复旦大学：《医学免疫学 Medical Immunology》课程教学资源（PPT课件讲稿，英文版）Immunologic Tolerance

Chapter 10 Immunologic Tolerance General Features and Mechanisms T Lymphocyte tolerance o B lymphocyte tolerance Tolerance induced by Foreign Protein Antigens Homeostasis in the Immune System

Chapter 10 Immunologic Tolerance ⚫ General Features and Mechanisms ⚫ T Lymphocyte Tolerance ⚫ B Lymphocyte Tolerance ⚫ Tolerance induced by Foreign Protein Antigens ⚫ Homeostasis in the Immune System

What is Immunologic Tolerance? mmunologic Tolerance— an antigen induced specific unresponsiveness o Tolerogens 4 >Immunogens Failure ● Self-tolerance→→ Autoimmunity o Tolerance induced by foreign antigens

⚫ Immunologic Tolerance—— an antigen induced specific unresponsiveness ⚫ Tolerogens  Immunogens ⚫ Self-tolerance →→ Autoimmunity ⚫ Tolerance induced by foreign antigens What is Immunologic Tolerance? Failure

General Features and mechanisms o Immunologically specific o A result of antigen recognition by specific lymphocytes

General Features and Mechanisms ⚫ Immunologically specific ⚫ A result of antigen recognition by specific lymphocytes

Studies of graft rejection in inbred mice Strain A Strain CBA Strain A cBA Neonate CBA CBA Balb/c Adult CBA Skin graft relection During lymphocyte maturation in the generative lymphoid organs, all Immunologically specific lymphocytes pass through a stage in. a result of the recognition of which encounter with Ag leads to antigens by specific lymphocytes tolerance

Neonate Adult Skin graft rejection + + _ Studies of graft rejection in inbred mice ⚫ Immunologically specific ⚫ a result of the recognition of antigens by specific lymphocytes During lymphocyte maturation in the generative lymphoid organs, all lymphocytes pass through a stage in which encounter with Ag leads to tolerance Strain A Strain A Strain A

General Features and mechanisms Immunologically specific ● Centra|to| erance: induced in generative lymphoid organs immature self-reactive lymphocyte The repertoire of mature lymphocytes cannot recognize ubiquitous or widely disseminated self antigens

General Features and Mechanisms ⚫ Immunologically specific ⚫ Central tolerance: induced in generative lymphoid organs immature self-reactive lymphocyte The repertoire of mature lymphocytes cannot recognize ubiquitous or widely disseminated self antigens The repertoire of mature lymphocytes cannot recognize ubiquitous or widely disseminated self antigens

Burnet: Clonal selection hypothesis A single progenitor cell gives rise to a large number of lymphocytes, each Pool of mature naive lymphocytes with a different specificity foreign antigen Proliferation and differentiation of activated specific lymphocytes to form a clone Removal of potentially self-reactive of effector cells immature lymphocytes by clonal deletion Effector cells elim nate antigen self antigens solf antigens

Burnet: Clonal selection hypothesis

General Features and mechanisms o Immunologically specific ● Central tolerance generative lymphoid organs immature self-reactive lymphocyte The repertoire of mature lymphocytes cannot recognize ubiquitous or widely disseminated self antigens o Peripheral tolerance: peripheral sites mature self-reactive lymphocytes Important for maitaining unresponsiveness to self antigens that are not expressed in the generative lymphoid organs

General Features and Mechanisms ⚫ Immunologically specific ⚫ Central tolerance: generative lymphoid organs immature self-reactive lymphocyte ⚫ Peripheral tolerance: peripheral sites mature self-reactive lymphocytes The repertoire of mature lymphocytes cannot recognize ubiquitous or widely disseminated self antigens The repertoire of mature lymphocytes cannot recognize ubiquitous or widely disseminated self antigens Important for maitaining unresponsiveness to self antigens that are not expressed in the generative lymphoid organs

Antigen recognition (1) Ag recognition 1)+costimulatory(2) APC VACM-1 LFA-3 ICAM-1 MHC class Il B7 molecules CD4 TCR-CD3 complex CD28 LFA-1 CD2 2) VLA-4 Th Anergy Activation and Proliferation Peripheral tolerance is induced when mature lymphocytes recognize antigens without adequate levels of the costimulators

Peripheral tolerance is induced when mature lymphocytes recognize antigens without adequate levels of the costimulators

The principal mechanisms of lymphocyte tolerance Deletion: Central tolerance apoptotic cell death Anergy functional inactivation without cell death Treg Peripheral tolerance

The principal mechanisms of lymphocyte tolerance ⚫ Deletion: apoptotic cell death ⚫ Anergy: functional inactivation without cell death ⚫ Treg Central tolerance Peripheral tolerance

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Apoptosis