Chapter 7
Adaptive Immunity
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Adaptive Immunity


Works together with innate immunity, aka
inflammation
Specificity


Each T or B cell recognizes only one antigen, but
together a group of T and B cells recognize a host of
foreign antigens
Memory

Confers long-term protection
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End Products
of Adaptive Immunity


Lymphocytes (cellular immunity): T and B cells
Antibody (humoral immunity): immune
globulins
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Adaptive Immunity

Clonal diversity




Production of T and B lymphocytes
Antigen recognition
Lymphocyte specificity
Clonal selection


Antigen processed and presented to immune cells
by APCs
Cellular interaction of T cells and APCs
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Clonal Diversity
Primary (central) and
secondary
(peripheral)
lymphoid tissues
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Clonal Diversity and Selection
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Types of Immunity

Natural immunity

Active immunity

Passive immunity
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Humoral and
Cell-Mediated Immunity


The cellular and humoral responses are not
independent
Humoral immunity



“Fluid” immunity
Circulating antibody
Cell-mediated immunity

T cell differentiation
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Active vs. Passive Immunity

Active immunity


Antibodies or T cells produced after either a
natural exposure to an antigen or after
immunization
Passive immunity

Preformed antibodies or T lymphocytes are
transferred from a donor to a recipient
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Recognition and Response


Required for a successful immune response
Clusters of differentiation (CD)


Originally used to describe proteins found on the
surface of lymphocytes
Now it is a labeling system used to identify a
family of proteins on many cells
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Antigen


A molecule that can react with (or be recognized
by) the immune system
Recognized as nonself

Pathogens (viruses, bacteria, fungi, etc.)
 Bee venom
 Pollen
 Foods
 Tissue
 Blood products
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Recognition and Response

Antigens vs. immunogens


Antigen (Ag): a molecule that binds and reacts
with antibody (Ab) or lymphocyte receptors
Immunogen: an Ag that can trigger an immune
response
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Self-Antigen and Tolerance

Degree of foreignness to host


Size



Most important
Small molecular weight Ag’s called haptens; can’t
trigger immune response themselves but can
when bound to a carrier protein
Chemical complexity
Amount
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Self-Antigen and Tolerance

Tolerance: we recognize ourselves as not
foreign


Central tolerance: lymphocytes with receptors
against self-antigens are eliminated
Peripheral tolerance: prevents recognition by
lymphocytes and Ab’s
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Antigen Presentation


Antigen-presenting cells (APCs)
Major histocompatibility complex (MHC)

Glycoproteins on the surface of all human cells
(except RBCs)
 Also called human leukocyte antigens (HLAs)
 MHC class I molecules
• A, B, and C
 MHC class II molecules
• DR, DP, and DQ
 MHC class III molecules
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Molecules That Present Antigen



Ag is processed within cells
Expressed on the cell surface in a specific
manner
Some Ag’s need special APCs; others can be
processed by most any cell type
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Molecules That Present Antigen

MHC
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Transplantation



Cells in transplanted tissue from one
individual have a different set of MHC surface
antigens than those of recipient
Thus recipient can mount an immune
response against foreign MHC molecules
Haplotype

Combination of A, B, C, DR, DQ, and DP alleles
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Tissue/Organ Transplantation

Inheritance of human leukocyte antigens
(HLAs) (synonym for MHC molecules)
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CD1



Antigen-presenting molecules
Found on antigen-presenting and thymus
cells
Present lipid antigens

Mycobacterium, tuberculosis
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Antigen Recognition

Antigen is directly recognized by circulating
antibody, antigen receptors on B cells (BCR),
and T lymphocytes (TCR)
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Antibodies



Also called immunoglobulins
Produced by plasma cells
Classes of antibody

IgG, IgA, IgM, IgE, and IgD
• Characterized by antigenic, structural, and functional
differences
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Molecules That Recognize Antigen

Antibodies: classes of immunoglobulins
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Molecules That Recognize Antigen

B-cell receptor complex: antibodies and
accessory molecules
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Antibodies



Protein
Part of the adaptive immune response that
interacts with antigen
Usually classes of immunoglobulins
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Antibody Structure

Antigen-binding fragment (Fab)


Crystalline fragment (Fc)


Recognition sites (receptors) for antigenic
determinants
Responsible for biologic function
Polypeptide chains (4)

Light chains (2) and heavy chains (2)
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Antigen Binding



Amino acid sequences of the variable regions
of the heavy and light chains
Framework regions control antibody folding
Lock and key


Noncovalent chemical interactions
Antibody valence



IgG, IgD, and IgE—2
IgA—4
IgM—theoretically 10, likely 5
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Antibodies






Classes
IgM
IgG
IgA
IgE
IgD
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Antibodies: Products of
Adaptive Immunity
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Antibodies

Classes—IgM
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Immunoglobulin M (IgM)




Largest of the immunoglobulins
Pentamer stabilized by a J-chain
First antibody produced during the primary
response to an antigen
Synthesized during fetal life
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Antibodies

Classes—IgG
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Immunoglobulin G (IgG)



Most abundant class (80%-85%)
Transported across the placenta
Four classes

IgG1, IgG2, IgG3, and IgG4
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Antibodies

Classes—IgA
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Secretory (Mucosal)
Immune System



Lymphoid tissues that protect the external
surfaces of the body
Antibodies present in tears, sweat, saliva,
mucus, and breast milk
IgA is the dominant immunoglobulin

Small numbers of IgG and IgM are present
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Immunoglobulin A (IgA)

Two classes



IgA1 molecules: predominantly in the blood
IgA2 molecules: predominantly in normal body
secretions
IgAs in body secretions are dimers anchored
by J-chain and “secretory” piece

Secretory piece may function to protect IgAs
against enzyme degradation
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Antibodies

Classes—IgE
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Immunoglobulin E (IgE)


Least concentrated of the immunoglobulin
classes in the circulation
Mediator of many common allergic responses


Fc portions of IgEs are bound to mast cells
Defender against parasites
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IgE
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Antibodies

Classes—IgD
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Immunoglobulin D (IgD)




Limited information on IgD function
Low concentration in the blood
Located primarily on the surface of
developing B lymphocytes
Function as one type of B cell antigen
receptor
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T-Cell–Receptor Complex


Antibody-like transmembrane protein (TCR)
Accessory proteins for intracellular signaling


Referred to as CD3
T-cell–receptor complex: transmembrane
proteins and accessory proteins
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B-Cell–Receptor Complex


Located on surface of B cells
Consists of:


Antigen-recognition molecules
• Monomer IgM and IgD
Accessory intracellular-signaling molecules
• Ig-alpha and Ig-beta heterodimers
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Generation of Clonal Diversity




All necessary receptor specificities are
produced
Takes place in the primary (central) lymphoid
organs
Results in immature but immunocompetent T
and B cells
Primarily occurs in the fetus
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Clonal Selection




Immunocompetent T and B cells migrate from
the primary to the secondary lymphoid organs
to await antigen
Primarily after birth
Clonal selection is initiated by antigen
Final products

Plasma cells that produce antibody, effector cells
that help Th, Tc, or Treg, and memory B and T
cells
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T-Cell Maturation



The thymus is the central lymphoid organ of T
cell development
T cells move from thymic cortex to the
medulla
Changes


Development of the T cell receptors and
expression of surface molecules
T cells are released into the blood and take
up residence in the secondary lymph organs
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The Immune Response Process




Antigen processing
Clonal selection
Mounting a defense against the foreign
antigen
Production of memory cells
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Antigen Processing and
Presentation

Antigens require processing and presentation
by APCs


Dendritic cells, macrophages, B lymphocytes
For this to occur, antigen must be the
appropriate type, the lymphocytes must
recognize the presented antigen, and the
antigen must be presented appropriately
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Antigen Processing and
Presentation
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Antigen Processing and
Presentation
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Helper T Lymphocytes



“Help” the antigen-driven maturation of B and
T cells
Facilitate and magnify the interaction
between APCs and immunocompetent
lymphocytes
Steps



Th interacts through antigen-specific and antigenindependent mechanisms
Undergoes differentiation
Mature Th interacts with plasma or T-effector cells
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Helper T Lymphocytes

Subsets



Th1 cells provide help in developing cell-mediated
immunity
Th2 cells provide help in developing humoral
immunity
Differences based on cytokine production
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B-Cell Activation



When an immunocompetent B cell encounters an
antigen for the first time, B cells with specific
BCRs are stimulated to differentiate and
proliferate
Differentiated B cell becomes a plasma cell
A plasma cell is a factory for antibody production

Single class or subclass of antibody
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B-Cell Activation

Antibody class switch




Major component of B cell maturation
During clonal selection B cell can change class of
Ab (IgG, IgA, IgE)
DNA cut then mended
Specificity maintained
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B-Cell Activation

Primary vs. secondary immune response
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Primary and Secondary
Responses

Primary response




Initial exposure
Latent period or lag phase
• B-cell differentiation is occurring
After 5 to 7 days, an IgM antibody for a specific
antigen is detected
An IgG response equal or slightly less follows the
IgM response
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Primary and Secondary
Responses

Secondary response




More rapid
Larger amounts of antibody are produced
Rapidity is due to the presence of memory cells
that do not have to differentiate
IgM is produced in similar quantities to the primary
response, but IgG is produced in considerably
greater numbers
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Class Switch


Immunocompetent B cells use IgM and IgD
as receptors
During clonal selection, B cells have the
option of changing the class of the antibody

One of four IgGs, one of two IgAs, IgE, or an IgM
in a pentamer form
 DNA rearrangement
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B Cell Clonal Selection
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T Cell Activation


Binding antigen to T cell receptors
Allows:



T regulatory cells (Treg)


Direct killing of foreign or abnormal cells
Assistance or activation of other cells
Regulate the immune response to avoid attacking
“self”
Memory T cells
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T Cell Activation
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T Cell Activation
T regulatory cells (Tregs)
(previously called T suppressor cells)




To avoid overactivation of immune system
To avoid attacking self-antigens
Subject of much research
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Antibody Function

Direct




Indirect


Neutralization
Agglutination
Precipitation
Opsonization
Degree of antibody protection is assessed by
an antibody titer
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Antibody Function

Neutralizing bacteria
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Antibody Function

Neutralizing viruses
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Antibody Function

Forming antigen-antibody complexes
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Antibody Function

Opsonization
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Cell-Killing Mechanisms

Cytotoxic T lymphocytes


Destroy cancer cells or cells infected with virus
Perforin, granzymes, or direct receptor
interactions
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Other Cells

Natural killer (NK) cells


Complement Tc cell mechanisms
Tregs


Provide peripheral tolerance
Affect recognition of antigen and suppress
proliferative steps of antigen recognition
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Cell-Killing Mechanisms
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Fetal and Neonatal Immunity

Antibody function is deficient


Capable of primary IgM response; unable to
produce an IgG challenge
Immunity provided by maternal antibody

Trophoblastic cells transport maternal IgG across
the placenta
 Newborn IgG levels are near adult levels
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Fetal and Neonatal Immunity
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Aging and Immune Function

Decreased T cell activity





Thymic size is 15% of its maximum size
Decreased production of specific antibodies
Increase in circulating antigen-antibody
complexes
Increase in circulating autoantibodies
Decrease in circulating memory B cells
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