医学免疫学课件：Hypersensitivity

1、InflammationInflammation is local response of a tissue to damage or infection. It has three principle components:1.An increased blood supply to the area, bring lymphocytes and serum molecules to the affected sites.2. An increase in capillary permeability allowing exudation of the serum proteins (ple

2、ments etc.) required to control the infection.3. An increase in leukocyte migration into the tissue.antigensImmune systemImmune responseImmune effectorsHypersensitivityHypersensitivity is a harmful immune response that is heightened reactivity to an antigen and characterized by tissue injury or func

3、tional disorder. Diseases caused by hypersensitivityTypes of hypersensitivity reactionsType I: immediate hypersensitivity, Type II:cytotoxic hypersensitivityType III:Immune complex type hypersensitivity Type IV:cell mediated hypersensitivity or delayed-type hypersensitivityType I hypersensitivity (a

4、llergy, anaphylaxis)Features: Occur and disappear rapidly immediate hypersensitivityThe major problem is functional disorder almost without tissue injury Be mediated by Ig E antibodyThere is a strong genetic predisposition for the development of SEVERE immediate hypersensitivity. Atopic individuals

5、are susceptible to allergic diseases.Urticaria from mosquito bite is due to type I hypersensitivity. The major components participating in Type I hypersensitivity1.Allergens2.IgE3.mast cells and basophils Allergens-antigens which cause hypersensitivity reactionsAllergens include some plant pollens,

6、some drugs, some food, some insect venom, some mold spores, animal hair and dander IgE1) Very little present in serumThe concentration of IgE in serum of normal individals is less than 1 ug/mL, which can rise to 1000ug/mL in serum of some atopic individuals.2) IgE produced by B cells binds to the Fc

7、 receptors on Mast cells and basophils.Mast cells and basophils :There is FcR on these cells.There are many granules in their cytoplasm.Mast cells are found throughout connective tissue, particularly near blood vessels.Basophils are blood granulocytes with structural and functional similarities to m

8、ast cells. They can be recruited into tissue sites where antigen is present. Mechanism of type I hypersensitivity 1. Sensitization phase 2.Excitation phase 3. Effector phase Sensitization phase Allergen Production of Ig E IgE binds to FcR I on mast cells and basophils 2.Excitation phase Antigen bind

9、ing to IgE cross-links FcRI molecules on the mast cellsinduces the release of mediators (degranulation) restored mediators new synthesized mediators (histamine) (leukotrienes, prostaglandin and PAF) degranulation IgEFceRIallergeninflammation静息肥大细胞激活后 5 分钟激活后 60 分钟3 . effect periodThe effect of media

10、tors : increase vascular permeability, vasodilatation promote bronchial and visceral smooth muscle contraction increase secretion of glands early phase reaction : occurs within minutes , mainly caused by histamine late phase reaction :occurs within hours, caused by the induced synthesis and release

11、of mediators including leukotrienes, prostaglandins, chemokines, and cytokines from the activated mast cells. A second reason is inflammation characteristic of Th2 and eosinophil infiltrationAllergenType I: IgE mediatedB cellPlasma CellPlasma CellMast cell granulesFcRIAllergenActivated Mast cellHist

12、amineLeukotrienesProstaglandinCytokinesLate phase response occurs within hours.Common diseases caused by type I hypersensitivity1. Systemic allergy: anaphylactic shock2. Hypersensitivity reaction in respiratory tract allergic rhinitis， allergic asthma3. Hypersensitivity reaction in gastrointestinal

13、tract Food allergies4.hypersensitivity reaction in skin: urticariaIV Therapy for allergy1.Separated from allergens2.Desensitization3.anti-allergic drugs:to block the production or release of mediators or to antagonize mediator actions on target cells Skin test for allergyFeatures of type II hypersen

14、sitivityMechanism of type II hypersensitivityThe diseases caused by type II hypersensitivityPart II Type II hypersensitivityTransfusion reaction is an example of type II hypersensitivity.If a type A individual is transfused with blood containing type B cells, a transfusion reaction occurs in which t

15、he anti-B antibody bind to the B blood cells and mediate their destruction by means of activation of complement, ADCC or opsonization。NaturalKiller cellRelease of perforin andgranzymesAntibody dependent cell-mediated cytotoxicity (ADCC)Alternatively, cells can belysed via complement.C1OpsonizationFe

16、atures1)Ag is on surface of cells2)Ab is IgG or IgM3) Complements, macrophage and NK cells are involved.4) cell lysis or tissue injuryMechanism of type II hypersensitivity Ab is produced Binding of the antibody to the antigen on cells can cause cell lysis and tissue injury by activation of complemen

17、ts, opsonization or ADCC. activate complement opsonization cell lysis tissue injury ADCC Thyroid-stimulating hormoneThe diseases caused by Type II hypersensitivityTransfusion reactionHemolytic disease of the newborn Autoimmune hemolytic anemiaDrug-induced hemolytic anemiaGraves diseaseHemolytic dise

18、ase of the newborn most commonly caused by Rh incompatibilityHemolytic disease of the newborn can be prevented by administering anti-Rh antibodies to the mother within 24-48h after the first delivery.Autoimmune hemolytic anemiaDrug-induced hemolytic anemia Some antibiotics (penicillin, cephalosporin

19、 and streptomycin) stick nonspecifically to proteins on red blood cells.An antibody response can develop to the drug/protein complex.Lysis of the red blood cells causes anemia.Clemens von PirquetSerum sickness Diphtheria infections were treated with serum from horses immunized with diphtheria toxin.

20、Joint inflammation, rash and fever developed in patients treated with horse serum containing anti-toxin.Nicolas Maurice Arthus Arthus reactionType III hypersensitivityClemens Pirquet 1874-1929Type III hypersensitivityFeatures1)Antigen is soluble 2)antibody is Ig G or IgM3) immune complex disease Ag+

21、AbImmune complex,ICLarge ICPhagocytosis by phagocytesSmall ICExist in circulation, and depositMechanism of type III hypersensitivity 1. Formation of a large quantity of immune complexes2. Deposition of the IC on basement membrane of blood vessels3. The complements are activated by the IC, producing

22、C3a and C5a, which mediate a local inflammation by activating mast cells and basophils and recruiting neutrophilsRecruited neutrophils release hydrolytic enzymesPlatelet activation leads to thrombosisType III hypersensitivity mechanismDiseases caused by type III hypersensitivity1. Arthus-like reacti

23、on2. Inhaled antigen-induced type III hypersensitivity3.Serum sickness4. Poststreptococcal glomerulonephritis5.Rheumatoid arthritis6.Systemic lupus erythematosusArthus-like reactionArthus reactions are characterized by severe pain, swelling, edema, hemorrhage, and occasionally by necrosis. Inhaled a

24、ntigen-induced type III hypersensitivityFarmers lungPigeon fanciers diseaseSerum sickness fever, rashes, joint inflammation, swollen lymph nodes glomerulonephritis Poststreptococcal glomerulonephritisRA , Rheumatoid arthritisSystemic lupus erythematosusAntibodies Anti-nuclear, Anti-dsDNA, Anti-Sm an

25、d anti-histone SLE most often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system.Type IV hypersensitivityFeaturesComponentsMechanismDiseasesFeatures of type IV hypersensitivity 1. mediated by T cells 2.pathological change is an inflammation characterized by infil

26、tration of mononuclear cells 3.DTHdelayed type hypersensitivity It arises about 24 h after the second contact with the same antigens, and peaks 48-72 hr after second contact. 4. Antibodies and complements are not involvedComponentsAgMicrobes in particular, intracellular microbes such as mycobacteriu

27、m tuberculosis.Chemical substances Effector cells CD4+ T cells (Th1) and CD8+ T cells, both of which secret cytokines ( e.g.IFN-) and chemokinesActivated macrophages secret cytokines (e.g. TNF), lysosomal enzymes to induce inflammation.Continuous activation of macrophages can induce granuloma. Mecha

28、nism of type IV hypersensitivity1.Sensitization phaseAntigens are presented to CD4+Tcells by APCs. The CD4+Tcells are activated, clonally expanded and differentiated to sensitized Th1.CD8+Tcells -CTL2. Effector phase After the second contact with the same antigens, the sensitized Th1 secrete cytokin

29、es to induce an inflammation characterized by infiltration of macrophages and other inflammatory cells.The activated macrophages and other inflammatory cells release lytic enzymes, which can induce nonspecific tissue injury.CTL specifically recognizes the antigen expressed on the target cells and kill them.被膜输出淋巴管外 来 抗 原 的 捕 获 与 递 呈 局 部 组 织引流淋巴管树突细胞异物抗原输入淋巴管皮质淋 巴 结Diseases caused