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1、INNATE DEFENSES Bodys 1st line of defense: anatomic barriers The skin & mucous membranes If these defenses are penetrated: Mechanical clearance 2nd line of defense: Inflammatory response第1页/共60页IMMUNE RESPONSE 3rd Line of defense: Immune Response Slower & specific compared to inflammatory re

2、sponse Inflammatory & immune responses complement each other & interact in complex ways第2页/共60页THE IMMUNE SYSTEM Extraordinary complex system Elaborate & dynamic communication network Recognizes & responds to antigens第3页/共60页Cells & molecules of the immune system protect the nose

3、 from attack by a virus第4页/共60页CHARACTERISTICS OF IMMUNE RESPONSE Immunity State of protection, primarily against infections Characterized by memory & specificity Antigens Chemical substances that react with preformed components of the immune response Immunogens Antigens that induce an immune re

4、sponse Haptens Antigens must be bound to carriers to induce an immune response第5页/共60页 Self-Antigens Antigens on host cells Not recognized as immunogenic by hosts immune system A condition called toleranceCHARACTERISTICS OF IMMUNE RESPONSE第6页/共60页INDUCTION OF IMMUNE RESPONSE Most immune system cells

5、 are WBCs Immunocytes (lymphocytes) are 1 type of WBC 2 major classes of immunocytesT lymphocytes (T cells) & B lymphocytes (B cells) Immune response is characterized by the activation of B cells & T cells第7页/共60页B CELLS Develops from a stem cell that matures under hormonal control in bursal

6、-equivalent tissues (bone marrow) Develops into a mature plasma cell capable of producing antibody against a specific antigen Antibody marks the antigen for destruction by other immune cells第8页/共60页ANTIBODIES Plasma glycoproteins Classified by chemical structure & biologic activity IgG, IgM, IgA

7、, IgE, or IgD Protect host from harmful antigens Recognize and bind with antigens Functions: Opsonize bacteria, neutralize toxins & viruses Activates inflammatory response第9页/共60页ANTIBODY CLASSIFICATION IgG 80% plasma Ig, in all body fluids, secondary response, activates complement IgM Primary r

8、esponse, large molecule, vascular system, activates complement IgA 95% of body secretion Ig, respiratory and GI tract, coats bacteria & some viruses IgD Plasma, B cell surfaces, antigen receptor IgE Hypersensitivity and allergic reactions (asthma)第10页/共60页 Develop from stem cells that mature und

9、er hormonal control in thymus Make up the cell-mediated immune response Help to destroy infected cells Coordinate the overall immune responseT CELLS第11页/共60页TYPES OF T CELLS Cytotoxic T cells Kill target cells directly Delayed hypersensitivity T cell Produces lymphokines that affect other cells (esp

10、ecially macrophages) Helper T cell Induces B cells to produce antibody Recognize antigen fragments Suppressor T cell Suppresses antibody production & immune function第12页/共60页T-CELL RECEPTOR T cell has molecule on its surface called T-cell receptor Interacts with molecules called MHC (major histo

11、compatibility complex)第13页/共60页T cell (lymphocyte) with aT-cell receptor on its surface第14页/共60页ANTIBODY PRODUCTION Final stage of the process Requires interaction of: B cells Helper T cells Antigen-presenting cells第15页/共60页Histocompatibility Antigens (Human Leukocyte Antigens) Proteins found on the

12、 surface of nearly every cell in the body Recognizes substance is foreign第16页/共60页Major Histocompatibility Complex (MHC) MHC (or HLA complex) Major group of genes producing the HLA antigens 4 closely linked foci located on short arm of chromosome 6 (A, B, C & D complex) Antigens produced by A, B

13、 & C loci found on surface of most cells except erythrocytes D complex consists of 3 independent loci (DR, DP, DQ) Confined to B cells, macrophages, some epithelial cells & some stimulated T lymphocytes第17页/共60页INNATE IMMUNITY Nonspecific (species specific) First line of defense Present at b

14、irth Found in multi-cellular organisms Permanent immunity Not product of immune response第18页/共60页INNATE IMMUNITYEffectors Neutrophils Macrophages Eosinophils NK cells第19页/共60页Main Mediatorsv Lysosomal enzymesv Cytokinesv Complement proteinsv Acute phase proteinsINNATE IMMUNITY第20页/共60页ACQUIRED IMMUN

15、ITY Highly specific, inducible discriminatory, unforgetting T lymphocyte- dependent Gained after birth第21页/共60页Activeo Natural exposureo ImmunizationACQUIRED IMMUNITY第22页/共60页Passive Doesnt involve hosts immune response Antibodies & T cells transferred to recipient Temporary immunityACQUIRED IMM

16、UNITY第23页/共60页 Primary 5 7 days after exposure Dominated by IgM Lesser amounts of IgG Secondary 2nd challenge by same antigen Rapid production of antibody IgM same production as primary IgG predominantIMMUNE RESPONSE第24页/共60页HUMORAL IMMUNITY Antigens stimulate B cells plasma cells Mediated by antibo

17、dies secreted by B cells第25页/共60页CELL-MEDIATED IMMUNITY Activation of sensitized T cells T cells secrete cytokines T cells become cytotoxic cells T cells kill virus-infected or abnormal host cells第26页/共60页ACUTE INFLAMMATORY RESPONSE Rapid & nonspecific Protective response to cellular injury Occu

18、rs only in vascularized tissue第27页/共60页MACROSCOPIC HALLMARKS OF INFLAMMTION Redness Heat Pain Loss of function of the inflamed tissues第28页/共60页 Accumulation of fluid and cells at the inflammatory siteMICROSCOPIC HALLMARKS OF INFLAMMATION第29页/共60页MAST CELLS Most important activator of inflammatory re

19、sponse Releases biochemical mediators Histamine Chemotactic factors Synthesizes other mediators Prostaglandins Leukotrienes Platelet-Activating Factor (PAF)第30页/共60页MAJOR VASOACTIVE AMINES OF INFLAMMATION Histamine & serotonin Effects: Constricts vascular smooth muscles Dilation of capillaries R

20、etraction of endothelial cells lining capillaries Increases vascular permeability第31页/共60页ACUTE PHASE RESPONSE Systemic changes present if inflammation is severe enough May be transient, dissipating with recovery or persistent in chronic disease Mediated by inflammation-associated cytokines Changes

21、in concentrations of large number of plasma proteins第32页/共60页 Fever Somnolence Anorexia Changes in plasma protein synthesis Altered synthesis of endocrine hormones Hormones effected: CRH Glucagon Insulin ACTH Cortisol Catecholamines Growth Hormones TSH, Thyrpxine Aldosterone AVPACUTE PHASE RESPONSE第

22、33页/共60页 Major acute phase proteins (APP) C-Reactive protein (CRP) Serum amyloid A (SAA) Negative APP Albumin Transthyretin Transferrin Other positive APP Complement proteins Ferritin -1- antitrypsin (antiprotease) Fibrinogen Fibronectin Hempexin Haptoglobin CeruloplasminACUTE PHASE PROTEINS第34页/共60

23、页C-REACTIVE PROTEIN Influences inflammatory & tissue repair processes Recognizes some foreign pathogens Activates complement system Bonds to phagocytic cells Induces production of inflammatory cytokines Main initiator of blood coagulation Net effect may be antiinflammatory 第35页/共60页PLASMA PROTEI

24、N SYSTEM Inflammation is mediated by 3 key plasma proteins systems Complement system Clotting system Kinin system第36页/共60页COMPLEMENT SYSTEM The “complement cascade” (Fig 7-7) Activated by antigen-antibody reactions (classic pathway) Activated by other products especially bacterial polysaccharides al

25、ternate (nonantibody) pathway Produces biologically active (anaphylactic or chemotactic) fragments Produces target cell lysis Phagocytosis Increases vascular permeability第37页/共60页CLOTTING SYSTEM Extrinsic & Intrinsic pathways (Fig 7-9) Stops bleeding Localizes microorganisms Provides a meshwork

26、for repair & healing第38页/共60页KININ SYSTEM Bradykinin most important kinin protein Dilates vessels (low dosage) Induces pain (along with prostaglandins) Contracts extravascular smooth muscle Increases vascular permeability May increase leukocyte chemotaxis (Fig 7-6)第39页/共60页INHIBITORY INFLAMMATOR

27、Y ENZYMES Histaminase Carboxypeptidase C1 esytrase inhibitor 1-antitrypsin第40页/共60页 Phagocytic leukocytes Neutrophils Macrophages Eosinophils Platelets LymphocytesCELLULAR COMPONENTS OF INFLAMMATION第41页/共60页PHAGOCYTIC CELLS Engulf & destroy microorganism (Fig 7-16) Enclose in phagocytic vacuoles

28、 (phagolysosomes) Toxic products & degradative lysosome enzymes kill & digest第42页/共60页OPSONINS Antibody & complement component (C3b) coat microorganisms (Fig 7-15) This makes them more susceptible to phagocytosis Binds microorganism more tightly to the phagocyte第43页/共60页ENDOTHELIAL CELLS

29、 Line the blood vessels & capillaries Retract during inflammation Permit fluid, nutrients & phagocytic cells into area of injury第44页/共60页POLYMORPHONUCLEAR NEUTROPHIL (PMN) Predominant phagocytic cell in early inflammatory response Enters inflammatory site within 6-12 hours Attracted by chemo

30、tactic factors Short lived Gradually replaced by macrophages & lymphocytes Primary role: removal of debris & phagocytosis第45页/共60页MONOCYTES Largest normal blood cell Produced in bone marrow Enters circulation & migrates to inflammatory site Develops into a macrophage第46页/共60页MACROPHAGES

31、Larger & more active phagocyte Characterizes chronic inflammation May appear within 24 hours of injury Usually arrive 3-7 days later Attracted by chemotactic factor released by PMN & monocytes Survive longer at site第47页/共60页ROLE OF MACROPHAGES Responsive to products secreted by T cells Parti

32、cipate in activating the immune response Stimulates the growth & differentiation of granulocytes & monocytes in bone marrow Produce inflammatory cytokines Secrete substances to promote wound healing Phagocytic activity第48页/共60页EOSINOPHILS Release products to control inflammatory response Con

33、tain biochemical mediators to control effects of histamine & serotonin Contains a caustic protein that dissolves surface membranes of parasites Induced by IgE-mediated mechanisms of hypersensitivity (Fig 7-18)第49页/共60页CELLULAR PRODUCTS Interleukins Lymphokines Chemokines Interferon See Fig 7-19第

34、50页/共60页INTERLEUKINS Biochemical messengers Cytokines produced by macrophages or lymphocytes Stimulated by antigens or inflammation Stimulate other leukocytes to proliferate ( immune function) Chief effect: the immune response第51页/共60页LYMPHOKINES Cytokines produced by T cells Also biochemical mediat

35、ors Most important effects on macrophages Tumor necrosis factor (TNF) 第52页/共60页CHEMOKINES Generally proinflammatory cytokines Effects on leukocytes Chemotaxis Growth Activation Release stored chemicals from intracellular storage granules (degranulation)第53页/共60页INTERFERON Defense against viral infec

36、tions Cytokine produced & released by host cells invaded by virus Prevents virus from infecting healthy cell Stimulates uninfected cells to produce antiviral proteins (Fig 7-20) INF- & INF- are antiinflammatory INF- is proinflammatory and enhances cell-mediated immunity第54页/共60页CHRONIC INFLAMMATION Lasts 2 or

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