Humoral Ir mediated by B cells

Chapter 12

Concept

Response to TD-Ag

Characteristics of primary and secondary Ir

Response to TI-Ag

Effect of B cell response

Major content

体液免疫应答(humoral immunity)

B cells encounter specific Ag, activate ,proliferate and differentiate to plasma cells ， produce Abs, eliminate Ags.

Ab exist in blood, important effector.

Classification B cells Respond to TD-Ag （ pr

otein)

B cells Respond to TI-Ag (Glucose and Glylipid ）

B cells response to TD-Ag

B cell antigen receptor complex

BCR direct recognize B cell epitope

载体效应

B cell and Th cell recognize different epitope on the same Ag

BCR recognize Ag and activation of B cell

信号 1

* B 细胞特异性结合抗原，向 B 细胞传递抗原刺激信号；* 通过 BCR 摄取抗原，并将抗原降解为肽段，形成抗原肽 -MHC-II 类分子复 合物，供抗原特异性 Th 细胞识别；

* B cells recognition to TD Ag

* B cells activation, proliferation and differ

entiation

* Primary and secondary response

* Effect of B cell response

B cells response to TD-Ag

B cell activation （一） active siganl 1 (Ag)

* BCR specific bind epitope on B cell ； *co-receptor ： CD21/CD19/CD81 bind C3d linked with

Ag ； * Igα/Igβ ： signal transduct ；（二） active siganl2 (co-stimulatory molecule)

*activation of naive Th ： APC （ DC) present double siganls and CK to naive CD4+T.

develop to effective Th ； * B cell present Ag ： B cell take in Ag via BCR ， process it ， form

ation of peptide-MHC complex ， present to Th ； * Effective Th combines with B cell specifically ： TCR recognize A

g presented by B ； *Co-stimulatory sgnal ： CD40L(on active T) bind CD40(on B cell) ；（三） CKs IL-1/APC 、 IL-4/Th promote activation of B cell.

BCR and co-receptor complex

Th细胞和B 细胞间相互作用

Interaction of T and

B cells

Th help B cell activating, proliferating and differentiating

Cytokines

promoting B

cell activation,

proliferation

and

differentiation

Active B cell express many CKR

receive stimuli of CK from Th

IL-2,IL-4,IL-5 promote B cell proliferation ，

IL-4,IL-6,IFN-promote B cell differentiation.

B cells proliferation and differentiation

* Somatic hyper-mutation and Ig affinity maturation

*Antigenic receptor editing ： Ig gene rearrangement occur in auto-reactive B cell, edited BCR point at none-self Ag.

*Ab class switch ： V region does not change ， only C region of H chain change. 。

B cell mature in germial center

Cytokines and antibody isotype switch

Flash

* Somatic hypermutation and Ig affinity maturation

*Antigenic receptor editing ： Ig gene rearrangement occur in autoreactive B cell, edited BCR point at none-self Ag.

*Ab class switch ： V region does not change ， only C region of H chain change. 。

B cell mature in germial center

TD Ag

BCR recognize B cell epitope

B/Th interactionCD40/CD40L binding

secretIL-2、IL-4、 IL-5、 IL-6

Memory B PC （ late ） IgG

Signal1 Signal 2

B cell primary response toTD-AgAPC take in,process and present Ag

Th develop

TCR recognize peptide/MHCIIB7-CD28

IL-1

B cell develop

Mature in germinal center（ early ） IgMPC

（ die after 2 Wk ）

（ enter lymphocyte re-cycle ） （ in bone marorw ）

Primary and secondary response

Ir induced by pathogen first invaded human body.

Properties ： - longer lag phase ； - Most class of Ab is IgM ； - Level of Ab is low ； - Affinity of Ab is low.

初次免疫应答（ Primary immune response ）

Four phases

潜伏期 对数生长期 平台期 下降期

The same Ag reenter body, stimulate memory cells to elicit prompt, efficacy and specific response.

Properties ： - APC (memory B) interact with memory T ； - Low amount of Ag for simulation ； - Lag phase shorter ； - Ab Level higher, Ab duration longer ； - Most class of Ab is IgG ， affinity higher 。

再次免疫应答（ secondary immune response ）

Primary and secondary humoral immune responses

Memory B cells present antigen to T cell

Raising Ab

production

and affinity

after repetit

ive immuniz

ation

Primary and Secondary Immune Response

Ab

concen

tration

Days

10 3

Total amount of Ab

Lag phase

IgG

IgM

First stimuli of Ag Repetitive stimuli of the same Ag

Lag phase

PrimaryFeatures secondary

Ag stimulation

Lag phase

Ab peak duration Ig Class affinity

first second

5-10 days

lower

shorter

IgM

low

2-5 days

higher

longer

IgG 、 IgA

high

Difference of primary and secondary response

Effect of B cell response

Neutralization By Antiviral Antibodies

Fc receptorbinding

Effector mechanisms against extracellular pathogens

(2) OPSONISATION

OPSONISATION Phagocytosis

Bacteria in extracellular space

Ab

+

Action of phygosytosis

(3)Complement activation

Effector mechanisms against extracellular pathogens

COMPLEMENT ActivationBacteria in plasma

Ab & COMPLEMENT

+

Phagocytosis

binding

Complement &Fc receptor

Lysis

Opsonisation

FcgR and Complement Receptors Cooperate To Induce Greater Phagocytosis

(4) .Effector cells of ADCC

(4)

(5) IgA against adhesins

(6) Immune damage IgE Antibody Binds To Mast Cells & Basophils To Arm Them For Mediator Release

B cell response to TI Ag

•TI-1Ag activate B cell - At high concentration,TI-1Ag induce activation of many B cells (polyclonal activation)

- At low concentration, TI-1Ag induce activation of specific B cell.

* TI-2 Ag direct activate mature B1 cell

- Repetitive epitopes bind BCR→BCR cross-linkage→produce IgM

Do not require Th ， without immune memory ， occur earlier.

Mechanism for TI-Ag activate B cell

（ A ）： TI-1 Ag （ B ）： TI-2Ag

B cell activation induced by TI

antigen

epitope

mitogen

High Repeatitive epitopes

Comparison items

Thymus dependent Ag(TD—AgTD—Ag)

Thymus independent Ag(TI—AgTI—Ag)

Th require No require

Class of Ir Humoral and cellular Only humoral

Class of Ab most are IgG Only IgM

Memory reaction

Yes Not

* Neutralization ： Neutralize toxin 、 virus* Opsonization ： Ag coated with IgG and IgA ， promote phygocyt

osis* Activation of complement ：（ IgG/IgM ） IC ， activate classical p

athway - CDC - Opsonization* ADCC ： NK 、 M 、 NC 、 EC* Mucous defense of secretary IgA* Immune damage: - hypersensitivity and AID - Graft rejection reaction ： preformed Ab cause hyper acut reactio

n - promote tumor growth ： blocking factor ， interrupt CTL reorg

anization to tumor Ag

Effect of B cell mediated Ir

Review Question

Describe the process of B cell response to TD Ag in primary immune response 简述 B 细胞对 TD-Ag 的初次免疫应答过程。

Compare primary and secondary immune response , describe their significance in application 简述体液免疫应答的一般规律和了解此规律的意义。

Describe the admission molecules and their functions involved in T-B interaction 简述参与 T-B 细胞相互作用的黏附分子及其功能。