Concept of

Immunology and
Hypersensitivity
reactions, its types
and Concept of
Autoimmunity
Immunity
 Immunity is an adaptive internal protection that results
in long-term resistance to the effects of invading
microorganisms. This means that the responses are
not automatic. The body has to learn to generate
specific immune responses when it is infected by or
exposed to specific organisms.
 Lymphocytes develop actions and products that
provide the protection of true immunity. These cells
develop specific actions in response to specific
invasion.
Antibody-Mediated Immunity
 Antibody-mediated immunity (AMI), also known as
humoral immunity, involves antigen-antibody
interactions to neutralize, eliminate, or destroy foreign
proteins.
 Antibodies are produced by sensitized B-lymphocytes
(B-cells).
 B-cells become sensitized to a specific foreign protein
(antigen) and produce antibodies directed specifically
against that protein.
 The antibody, rather than the actual B-cell, then
causes one of several actions to neutralize, eliminate,
or destroy that antigen.
 Antibody-Mediated Immunity
 B-cells have the most direct role in AMI.
 Macrophages and T-lymphocytes work with B-cells
to start and complete antigen-antibody interactions.
 For optimal AMI, the entire immune system must
function adequately.
 B-cells start as stem cells in the bone marrow, the
primary lymphoid tissue, that commit to the
lymphocyte pathway and are then restricted in
development.
 The lymphocyte stem cells are released from the
bone marrow into the blood.
 They then migrate into many secondary lymphoid
tissues to mature. The secondary lymphoid tissues
for B-cell maturation are the spleen, parts of lymph
 Antigen-Antibody Interactions

 The body learns to make enough of any

specific antibody to provide long lasting
immunity against specific organisms or toxins.
 Seven steps needed to produce a specific
antibody directed against a specific antigen
whenever the person is exposed to that
antigen.
 Exposure or invasion is needed because
antibody actions occur inside the body or on a
few body surfaces.
 The antigen must first enter the person to
generate an antibody, although not all
exposures result in antibody production.
 Invasion by the antigen must occur in
such large numbers that some of the
antigen evades detection by the body's
natural nonspecific defenses or
overwhelms the ability of the inflammatory
response to get rid of the invader.
 Antigen-Antibody Interactions
 For example, a person who has never been exposed to the viral disease influenza A
now baby-sits for three children who develop influenza symptoms within the next 10
hours. These children, in the pre-symptomatic stage, shed many millions of live
influenza A virus particles by droplets from the upper respiratory tract.
 They expose the baby-sitter by drinking out of the baby-sitter's cup, kissing him or her
directly on the lips, and sneezing and coughing directly into his or her face.
 During the 5 hours spent with the children, the baby-sitter is heavily invaded by the
influenza A virus and will become sick with this disease within 2 to 4 days.
 While the virus is growing and the disease is developing, the baby-sitter's white blood
cells are taking part in antibody-antigen actions to prevent him or her from having
influenza A more than once.
 Antigen recognition is the next step to begin making antibodies against an antigen.
 The unsensitized B-cell must first recognize the antigen as non-self.
 B-cells need the help of macrophages and helper/inducer T-cells to recognize an
antigen.
 Recognition is started by the macrophages. After the antigen surface has been
altered by opsonization the macrophage recognizes the invading antigen as non-self
and attaches itself to the antigen.
 Antigen-Antibody Interactions
 This attachment allows the macrophage to “present” the attached antigen to the
helper/inducer T-cell. Then the helper/inducer T-cell and the macrophage together
process the antigen to expose the antigen's recognition sites (universal product
code).
 After processing the antigen, the helper/inducer T-cell brings the antigen into contact
with the B-cell so that the B-cell can recognize the antigen as non-self.
 Sensitization occurs when the B-cell recognizes the antigen as non-self and is now
“sensitized” to this antigen.
 A single unsensitized B-cell can become sensitized only once. So, each B-cell can
be sensitized to only one type of antigen.
 Sensitizing allows this B-cell to respond to any substance that carries the same
antigens (codes) as the original antigen.
 The sensitized B-cell always remains sensitized to that specific antigen. In
addition, all cells produced by that sensitized B-cell also are already pre-sensitized
to that same specific antigen.
 Immediately after it is sensitized, the B-cell divides and forms two types of B-
lymphocytes, each one remaining sensitized to that specific antigen.
 Antigen-Antibody Interactions
 One new cell becomes a plasma cell, which starts immediately to produce antibodies against
the sensitizing antigen.
 The other new cell becomes a memory cell. The memory cell is a sensitized B-cell but does
not produce antibodies until the next exposure to the same antigen.
 Antibody production and release allow the antibodies to search out specific antigens.
 Antibodies are produced by plasma cells, and each plasma cell can make as many as 300
molecules of antibody per second.
 Each plasma cell produces antibody specific only to the antigen that originally sensitized the
parent B-cell.
o For example, in the case of the baby-sitter who was invaded by the influenza A virus, the
plasma cells from those B-cells sensitized to the influenza A virus can make only anti–
influenza A antibodies.
 The antibody class (e.g., immunoglobulin G [IgG] or immunoglobulin M [IgM]) that the plasma
cell produces may vary, but the antibody can be forever directed only against the influenza A
virus.
 Antibody molecules made by plasma cells are released into the blood and other body fluids as
free antibody. Because the antibody is in body fluids (or body “humors”) and is separate from
the B-cells, this type of immunity is sometimes called humoral immunity.
 Circulating antibodies can be transferred from one person to another to provide the receiving
person with immediate immunity of short duration.
Antigen-Antibody Interactions  Antibody-antigen binding is needed for anti-
antigen actions. Antibodies are Y-shaped
molecules.
 The tips of the short arms of the Y recognize
the specific antigen and bind to it. Because
each antibody molecule has two tips (Fab
fragments, or arms), each antibody can bind
either to two separate antigens or to two
areas of the same antigen.
 The stem of the Y is the “Fc fragment.” This
area can bind to Fc receptor sites on white
blood cells (WBCs).
 The WBC then not only has its own means
of attacking antigens but also has the added
power of having surface antibodies that can
stick to antigens.
 The binding of antibody to antigen may not
be lethal to the antigen. Instead, antibody-
antigen binding starts other actions that
neutralize, eliminate, or destroy the antigen.
 Agglutination is a clumping action that
results from the antibody linking antigens
together, forming large and small
immune complexes.

Agglutination slows the movement of the antigen

in body fluids. Also, the irregular shape of the
antigen-antibody complex increases the actions
of macrophages and neutrophils.

Lysis is cell membrane destruction, and it

occurs now because of antibody binding to
membrane-bound antigens of some
invaders. The actual binding makes holes
in the invader's membrane, weakening the
invader, especially bacteria and viruses.
This response usually requires that
complement be activated and “fixed” to the
immune complex.
Complement activation and fixation are actions Inactivation (neutralization) is the process of
triggered by the IgG and IgM classes of making an antigen harmless without destroying it.
antibodies that can remove or destroy antigen. • Usually only a small area of the antigen, the
• Binding of either IgG or IgM to an antigen active site, causes the harmful effects. When
provides a binding site for the first component an antibody binds to an antigen's active site,
of complement. Once the first complement covering it up, the antigen is made harmless
molecule is activated, other proteins of the without destroying it.
complement system are activated in a
cascade.
Sustained immunity (memory) provides us with
long-lasting immunity to a specific antigen.
Precipitation is similar to agglutination but has a • Sustained immunity results from memory B-
larger response. cells made during the lymphocyte sensitization
• With precipitation, antibody molecules bind so stage.
much antigen that large antigen-antibody • These memory cells remain sensitized to the
complexes are formed. These complexes specific antigen to which they were originally
cannot stay in suspension in the blood. exposed.
Instead, they form a large precipitate, which • On re-exposure to the same antigen, the
then can be acted on and removed by memory cells rapidly respond by first dividing
neutrophils and macrophages. and forming new sensitized blast cells and
plasma cells.
Sustained immunity (memory) Antibody Classification
• The blast cells continue to divide, producing many  All antibodies are immunoglobulins,
more sensitized plasma cells. These new also called gamma globulins. These
sensitized plasma cells rapidly make large amounts names are based on the structure and
of the antibody specific for the sensitizing antigen. function of antibodies.
• This ability of the memory cells to respond on re-  A globulin is a protein that is globular
exposure to the same antigen that originally rather than straight. Because
sensitized the B-cell allows a rapid and large antibodies are globular proteins, they
immune response (anamnestic response) to the are “globulins.”
antigen.  The term immunoglobulin is used for
• Because so much antibody is made, often the antibodies because they are globular
invading organisms are removed completely and proteins that provide immunity.
the person does not become ill.  Antibodies also are called gamma
• This process prevents people from becoming ill globulins because all free antibodies in
with chickenpox or any infectious disease more the plasma separate out in the gamma
than once, even though they are exposed many fraction of plasma proteins during
times to the causative organism. electrophoresis.
• Without immunologic memory, people would  The five antibody types are classified
remain susceptible to specific diseases on by differences in size, location,
subsequent exposure to the organisms and no amount, function, and timing.
long-term immunity would be generated.
Antibody Classification Acquiring Antibody-Mediated Immunity
 On first exposure to an antigen, the newly  Antibody-mediated immunity (AMI) is a
sensitized B-cell produces the IgM antibody type of adaptive immunity in which a
type against the antigen. person's body learns to make as an
 IgM is special because it forms itself into a adaptive response to invasion by
five-member group. Each IgM group, then, has organisms or foreign proteins.
ten antigen binding sites.  Thus antibody-mediated immunity is an
 So, even though antibody production is slow acquired immunity. Adaptive immunity
on first exposure, the antibody type produced occurs either naturally or artificially
forms groups that are very efficient at antigen through lymphocyte responses and can be
binding. This process ensures that the initial either active or passive.
illness, like influenza A, lasts only 5 to 10 days.  Active immunity occurs when antigens
 On re-exposure to the same antigen, the enter a person's body and it responds by
already sensitized B-cell makes large amounts making specific antibodies against the
of the IgG type of antibody against that antigen.
antigen.  This type of immunity is active because
 Although IgG does not form groups of five, the the body takes an active part in making
enormous amounts produced make IgG antibodies.
antibodies efficient at clearing the antigen and  Active immunity occurs under natural or
protecting the person from becoming ill with artificial conditions.
the disease again.
Acquiring Antibody-Mediated Immunity Artificial active immunity
 Natural active immunity occurs when an  The person's immune system responds
antigen enters the body naturally without by actively making antibodies against the
human assistance and the body responds by antigen.
actively making antibodies against that antigen  Because antigens used for this procedure
(e.g., influenza A virus). have been specially processed to make
 Usually, the invasion that triggers antibody them less likely to grow in the body
production also causes the disease. (attenuated), this exposure usually does
 However, processes occurring in the body at not cause the disease.
the same time as infection create immunity to  Artificial active immunity lasts many
that antigen. Thus the person will not become years, although repeated but smaller
ill after a second exposure to the same antigen. doses of the original antigen are required
 Natural active immunity is the most effective as a “booster” to retain the protection.
and the longest lasting.  Passive immunity occurs when the
 Artificial active immunity is the protection antibodies against an antigen are
developed by vaccination or immunization. This transferred to a person's body after first
type of immunity is used to prevent serious and being made in the body of another person
potentially deadly illnesses (e.g., tetanus, or animal.
diphtheria, polio).  Because these antibodies are foreign to
 Small amounts of specific antigens are placed the receiving person, they are recognized
as a vaccination into a person. as non-self and eliminated quickly.
Passive immunity Cell-Mediated Immunity (CMI)
 Because these antibodies are foreign to the receiving  Cell-mediated immunity (CMI),
person, they are recognized as non-self and eliminated or cellular immunity, involves
quickly. many white blood cell (WBC)
 For this reason, passive immunity provides only actions and interactions.
immediate, short-term protection against a specific  CMI is another type of adaptive
antigen. or acquired true immunity that
 It is used when a person is exposed to a serious disease is provided by lymphocyte stem
for which he or she has little or no actively acquired cells that mature in the
immunity. secondary lymphoid tissues of
 Instead, the injected antibodies are expected to inactivate the thymus and pericortical
the antigen. areas of lymph nodes.
 Artificial passive immunity may be used to prevent disease  Certain CMI responses
or death for patients exposed to rabies, tetanus, and influence and regulate the
poisonous snake bites. activities of antibody-mediated
 Natural passive immunity occurs when antibodies are immunity (AMI) and
passed from the mother to the fetus via the placenta or to inflammation by producing and
the infant through colostrum and breast milk. releasing cytokines.
 AMI works with inflammation to protect against infection.  For total or full immunity, CMI
However, AMI can provide the most effective long-lasting must function optimally.
immunity only when its actions are combined with those of
Cell Types Involved in Cell-Mediated Immunity
 The WBCs with the most important roles in CMI include several specific T-lymphocytes (T-cells)
along with a special population of cells known as natural killer (NK) cells. T-cells have a variety of
subsets, each of which has a specific function.
 Different T-cell subsets can be identified by the presence of “marker proteins” (antigens) on the
cell membrane's surface.
 More than 200 different T-cell proteins have been identified on the cell membrane, and some of
these are commonly used clinically to identify specific cells.
 Most T-cells have more than one antigen on their cell membrane. For example, all mature T-cells
contain T1, T3, T10, and T11 proteins.
 The names used to identify specific T-cell subsets include the specific membrane antigen and the
overall actions of the cells in a subset.
 The three T-lymphocyte subsets that are critically important for the development and continuation
of CMI are helper/inducer T-cells, suppressor T-cells, and cytotoxic/cytolytic T-cells.
 An additional cell, the natural killer cell, although not a true T-cell, also contributes to CMI.
 Helper/inducer T-cells have the T4 protein on their membranes. These cells are usually called T4+
cells or TH cells. The most correct name for helper/inducer T-cells is CD4+ (cluster of
differentiation 4).
 Helper/inducer T-cells easily recognize self cells versus non-self cells. When they recognize non-
self (antigen), helper/inducer T-cells secrete cytokines that can enhance the activity of other
WBCs and increase overall immune function.
Cell Types Involved in Cell-Mediated Immunity
 Helper/inducer T-cells
 These cytokines increase bone marrow production of stem cells and speed up their maturation.
Thus helper/inducer T-cells act as organizers in “calling to arms” various squads of WBCs involved
in inflammatory, antibody, and cellular protective actions.
 Suppressor T-cells have the T8-lymphocyte antigen on membrane surfaces. These cells are
commonly called T8+ cells, CD8+ cells, or TS-cells.
 Suppressor T-cells help regulate CMI. Suppressor T-cells prevent hypersensitivity (immune
overreactions) on exposure to non-self cells or proteins.
 This function is important in preventing the formation of antibodies directed against normal,
healthy self cells, which is the basis for many autoimmune diseases.
 The suppressor T-cells secrete cytokines that have an overall inhibitory action on most cells of the
immune system.
 Suppressor T-cells have the opposite action of helper/inducer T-cells.
 For optimal function of CMI, then, a balance between helper/inducer T-cell activity and suppressor
T-cell activity must be maintained. This balance occurs when the helper/inducer T-cells outnumber
the suppressor T-cells by a ratio of 2 : 1.
 When this ratio increases, indicating that helper/inducer T-cells vastly outnumber the suppressor
cells, overreactions can occur, some of which are tissue damaging as well as unpleasant. When
the helper/suppressor ratio decreases, indicating fewer-than-normal helper/inducer T-cells,
immunity is suppressed and the person's risk for infections increases.
 Cytotoxic/cytolytic T-cells are also called TC-cells. Because they have the T8 protein
present on their surfaces, they are a subset of suppressor cells.
 Cytotoxic/cytolytic T-cells destroy cells that contain a processed antigen’s human
leukocyte antigens (HLAs). This activity is most effective against self cells infected by
parasites, such as viruses or protozoa.
 Parasite-infected self cells have both self HLA proteins (universal product code) and the
parasite's antigens on the cell surface. This allows the person's immune system cells to
recognize the infected self cell as abnormal, and the cytotoxic/cytolytic T-cell can bind
to it, punch a hole, and deliver a “lethal hit” of enzymes to the infected cell, causing it to
lyse and die.
 Natural killer (NK) cells are also known as CD16+ cells and are very important in
providing CMI. The actual site of NK cell differentiation and maturation is unknown, and
it is not a true T-cell subset.
 NK cells have direct cytotoxic effects on some non-self cells without first being
sensitized. They conduct “seek and destroy” missions in the body to eliminate non-self
cells.
 NK cells are most effective in destroying unhealthy or abnormal self cells. The non-self
cells most often harmed by NK cells are cancer cells and virally infected body cells.
Cytokines Cytokines
 Cell-mediated immunity (CMI) regulates the  Thus, cytokines act like “messengers” that
immune system by the production and activity tell specific cells how and when to
of cytokines. respond.
 Cytokines are small protein hormones  The cells that change their activity when a
produced by the many WBCs (and some other cytokine is present are “responder” cells.
tissues). For a responder cell to respond to the
 Cytokines made by the macrophages, presence of a cytokine, the
neutrophils, eosinophils, and monocytes are  responder cell must have a specific
called monokines. receptor to which the cytokine can bind.
 Those produced by T-cells are called Once the cytokine binds to its receptor,
lymphokines. In addition, we now know that the responder cell changes its activity.
many other body cell types can produce and  Cytokines control many inflammatory and
respond to cytokines. immune responses and are controlled by
 Cytokines work like hormones: one cell interactions with other systems, especially
produces a cytokine, which in turn exerts its the nervous system.
effects on other cells of the immune system  Cytokines include the interleukins (ILs),
and on other body cells. interferons (IFNs), colony-stimulating
 The cells responding to the cytokine may be factors, tumor necrosis factors (TNFs),
located close to or remote from the cytokine- and transforming growth factors (TGFs).
secreting cell.
Cytokines
 The interleukins are the largest group
of cytokines, with interleukin-33 (IL-33)
being the most recently defined.
 There are many cytokines, and
cytokine classification is undergoing
changes. Some are considered
“proinflammatory” and increase the
actions of natural immunity
(inflammation).
 These currently include TNF-α, IL-1, IL-
10, IL-12, and interferons (α [alpha], β
[beta], and γ [gamma]).
 Other cytokines have a major influence
on AMI and CMI activities. These
include IL-2, IL-4, IL-5, IL-10, TGF-β,
and IFN-γ.
 Although there are many cytokines, not
all their functions are known or clinically
useful at this time; however, this is an
area of continuing research and
Protection Provided by Cell-Mediated
Immunity
 Cell-mediated immunity (CMI) helps protect the
body through the ability to differentiate self from
non-self.
 The non-self cells most easily recognized by

THANK
CMI are cancer cells and those self cells
infected by organisms that live within host cells,
especially viruses.
 CMI watches for and rids the body of self cells
that might potentially harm the body.
 CMI is important in preventing the development
YOU FOR
of cancer and metastasis after exposure to
carcinogens.
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