chapter 15 b cell mediated immune response. chapter 15 b cells mediated immune response humoral...
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Chapter 15 Chapter 15
B cell mediated immune respB cell mediated immune resp
onseonse
Chapter 15 Chapter 15
B cell mediated immune respB cell mediated immune resp
onseonse
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Chapter 15 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 PartⅠ Immune response of B2 cell to TD-A
g
PartⅡ Rules of humoral immunity
PartⅢ Immune response of B1 cell to TI-Ag
PartⅣ Signal transduction of T and B cells
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PartⅠ Immune response of B2 cell to PartⅠ Immune response of B2 cell to TD-AgTD-Ag
Characteristics of TD-Ag:• Most native Ag• Protein, 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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PartⅠ Immune response of B2 cell to PartⅠ Immune response of B2 cell to TD-AgTD-Ag
• 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 B cells recognize antigenantigen
• BCRs directly recognize the epitope on the surface of Ag
• No APC , no MHC restriction• Capture Ag by BCR, present Ag signal
to T cells
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2. B cells activation, 2. B cells activation, proliferation and proliferation and differentiationdifferentiation
(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 activa
ted 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 e
xpress 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 to Th cells.• B cells provide B7 for Th cells.
Th cells act on B cells:• Activated Th cells provide co-stimulatory mo
lecule 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 switch 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.
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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 isotyisotype switchingpe switching or or class switchingclass switching to secrete antibodies of different isotypes: IgG, IgA, and IgE. Isotype switching does not affect antibody specificity significantly.
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3. Stage of effect----the function of Ab3. Stage of effect----the function of Ab
• Neutralization• Activate complement system• ADCC — NK, macrophage, neutrophil• Opsonization — macrophage • Type Ⅰ hypersensitivity
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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
2. Secondary response
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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 diseaseOn vaccination: To obtain secondary re
sponse by more times of vaccination
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PartPartⅢⅢ Immune response of B1 cell Immune response of B1 cell
to TI-Agto 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 Immune response of B1 cell
to TI-Agto 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 pro
liferation and differentiation.• Low TI-1 Ag only stimulate B cell clone with s
pecific BCR.• Response of B1 cell to TI-1 Ag earlier than tha
t of B2 cell to TD-Ag.• No Ig isotype swicth, affinity maturation, and
memory B cells.
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M
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PartPartⅢⅢ Immune response of B1 cell Immune response of B1 cell
to TI-Agto TI-Ag
B1 cells recognize TI-2 Ag :• Most TI-2 Ags belong to cell wall of bacteria a
nd 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 extra
cellular bacteria under antibody of capsule polysaccharide.
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PartPartⅢⅢ Immune response of B1 cell Immune response of B1 cell to TI-Agto TI-Ag
Significance:Significance:• Play important role in Play important role in defense against e
xtracellular microbe infection.• Play an important role in Play an important role in defense again
st bacteria with capsule polysaccharide.
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PartⅣ signal transduction of T and B cell activation
TCR recognition and linkage
Activation of PTK( p56lck, p59fyn, ZAP-70)
Signal transduction in the cell
Activation of transcription factor
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APC
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