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1、1. Immunology is the study of the ways in which the body defends itself from infectious agents and other foreign substances in its environment. Immunity: refers to all mechanisms used by the body as protection against environmental agents that are foreign to the body. (to recognize and eliminate for
2、eign substances) 2.Innate immunity It refers to any inborn immunity that is already present the first time a pathogen is encountered. 3.Adaptive immune response The T cells and B cells in the body recognize the antigen and, in turn, become activated. The activated lymphocytes then proliferate and ca
3、rry out their specific effector functions 4.Humoral immunity: mediated by B cells and defense against extracellular microbes. 5.Cell-mediated immunity: mediated by T cells and defense against intracellular microbes. The innate and adaptive immune response Introduction Characteristics Cells Molecules
4、 Innate immunity Responds rapidly No memory No or low specificity Physical barriers Phagocytes (PMNs and macrophages) Natural killer cells Humoral factors Complement Acute phase Proteins Cytokines Adaptive immunity Responds Slowly Memory Highly specific T cells B cells Dendritic cells Antibodies Cyt
5、okines Granzymes Clonal selection theory 全身的免疫细胞是由众多识别不同抗原的细胞克隆所组成，同一种克隆细胞表达相同的特异性受体，淋巴细胞识别抗原的多样性是机体接触抗原前就有的，是生物在长期进化过程中形成的。抗原进入机体只是从免疫细胞中找出能识别这种抗原的淋巴细胞克隆，活化，增殖，扩增出许多具有相同特异性的子代细胞，产生大量特异性抗体清除入侵的抗原。 日 T Lymphocytes TCR: T-cell antigen receptor TCRab+ 95% TCRgd+ 15% 1. Cytotoxic T cells (CTL) 2. helper
6、 T cells: Th1, Th2, Th17 3. Regulatory T cells (Treg) and suppressor T cells (Ts) Th1 巨噬细胞活化 IgGTh2 肥大 嗜酸 IgEBone marrow1.the place in which proliferation of HSC takes place 2.the place in which development and maturation of B cells occur The lymphoid progenitor cells are transported by circulating
7、blood to the thymus and differentiate into functional T lymphocytes The thymus 1. Cells: thymic stromal cells (TSC) epithelial cells, monocytes (macrophage), TDC thymocytes T cell (ab+) 2. Structure: cortex-immature thymocytes medulla-mature thymocytes Mf, TDC 3. Function: It is the site of T cell m
8、aturation/selection; It determines the specificity of the TCR expressed on the T cells released to periphery The lymph node 1.Human:2-10mm in diameter 2.round and kidney shaped 3.Consists of cortex (B-cell area) paracortex (T-cell area) central medulla (B-cell area) The spleen 180-250g germinal cent
9、er (B) 1. the white pulp periarterial lymphatic sheath (T) the red pulp (B) 2. function: destroy the Ag, aged platelets immune response Lymphocyte recirculation 1.Lymphocytes leave the blood via high-walled endothelium of the post-capillary venules. 2.Lymphocyte trafficking exposes antigen to a larg
10、e number of lymphocytes. Lymphocyte homing血液中淋巴细胞选择性趋向迁移并定居在外周免疫淋巴器官的特定组织的过程Lymphocyte recirculation定居在外周免疫器官的淋巴细胞，由输出淋巴管进入血液循环，经血液循环到达外周淋巴器官后，穿过HEV，重新分布于全身淋巴器官和组织的过程Double negative cells (DN) CD4-CD8-; CD2+, CD5+, cytoplasmic CD3+ nDouble positive cells (DP) CD4+CD8+, CD1+, CD3+, gdTCRlow, abTCRlow
11、 nMature T cells (single positive T cells) CD4+ or CD8+, CD2+, CD3+, TCR+ 4. Positive and negative selection Positive selection: DP cells that bind, with moderate affinity, to MHC-Ag on thymic stroma cells survive-MHC restriction MHC I-CD8+ T cells MHC II-CD4+ T cells Negative selection: Cells that
12、bind to MHC-Ag on thymic stroma cells (or auto-reactive T cells, ART) with high affinity will undergo apoptosis Formation of central immune tolerance 1. CD4+ helper T cells (Th): Th0:Th cells that secrete broad spectrum of cytokines at low level. Th1: produce IL-2 and IFN-, but not IL-4. They are ch
13、iefly responsible for cell-mediated immune responses, but can also help B cells to produce IgG2a, but not much IgG1 or IgE; Th2: secrete IL-4, 5, 10, 13, but not IL-2 and IFN-, are very efficient helper cells for production of antibody, especially of IgG1 and IgE ; Th17: secrete IL-17 and IL-21, med
14、iate innate immunity and inflammation, especially autoimmune disease. Key point Immune tolerance Immune tolerance or Immunological tolerance is a state of unresponsiveness that is specific for a particular antigen; it is induced by prior exposure to that antigen.Tolerogen 耐受原B cell central tolerance
15、Clonal deletion During maturation of B lymphocytes in bone marrow , immature lymphocytes that recognize membrane-bound self-antigen with high affinity are deleted by apoptosisClonal anergy During maturation of B lymphocytes in bone marrow , immature lymphocytes that recognize soluble self-antigen are not deleted but are inactivated Receptor editing: light chain rearrangementT cell central tolerance1
