ADAPTIVE IMMUNITY (Rev - DR. Amoani)

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ADAPTIVE IMMUNITY

Adaptive immunity is triggered when an infection


eludes or overwhelms the innate defense
mechanisms and generates a threshold dose of
antigen.

Adaptive (acquired) immunity refers to antigen-


specific defense mechanisms designed to remove a
specific antigen. This is the immunity one develops
throughout life.
There are two major branches of the adaptive
immune responses: (1) humoral immunity and (2)
cell-mediated immunity.

1. Humoral immunity: humoral immunity involves the


production of antibody molecules in response to an
antigen and is mediated by B-lymphocytes.

2. Cell-mediated immunity: Cell-mediated immunity


involves the production of cytotoxic T-lymphocytes,
activated macrophages, activated NK cells, and
cytokines in response to an antigen and is mediated
by T-lymphocytes
FUNDAMENTAL CHARACTERISTICS OF THE ADAPTIVE IMMUNE RESPONSE

1. Specificity: The fundamental characteristics of


adaptive immunity are: its response to a pathogen
is specific and inducible: It reacts only to the
specific microorganism causing an infection, and,
in doing so, induces the creation of more of the
anti-microbial elements necessary to eliminate the
threat. However, it will not react with other
antigens.
• The specificity of the immunological response
is explained on the basis of the clonal
selection hypothesis:

• During the primary immune response, a


specific antigen selects a pre-existing clone of
specific lymphocytes and stimulates
exclusively its activation, proliferation and
differentiation.
2.  Memory. The immunological system has a
"memory". Once the immunological response has
reacted to produce a specific type of antibody or
reactive T-cell, it is capable of producing more of
the antibody or activated T-cells rapidly and in
larger amounts.

• Antibody production resulting from the first


exposure to antigen is called a primary response.
This differs remarkably from that seen on
subsequent exposures.
• A second exposure to the same antigen usually
produces a dramatic rise in antibody level.

• The antibody production resulting from this second


exposure is referred to as secondary response and is
frequently called a specific anamnestic response,
from the Greek term anamnesis, meaning ‘recall
(remember)’.
• The antibody levels associated with this specific
anamnestic response, occur with little or no lag
period, and remain for long periods.

• The primary and secondary responses are


characteristic of memory.

• Vaccination utilizes the principle of memory by the


injection of avirulent form of the antigen (e.g. killed
virus) into an animal to serve as a stimulus to print
memory.
• The body’s immune system therefore
becomes alert and any subsequent exposure
to the virulent form of the same organism
leads to an almost immediate production of
antibody, the peak levels being hundred fold
greater than primary response.

• This will usually prevent the infection from


being established.
3. Discrimination of self from non-self

• The success of the immune system depends


on its ability to discriminate between foreign
(non-self) and host (self) cells.

• Survival requires both the ability to mount a


destructive immune response against nonself
and the inability to mount a destructive
response against self.
• When an organism is threatened by
microorganisms, viruses, or cancer cells, the
immune response acts to provide protection.

• Normally, the immune system does not mount a


response against self. This lack of an immune
response is called tolerance. In some cases, the
immune system does not mount an immune
response against self.

• If an error is made, and an immune response is


made against self, tolerance to self is lost. This
condition is called autoimmunity.
O the r Ch ara cte ris tics O f Th e Im m un e R es p ons e

1. Diversity – The total number of antigenic


specificities of the lymphocytes in an individual,
called the lymphocyte repertoire, is extremely
large.

• It is estimated that the mammalian immune


system can discriminate at least 109 distinct
antigenic determinants.
• This extraordinary diversity of the repertoire is a
result of variability in the structures of antigen-
binding sites of lymphocytes receptors for antigens.

• In other words, different clones of lymphocytes


differ in the structures of their antigen receptors,
and therefore, in their specificity for antigens,
creating a total repertoire that is extremely diverse.

2. Self-Regulation – All normal immune response


wane with time after antigenic stimulation.
Active vs passive immunity

• Although adaptive immunity develops in an animal


which is undergoing a specific immunological
response to an antigen, the immune cells and
factors generated can be shared among two or
more animals.

• Hence, adaptive immunity can be acquired by an


animal in two ways: active immunity and passive
immunity.
Examples of Active and Passive Immunity
How Acquired by Host Examples

Natural: Antibodies are


produced by the host in
response to the infectious agent
itself (e.g. recovery from the
disease).
As a result of exposure to
Active Immunity an infectious agent or one  Artificial: immunization
of its products (antigens) (vaccination) with some product
derived from the infectious
agent (e.g. toxoid, killed cells,
structural components of cells,
inactivated or attenuated
viruses, etc.).
Natural: Transplacental
transfer of antibodies from
mother to fetus; transfer of
antibodies from mother to
As a result of the acquisition
infant in milk by nursing.
of antibodies which have
been produced in another
Artificial: Injection of
Passive Immunity animal (by active means) or
immune serum from an
derived from cells grown in
individual previously
tissue culture (e.g.
immunized or recovered
monoclonal antibodies)
from disease, e.g. hepatitis;
injection of serum from an
animal hyperimmunized with
tetanus toxoid.
Anatomy of the Immunological System

• The major components of the immunological system are


lymph nodes connected by lymph ducts, Peyer's patches
(masses of lymphocytes in the lower gastrointestinal
tract), thymus, spleen, and bone marrow.

• A lymph node. Afferent lymph ducts bring lymph-


containing antigens into the lymph node. Macrophages,
dendritic cells and  B-cells in the cortical region make
contact with the antigen and process it for presentation to
immunocompetent B-cells and T- cells, thereby initiating
an immune response.
• As a result, B-cells are stimulated to develop into
antibody-secreting plasma cells, and T-cells are
stimulated to develop into effector T cells of various
classes. Antibodies leave the lymph node by the
efferent ducts that empty into the blood stream.

• A single lymphocyte completes a circuit through the


circulating blood and lymphatic systems once every
24 hours.
Cells of the immune system
• B-cells: The major function of B lymphocytes is to
develop into antibody-secreting plasma cells
following stimulation by foreign antigens of
bacteria, viruses and tumor cells.

• Antibodies are specialized proteins that specifically


recognize and bind to specific antigens that caused
their stimulation.

• Antibody production and binding to foreign


antigens is often critical as a means of signaling
other cells to engulf, kill or remove that substance
from the body.
• T-cells: T lymphocytes are usually divided into
two major subsets that are functionally and
phenotypically different.

• T helper (TH) cells, also called CD4+ T cells, are


involved in coordination and regulation of
immunological responses.

• They function to mediate responses by the


secretion of lymphokines that stimulate or
otherwise affect other cells involved in the
immune responses.
• The second subset type of T lymphocytes are cytotoxic
T lymphocytes ( Tc cells or CTLs) or CD8+ T cells.

• These cells are involved in directly killing certain


tumor cells, virus-infected cells, transplant cells, and
sometimes eukaryotic parasites.

• CD8+ T cells are also important in down-regulation of


immune responses. In this case they are referred to as
T-suppressor cells(Ts).
• Both types of T cells can be found throughout the
body, most conspicuously in lymphoid organs
(lymph nodes and spleen) but also the liver, lung,
blood, and the intestinal tract.

• Natural killer cells, known as NK cells, are similar to


CTLs (CD8+ T cells).

• They function as effector cells that directly kill


certain tumors such as melanomas, lymphomas and
virus-infected cells, most notably herpes and
cytomegalovirus-infected cells.
• However, NK cells, unlike the CD8+ (Tc) cells,
kill their target cells without need for
recognition of antigen in association with MHC
molecules. 

• NK cells that have been activated by


secretions from CD4+ T cells will kill their
tumor or viral-infected targets more
effectively.
• Macrophages are important in the regulation of
immune responses.

• Besides their role in phagocytosis, they may function


as antigen-presenting cells (APCs) because they ingest
foreign materials and present these antigens to other
cells of the immune system such as T-cells and B-cells.
• Macrophages, stimulated by certain lymphokines,
exhibit increased levels of phagocytosis and also
secrete cytokines that modulate immune
responses.

• Dendritic cells also originate in the bone marrow


and function as antigen presenting cells (APCs). In
fact, the dendritic cells are more efficient APCs
than macrophages.

• These cells are usually found in structural


compartments of the lymphoid organs such as the
thymus, lymph nodes and spleen.
• However, they are also found in the bloodstream
and other tissues of the body.

• It is believed that they capture and process antigens


in lymphoid organs where an immunological
response is initiated.

• Of particular interest is the recent finding that


dendritic cells bind large numbers of HIV particles,
and may be a reservoir of virus that is transmitted
to CD4+ T cells.
The Immunological Response
• Immunological responses are associated with
macrophages or dendritic cells and two
subpopulations of lymphocytes, B-cells and T-cells.

• Under antigenic stimulus, B-lymphocytes become


transformed into antibody-secreting plasma cells.

• The plasma cells synthesize large amounts of


immunoglobulins (antibodies) which will react
stereochemically with the stimulating antigen.
• Under antigenic stimulus, pre T-lymphocytes
differentiate into several classes of effector T cells
which are committed to various activities upon
recognition of the specific antigen that induced their
formation.

• T cells have many activities relevant to immunity


including

(1). Mediation of the B-cell response to antigen;

(2) ability to recognize and destroy cells bearing foreign


Ag on their surface;
(3)Production of a variety of diffusible compounds
called cytokines and/or lymphokines, which include
substances that are activators of macrophages,
mediators of inflammation, chemotactic attractants,
lymphocyte mitogens, and interferon.

• Cytokines and lymphokines are molecules


(peptides, proteins) produced by cells as a means of
intercellular communication.

• Generally, cytokines are secreted by a cell to


stimulate the activity of itself or another cell.
• The overall aspects of the induction of an
immunological response (AMI and CMI) are shown in
the following schematic diagram.
ANTIBODY-MEDIATED (HUMORAL) AND CELL-MEDIATED
IMMUNITY (AMI & CMI)

• Antibody-mediated immunity (AMI) is the type of


adaptive immunity that is mediated by soluble
host proteins called antibodies or
immunoglobulins.

• Because it is largely due to the presence of


circulating antibody molecules in the serum, is
also called circulating immunity or humoral
immunity.
• If a naive (unstimulated) B cell encounters an
antigen, it is stimulated to develop into a plasma
cell which produces the antibodies that will react
with the stimulating antigen.

• They also develop into clones of identical reactive B-


cells called memory B-cells.
• Cell-mediated immunity (CMI) is the type of
adaptive immunity that is mediated by specific
subpopulations of T-lymphocytes called effector T-
cells.

• In non immune animals precursor T-cells (pT cells)


exist as "resting T cells".

• They bear receptors for specific antigens.


Stimulation with Ag results in their activation.
• The cells enlarge, enter into a mitotic cycle,
reproduce and develop into effector T-cells
whose activities are responsible for this type of
immunity.

• They also develop into clones of identical


reactive T-cells called memory T-cells.
Membrane receptors on B-cells and T-cells
• The nature of the membrane receptors for antigen on
B-cells and T-cells is fairly well understood.

• Each B cell has approximately 105 membrane-bound


antibody molecules (IgD or IgM) which correspond in
specificity to the antibody that the cell is programmed
to produce.

• Each T cell has about 105 molecules of a specific


antigen-binding T cell receptor (TCR) exposed on its
surface. The TCR is similar, but not identical, to
antibody.
• In addition, T cell subsets bear some distinguishing
surface markers, notably CD4 or CD8.

• T cells bearing CD4 always recognize antigens in


association with class II major histocompatability
complex (class II MHC) proteins on the surfaces of
other cells.

• CD4+ T lymphocytes generally function as T


helper cells or in modulation of immune
responses.
• T cells bearing CD8 ( CD8+ ) always recognize
antigen in association with class I MHC
proteins and typically function as cytotoxic T
cells.

• The important markers, actions and


interactions of T cells, B cells and Antigen
Presenting Cells (APC) are illustrated below.
Induction of primary immunological responses

• Induction of a primary immunological response begins


when an antigen penetrates epithelial surfaces.

• It will eventually come into contact with macrophages


or certain other classes of Antigen Presenting cells
(APCs), which include B cells, monocytes, dendritic
cells, Langerhans cells and endothelial cells.

• Antigens, such as bacterial cells, are internalized by


endocytosis and "processed" by the APC, then
"presented" to immunocompetent lymphocytes to
initiate the early steps of the immunological response.
• Processing by a macrophage (for example) results in
attaching antigenic materials to the surface of the
membrane in association with MHC II molecules on
the surface of the cell .

• The antigen-MHC II complex is presented to a T-


helper (TH2) cell which is able to recognize
processed antigen associated with a class II MHC
molecule on the membrane of the macrophage.

• This interaction, together with stimulation by


Interleukin 1 (IL-1), produced by the macrophage,
will activate the TH2 cell.
• Activation of the TH2 cell causes it to begin to
produce Interleukin 2 (IL-2), and to express a
membrane receptor for IL-2.

• The secreted IL-2 auto stimulates proliferation of


the TH2 cells.

• Stimulated Antigen stimulated TH2 cells produce a


variety of lymphokines including IL-2, IL-4, IL-6, and
gamma Interferon, which mediate various aspects
of the immune response.
• For example, IL-2 binds to IL-2 receptors on other T
cells (which have bound the Ag) and stimulates their
proliferation, while IL-4 causes B cells to proliferate
and differentiate into antibody-secreting plasma
cells and memory B cells.

• IL-4 activates only B cells in the vicinity which


themselves have bound the antigen, and not others,
so as to sustain the specificity of the immunological
response.
• B-cell can react with a homologous antigen on the
surface of the macrophage or with soluble antigens.

• When a B-cell is bound to Ag, and simultaneously is


stimulated by IL-4 produced by a nearby TH2 cell,
the B cell is stimulated to grow and divide to form a
clone of identical B cells, each capable of producing
identical antibody molecules.

• The activated B cells further differentiate into


plasma cells which synthesize and secrete large
amounts of antibody, and into a special form of B
cells called memory B cells.
• The antibodies produced and secreted by the
plasma cells react specifically with the
homologous antigen that induced their
formation.

• Many of these reactions lead to host defense


and to prevention of reinfection by pathogens.
Memory cells play a role in secondary immune
responses.
• Plasma cells are relatively short-lived (about
one week) but produce large amounts of
antibody during this period.

• Memory cells, on the other hand, are


relatively long-lived and upon subsequent
exposure to Ag they become quickly
transformed into Ab-producing plasma cells.
• Generation of cell mediated immunity (CMI) begins
when (for example) a Tc cell recognizes a processed
antigen associated with MHC I on the membrane
of a cell (usually an altered self cell, but possibly a
transplanted tissue cell or a eucaryotic parasite).

• Under stimulation by IL-2 produced by TH2 cells


the Tc cell becomes activated to become a
cytotoxic T lymphocyte (CTL) capable of lysing the
cell which is showing the new (foreign) antigen on
its surface, a primary manifestation of CMI.
• The interaction between an antigen-presenting
macrophage and a TH cell stimulates the
macrophage to produce and secrete a cytokine
called Interleukin-1 (IL-1) that acts locally on the TH
cell.

• The IL-1 stimulates the TH cell to differentiate and


produce its own cytokines (which in this case might
be called lymphokines because they arise from a
lymphocyte).
• These lymphokines have various functions.
Interleukin-4 has an immediate effect on
nearby B-cells.

• Interleukin-2 has an immediate effect on T


cells as described above.

• Time is required before a primary


immunological response becomes effective as
a host defense.
• It may take several days or weeks to reach a level
of effective immunity, even though this immunity
may persist for many months, or years, or even a
lifetime due to the presence of the antibodies.

• In natural infections, the inoculum is small, and


even though the antigenic stimulus increases
during microbial replication, only small amounts of
antibody are formed within the first few days, and
circulating antibody is not detectable until about a
week after infection.
Induction of a secondary immunological response

• On re-exposure to microbial antigens (secondary


exposure to antigen), there is an accelerated
immunological response, the secondary or memory
response.

• Larger amounts of antibodies are formed in only 1-2


days. This is due to the activities of specific memory
B cells and memory T cells which were formed
during the primary immune response.
• These memory cells, when stimulated by
homologous Ag, "remember" having previously
seen the Ag, and are able to rapidly divide and
differentiate into effector cells.
• This is not to say that a protective level of
antibody may not be reached by primary
exposure alone, but usually to ensure a high
level of protective antibody that persists over
a long period of time, it is necessary to have
repeated antigenic stimulation of the immune
system.

• Humoral immunity arm of the adaptive immunity,


comprises mainly of antibody responses, which we
discussed last
Functions of Antibodies in Host Defense

• The functions of  antibodies, and hence the AMI


response, in host defense against pathogenic
microbes is summarized below.

• Opsonization Antibodies enhance phagocytic


engulfment of microbial antigens. IgG and IgM Abs
have a combining site for the Ag and a site for
cytophilic association with phagocytes. Bacteria and
viral particles are ingested with increased efficiency.
• Steric hindrance Antibodies combine with the
surfaces of microorganisms and may block or
prevent their attachment to susceptible cells or
mucosal surfaces. Ab against a viral component can
block attachment of the virus to susceptible host
cells and thereby reduce infectivity. Secretory IgA
can block attachment of pathogens to mucosal
surfaces.

• Toxin Neutralization Toxin-neutralizing antibodies


(antitoxins) react with a soluble bacterial toxin and
block the interaction of the toxin with its specific
target cell or substrate in the host
• Agglutination and Precipitation Antibodies combine
with the surfaces of microorganisms or soluble
antigens and cause them to agglutinate or
precipitate.

This reduces the number of separate infectious


units and makes them more readily phagocytosed
because the clump of particles is larger in size. Also,
floccules or aggregates of neutralized toxin may be
removed by phagocytes.
• Activation of Complement Antibodies combined
with the surface antigens of microbes activate the
complement cascade which has four principal
effects related to host defense:

1. Induction of the inflammatory response


2. Attraction of phagocytes to the site of
immunological encounter
3. Opsonization of cells which increases efficiency
of phagocytosis
4. Lysis of certain bacteria or viruses
• Antibody-dependent cell cytotoxicity (ADCC):
IgG can enable certain cells (Natural Killer or NK
cells) to recognize and kill opsonized target cells.

• Certain other types of cells including monocytes


and neutrophils also act this way.

• NK cells attach to opsonized target cells by


means of an IgG Fc receptor and kill by an
extracellular mechanism after attachment. ADCC
will be discussed as part of cell-mediated
immunity.
CELL-MEDIATED IMMUNITY

• Cell-mediated Immunity (CMI )is a type of


resistance in which cells of the immunological
system are directly involved, but antibody
production or activity is of minor importance.

• CMI differs from AMI in that immunity cannot be


transferred (passively) from animal to animal by
antibodies or serum, but can be transferred by
lymphocytes removed from the blood.
The CMI response
• During the cell-mediated immune response,
various subsets of T lymphocytes are activated
and develop into effector T cells.

• These include cytotoxic T lymphocytes (CTLs or Tc


cells) and T helper cells of the TH1 and TH2
subsets.

• TH1 cells secrete lymphokines that activate


macrophages and mediate delayed type
hypersensitivity responses.
• TH2 cells secrete lymphokines that stimulate B cell
development and may help activate Tc cells to their
full cytotoxic capacity.

• T cells that generate CMI are present in lymphoid


organs, blood and lymph nodes.

• Due to constant recirculation between blood and


lymph nodes via lymphatics and back to the blood,
one T-cell circulates once in about 24 hours.
• Each carries receptors for the specific Ag with which
it can react.

• T-cell recognition of Ag only occurs when the Ag is


associated with proteins of the MHC complex.

• T-cells have receptors (TCR) complementary to the


complexed MHC determinant and the antigenic
epitope.
• TH1 cells and TH2 cells recognize Ag in
association with MHC II (as displayed by
macrophages and other APCs);

• Tc cells recognize Ag on cells complexed with


MHC I (as displayed by altered self cells).
Stepwise Activation of Tc cells
• During a primary CMI response, antigen is
presented to the precursor Tc lymphocytes (CD8+)
in association with MHC Class I proteins.

• All nucleated cells express MHC I on their surfaces,


so virtually any cell in the animal expressing a new
("nonself") Ag on its surface will activate the
cytotoxic T lymphocytes.

• TH2 cells can augment activation of Tc cells, but


they probably are not required.
Activation of TH cells
• TH-cells (CD4+) reacting with Ag may produce a
variety of lymphokines.

• Notably, Interleukin-2 (IL-2) stimulates T-cell


activation and IL-4 stimulates B cells.

• T-helper cells are composed of distinct subsets


that are best distinguished on the basis of their
patterns of lymphokine production.
• Both types of TH cells develop under most
conditions but their ratios and the
predominance of certain lymphokines can
vary, and this may mediate the pathology and
outcome of certain bacterial infections.

• TH1 cells "see" foreign Ag on the surface of


APCs in the context of MHC II.

• Mainly, TH1 cells produce IL-2, gamma


interferon (IFN) and lymphotoxin.
• This results in macrophage activation and the
delayed-type hypersensitivity reaction, as well as
help for Tc cell activation.

• TH2 cells also see foreign Ag on the surface of


APCs in the context of MHC II.

• Their response is to secrete IL-4, IL-5, IL-6, IL-10


and IL-13 that help activate B cells, provide help
for the production of IgE that attaches to mast
cells, and promote mast cell and eosinophil
activation.
• The lymphokines produced by TH cells stimulate B
cells and pTc cells, inducing them to proliferate and
mature into effector cells.

• Gamma Interferon activates macrophages and


Natural Killer (NK) cells to their full cytolytic
potential.

• Lymphotoxins, such as tumor necrosis factor (TNF)


cause fever and kill cells at a distance.
Function of cytotoxic T-lymphocytes
• Tc cells (CTLs) can destroy cells bearing new
antigens on their surfaces (as might result in a viral
infection, a tumor cell, or an infection by a bacterial
intracellular parasite).

• Tc cells exert their cytotoxic activity when they are


in physical contact with cells bearing new Ag in
association with MHC I protein.

• Contact between the Tc cell and the target cell is


required for lysis, although the exact mechanism of
lysis is not well understood.
• The target cell membrane is damaged at the site of
contact (the "kiss of death") leaving a gaping hole
about 40 nm in diameter that cannot be repaired.

• When the Tc cell moves away 30-60 seconds later,


there is leakage of the cell components, an influx
of H2O, and the target cell swells up and dies.

• Apparently the Tc cell releases some of its cytolytic


contents directly into the target cell, so that within
a few minutes the target cell literally disintegrates.
The Tc cell can move away and kill again.
• Tc cells generally respond to Ag in association with
MHC I proteins on the surface of a target cell.

• If they responded to Ag by itself, they could react


with it when it was free in extracellular fluids, and
their cytotoxic activity would be triggered with no
purpose.

• As stated above, almost all host cells, including


macrophages, display MHC I.
• Hence, an effector Tc cell can destroy a
macrophage which is otherwise carrying out a
useful function by presenting Ag to TH
lymphocytes as part of the AMI or CMI
responses.

• Usually, the time course of the response is such


that TH cells have already developed and have
carried out their (helping) function when Tc cells
begin to become active.
Delayed Type Hypersensitivity
• TH1-cells (CD4+) are a subset of T-lymphocytes that
recognize Ag in association with Class II (and
possibly Class I) MHC proteins.

• When TH1-cells are presented with Ag in


association with MHC II by a macrophage, their
development is stimulated by macrophage
Interleukin-1 (IL-1), and auto stimulated by IL-2,
which the TH cell produces.
• They respond by differentiating and producing a
variety of lymphokines that induce a local
inflammatory response, and which attract, trap, and
activate phagocytes at the site.

• One aspect of this response is a state of delayed-


type hypersensitivity in the host.

• This is usually evident in chronic infections wherein


CMI is largely involved (e.g. tuberculosis).
Roles of the AMI and CMI Responses in Host Defense Against Infections

• AMI and CMI responses are generated during almost all


infections, but the relative magnitude and importance of
each type of response shows great variation in different
hosts and with different infectious agents.

• In some types of infections antibody plays a major role in


immunity or recovery.

• For example, viruses producing systemic disease with a


viremia stage (viruses free in the blood as they spread
from infected to uninfected cells), such as poliomyelitis or
yellow fever, can be neutralized by circulating antibody.
• Pathogenic bacteria that multiply outside of cells
(nearly all bacteria) at sites accessible to antibody
can be stopped by the forces of AMI.

• Diseases caused by circulating bacterial toxins (e.g.


diphtheria and tetanus) are controlled by
circulating antibodies that neutralize toxins.

• Circulating antibodies (and perhaps secretory IgA,


as well) present in immune animals can prevent
reinfection by pathogens.
• In other types of infections CMI is of supreme
importance in recovery.

• These tend to be infections where the microbe


grows or multiplies intracellularly.

• Bacterial infections of this nature include


tuberculosis, brucellosis and syphilis.

• Recovery is associated with development of a


pronounced CMI response, even though it is CMI
that contributes to the pathology of the disease.
• The clearest picture of the importance of CMI in
recovery from disease is seen in certain viral
infections (e.g. herpes, pox viruses and measles).

• Viruses are always intracellular parasites and may


only rarely expose themselves to the extracellular
forces of AMI.

• Antibodies could neutralize free virus particles


liberated from cells but often have little influence
on infected cells.
• The best strategic defense against virus-infected
cells seems to be to kill the infected cell when the
virus may be in a replicative (noninfectious) form.

• Many viruses, as they mature, cause foreign (viral)


antigens to appear on the infected cell surface.

• These cells are recognized by the host's CMI


defenses and they become target cells for cytolysis.

• The infected cell can be destroyed before virus is


liberated.
• The CMI response also plays a role in destruction
of tumor cells and in rejection of tissue
transplants in animals.

• A major problem in transplantation of tissues


from one individual to another is rejection which
is often based on CMI response to "foreign" cells
(not a perfect match antigenically).

• Since tumor cells contain specific antigens not


seen on normal cells they also may be recognized
as foreign and destroyed by the forces of CMI.
• If tumor cells develop on a regular basis in animals,
it may be the forces of CMI that eliminate them or
hold them in check.

• The increase in the incidence of many types of


cancer (tumors) in humans with advancement of
age may be correlated with a decline in the peak
efficiency of the immune system that begins about
25 years of age.
• In summary, antibody-mediated immunity (AMI) is
probably most useful as an immune defense
because of its ability to neutralize or destroy
extracellular pathogens and to prevent occurrence
of reinfection.

• Cell-mediated immunity (CMI) plays the major role


in immune defense against infections caused by
intracellular parasites, infections caused by viruses
(either virulent or oncogenic), rejection of
transplanted tissues or cells, and in the destruction
of tumor cells.

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