上海交通大学：《药理学 Pharmacology》课程教学资源（讲义课件）免疫药物（免疫药理学）Immunopharmacology

上泽充通大学 Shanghai Jiao Tong Univer.. Immunopharmacology 免疫药理学 2010.12

Immunopharmacology 免疫药理学 2010.12

h 上游充通大￥ 后 Shanghai Jiao Tong University Types of Drugs Immunosuppressants (important!) Immunostimulants Immunomodulators e Induction of tolerance(tolerogens) Cytokines Hematopoetic growth factors Antibodies targeting key cell receptors/ligands

Shanghai Jiao Tong University Types of Drugs Immunosuppressants (important!) Immunostimulants Immunomodulators • Induction of tolerance (tolerogens) • Cytokines • Hematopoetic growth factors • Antibodies targeting key cell receptors/ligands

上游充通大 Simplified schematic of an immune response Shanghai Jiao Tong University proliferation differentiation CD8+T cells -CD8+cytolytic T cells Class I IFNy,IL-2 proliferation APC Class Il CD4+T cells differentiation CD4+immune cells Cytokines (delayed hypersensitivity Costim.Mol. L-4,-5,-6 Protein antigens B cells Plasma cells proliferation ↓ MHC class Il/peptides differentiation antibody APCs production

Shanghai Jiao Tong University Simplified schematic of an immune response Class I MHC class II/peptides APCs Protein antigens CD8+ T cells CD4+ T cells B cells Plasma cells CD8+ cytolytic T cells CD4+ immune cells (delayed hypersensitivity) antibody production proliferation & differentiation IFNg, IL-2 Cytokines Costim. Mol. IL-4,-5,-6 proliferation & differentiation APC Class II proliferation & differentiation

上商充通大 Major steps in immune responses 后 Shanghai Jiao Tong University Antigen CD8 T cell IL-2 ◆cytotoxic 4 T cells primed CD4 L-1 IL-2 T helper antigen CD4 cell presenting T helper plasma cell cell 4 cells (macrophage, IL-2 dendritic cell) B cell

Shanghai Jiao Tong University Antigen antigen presenting cell (macrophage, dendritic cell) CD4 T helper cell primed CD4 T helper cell CD8 T cell cytotoxic T cells plasma cells 1 2 3 4 4 IL-1 IL-2 IL-2 IL-2 Major steps in immune responses B cell

上游充通大￥ Sites of action of 后 Shanghai Jiao Tong University immunosuppressive drugs Antigen CD8Tce生 IL-2 cytotoxic E T cells 3 X primed D CD4 BIL-1 IL-2 T helper antigen CD4 cell presenting T helper 4 plasma cell cell X→ cells cytokines

Shanghai Jiao Tong University Antigen antigen presenting cell CD4 T helper cell primed CD4 T helper cell CD8 T cell cytotoxic T cells plasma cells 1 2 3 4 4 IL-1 IL-2 IL-2 cytokines Sites of action of immunosuppressive drugs X X X X X A B D D E C X

上商充通大￥ Shanghai Jiao Tong University antibody CD40 ligand Interaction between secretion 3.Interactions between 4.Activated helper T cell the TH2 cell and B proteins on the proliferates into cytokine release cell causes the B antigens macrophage and helper either TH1 or TH2 cells, cellto proliferate T cell occur,activating which secrete different CD40 differentiate,and the helper T cell. types of cytokines. produce antibodies. 2.Macrophage presents Humoral immune a fragment of the activated response activated antigen on its surface. helper T cell. B cell antibody-producing TH2 cell plasma cell class II MHC B-cell receptor (mature B cel1) protein presenting class II MHC antigen 1.Macrophage antigen fragment Cell-mediated protein presenting captures, immune response antigen fragment antigens engulfs,and helper T-cell digests T cell receptors Cutokines secreted an antigen. by the TH1 cell class I MHC protein activate cytotoxic presenting antigen CD28 TH1 cell T cells to kill the fragment Cell infected infected target cell. with antigen B7 cytokine presents antigen D。1·0 release● fragments on its 。。 surface. cytotoxic T cell Activated cytotoxic T cell Cytokines secreted by the TH1 proliferates and differentiates into a mature cytotoxic T cell, macrophage cell stimulate the macrophage which binds to an infected to destroy ingested antigens target cell and initiates the more efficiently destruction of that cell. 1999 Encuclopaedia Britannica,Inc. mature cytotoxic T cell

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上浒文通大学 Immune response 后 Shanghai Jiao Tong University The cell-mediated arm of the immune response involves the ingestion and digestion of antigen by antigen-presenting cells such as macrophages. Activated TH cells secrete IL-2,which causes proliferation and activation of cytotoxic T lymphocytes, and TH1 and TH2 cell subsets.TH1 cells also produce IFN-y and TNF-B,which can directly activate macrophages and NK cells. The humoral response is triggered when B lymphocytes bind antigen via their surface immunoglobulin.They are then induced by TH2-derived IL-4 and IL-5 to proliferate and differentiate into memory cells and antibody-secreting plasma cells.Regulatory cytokines such as IFN-y and IL-10 down-regulate TH2 and TH1 responses,respectively

Shanghai Jiao Tong University The cell-mediated arm of the immune response involves the ingestion and digestion of antigen by antigen-presenting cells such as macrophages. Activated TH cells secrete IL-2, which causes proliferation and activation of cytotoxic T lymphocytes, and TH1 and TH2 cell subsets. TH1 cells also produce IFN-γ and TNF-β, which can directly activate macrophages and NK cells. The humoral response is triggered when B lymphocytes bind antigen via their surface immunoglobulin. They are then induced by TH2-derived IL-4 and IL-5 to proliferate and differentiate into memory cells and antibody-secreting plasma cells. Regulatory cytokines such as IFN- γ and IL-10 down-regulate TH2 and TH1 responses, respectively. Immune response

h 上浒充通大睾 后 Shanghai Jiao Tong University Purpose of immunosuppressive drugs .Prevention of organ transplant rejection .Treatment of autoimmune diseases >Multiple Sclerosis(多发性硬化) >Lupus(红斑狼疮) >Rheumatoid Arthritis(类风湿性关节炎) >Crohn's Disease(节段性回肠炎) >ype I Diabetes(1型糖尿病) >…

Shanghai Jiao Tong University Purpose of immunosuppressive drugs •Prevention of organ transplant rejection •Treatment of autoimmune diseases ØMultiple Sclerosis（多发性硬化） ØLupus （红斑狼疮） ØRheumatoid Arthritis （类风湿性关节炎） ØCrohn’s Disease（节段性回肠炎） ØType I Diabetes （1型糖尿病） Ø …

上商充通大 Glucocorticoids Shanghai Jiao Tong University reducing the size and lymphoid content of the lymph nodes and spleen interfering with the cell cycle of activated lymphoid cells lowering the effective concentration of specific antibodies

Shanghai Jiao Tong University Glucocorticoids • reducing the size and lymphoid content of the lymph nodes and spleen • interfering with the cell cycle of activated lymphoid cells • lowering the effective concentration of specific antibodies

Targets for Immunosuppressant Drugs Costimulatory Antigenic Antigen-Presenting Cell Signal Signal -Cell Receptor IL-2 Receptor Ca2+ Cyclosporine曰b日 IL-2 Sirolimus Tacrolimus Purine Synthesis Activated Calcineurin NFAT-P Mycophenolate Mofetil TCell Cell Nuclear Factor of Activated T Cells Steroid Cycle Azathioprine (NFAT) Interleukin-2(IL-2)Gene Promoter Denton et al.Lancet.1999;353:1083-1091

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