chapter 15 b cell mediated immune response. b cells lymphocytes that react directly with antigens...
TRANSCRIPT
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Chapter 15
B cell mediated immune response
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B Cells
• Lymphocytes that react directly with antigens
• Require stimulation from Helper T Cells
• Offspring become– Plasma cells– Memory B cells
• Humoral Immunity:is immunity provided by antibodies
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Plasma Cells
• Plasma cells are antibody factories
• Are also called Antibody Forming Cells
• Produce huge numbers of antibodies– 2000/second
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B cells mediated immune response
Humoral immunity (HI) or antibody mediated immunity:
The total immunological reaction that B cells recognize antigen, then activate, proliferate, differentiate into plasma cells and produce Ab.
• B2 cells mediated immune response to TD-Ag• B1 cells mediated immune response to TI-Ag
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Contents
Part Immune response of B2 cell to TD-AgⅠ
Part Rules of humoral immunityⅡ
Part Ⅲ Immune response of B1 cell to TI-Ag
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Part Immune response of B2 cell to TD-AgⅠPart Immune response of B2 cell to TD-AgⅠ
Characteristics of TD-Ag:• Most are native antigen• proteins, large molecules• Possess T cell epitope and B cell epitope• Both CMI and HI• Need Th cells participation• Produce several types of antibodies: IgG• Produce immune memory
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Part Immune response of B2 cell to TD-AgⅠPart Immune response of B2 cell to TD-AgⅠ
• B2 cells recognize TD-Ag activate, proliferate,
differentiate plasma cells
produce Ab
Ag
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B cells can recognise native antigens directly
YY Y Y YYY
B
Proliferation and antibody production
Cross-linking of surface membrane Ig
Y
B
Y
B Y
B
Y
B
Y
B Y
B
Y
BYY
B
Th
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1.1. B cells recognize antigenB cells recognize antigen
• BCRs directly recognize the epitope on the surface of Ag
• No APC, no MHC restriction
• Capture Ag by BCR, present Ag-MHC to T cells
• Specificity
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2. B cells activation, proliferation 2. B cells activation, proliferation and differentiationand differentiation
(1) B cell activation: dual signals
• First signal: antigen signal BCR-- determinant on the surface of Ag Igα/Igβtransduct the first signal CD19/CD21/CD81 (co-receptor) binds to C3dg on Ag
• Second signal: co-stimulatory signal The CD40 on B cells binds to CD40L on
activated Th cells
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BCR complex
Ag
ITAM
Ag
( BCR)
ITAM
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g
B cell
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Activation of Th cells: DCs present peptide-class Ⅱ MHC complex and provide B7 for T cells, Th cells are activated and express CD40L.
Th cells provide co-stimulatory signal for B cells: TCRs on activated Th cells recognize antigen peptide-class Ⅱ MHC complex presented on B cells, and CD40L on T cells bind to CD40 on B cells which provide co-stimulatory signal for B cells.
Second signal: --the help of Th cells to B cells
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Dendritic cell
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Interaction between Th cells and B cells
B cells act on Th cells:• B cells present Ag-class II MHC molecules to
Th cells----first signal for Th activation.• B cells provide B7 for Th cells----second
signal for Th activation.
Th cells act on B cells:• Activated Th cells provide co-stimulatory
molecule for B cells: CD40L- CD40.• Activated Th cells secrete Cks ( IL-4 、 IL-5 、
IL-6 、 IL-10 、 IL-13 ) which help B cells proliferate and differentiate.
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①
②
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(2) B cells proliferation and differentiation------help of Th cells
• Activated B cells express receptors of cytokines such as IL-4R, IL-5R.
• Activated Th2 cells secrete cytokines such as IL-4, IL-5 to enhance proliferation and differentiation of B cells.
• B cells differentiate into plasma cells (antibody forming cells)----produce Ab, partial into memory B cells.
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免疫记忆免疫记忆
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Differentiation of B cells in germinal Center
• During proliferation and differentiation, Somatic hypermutation of B cells induces affinity maturation of Ab.
• Some B cells differentiate to the plasma cells which produce IgM.
• Some B cells have an isotype switching to produce other types of Ig.
• Production of memory B cells.
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• Affinity maturationAffinity maturation refers to the increase in the affinity for the specific antigen of the antibodies produced during the course of a humoral immune response with the help of Th cells. Affinity maturation is the result of somatic hypermutation of Ig genes.
• Result in Ig with high affinity
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Plasma cells are antibody factories;Also called antibody forming cells;Produce huge numbers of antibodies:2000/second
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• The first antibodies produced in a humoral immune response are IgM, but activated B cells subsequently undergo isotype isotype switchingswitching or or class switchingclass switching to secrete antibodies of different isotypes: IgG, IgA, and IgE. Isotype switching does not affect antibody specificity significantly.
• Occurred when Ag-activated B encounter helper T cell signals(CD40L and CKs)
• Result in the change of Ig Fc
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3. Stage of effect----the functions of Ab3. Stage of effect----the functions of Ab
• Neutralization
• Activate complement system
• ADCC — NK, macrophage, neutrophil
• Opsonization — macrophage
• Type hypersensitivity Ⅰ
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Neutralization Opsonization Activate complement system
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ADCC
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PartPartⅡⅡ Rules of humoral immunity Rules of humoral immunity
1. Primary response: B cells first encounter antigens
2. Secondary response : B cells encounter the same antigen secondary
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Characteristic of primary Ir and secondary Ir lag phase affinity type maintaining
time
primary Ir longer low IgM shorter
secondary Ir shorter high IgG longer
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Mechanisms?Mechanisms?
Bm/TmBm/Tm
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Significance: On diagnosis: IgM is a marker for early
diagnosis of infectious disease
On vaccination: To obtain secondary response by more times of vaccination
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PartPartⅢⅢ Immune response of B1 cell to TI-Ag Immune response of B1 cell to TI-Ag
Characteristics of TI-Ag:• Repeat B cell epitope• No T cells participation• Only humoral immunity• Only produce IgM• No immune memory
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PartPartⅢⅢ Immune response of B1 cell to TI-Ag Immune response of B1 cell to TI-Ag
B1 cells recognize TI-1 Ag: • TI-1 Ag usually called B cell mitogen. • High TI-1 Ag can induce polyclonal B cells
proliferation and differentiation.• Low TI-1 Ag only stimulate B cell clone with
specific BCR.• Response of B1 cell to TI-1 Ag earlier than that
of B2 cell to TD-Ag.• No Ig isotype swicthing, affinity maturation, and
memory B cells.
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M
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PartPartⅢⅢ Immune response of B1 cell to TI-Ag Immune response of B1 cell to TI-Ag
B1 cells recognize TI-2 Ag :• Most TI-2 Ags belong to cell wall of bacteria
and capsule polysaccharide with high repeat structure.
• Density of epitope is key to TI-2 Ag activating B cells.
• Only stimulate mature B1 cells.• Help macrophage phagocyte and digest
extracellular bacteria under antibody of capsule polysaccharide.
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PartPartⅢⅢ Immune response of B1 cell to TI-Ag Immune response of B1 cell to TI-Ag
Significance:Significance:• Play important role in Play important role in defense against
extracellular microbe infection.
• Play an important role in Play an important role in defense against bacteria with capsule polysaccharide.