Chapter 15 B cell mediated immune response. B Cells Lymphocytes that react directly with antigens...

Chapter 15

B cell mediated immune response

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

Plasma Cells

• Plasma cells are antibody factories

• Are also called Antibody Forming Cells

• Produce huge numbers of antibodies– 2000/second

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

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

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

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

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

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

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

BCR complex

Ag

ITAM

Ag

（ BCR）

ITAM

g

B cell

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

Dendritic cell

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.

①

②

(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.

免疫记忆免疫记忆

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.

• 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

Plasma cells are antibody factories;Also called antibody forming cells;Produce huge numbers of antibodies:2000/second

• 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

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

Neutralization Opsonization Activate complement system

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

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

Mechanisms?Mechanisms?

Bm/TmBm/Tm

Significance: On diagnosis: IgM is a marker for early

diagnosis of infectious disease

On vaccination: To obtain secondary response by more times of vaccination

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


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.


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.


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.

Chapter 15 B cell mediated immune response. B Cells Lymphocytes that react directly with antigens...

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