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Regulation by antigen
A decline in Ag levels ultimately results in diminished clonal proliferation and a decline in further homuoral or cell-mediated responses.
II. Factors Affecting Tolerogenicing of Antigen III. Mechanisms of Tolerance Induction IV. Clinical significance of immunologic tolerance
Concept
Immunological tolerance is a state of unresponsiveness that is specific for a particular antigen; it is induced by prior exposure to that antigen.
10-12
10-9
10-6
10-3
1.0
Experimental induction of tolerance at low and high doses of antigen
Priming dose of BSA,g
III. Mechanisms of Tolerance Induction
1. Clonal deletion therapy
II. Factors Affecting Tolerogenicing of Ag
1. The structure of antigen 2. The antigen dosage 3. The route of administration
Low –zone tolerance tolerance
Chapter14 Regulation of the Immune Response (4)
• • • • • • Regulation by antigen Regulation by antibody Regulation by lymphocytes Idiotypic modulation of responses Neuroendocrine modulation of immune responses
Central thymic tolerance to self Ags-positive and negative selection.
2. Clonal anergy
a. Lack of signal of activation can cause unresponsiveness
b. The blocking of immunocompetent cells
c. Lack of helper cells
3. The Suppressant effect of various cells
Mechanisms of Tolerance Induction
• Clonal deletion: physically deleting cells from the repertoire at come stage during their lifespan. • Clonal anergy: downregulating the intrinsic mechaism of the immune response. • Suppression: inhibiting cellular activity through interaction with other cells, such as those producing inhibitory cytokines or idiotypespecific lymphocytes which recognize the antigen receptor itself.
Serum anti-BAS Response to secondary immunogenic dose of BSA% of control
100%
Low-zone tolerance
Immunity
Control: signal Immunogenic Dose of BSA
High-zone tolerance
Immune complexes
BCR FcR
B
B
suppress
enhance
Immune regulation by immune complexes
M
TNF- IL-10R B7 IL-12 TH1 IL-2 IFN-
IL-10
IL-4 IL-5 IL-6 IL-10 IL-13
TH2 IFN-R IFN-
Immune regulation by TH
(A)
B
(B)
B
B
B
(C)
Bபைடு நூலகம்
B
Blocking of BCR
IV.
Clinical significance of immunologic tolerance
1. The induction and maintenance of immunologic tolerance
2. The elimination of immunologic tolerance
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凡大医治病，必当安神
定志，无欲无求，先发大慈恻 隐之心，誓愿普救含灵之苦。
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Chapter 13 Immunological Tolerance (3)
I. Introduction
Concept Natural tolerance Acquired tolerance
Tolerance cells
Speeds Time
High –zone
T cells
24 hours long (months)
T and B cells
slow ( 1-2 weeks) short (weeks)
Antigens
TD-Ag (low-dose)
all Ag (high-dose)