Presentation on theme: "The Immune System The body’s defense 1. Nonspecific 2. Specific"— Presentation transcript:
1 The Immune System The body’s defense 1. Nonspecific 2. Specific Cell mediatedAntibody mediated
2 Three cooperative lines of defense have evolved to counter these threats. Two of these are nonspecific - that is, they do not distinguish one infectious agent from another.
3 Nonspecific defenses“Nonspecific” = don’t have to recognize an invader to fight itSkin: physical barrierSweat glands: chemical defenseMucous membranes:Line body openings- physical barrierSecretions:Antimicrobial proteins present in secretionsMucous traps particlesAcid in stomach-destroy most except hept.AChemical defense = ph is 3-5, dry acidic environment is intolerable to bacteria
4 Besides being a physical barrier, the skin and mucous membranes chemically destroy pathogens. Secretions from oil and sweat glands give the skin a pH ranging from 3 to 5, acidic enough to kill most microbes.Growth is also inhibited by saliva, tears, and mucous secretions that continually bathe the exposed epithelium.All these secretions contain antimicrobial proteins.One of these, the enzyme lysozyme, digests the cell walls of many bacteria, destroying them.
5 2ND LINE-InternalMicrobes that penetrate the first line of defense face the second line of defense, which depends mainly on phagocytosis, the ingestion of invading organisms by certain types of white cells.Phagocyte function is intimately associated with an effective inflammatory response and also with certain antimicrobial proteins.
6 Second line of defense cells function like roaming patrols 1. Nonspecific defenses of chemicals and cells-Stimulated by cytokinnins2. Act rapidly with infection3. Employ negative test that cannot be foiled by copycat foreign cells
7 4. All cells possess major histocompatibility complex (MHC) proteins 5. Different in each individual. Distinguish self from non self. Due to MHC proteins-before birth1. MHC 1-nucleated cells-body cells2. MHC II- Nucleated cells-macrophages-B cells-some t cellsa. 50 alleles-20 genesb. In autoimmune diseases defensive cells attack body's own tissuesc.Autoimmune diseases like arthritis have inflammation without infection
8 Major Histocompatibility Complex The basis of “self”Genes for cell surface glycoproteinsIn humans: human leukocyte antigens (HLA)ENORMOUS variation (polymorphic)2 Types:Class 1: found on all nucleated cellsClass 2 : found on macrophages, B cells, CD4 T cells
10 Phagocytic and Natural Killer Cells Neutrophils:Most abundant WBC’sChemotaxicEngulf invaders, then self-destructMonocytes:Less abundant, but more effective than neutrophilsForm macrophagesReach pathogen with pseudopodiaEngulf pathogen, fuse it with a lysosomeKill pathogen with toxic oxygen or enzymesPhagocytosis = engulfing invaders; nonspecificChemotaxic = cells damaged by microbes release chemical signals, neutrophils travel to the site of damageMacrophages live longer than neutrophilsToxic oxygen = superoxide anionProblem: bacteria that pseudopodia can’t grab
14 The Inflammatory Response Histamine is released by circulating leucocytes called basophils and by mast cells in connective tissue.Histamine triggers both dilation and increased permeability of nearby capillaries.Also discharge prostaglandins and other substances that promote blood flow to the site of injury.Greater clotting capacity, faster repairInitiated by chemical signalsFrom microbe- Chemotactic factorFrom damaged ‘self’ cells (ex: histamine)Chemokines from damaged cells attract phagocytesPus = dead phagocytes + fluidsExtreme = septic shockMech of increased blood flow:precapillary sphincters dilate, postcapillary sphincters constrictPhagocytosis: most important part of inflammationSeptic shock:extreme, widespread infection, WBC production, fever, BP*Most common cause of death in CCU’s
15 The Complement System Antimicrobial proteins ~ 20 serum proteins Function: microbe lysisInterferons:1 activates phagocytescan be made by recombinant DNA
17 Another set of proteins that provide nonspecific defenses are the interferons, which are secreted by virus-infected cells.While they do not seem to benefit the infected cell, these proteins diffuse to neighboring cells and induce them to produce other chemicals that inhibit viral reproduction.Interferon limits cell-to-cell spread of viruses, helping to control viral infection.Because they are nonspecific, interferons produced in response to one virus may confer short-term resistance to unrelated viruses.One type of interferon activates phagocytes.
18 Temperature Response Pyrogens Ex: Interleukin-1Detected in blood by hypothalamus -- raise in body tempHow it works:Speeds cellular reactionsStimulates phagocytosisStimulates liver/spleen to store FeEndotherms - may regulate behaviorally
20 Immunity terms Humoral vs Cell mediated Acquired/active vs Passive Lymphocytes: T and B cells, specificAntigen: Foreign molecule (from pathogens, pollen, transplanted tissue, etc.)Antibodies: made by B cells, specificAntigen receptors: on membranes of T & B cellsB cells: membrane antibodiesT cells: similar, but never secretedT & B begin developing in bone marrowT finish in thymusB finish in bone marrow (but actually named after bursa)Pathogen: disease causing agent
21 T cells TI = inducer TC = cytotoxic TH = helpers TS = suppressor killersTH = helpersActivate othersTS = suppressorCauses B cells to ignore antigens
22 Antigen presentation Antigen binds to MHC within cell MHC molecules bring proteins to surface
27 Mechanism T cytotoxic cell releases perforin Forms pores in membrane of target cellCell lyses, pathogen inside is exposed to circulating antibodiesT cytotoxic cell moves on to other cells infected w/ same pathogenTumor cells have ‘tumor antigens’Some cancers, epstein-barr virus: class 1 MHC moleucles, escape defense
31 Antibody mediated immunity Aka Humoral immunity, B cells activated, antibody productionEx: macrophage engulfs a bacteriumClass 2 MHC picks up bacterial peptideMHC + antigen move to cell surfacePresents to T helper cell/releases Il-1Enhanced by CD4 receptor on T helper cellT cell proliferatesActivated T helper cells: secrete cytokines to stimulate other lymphocytesCytokines: ex = IL-2helps activate B cells become plasma cellsactivates cytotoxic T cells
32 Humoral response in detail B cell activation by IL-2, proliferate into plasma and memory cellsPlasma cells: secrete antibodiesMemory cells: long-livedSome antigens are T-independentBind to membrane antibodies on B cellsPlasma cells made w/ out signal from T cellsQ: which cells secrete IL-2 to activate the B cells?A: helper T
36 Structure of antibodies Globular protein, in plasma,aka: immunoglobulins (Igs)Structure: 4 chains: 2 heavy, 2 lightConstant regionVariable regionEpitope: part of the antigen where antibody binds5 classesMade in vitroPolyclonal: made from many B cell clonesWork on different epitopes of the same antigenMonoclonal: made from one B cell cloneAll work at the same epitope of the same antigen
39 How antibodies work Neutralization: Opsonization: Agglutination: Block antigen activityOpsonization:Enhance macrophage attachment/phagocytosisAgglutination:ClumpingComplement fixation:can be activated by antibodies or by pathogensAntibodies attach to antigensComplement proteins activate, cause lysisEx of neutralization:attach to the molecules on a virus that the virus needs to attach to the host cellAgglutination: neutralizes & opsonizes
40 Active vs. Passive Immunity Active immunity: your own responseNatural: from infectionArtificial: from vaccinationsPassive: antibodies from another individualEx: across placenta, through breast milkEx: antivenoms,RhogamRhogam: injection given to Rh- mothers after birth of Rh+ child.Destroy fetal cells before her immune system responds to them, develops antibodiesAnti Rh antibodies are class IgG - can cross placentaRhogam: injection given to Rh- mothers after birth of Rh+ child.Destroy fetal cells before her immune system responds to them, develops antibodiesAnti Rh antibodies are class IgG - can cross placentaAnti A, Anti B are class are IgM - can’t cross
41 Tissue transplantation Blood types: ‘A’ and ‘B’ antigensT-independent humoral responseAntibodies don’t cross the placentaOrgan transplantsRejection due to MHCs that are too dissimilarSuppress immune system to decrease rejectionBone marrow: graft rejection
42 Overactive/under active Immune Systems Allergies: antigen induces inflammatory responseHistamine released from mast cellsAnaphylactic shock: severe allergic reaction, may cause death (due to BP)Epinephrine may counteractAutoimmune diseases: immune system attacks self tissueLupus, rheumatoid arthritis, MS, type 1 diabetesLupus: autoantibodies against histones, DNA, etc.R. arthritis: joint bones/carilegeMS: myelinType 1 diabetes: beta cells in pancreas (insulin dependent)
43 Under active Immune System Immunodeficiency diseases:Severe combine immunodeficiency (SCID)Genetic, need marrow transplantMay treat w/ gene therapyHodgkin’s: damages lymphatic systemAIDSSusceptible to opportunistic infectionsCaused by HIV, 2 strainsInfect CD4 cells: requires CD4 receptor and co-receptorImplications for treatment:Chemokines bind to coreceptor - may block entryDefective CD4 receptors prevent infection
44 More on AIDS High mutation rate Test is actually for HIV antibodies T cell count indicates disease progressionDrugs only slow the progression, are very expensive30-40 million (?) world wide cases70% in sub-saharan Africa