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8/3/2019 Ch 6 Adaptive Immune
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Chapter 6
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The Adaptive ImmuneThe Adaptive ImmuneResponseResponse
In adaptive immunity, nonspecific
phagocytes present antigen to specific Tcells, triggering the production of effector
T cells and antibodies. Immune T cells
and antibodies react directly or indirectlyto neutralize or destroy the antigen.
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The adaptive immune response is characterized byspecificityfor the antigen,
the ability to respond more vigorously when reexposed to thesame antigen (memory),
the ability to discriminate self antigens from nonself antigens(tolerance).
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Acquired/Adaptive/Specific ImmunityFeatures
Specificity
Memory
Specialization
Self/Nonself recognition
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Innate vs. adaptive immunityInnate vs. adaptive immunity Innate immunity
First line of defense (present in all individuals at alltimes)
Immediate (0 4 hours)
Non-specific
Does not generate lasting protective immunity
Adaptive (acquired) immune response(late: > 96 hours)
Is initiated if innate immune response is not adequate (>4 days)
Antigen-specific immunity
Generates lasting protective immunity (e.g. Antibodies,memory T-cells)
Humoral and cell-mediated
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Immune system cellsImmune system cells
Innate immunityGranulocytes(i.e.neutrophils)
Macrophages
Dendritic cells
Natural killer (NK) cells
Adaptive immunity
LymphocyteB cells
T cells Cytotoxic T cells (CTLs)
Helper T cells (Th)
Memory cells
www.gcarlson.com/cellular_active_neutrophils.htmhttp://
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Cells of the adaptive immune
systemDendritic cells (most importantAPC cell)
B-cells
Humoral immune responseProduce antibodies
APC cells
T- cells
Cell-mediated immune responseCytotoxic T cells (CD8)
Helper T cells (CD4)
Memory cellshttp://www.biology.arizona.edu/immunology/tutorials/immunology/graphics/T_helper_act.gif
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Induction of the adaptiveInduction of the adaptive
immune responseimmune response
Pathogen ingested byPathogen ingested by
immature dendritic cellimmature dendritic cell
Migrate to the lymphMigrate to the lymph
nodesnodes
Interact with nave TInteract with nave T
lymphocyteslymphocytes
Activates
TH1
MHC II
Macrophage
Dead intracellular bacteria
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Lymphocytes (effector cells ofLymphocytes (effector cells of
the adaptive immune system)the adaptive immune system)
Lymphocytes (effector cells ofLymphocytes (effector cells of
the adaptive immune system)the adaptive immune system) Antigen receptors with single specificity (T and B cells)
GeneGene rere--arrangementarrangement
Clonal selection
InteractionInteraction ofof antigenantigen andand lymphocytelymphocyte receptorreceptor ActivationActivation ofof lymphocytelymphocyte
DifferentiationDifferentiation (progeny(progeny withwith identicalidentical specificity)specificity)
T and B cells have 2 distinct recognition systems for detectingpathogens
TT cellscells -- recognizerecognize intracellularintracellular pathogenspathogens (T(T cellcell receptors,receptors,TCR)TCR)
BB cellscells recognizerecognize extracellularextracellular pathogenspathogens(Immunoglobins,(Immunoglobins, BCRBCR
Antigen receptors with single specificity (T and B cells)
GeneGene rere--arrangementarrangement
Clonal selection
InteractionInteraction ofof antigenantigen andand lymphocytelymphocyte receptorreceptor ActivationActivation ofof lymphocytelymphocyte
DifferentiationDifferentiation (progeny(progeny withwith identicalidentical specificity)specificity)
T and B cells have 2 distinct recognition systems for detectingpathogens
TT cellscells -- recognizerecognize intracellularintracellular pathogenspathogens (T(T cellcell receptors,receptors,TCR)TCR)
BB cellscells recognizerecognize extracellularextracellular pathogenspathogens(Immunoglobins,(Immunoglobins, BCRBCR
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A single progenitor cellgives rise to a large
number of lymphocytes,each with a different
specificity
Clonal selection
Pool of navelymphocytes
Selfantigen
Selfantigen
Removal of potentially
self-reactive immaturelymphocytes by clonal
deletion
Foreign antigenProliferation anddifferentiation ofactivated specific
lymphocytes to forma clone of effector
cellsEffector cellseliminate antigen
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Membrane-bound form of the
antibody
V-region (variable) Antigen-binding specificity
Fc-region (constant)
Determines how the
antibody disposes of thebound pathogen
Fc region
V region; At binding
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Single antigenrecognition site
Always a cell surfacemolecule
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Effector cellsActive-duty cells
Die off during or just
afterbattle
Memory cellsReserve cellsCalled up to the
front for later battles
Antigen
T cellor
B cell
Active duty?
Reserves?
cloneclonefamily of cellsfamily of cells
descended from onedescended from one
ancestor cellancestor cell
cloneclonefamily of cellsfamily of cells
descended from onedescended from one
ancestor cellancestor cellNaveActiveChemicalsignal
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Humoral immune responseHumoral immune response
Cell-surface immunoglobulin receptors
(BCR) detect extracellular pathogens
Once activated, secrete immunoglobulins as
soluble antibodies
Antibodies
Variable region (2 identical antigen-binding
sites) Constant region (determines how antibody
disposes of the pathogen once it is bound)
Cell-surface immunoglobulin receptors
(BCR) detect extracellular pathogens
Once activated, secrete immunoglobulins as
soluble antibodies
Antibodies
Variable region (2 identical antigen-binding
sites) Constant region (determines how antibody
disposes of the pathogen once it is bound)
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Generation of Antibody Diversity: Production
of Unique Fab Sites through Gene
Translocation
the immune system of the body has no idea as to whatantigens it may eventually encounter.
Therefore, it has evolved a system that possesses thecapability of responding to any conceivable antigen.
The immune system can do this because both B-
lymphocytes and T-lymphocytes have evolved aunique system of gene-splicing called genetranslocation , a type ofgene-shuffling process wherevarious different genes along a chromosome are cutout of one location and joined with other genes
along the chromosome.
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Clonal Selection and Clonal
Expansion
Clonal Selection and Clonal
Expansion
During its development, each B-lymphocytebecomes genetically programmed, through aprocess called gene translocation, to make aunique antibody molecule that will functionas a B-cell receptor.
Molecules of that antibody are then placedon the cell's surface where it can react withepitopes of an antigen.
Cytokines from an activated T4-lymphocytenow enable the activated B-lymphocyte toproliferate into a large clone of identical B-lymphocytes.
The B-lymphocytes now differentiate intoantibody-secreting B-lymphocytes andplasma cells that secrete large quantities ofantibodies "fitting" the original epitope.Some B-lymphocytes differentiate into B-memory cells capable of anamnesticresponse .
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Antibody interactions
Antibodies can participate in host defenses in 3 mainways:
Neutralization
Ab bind and neutralize bacterial toxins, bacteria andvirus particles preventing interaction with host cells
Ingestion by macrophages
Opsonization Allows recognition by phagocytes or NK cells (antibody-
dependent cell mediated cytotoxicity, ADCC)
Ingestion or killing
Complement activation Activation of complement system
Ingestion by phagocytes
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Antigen recognition by T-cells
T cells detect presence of intracellular
pathogens
T cells receptors
Peptide fragments
Major histocompatibility complex (MHC)
MHC I (cytotoxic T cells /CD+8)
MHC II (T helper (1 and 2)/ CD+4)
Cell death
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Antigen recognition by T-cells
Cytotoxic T cells (CD8)recognize antigen
presented by MHC I
and kills thecell
Kills
CytotoxicT cell
MHC I
TH1 cells (CD4)recognize antigen
presented by MHC II
and activatesmacrophages
TH2 cells (CD4)recognize antigen
presented by MHC II
and activates B cells
Activates
TH1
MHCII
Macrophage
Virus-infected cell
Apoptoticcell
Dead intracellularbacteria
Activates
TH2
MHCII
B cell
Anti-toxin antibodies