Transcript Chapter_007.ppt

Adaptive Immunity
Chapter 7
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Adaptive Immunity
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Antigens
Specificity
Memory
Antibodies
Lymphocytes
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Adaptive Immunity
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Clonal diversity
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Production of T and B lymphocytes
Antigen recognition
Lymphocyte specificity
Clonal selection
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Antigen processing
Cellular interaction
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Humoral and Cell-Mediated
Immunity
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The cellular and humoral responses are not
independent
Humoral immunity
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“Fluid” immunity
Circulating antibody
Cell-mediated immunity
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T cell differentiation
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Active vs. Passive Immunity
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Active immunity
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Antibodies or T cells produced after either a
natural exposure to an antigen or after
immunization
Passive immunity
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Preformed antibodies or T lymphocytes are
transferred from a donor to a recipient
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Recognition and Response
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Required for a successful immune response
Clusters of differentiation (CD)
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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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Antigens
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Immunogens vs. antigens
Antigenic determinant (epitope)
Self-antigen
Tolerance
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Molecular size
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Central and peripheral tolerance
Haptens
Allergens
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Antigen Presentation
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Antigen-presenting cells (APCs)
Major histocompatibility complex (MHC)
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Glycoproteins on the surface of all human cells (except
RBCs)
Also referred to as human leukocyte antigens (HLAs)
MHC class I molecules
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MHC class II molecules
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A, B, and C
DR, DP, and DQ
MHC class III molecules
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Antigen Presentation
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Transplantation
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Cells in transplanted tissue from one
individual will have a different set of MHC
surface antigens than those of the recipient
Therefore, a recipient can mount an immune
response against the foreign MHC molecules
Haplotype
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Combination of A, B, C, DR, DQ, and DP alleles
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Transplantation
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CD1
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Antigen-presenting molecules
Found on antigen-presenting and thymus cells
Present lipid antigens
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Antigen Recognition
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Antigen is directly recognized by circulating
antibody, antigen receptors on B cells (BCR),
and T lymphocytes (TCR)
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Antibodies
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Also called immunoglobulins
Produced by plasma cells
Classes of antibody
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IgG, IgA, IgM, IgE, and IgD
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Characterized by antigenic, structural, and functional
differences
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Antibodies
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Antibodies
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Immunoglobulin G (IgG)
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Most abundant class (80%-85%)
Transported across the placenta
Four classes
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IgG1, IgG2, IgG3, and IgG4
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Immunoglobulin A (IgA)
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Two classes
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IgA1 molecules are found predominantly in the
blood
IgA2 molecules are found predominantly in
normal body secretions
IgAs found in body secretions are dimers
anchored by a J chain and a “secretory” piece
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Secretory piece may function to protect IgAs
against enzyme degradation
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Immunoglobulin M (IgM)
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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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Immunoglobulin D (IgD)
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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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Immunoglobulin E (IgE)
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Least concentrated of the immunoglobulin
classes in the circulation
Mediator of many common allergic responses
Defender against parasites
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Antibody Structure
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Antigen-binding fragment (Fab)
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Crystalline fragment (Fc)
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Recognition sites (receptors) for antigenic
determinants
Responsible for biological function
Polypeptide chains (4)
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Light chains (2) and heavy chains (2)
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Antibody Structure
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Hinge region
Constant and variable regions
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Complementary determining regions (CDRs)
Framework regions (FRs)
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Antigen Binding
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Amino acid sequences of the variable regions of the
heavy and light chains
Framework regions control antibody folding
Lock and key
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Noncovalent chemical interactions
Antibody valence
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IgG, IgD, and IgE—2
IgA—4
IgM—theoretically 10, likely 5
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B Cell Receptor Complex
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Located on surface of B cells
Consists of:
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Antigen-recognition molecules
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Monomer IgM and IgD
Accessory intracellular-signaling molecules
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Ig-alpha and Ig-beta heterodimers
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T Cell Receptor Complex
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Antibody-like transmembrane protein (TCR)
Accessory proteins for intracellular signaling
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Referred to as CD3
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Generation of Clonal Diversity
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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
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Immunocompetent T and B cells migrate from
the primary lymphoid organs to the secondary
lymphoid organs to await antigen
Primarily after birth
Clonal selection is initiated by antigen
Final products
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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
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The thymus is the central lymphoid organ of T cell
development
T cells move from the thymic cortex to the medulla
Changes
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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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Antigen Processing and
Presentation
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Antigens require processing and presentation
by antigen-presenting cells (APCs)
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Dendritic cells, macrophages, and B lymphocytes
For processing and presentation to occur, the
antigen must be of the appropriate type, the
lymphocytes must be prepared to 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
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“Help” the antigen-driven maturation of B and T
cells
Facilitate and magnify the interaction between APCs
and immunocompetent lymphocytes
Steps
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Th interacts through antigen-specific and antigenindependent mechanisms
Undergoes differentiation
Mature Th interacts with plasma or T-effector cells
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Antigen Processing and
Presentation
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Helper T Lymphocytes
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Subsets
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Th1 cells provide help in developing cellmediated immunity
Th2 cells provide help in developing humoral
immunity
Differences based on cytokine production
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B Cell Activation
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When an immunocompetent B cell encounters
an antigen for the first time, B cells with
specific BCRs are stimulated to differentiate
and proliferate
A differentiated B cell becomes a plasma cell
A plasma cell is a factory for antibody
production
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Single class or subclass of antibody
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Primary and Secondary Responses
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Primary response
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Initial exposure
Latent period or lag phase
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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
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Secondary response
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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
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Immunocompetent B cells use IgM and IgD
as receptors
During clonal selection, B cells have the
option of changing the class of the antibody
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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
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Binding antigen to specific T cell receptors
Allows:
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T regulatory cells (Treg)
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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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Superantigens (SAGs)
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Bind the variable portion of the TCR and the
MHC class II molecules outside of their
antigen-presentation sites
Activates a large population of T lymphocytes
regardless of antigen specificity
SAGs induce an excessive production of
cytokines
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Causes fever, low blood pressure, fever, and
potentially shock
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Antibody Function
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Direct
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Indirect
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Neutralization
Agglutination
Precipitation
Opsonization
Degree of antibody protection is assessed by
an antibody titer
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Secretory (Mucosal) Immune
System
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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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Secretory (Mucosal) Immune
System
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IgE Function
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Provides protection from large parasites
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Initiates an inflammatory reaction to attract
eosinophils
When produced against innocuous
environmental antigens, they are a common
cause of allergies
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Fc portions of IgEs are bound to mast cells
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IgE Function
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Cell-Killing Mechanisms
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Cytotoxic T lymphocytes
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Destroy cancer cells or cells infected with virus
Perforin, granzymes, or direct receptor
interactions
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Cell-Killing Mechanisms
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Other Cells
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Natural killer (NK) cells
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Complement Tc cell mechanisms
Regulatory T cells (Treg)
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Provide peripheral tolerance
Affect recognition of antigen and suppress
proliferative steps of antigen recognition
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Fetal and Neonatal Immunity
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Antibody function is deficient
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Capable of primary IgM response; unable to
produce an IgG challenge
Immunity provided by maternal antibody
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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
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Decreased T cell activity
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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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