active
Immunity
Active: results from vaccination (also called immunization) introduces
specially prepared antigens called vaccines into the body
vaccines may be:
inactivated bacterial toxins (toxoids)
killed microorganisms
living but attenuated microorganisms
parts of microorganisms (such as capsules)
these substances no longer cause disease, but can stimulate an immune
response – these inactivated, harmless antigens stimulate production of
antibodies which recognize the dangerous version (‘wanted poster’)
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Artificially Acquired
Passive Immunity
Passive: from the introduction of antibodies into the body (come from
an animal or person who is immune)
This is a temporary immunity. All proteins have a finite lifespan.
When these are used up they are not replaced by the body.
artificially acquired passive immunity is immediate, but short lived
(half-life of about 3 weeks) “Gamma globulin shot”
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Serum
antibodies are found in the serum of the blood of immune animals or
individuals. Serum: fluid portion of blood
antisera is a generic term for blood-derived fluids containing antibodies
serology is the study of reactions between antibodies and antigens
the protein fractions are called globulins (fig. 17.2)
most antibodies are found in the gamma fraction, thus this antibodyrich serum component is called immune serum globulin or gamma
globulin
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serum proteins can be separated by gel electrophoresis
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Duality of the Immune System
Two mechanisms for dealing with invading antigens…
Humoral (antibody-mediated) immune system
Cell-mediated immune system
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Humoral Immunity
involves the production of antibodies against foreign organisms or
substances
found in extracellular fluids (blood plasma, lymph, mucus secretions)
B-cells (β lymphocytes) produce antibodies
this defense system is primarily against bacteria, bacterial toxins, and
viruses which are circulating freely in the body’s fluids
also involved in some reactions against transplanted tissue
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Cell-mediated Immunity
involves special lymphocytes called T cells (T lymphocytes) that act
against foreign organisms or tissues.
T cells also regulate activation and proliferation of other immune
system cells (such as macrophages)
effective against bacteria or viruses located within phagocytic or
infected host cells, and also against fungi, protozoa and helminths
primary responder against transplanted tissue. Mounts a response to
reject foreign tissue
…also an important factor in defense against cancer
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Antigens
also sometimes called immunogens
antigens are typically either proteins or large polysaccharides
lipids and nucleic acids usually only antigenic when combined with
proteins or polysaccharides
Antigens are often components of invading microbes
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Examples of Antigens
Antigenic materials might include . . .
capsules
cell walls
flagella
fimbriae
bacterial toxins
viral coats
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Non-Microbial Antigens
pollen, egg white, blood cell surface molecules, serum proteins from
other individuals or species, surface molecules of transplanted tissues
antibodies recognize specific regions called antigenic determinants or
epitopes
most antigens have molecular weights of 10,000 or higher
low molecular weight molecules are generally not antigenic unless
attached to a carrier molecule (too small on their own)
these molecules called haptens - penicillin is an example of a hapten
once an antibody has formed, it can interact with the hapten even when
it is no longer bound to the carrier
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Antibodies
proteins made in response to an antigen
can recognize and bind to that antigen - very specific in recognizing
the antigen which stimulated their formation
each antibody has two identical sites for binding the antigen - these are
called antigen-binding sites
since most human antibodies have two sites, they are said to be bivalent
(valence = the number of antigen binding sites on the antibody)
antibodies are members of the group of soluble proteins collectively
known as immunoglobulins (Igs)
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Antibody Structure
a single bivalent antibody is known as a monomer, and a typical
antibody monomer has four protein chains (fig. 17.5)
two identical light (L) chains and two identical heavy (H) chains
the chains are joined by disulfide links & other bonds to form Yshaped, flexible molecules
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Antibody Structure…
two sections near the ends of the Y’s arms are called variable (V)
regions
these are the antigen-binding regions
the variable regions of each arm of the Y are identical in amino acid
sequence
the stem and lower part of the Y arms are called constant (C) regions (5
major kinds)
Fc region in stem important, can bind between antibodies bound to a
bacterium and lead to destruction of the bacterium
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Immunoglobulin Classes
the five classes designated: IgG, IgM, IgA, IgD, and IgE (Table 17.1)
IgG, IgD, and IgE resemble the Y-structure
IgM and IgA usually consist of two or more monomers joined together
by disulfide bonds
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IgG
IgG - 80% of all antibodies in serum
IgG easily cross walls of blood vessels and enter tissue fluids, maternal
IgG can cross placenta and confer passive immunity
protect against circulating bacteria and viruses, neutralize bacterial
toxins, trigger complement system, and when bound to antigens,
enhance effectiveness of phagocytic cells
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IgM
M - is for macro (large) - make up 5-10% of antibodies in serum
has a pentamer structure - 5 monomers
held together by a polypeptide called a J (joining) chain & remain in
blood vessels (to large to diffuse out)
predominant antibody type in response to ABO blood group antigens
enhance phagocytosis
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first antibodies to appear in response to antigen exposure, but relatively
short lived.
Important in diagnosis (detection of IgM for an antigen makes it likely
the disease is caused by that pathogen)
IgA
only 10-15% of antibodies in serum, but most abundant form in
mucous membranes and body secretions (the most abundant in body,
but IgG is most abundant in serum)
serum IgA in the serum, mostly as monomer
secretory IgA is the most effective form - dimer of two monomers
joined by a J chain, this form produced by plasma cells in mucous
membranes)
passes through a mucosal cell where a polypeptide called a secretory
component is added to protect it from enzymatic digestion & helps
prevent attachment of pathogens to mucosal surfaces
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presence in colostrum probably protects infants from gastrointestinal
infections
IgD
only 0.2% of total serum antibodies
resemble IgG in structure
found in blood, lymph, and on surface of βcells
act as antigen receptors for βcells
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IgE
only 0.002% of total serum antibodies
slightly larger than IgG molecules
bind tightly by their Fc regions to receptors on mast cells and basophils
cells responsible for allergic reactions
antigen (such as pollen) bound IgE antibodies attach to the cell and
induce relases of histamine and other chemicals
can trigger an allergic response as well as be protective by attracting
IgG, complement, and phagocytic cells
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expecially useful against parasitic worms
β Cells and Humoral Immunity
activated β cells produce antibodies
process begins when β cells are exposed to free (extracellular) antigens
the β cell becomes activated, divides and differentiates into a many
clones -- called plasma cells
produce antibodies directed against the specific antigen which activated
the original β cell
the process is associated with assistance from T cells (covered later)
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Cell Lifespan & Death
100 million new lymphocytes formed each day, equivalent number die
(to maintain a constant number, otherwise leads to leukemia)
All ‘normal’ cells are programmed to die at a certain time
Apoptosis - preprogrammed cell death
for β cells, those which are not activated within a certain time will die
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Activation by Clonal Selection
an individual’s β cell population can produce many different antibodies,
but each β cell can produce only one kind of antibody
IgM and IgD antibodies on the surface of the β cell allow it to
recognize the specific antigen
clonal selection occurs when the appropriate antigen binds the cell
the cell proliferates into a large population of clone cells
all the clones have the same antigen specificity
some become memory cells (for long-term immunity) may remain in
circulation for years
others become plasma cells which secrete the appropriate antibody
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Antigen-Antibody Binding
Join to form the antigen-antibody complex
rapidly forms when the antibody encounters the specific antigen
binding of antibody to antigen protects the host by tagging foreign cells
and molecules for destruction by phagocytes and complement
Simply being ‘grabbed’ by the antibody does not directly damage the
antigen…
So you might ask, how does the antibody harm the antigen???
(see next slide for several mechanisms)
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Mechanisms For Making The Foreign
Organisms Or Toxin Harmless
agglutination (clumping)
opsonization (invader cells coated with antibody promotes phagocytosis)
neutralization
antibody-dependent cell-mediated cytotoxicity
promotion of inflammation
activation of complement
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Immunological Memory
antibody titer = the amount of antibody in the serum
Level of titer is a direct reflection of the humoral response strength
after initial exposure to the antigen, there are no detectable antibodies
in the serum for several days, then there is a slow rise in antibody titer
(fig. 17.9)
first, IgM antibodies are produced, then IgG
finally, there is a gradual decline of titer
this is the primary response
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Secondary Response
on second exposure, the response is intense & rapid
secondary response is also called memory or anamnestic response
Response by the β lymphocytes that became memory cells rapidly
differentiate into antibody-producing plasma cells
So… having ‘memory cells’ available which recognize the antigen
makes this secondary response quite rapid!
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Monoclonal Antibodies
antibodies can be used for diagnostic purposes but should be pure;
ie: specific for a particular antigenic unit (interested parties may check
out Ch. 18),
animals have a mixture of many antibodies
ideally, antibody-producing β cells could be cultured in cell culture
unfortunately, naturally occurring β cells only reproduce a few times in
culture
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Monoclonal Antibodies
in 1984, Jerne, Kohler, and Milstein received Nobel Prize for discovering a
way to prolong β cell cultures
fuse a cancerous β cell (myelomas) with an antibody-producing β cell to make
a hybridoma
the hybridoma can be grown indefinitely
since all the antibodies produced from a hybridoma clone are the same, they
are called monoclonal antibodies
So in the lab we can grow an immortal cell like which makes a ‘pure’ strain of
antibodies
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Mouse injected with antigen
We desire an antibody against
Initial source of antibody
producing cells
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Cell-mediated Immunity
based on the activity of certain specialized lymphocytes, primarily T
cells
Chemicals from immune cells regulate many other cells of the immune
system, these factors are known as cytokines
interleukins are cytokines which serve as communicators between
leukocytes
other cytokines:
interferons
tumor necrosis factor
colony-stimulating factor
chemokines (chemotaxis of leukocytes to infected area)
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T Cells
develop from stem cells in bone marrow
differentiate into mature cells in the thymus gland
migrate to the lymphoid organs where they may encounter antigens
similar response to antigens as β cells (each T cell is specific, clones
proliferate in response to antigen, some memory cells produced)
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Types of T Cells
Four main functional types
Helper T cells (TH)
Cytotoxic T cells (TC)
Delayed hypersensitivity T cells (TD)
Suppressor T cells (TS)
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Helper T Cells
play central role in immune response
induce formation of cytotoxic T cells and macrophages
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Cytotoxic T Cells
This cell type releases perforin which makes holes in target cell
membranes - Perforin destroys target cells on contact
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Delayed Hypersensitivity T Cells
NOT a separate population of cells… these are primarily TH and some
TC cells
associated with certain allergic reactions (including poison ivy,
transplant rejection)
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Suppressor T Cells
not well understood
appear to regulate immune response by turning it off when an antigen is
no longer present
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Nonspecific Cellular Immunity
Not linked to individual antigens…
Two cell types
Active Macrophages & Natural Killer Cells
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Activated Macrophages
phagocytic capabilities are greatly increased when stimulated to
become activated.
Can be activated either by ingesting antigens, or by cytokines from T
cells.
Have an enhanced ability to eliminate certain virally-infected cells or
those with intracellular bacteria
can also function as antigen presenting cells – ‘showing’ antigen to T
cells (see fig 17.13)
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Natural Killer Cells
can destroy other cells, especially virus-infected and tumor cells
unlike cytotoxic T cells, do not need to be stimulated by an antigen
are not phagocytic
but must contact cell to lyse (rupture) the invader
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