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The Immune System, Part II
Medgar Evers College, CUNY
Bio 261
Prof. Santos
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In acquired immunity, lymphocytes provide
specific defenses against infection
• Acquired immunity
– Is the body’s second major kind of defense
– Involves the activity of lymphocytes
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The nature of the antigen
• An antigen is any foreign molecule
– That is specifically recognized by lymphocytes
and elicits a response from them
• A lymphocyte actually recognizes and binds
– To just a small, accessible portion of the antigen
called an epitope
Antigenbinding
sites
Antibody A
Antigen
Antibody B
Antibody C
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Epitopes
(antigenic
determinants)
Antigen Recognition by Lymphocytes
• The vertebrate body is populated by two main
types of lymphocytes
– B lymphocytes (B cells)
– T lymphocytes (T cells)
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T Cells
• Produced in the bone marrow
• Mature in the thymus
• Have T cell receptors that interact with a
specific antigen
• T cell receptors consist of 2 chains (Alpha and
Beta)
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• The T cell receptor is always attached to the
cell
• The receptor only interacts with antigens
presented to them.
• A T cell will only recognize an antigen when
complemented with an MHC protein
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T Cell Receptors for Antigens and the Role of the MHC
• Each T cell receptor
– Consists of two different polypeptide chains
AntigenBinding site
Variable
regions
Constant
regions
V
V
C
C
Transmembrane
region
Plasma
membrane
a chain
b chain
Disulfide bridge
Cytoplasm of T cell
(b) A T cell receptor consists of one
a chain and one b chain linked by
a disulfide bridge.
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T cell
• T cells bind to small fragments of antigens
– That are bound to normal cell-surface proteins
called MHC molecules
• MHC molecules
– Are encoded by a family of genes called the
major histocompatibility complex
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MHC system
• Class I MHC molecules, found on almost all
nucleated cells of the body
– Display peptide antigens to cytotoxic T cells
Infected cell
Antigen
fragment
1
1 A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
Class I MHC
molecule
2
T cell
receptor
(a) Cytotoxic T cell
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2 The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
• Class II MHC molecules, located mainly on
dendritic cells, macrophages, and B cells
– Display antigens to helper T cells
Microbe
1 A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
Antigenpresenting
cell
Antigen
fragment
1
Class II MHC
molecule
2
2 The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
(b)
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T cell
receptor
Helper T cell
Helper T Cells: A Response to Nearly All Antigens
• Helper T cells produce CD4, a surface protein
– That enhances their binding to class II MHC
molecule–antigen complexes on antigenpresenting cells
• Activation of the helper T cell then occurs
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• Activated helper T cells
– Secrete several different cytokines that
stimulate other lymphocytes
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Cytotoxic T Cells: A Response to Infected Cells
and Cancer Cells
• Cytotoxic T cells make CD8
– A surface protein that greatly enhances the
interaction between a target cell and a
cytotoxic T cell
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• Cytotoxic T cells
– Bind to infected cells, cancer cells, and
transplanted tissues
• Binding to a class I MHC complex on an
infected body cell
– Activates a cytotoxic T cell and differentiates it
into an active killer
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• The activated cytotoxic T cell
– Secretes proteins that destroy the infected target
cell
2
1 A specific cytotoxic T cell binds to a
class I MHC–antigen complex on a
target cell via its TCR with the aid of
CD8. This interaction, along with
cytokines from helper T cells, leads to
the activation of the cytotoxic cell.
The activated T cell releases perforin
molecules, which form pores in the
target cell membrane, and proteolytic
enzymes (granzymes), which enter the
target cell by endocytosis.
Cytotoxic T cell
3 The granzymes initiate apoptosis within the
target cells, leading to fragmentation of the
nucleus, release of small apoptotic bodies,
and eventual cell death. The released
cytotoxic T cell can attack other target cells.
Released
cytotoxic
T cell
Perforin
Cancer
cell
Granzymes
1 TCR
Class I MHC
molecule
Target
cell
3
CD8
2
Peptide
antigen
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Apoptotic
target cell
Pore
Cytotoxic
T cell
B cells
• Are made in the bone marrow and mature in
other secondary lymphoid organs such as
peyer’s patches, spleen and lymph nodes.
• Have receptors called B cell receptors.
• 5 classes of B cells are immature, naïve,
activated, effector (plasma), and memory B
cells.
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B Cell Receptors for Antigens
• B cell receptors
– Bind to specific, intact antigens
– Are often called membrane antibodies or membrane
immunoglobulins
Antigenbinding
site
Antigenbinding site
Disulfide
bridge
Variable
regions
Light
chain
Constant
regions
C C
Transmembrane
region
Plasma
membrane
Heavy chains
B cell
Cytoplasm of B cell
(a) A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.
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• B cell receptors allow B cells to bind to a
specific antigens.
• B cells become activated and differentiate into
effector B cells that produce specific antibodies
against the antigen.
• 2 types of antigens are T cell dependent
antigen and T cell independent antigen,
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T cell dependent B cell activation
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T cell independent B cell activation
• The B cell does not need the T cell to become
activated! The antigens that can activate B
cells in this manner are carbohydrates in
nature.
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Antibody Classes
• The five major classes of antibodies, or
immunoglobulins
– Differ in their distributions and functions within
the body
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5 classes of Antibodies
• The five classes of immunoglobulins
IgM
(pentamer)
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
J chain
IgG
(monomer)
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
IgA
(dimer)
Secretory
component
J chain
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
Presence in breast milk confers passive immunity on
nursing infant
IgE
(monomer)
IgD
(monomer)
Transmembrane
region
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Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)
Present primarily on surface of naive B cells that have
not been exposed to antigens
Acts as antigen receptor in antigen-stimulated
proliferation and differentiation of B cells (clonal
selection)
• The roles of the major participants in the
acquired immune response
Cell-mediated immune response
Humoral immune response
First exposure to antigen
Intact antigens
Antigens engulfed and
displayed by dendritic cells
Antigens displayed
by infected cells
Activate
Activate
Activate
B cell
Gives rise to
Plasma
cells
Memory
B cells
Helper
T cell
Gives rise to
Active and
memory
helper
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
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Secreted
cytokines
activate
Cytotoxic
T cell
Gives rise to
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Defend against infected cells, cancer
cells, and transplanted tissues
Immunological Disorders
1- Hypersensitivities
2- auto-Immune disorders
3- Immune deficiencies
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• Type I Hypersensitivity: Immediate Ig E
mediated
• Localized anaphylaxis: hives, hay fever and
asthma
• Generalized anaphylaxis: antigens enter the
bloodstream and become widely spread
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• Type II Hypersensitivity: cytotoxic
• Cells are destroyed.
• Examples: transfusion reactions and hemolytic
disease of a newborn
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• Type III Hypersensitivities: Immune complex
mediated
• An immune complex consists of an antigen and
antibody bound together often with some
complement components.
• Example: Disseminated intravascular
coagulation and serum sickness
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• Type IV Hypersensitivities: Delayed cell
mediated
• Examples: tuberculin skin test, contact
hypersensitivities
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Auto immune disorders
• The immune system attacks its own cells
• Example: lupus, Diabetes mellitus type I,
Crohn’s disease, and rheumatoid arthritis
• Treatment includes immuno-suppressants.
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Immunodeficiency disorders
1- primary (genetic based)
2-secondary (caused by an environmental factor)
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