免疫与炎症

Immune and Allergic disease,Immunopathology,Immunopathology,Exaggerated immune response may lead to different forms of tissue damage1) An overactive immune response: produce more damage than it preventse.g. hypersensitivity reactions and graft rejection2) Failure of appropriate recognition: e.g. cancer,Allergic disease,The function of immune system:,Immune defenseImmune surveillancehomeostasis,Immune system:,burst forming unit-erythroid ，BFU-E,Colony forming unit-erythroid CFU-GEMM,多向祖细胞,爆式红细胞集落形成细胞,骨髓巨核细胞,Allergen (concept)Antibody (IGg, IGA,IGE) Mast cellEosinophils BasophilsDCNKB cell T cellMHC I-IITCR,BCRCytokine ,chemokineComplement systemCDFCRTh cell (Th1/Th2) Treg cell,Terms:,APC (DC, M,T ),Foreign body Molecular weight (大于10KD,protein,glocosidprotein)Chemical composition presentation,Allergen characteristic:,immunoglobulin,APC (DC,M,CD4+T ),CTL,LMP:低分子质量多肽,TAP:抗原加工相关转运蛋白,CLIP:II类结合的不变链多肽,癌基因产生的内源性抗原肽经I类分子提呈后激活肿瘤抗原特异性CTL,CD4T cell,B cell Ab(FC),Effective cell,Ag stimulate,Ag stimulate,Hypersensitivity reactions,type I, type II, type III,type IV,Plasma cell,Mechanisms of Allergic Immunity,APC cell,MHCII,TCR,Mechanisms of Allergic Immunity (Type I immediate hypersensitivity reaction),Concept:,Hypersensitivity refers to undesirable (damaging, discomfort producing and sometimes fatal) reactions and require a sensitized (immune) state of the host produced by the normal immune system. Classification : type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction. Frequently, a particular clinical condition (disease) may involve more than one type of reaction.,classification,(1)型变态反应 又称速敏型、IgE依赖型反应，此类反应是由于抗原与IgE为主的抗体相互作用所引起的。引起局部平滑肌痉挛、血管通透性增高、微血管扩张充血、血浆外渗水肿等组织学变化。属于型变态反应的皮肤病有荨麻疹、血管神经性水肿等。 (2)型变态反应 又称细胞毒型反应，是机体产生对细胞本身成分或固着于细胞抗原的抗体，当与相应抗原发生抗原抗体反应时，由于补体参与而发生细胞溶解或组织损伤。属于 型变态反应的皮肤病有药物性贫血、血小板减少性紫癜、天疱疮、类天疱疮等。 (3)型变态反应 又称免疫复合物型反应，免疫复合物是指对某种抗原产生的沉降性抗体与该抗原形成的抗原抗体复合物，该复合物较容易沉着于血管壁基底膜及其周围，发生以小血管壁为中心的变化，由此发生器官及组织的损伤。属于型变态反应的皮肤病有：变应性血管炎、狼疮肾、血清病等。 (4)型变态反应 又称迟发型反应，此类反应是由于机体受抗原刺激后，T淋巴细胞转化为相应的致敏淋巴细胞，当这种细胞再次遇到相应的抗原时，常在12天后释放一系列淋巴因子，引起组织损伤或直接对靶细胞的破坏。属于型变态反应的皮肤病有：接触性皮炎、湿疹、结核菌素型皮肤反应等,Type I Mechanisms of airway hypersensitivity reactions,Clinical examples of Type II responses include:Certain autoimmune diseases where Abs produced vs membrane AgsGraves Disease Abs produced vs thyroid hormone receptorMyasthenia Gravis Abs produced vs acetylcholine receptorsAutoimmune hemolytic anemia Abs produced vs RBC membrane AgsHemolytic Disease of the Newborn Hyperacute graft rejectionBlood Transfusion Graft rejection,Type II Hypersensitivity: Transfusion reactions,Produced by mismatched blood typesDestroys foreign RBC by complement-mediated lysis triggered by IgGProduces fever, intravascular clots, lower back pain, Hgb in urineFree Hgb result:passes to the kidneys hemoglobinuriaBreaks down to bilirubin can be toxic,Hemolytic Disease of the Newborn (Rh溶血 ),Concept: Antigen-antibody complex deposit in tissues to cause tissue damage through the activation of complement,Type III Hypersensitivity:Immune Complex-mediated cytotoxicity,Type III Hypersensitivity: Localized reactions,Arthus reaction:Exposure to an Ag for which there already is a high c of AbProduces edema/erythema from damage tissueInsect bitesInhalation of bacteria, fungi, dried fecal matter,Type III Hypersensitivity: Systemic (generalized) reactions,Produced when large amounts of Ag enter the bloodstreamThe sites of deposition vary; usually in tissues where plasma is filteredEsp. in kidneys, blood vessels, and jointsCan cause tissue damaging reactionSerum sicknessAutoimmune diseasesDrug reactionsInfectious diseases,Type IV Hypersensitivity: Delayed-Type Hypersensitivity,Concept： cell-mediated immunity reaction (CMI)also called delayed-type hypersensitivity( DTH) is mediated by T cells rather than by antibody. Upon activation ,the T cells release cytokines that cause accumulation and activation of macrophages , which, in true release lysosomal enzymes that cause local damage. This type of reaction has a delayed onset and may occur 1-2 days after challenge with antigen.,Body product IgE antibody against exogenous antigens. The antigen is common substance existing in the surrounding environment.,Concept:,Type I Hypersensitivity reactions,Pathogenic mechanisms,* First exposure to allergen Allergen stimulates formation of antibody (IgE type) Ig E fixes, by its Fc portion to mast cells and basophiles* Second exposure to the same allergen It bridges between Ig E molecules fixed to mast cells leading to activation and deregulation of mast cells and release of mediators.,Late phase reaction,Immediate reaction (15-30 minutes ),Processes of Hypersensitivity reactions,(allergic inflammation),Mechanisms,APC cell,MHCII +Ag,TCR,IL-13,Immediate reaction (15-30 minutes),IgE Fc-receptor,increased Ca+ influx,amplified and/or modified by platelets,Europhiles and eosinophils.,Immediate reaction (15-30 minutes ),Mechanisms,Histamine,tryptase,kininogenase.,Allergen Classification,Allergen Classification,Allergen action :,Repeated exposure,M Can not be activated; T cell Th2 cell Th1-related factors Th1/Th2 shifting ;Th2- related factors,Mast cell activation:,Causes:Physical injury Chemical substance Endogenous mediator IGE /non- IGE immune effect,_,_,IL-4,IL-5,IL-13,Th1/Th2 shifting,Basophils were activated and release chemokines to recruit eosinophil to the same local. eosinophil restrict the activity of basophils:produce prostaglandin E synthesis to inhibit the process of basophils release of bioactive substances Eosinophils engulf phagocytosis of particles and emitted from basophils , the biological active substances can not play a role;Eosinophils release histamine enzymes to destruct basophils to release histamine and other active substances.,Function of eosinophil,It is also known as immediate or anaphylactic hypersensitivity. The reaction may involve skin (urticaria and eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis). The reaction may cause from minor inconvenience to death. The reaction takes 15-30 minutes from the time of exposure to the antigen. Sometimes the reaction may have a delayed onset (10 -12 hours).,Characteristic :,Type I hypersensitivity,* Exposure to allergen to which a person is previously sensitized* Allergens: Drugs: penicillin Serum injection : anti-diphtheritic or ant-tetanic serum anesthesia insect venom * Clinical picture: Shock respiratory distress cyanosis edema urticaria,Methods of diagnosis：,1) History taking for determining the allergen involved2) Skin tests: Intradermal injection of battery of different allergens A wheal and flare (erythema) develop at the site of allergen to which the person