B lymphocyte mediate recognition of antigens and the immune response
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B lymphocyte-mediate recognition of antigens and the immune response. Contents. B cell-mediate immune response to T-dependent antigen B cell-mediate immune response to T-independent antigen The general rule of humoral immune response. Humoral immunity:

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B lymphocyte-mediate recognition of antigens and the immune response

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B lymphocyte mediate recognition of antigens and the immune response

B lymphocyte-mediate recognition of antigens and the immune response


B lymphocyte mediate recognition of antigens and the immune response

Contents

  • B cell-mediate immune response to T-dependent antigen

  • B cell-mediate immune response to T-independent antigen

  • The general rule of humoral immune response


B lymphocyte mediate recognition of antigens and the immune response

Humoral immunity:

A immune response mediated by B lymphocyte-secreted antibodies. Its funtion is to neutralize and eliminate the antigens which induced the antibodies.


B lymphocyte mediate recognition of antigens and the immune response

B cell-mediate recognition to antigens

B cell-mediate recognition to TI antigens

TI-antigen: T-independent antigen

This type of antigen can activate B cells without the T cell help,

and most of them are bacterial polysaccharides and lipopolysaccharide.

1. TI-1 aitigen

2. TI-2 antigen


B lymphocyte mediate recognition of antigens and the immune response

  • TI-1 antigen: also named B cell mitogen

  • Contains B cell mitogen and repeated B epitopes

  • Can induce immature and mature B cell-mediate immune response

  • In high concentrations, can induce polyclonal B-cell activation

  • In lower concentrations, only the BCR-binding TI-1 antigens can activate B cells

  • Not able to induce Ig class switch, antibody affinity maturation and memory B cells


B lymphocyte mediate recognition of antigens and the immune response

TI-1 antigen in high concentrations

B-cell mediate recognition and immune response to TI-1 antigens

polyclonal B-cell activation

non-specific antibody response

TI-1 antigen in lower concentrations

Specific antibody response to TI-1 antigen


B lymphocyte mediate recognition of antigens and the immune response

  • TI-2 antigen

  • Only contains multitude repeated B-cell epitopes

  • Merely induces mature B cell-mediated immune response

  • Unresponses or hyporesponsive to infantile B cells

  • Activates the B-1 cells


B lymphocyte mediate recognition of antigens and the immune response

TI-2 antigen alone activates B cells to secrete antibodies

cell

B cell-mediate recognition and immune response to TI-2 antigens

Plasma cell


B lymphocyte mediate recognition of antigens and the immune response

  • TI antigen mainly activates CD45+ B1 cells

  • The produced antibodies are mainly IgM

  • No MHC-restriction, without APC and Th cell help

  • Can not induce antibody class switch, affinity maturation and memory B cells


B lymphocyte mediate recognition of antigens and the immune response

(二)B cell-mediate recognition to TD antigens

  • BCR binds to antigen specifically and transfer the antigen stimulatory signal into B cells

  • BCR specific binding to the antigen and intake it through internalization, then the antigen was degradated into peptides and the peptide-MHC-II molecule complex was formed, which can be recognized by antigen specific Th cells


B lymphocyte mediate recognition of antigens and the immune response

Comparison of TD antigen with TI-1 and TI-2 antigens


B lymphocyte mediate recognition of antigens and the immune response

二. Activation of B Cells

1)The specific antigenic recognition signal of B cell activation (first signal)


B lymphocyte mediate recognition of antigens and the immune response

B cell coreceptor complex

The first signal of B cell activation


B lymphocyte mediate recognition of antigens and the immune response

2)Costimulatory signal of B cell activation (second signal)

With the help of T cells

1.The activation of naïve Th cell


B lymphocyte mediate recognition of antigens and the immune response

2. The combination of Th cell and specific B cell

TCR presented on Th cells specifically recognizes and binds antigenic peptide-MHC-II complex displayed on B cell surface

The interaction of many adhesion molecular pairs makes the binding tighter.


B lymphocyte mediate recognition of antigens and the immune response

☆Direct contact

T cells express CD40L,LFA-1,CD28, et al.

CD40/CD40L,ICAM-1/LFA-1,B7/CD28

The most important molecule is CD40L(CD154)


B lymphocyte mediate recognition of antigens and the immune response

B cell

Th cell

antigen

Signal 1

Th activation

Presentation of antigen

Signal 2

Signal 2

Signal 1

B activation


B lymphocyte mediate recognition of antigens and the immune response

3. The activation of specific B cells

Th cells can be induced to express many membranous molecules, for instance CD40L

The dark zone formation of the germinal center in lymph follicles

The clonal proliferation of B cells

B cells are differentiated to the cells in the germinal center

The formation of memory B cells


B lymphocyte mediate recognition of antigens and the immune response

The function of cytokines

IL-2, IFN- secreted by Th1 cells

IL-4、IL-5、IL-6 secreted by Th2 cells


B lymphocyte mediate recognition of antigens and the immune response

TD antigen

B cell

Th cell

cytokines

B cell


B lymphocyte mediate recognition of antigens and the immune response

三. The signal transduction of B cell activation

(一)the antigen recognition structure of B cells


B lymphocyte mediate recognition of antigens and the immune response

Signal transduction in B cells


B lymphocyte mediate recognition of antigens and the immune response

4. differentiation and maturation of B cells in the germinal center

  • FDC, B cell interaction ---B cell uptake antigens.

  • Antigen uptaken, process and presentation by B cells.

  • T, B cell interaction---Th cell activation.

  • CD40L upregulation and cytokine secretion in activated Th cells---further differentiation and maturation of B cells.


B lymphocyte mediate recognition of antigens and the immune response

Centroblasts

centrocytes

Germinal center

Blast proliferated B cells:

mantle zone formation

Non-proliferated B cells:


B lymphocyte mediate recognition of antigens and the immune response

B cell activation and GC formation


B lymphocyte mediate recognition of antigens and the immune response

(1) receptor editing

Further immunoglobulin gene rearrangement in seconary lymph organs---some potentially self-reactive B cells may be rescued.

Otherwise, self-reactive B cells undergo apoptosis or anergy.


B lymphocyte mediate recognition of antigens and the immune response

(2) somatic hypermutation and

affinity maturation

Ig+ B cells proliferate rapidly, and their already rearranged receptor genes undergo further diversification.

Some further diversifided Ig+ B cells acquir more affinitive BCR.


B lymphocyte mediate recognition of antigens and the immune response

B cell maturation, migration and GC formation

B cell proliferation

somatic hypermaturation

antigen recognition and affinity maturation

no antigen loading B cells undergoing cell death

generation of plasma or memory B cells

B cell differentiation and maturation in germinal center


B lymphocyte mediate recognition of antigens and the immune response

(3) immunoglobulin class switch


B lymphocyte mediate recognition of antigens and the immune response

(4) destiny of maturated GC B cells

  • plasma cell, PC

  • memory B cell


B lymphocyte mediate recognition of antigens and the immune response

(6) Humoral immune response

  • Primary immune response

  • Secondly immune response or

  • anamnestic response


B lymphocyte mediate recognition of antigens and the immune response

Primary immune response

☆lag phase

☆log phase

☆steady-state phase

☆decline phase


B lymphocyte mediate recognition of antigens and the immune response

Antigen

Steady-state phase

Lag phase

Antibody titer

Log phase

Decline pahse

Time


B lymphocyte mediate recognition of antigens and the immune response

  • Secondly immune response or anamnestic response:

  • Short lag phase

  • longer steady-state phase

  • lower dose of antigen needed

  • mainly IgG

  • highly avidity


B lymphocyte mediate recognition of antigens and the immune response

  • Master the general rule of B cell mediated immune response angainst TD-Ag.

  • Master similarities and differences betweenTI-Ag and TD-Ag inducing B cell immune response.

  • Understand mucosal immune response.

  • Understand mature , somatic hypermutation and affinity maturation and class switch of B cell.


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