Transcript Chapter 15 Immune response(Ir)

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
 PartⅠ Immune response of B2 cell to TD-Ag
 PartⅡ Rules of humoral immunity
 Part Ⅲ Immune response of B1 cell to TI-Ag
PartⅠ Immune response of B2 cell to TD-Ag
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
PartⅠ Immune response of B2 cell to TD-Ag
• B2 cells
differentiate
produce Ab
recognize TD-Ag
activate, proliferate,
plasma
cells
Ag
B
Y
Y
Y
Y
Y
Y
Y
Cross-linking of
surface membrane Ig
B B
B B BB
B B
YYY Y
Y Y Y Y
Th
Proliferation and
antibody production
B cells can recognise native antigens directly
1. B 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
and 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
Ag
Ag
（BCR）
BCR complex
ITAM
ITAM
g
B cell
Second signal: --the help of Th
cells to B cells
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.
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 IL4, 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
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 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
switching or class 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 Ab
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•
•
•
•
Neutralization
Activate complement system
ADCC — NK, macrophage, neutrophil
Opsonization — macrophage
Type Ⅰ hypersensitivity
Neutralization Opsonization
Activate
complement
system
ADCC
PartⅡ 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
primary Ir
longer
secondary Ir shorter
affinity
type maintaining time
low
IgM
shorter
high
IgG
longer
Mechanisms?
Bm/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
PartⅢ 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
PartⅢ 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.
M
PartⅢ 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.
PartⅢ Immune response of B1 cell to TI-Ag
Significance:
• Play important role in defense against
extracellular microbe infection.
• Play an important role in defense against
bacteria with capsule polysaccharide.