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IMMUNITY THE ABILITY TO RESIST DISEASE NONSPECIFIC VS SPECIFIC http://www.microbiologytext.com/ http://www.gsbs.utmb.edu/microbook /toc.htm NONSPECIFIC • • • • • PHYSICAL BARRIERS CHEMICAL BARRIERS CELLULAR BARRIERS INFLAMMATION FEVER SPECIFIC IMMUNITY • IMMUNE CELLS RECOGNIZE FOREIGN ANTIGENS • DIRECTLY OR INDIRECTLY ELIMINATE THEM ACQUIRED IMMUNITY NATURAL VS ARTIFICIAL ACTIVE VS PASSIVE NATURALLY ACQUIRED ACTIVE IMMUNITY • DUE TO ANTIGENIC STIMULUS FROM INFECTION • ANTIBODIES • SENSITIZED LYMPHOCYTES • SHORT TERM TO LONG TERM • MEMORY CELLS MADE NATURALLY ACQUIRED PASSIVE IMMUNITY • ANTIBODIES TRANSFERRED FROM MOTHER TO INFANT • ACROSS THE PLACENTA – Ig G – SHORT TERM IMMUNITY • IN THE CLOSTRUM AND MILK – IgA – AS LONG AS BABY IS NURSING • NO MEMORY CELLS ARE FORMED ARTIFICIALLY ACQUIRED ACTIVE IMMUNITY • VACCINATIONS/IMMUNIZATION – KILLED OR WEAKENED MICROBES – INACTIVATED TOXINS – COMPONENTS OF CAPSIDS, CAPSULES OR OTHER MICROBIAL COMPONENTS – VECTOR VACCINES • MEMORY CELLS ARE FORMED ARTIFICIALLY ACQUIRED PASSIVE IMMUNITY • TRANSFER OF ANTIBODIES FROM SOME OTHER ORGANISM • SHORT TERM IMMUNITY • NO MEMORY CELLS FORMED ANTIGENS • ANTIBODY GENERATING MOLECULES • IMMUNOGENS/ALLERGENS • SELF VS NONSELF • MARKERS ON CELLS, PROTEINS, VIRUSES AND ETC CHARACTERISTICS OF ANTIGENS • • • • • • LARGE COMPLEX PROTEINS NUCLEOPROTEINS POLYSACCHARIDES GLYCOLIPIDS ANTIGENIC DETERMINANT SITES • SITES ON ANTIGEN THAT CAUSE PRODUCTION OF ANTIBODY • MONOVALENT • MULTIVALENT • HETEROPHILE OR HETEROLOGOUS HAPTENS • • • • • SMALL ORGANIC MOLECULES NOT ANTIGENIC BY ITSELF MUST BIND TO CARRIER MOLECULE PENICILLIN NICKEL CELLS OF THE SPECIFIC IMMUNE RESPONSE LYMPHOCYTES LYMPHOCYTE FUNCTION B CELL B CELLS • MADE IMMUNOCOMPETENT IN FETAL LIVER AND BONE MARROW PLASMA CELLS • DERIVED FROM B CELLS • RESPOND TO ANTIGEN BY SECRETING ANTIBODIES • HUMORAL DEFENSE • DEFEND AGAINST BACTERIA, BACTERIAL TOXINS AND VIRUSES FOUND IN BODY TISSUES PLASMA CELL ANTIBODIES • GLYCOPROTEINS • GAMMA GLOBULIN PORTION OF SERUM • DIFFER IN MOLECULAR SIZE, STRUCTURE, CHARGE, AMINO ACID COMPOSITION AND CARBOHYDRATE COMPOSITION • FIVE CLASSES IMMUNOGLOBULINS • • • • • IgA IgD IgE IgG IgM CHARACTERISTICS OF ANTIBODIES • • • • • • • MOST ARE BIVALENT CRYSTALIZABLE FRAGMENT (Fc) ANTIBODY BINDING FRAGMENT (Fab) FOUR POLYPEPTIDE BONDS LIGHT AND HEAVY CHAINS HEAVY CHAINS DETERMINE CLASS FLEXIBLE HINGE REGION STRUCTURE OF ANTIBODY MOLECULE ANTIBODY SUBCLASSES • Ig A • Ig G FUNCTION OF IMMUNOGLOBULINS • • • • ALL ARE BIFUNCTIONAL Fab BINDS TO ANTIGEN Fc BINDS TO COMPLENT AND CELLS DOES NOT LEAD TO DIRECT DESTRUCTION • MARKS CELL FOR DESTRUCTION • ACTIVATES NONSPECIFIC RESPONSES IMMUNOGLOBULIN CLASSES IMMUNOGLOBULIN G • MAJOR Ig IN SERUM • 70-75 % OF IMMUNOGLOBULIN POOL • ACTS AGAINST BACTERIA AND VIRUSES • OPSONIZING AND NEUTRALIZING • ACTIVATES COMPLEMENT • CROSSES PLACENTA SUBCLASSES OF IgG • • • • • Ig1 Ig2 Ig3 Ig4 VARY IN COMPOSITION AND NUMBER AND ARRANGEMENT OF DISULFIDE BONDS IMMUNOGLOBULIN M • ABOUT 10 % OF IMMUNOGLOBULIN POOL • FOUND ONLY IN SERUM • MONOMERS, PENTAMERS, HEXAMERS • JOINING CHAINS • FIRST ANTIBODY PRODUCED • FOUND ON B CELL MEMBRANES FUNCTION OF IgM • FIRST ANTIBODY PRODUCED IN PRIMARY IMMUNE RESPONSE • AGGLUTINATES • ACTIVATES COMPLEMENT – BY CLASSICAL PATHWAY • OPSONIZES • MONOMERIC FORMS ARE FOUND ON SURFACE OF B LYMPHOCYTES – ACT AS RECEPTORS FOR ANTIGEN IMMUNOGLOBULIN A • 15 % OF POOL • MAINLY DIMER IN SERUM SECRETORY IgA • • • • • • • • SECRETORY IMMUNE SYSTEM SPECIAL SECRETORY COMPONENT GI TRACT RESPIRATORY TRACTS GENITOURINARY TRACT SALIVA TEARS SWEAT FUNCTION OF IgA • PROTECTS BODY SURFACES • IMMUNE EXCLUSION • BINDS TO TO ANTIGENS IN LAMINA PROPRIA • ACTIVATES COMPLEMENT BY ALTERNATIVE PATHWAY IMMUNOGLOBULIN D • • • • • TRACE AMOUNTS IN SERUM MAINLY FOUND ON B CELLS REGULATES IMMUNE SYSTEM MONOMER MAY PLAY ROLE IN ELIMINATING SELF-REACTIVE AUTOANTIBODIES IMMUNOGLOBULIN E • • • • LESS THAN 1% OF ANTIBODY SKIN SENSITIZING ANAPHYLACTIC BINDS TO MAST CELLS AND BASOPHILS • FIGHTS PARASITES ANTIBODY DIVERSITY • • • • REARRANGEMENT OF EXONS SOMATIC MUTATIONS POST TRANSCRIPTIONAL EDITING INDEPENDENT ASSORTMENT OF LIGHT AND HEAVY CHAINS ANTIBODY SPECIFICITY • INFINITE NUMBER OF ANTIBODIES POSSIBLE • BASED ON B CELL CLONES CLONAL SELECTION THEORY • SMALL SET OF CELLS THAT CAN RESPOND TO ANTIGEN • ALL ARE PRESENT IN FETUS • ANTIGEN SELECTS THE APPROPRIATE CLONE • EFFECTOR AND MEMORY CELLS ARE PRODUCED PRIMARY ANTIBODY RESPONSE • • • • • • INITIAL CHALLENGE LAG PHASE LOG PHASE PLATEAU PASTEUR PHASE LOW ANTIBODY AFFINITY SECONDARY IMMUNE RESPONSE • • • • • ANAMNESTIC RESPONSE PROVIDES IMMUNITY CLONES OF B OR T MEMORY CELLS SHORTER LOG PHASE HIGH ANTIBODY AFFINITY SPECIAL TYPES OF ANTIBODIES POLYCLONAL VS MONOCLONAL ANTIBODIES http://users.rcn.com/jkimball.ma.ultra net/BiologyPages/M/Monoclonals.ht ml IMMUNOTOXINS CHIMERIC MONOCLONAL ANTIBODIES • • • • • PART HUMAN --- PART MOUSE VARIABLE REGION—MOUSE CONSTANT REGION HUMAN 66% HUMAN LESS TOXIC HUMANIZED ANTIBODIES • THE ANTIGEN BINDING SITE IS THE ONLY PORTION OF THE ANTIBODY THAT CONTAINS MOUSE PROTEINS • 90% IS HUMAN FULLY HUMAN ANTIBODIES • TRANSGENIC MICE • GENETICALLY MODIFIED MICE CONTAIN HUMAN ANTIBODY GENES • WOULD PRODUCE FULLY HUMAN ANTIBODIES • MIGHT BE POSSIBLE TO PRODUCE THEM TO MATCH THE SPECIFIC PATIENT CATALYTIC ANTIBODIES • USED TO TRANSFORM SIMPLE COMPOUNDS – BLOOD CLOTS INHEART ANTIBODY FUNCTION • ACTIVATION OF COMPLEMENT • TOXIN NEUTRALIZATION • VIRAL NEUTRALIZATION • AHERANCE INHIBITION • PARASITIC INFECTIONS • ANTIBODY DEPENDENT CELL MEDIATED CYTOTOXITY • OPSONIZATION • REGULATING INFLAMMATION • IMMUNE COMPLEX FUNCTION OF COMPLEMENT • • • • • • MEDIATE INFLAMMATION CHEMOTAXIS PHAGOCYTE ACTIVATION CYTOLYSIS OPZONIZATION ACTIVATION OF OTHER IMMUNE CELLS COMPLEMENT ACTIVATION • COMPLEMENT MAKES UP A MAJOR PORTION OF SERUM ACTIVATORS OF THE ALTERNATE PATHWAY • MOLECULES WITH REPEATING CHEMICALS STRUCTURES • ENDOTOXINS • POLYSACCHARIDES • LIPOPOLYSACCHARIDES • TEICHOIC ACID • Ig A ACTIVATION BY THE CLASSICAL PATHWAY • • • • • Ig M IgG1 IgG2 IgG3 ANTIGEN ANTIBODY COMPLEXES COMPLEMENT IS A MAJOR REGULATOR OF THE INFLAMMATORY RESPONSE TOXIN NEUTRALIZATION • BLOCKS ABILITY OF TOXIN TO ENTER CELL OR ATTACH TO CELL RECEPTORS • ANTIBODIES ARE CALLED ANTITOXINS VIRAL NEUTRALIZATION • • • • IgG IgM IgA BIND TO VIRUSES IN EXTRACELLULAR FLUID AND INACTIVATE THEM • C4B AIDS IN THIS PROCESS ANTIBODIES THAT BLOCK ADHERANCE • SECRETORY Ig A • PROTECTS AGAINST PATHOGENS ON MUCOSAL SURFACES ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY • NATURAL KILLER CELLS • DESTROYS CELLS BY CYTOLYSIS OR BY CYTOTOXIC MEDIATORS ADDC DEATH BY APOPTOSIS APOPTOSIS ADDC CYTOLYSIS ANTIBODIES THAT FIGHT PARASITIC INFECTIONS • IgE • EOSINOPHILS ARE INVOLVED ALSO OPSONIZATION • COATING WITH ANTIBODIES • COATING WITH ANTIBODIES AND FIXED COMPLEMENT • INCREASES PHAGOCYTOSIS OR CAUSES EXTRACELLUAR DESTRUCTION IF TO BIG FOR PHAGOCYTOSIS • IgG1 • IgM OSPSONIZATION AND INTRACELLULAR DESTRUCTION OPSONIZATION AND EXTRACELLULAR DESTRUCTION ANTIBODIES AND THE INFLAMMATORY RESPONSE • MAY BE TRIGGERED BY SPECIFIC OR NONSPECIFIC IMMUNE SYSTEM • IgE ANTIBODIES ON MAST CELLS • C3a AND C5a OF THE COMPLEMENT SYSTEM IMMUNE COMPLEX FORMATION BY ANTIBODYANTIGEN • PRECIPITATION • AGGLUTINATION HEMAGGLUTINATION ANTIBODIES IN THE LAB SETTING • IN VIVO TESTING • IN VITRO TESTING IN VIVO TESTING • ALLERGY TESTING IMMEDIATE DELAYED (T-CELL) IMMEDIATE TESTING • WITHIN 20 MINUTES • USED FOR RESPIRATORY ALLERGIES DELAYED TESTING • CELL MEDIATED TESTING • FOOD ALLERGIES • CONTACT DERMATITIS • CANDIDA ALBICANS • TRICHOPHYTON • MUMPS • DIPTHERIA-TETANUS TOXOID • STREPTOKINASESTREPTODORNASE • TRICHOPHYTON • MUMPS • DIPTHERIA-TETANUS TOXOID • STREPTOKINASESTREPTODORNASE • TUBERCULIN ANTIGENS • HISTOPLASMA TUBERCULIN ANTIGENS T B TESTING POSITIVE TB TEST IN VITRO TESTING AGGLUTINATION • DIRECT AGGLUTINATION WIDAL TEST • LATEX AGGLUTINATION TEST HUMAN CHORIONIC GONADOTROPIN • HEMAGLUTINNATION • ANTIBODY TITER COMPLEMENT FIXATION • • • • • • WASSERMAN TEST VIRAL DISEASES FUNGAL DISEASES RICKETTSIAL DISEASES CHLAMYDIAL DISEASES PROTOZOAL DISEASES ELISA TESTS • ENZYME LINKED IMMUNOSORBENT ASSAY • LABELED ENZYMES LINKED TO ANTIGENS OR ANTIBODIES • HELIOBACTER PYLORI • SYPHILIS • BRUCELLOSIS SALMONELLOSIS • CHOLERA NEUTRALIZATION REACTIONS • DETERMINES WHETHER TOXINS OR VIRUSES HAVE BEEN INACTIVATED BY ANTIBODY • CLOTRIDIUM BOTULINUM • MANY VIRAL DISEASES B CELL BIOLOGY ANTIGEN SPECIFIC ---T DEPENDENT POLYCLONAL --- T INDEPENDENT T DEPENDENT ANTIGEN TRIGGERING • REQUIRES: ANTIGEN PRESENTING CELL HELPER T CELL B CELL • MAINLY PROTEINS AND HAPTENS B CELLS AND T CELLS ACTIVATE ONE ANOTHER ALL THE IMMUNE RESPONSES THAT PRODUCE IgA, IgE AND IgG ARE T DEPENDENT ANTIGEN TRIGGERED B CELL DIFFERENTIATION • AFFINITY MATURATION • CLASS SWITCHING • FORMATION OF PLASMA AND MEMORY CELLS AFFINITY MATURATION • DURING HUMORAL IMUNE RESPONSE AFFINITY OF THE ANTIBODIES TO ANTIGEN INCREASES 10010,000 TIME CLASS SWITCHING • ADDITIONAL REARRANGEMENT OF THEIR HEAVY CHAIN GENE SEGMENTS CAN OCCUR. • PRODUCES IgG, IgA AND IgE T INDEPENDENT ANTIGEN TRIGGERING • NOT ALL ANTIBODY RESPONSES REQUIRE T CELL HELP. • POLYMERIC • TUMOR PROMOTING AGENTS • ANTI-IMMUNOGLOBULIN (ANTI Ig) • BACTERIAL LIPOPOLYSACCHARIDES T INDEPENDENT ANTIGEN • • • • • T INDEPENDENT 1 T INDEPENDENT 2 GENERALLY WEAKER NO MEMORY CELLS FORMED IgM PRIMARY ANTIBODY T INDEPENDENT TYPE 1 • LIPOPOLYSACCHARIDE BACTERIAL CELL WALL COMPONENTS • MOST ARE MITOGENS--POLYCLONAL • CAN ACTIVATE UP TO ONE THIRD OF ALL B CELLS WHEN PRESENT AT HIGH LEVELS T INDEPENDENT TYPE 2 • POLYMERIC MOLECULES • BACTERIAL CELL WALL POLYSACHARIDES • POLYMERIC PROTEINS • DOES NOT REQUIRE DIRECT T HELPER CELL INVOLVEMENT • REQUIRES T HELPER CYTOKINES FOR CLASS SWITCHING DIFFERENCES BETWEEN T DEPENDENT AND T INDEPENDENT TRIGGERING T INDEPENDENT IS THE MAIN IMMUNE RESPONSE IN INFANTS UNTIL AGE TWO CHEMICAL MEDIATORS OF THE IMMUNE RESPONSE CYTOKINES • MEDIATE BOTH SPECIFIC AND NONSPECIFIC IMMUNE RESPONSE • GENERAL TERM • PRODUCTS OF ONE CELL POPULATION THAT AFFECTS ANOTHER TYPES OF CYTOKINES • • • • MONOKINES LYMPHOKINES INTERLEUKINS CHEMOKINES FUNCTIONS OF CYTOKINES • MEDIATE NONSPECIFIC IMMUNITY • ACTIVATE EFFECTOR CELLS • MEDIATE MATURE CELL ACTIVATION, DIFFERENTIATION, GROWTH AND BEHAVIOR • MEDIATE IMMATURE GROWTH AND DIFFERENTIATION CYTOKINE EFFECTS ON NONSPECIFIC IMMUNITY • INTERFERON ALPHA • INTERFERON BETA INTERFERON ALPHA • PRODUCED BY MACROPHAGES AND MONOCYTES • INDUCES THE ANTIVIRAL STATE • INCREASES EXPRESSION OF CLASS I MHC MARKERS ON MACROPHAGES • INCREASES EXPRESSION OF Fc RECEPTORS ON MACROPHAGES • ACTIVATES NATURAL KILLER CELLS INTERFERON BETA • PRODUCED BY FIBROBLASTS INDUCES ANTIVIRAL STATE • MODULATES ANTIBODY PRODUCTION • INDUCES DIFFERENTIATION OF FIBROBLASTS • STIMULATES EXPRESSION OF MHC MARKERS • ENHANCES SECRETION OF INTERLEUKIN 1 alpha AND TUMOR NECROSIS FACTOR BY MACROPHAGES INTERLEUKIN 1 • MEDIATES BOTH SPECIFIC AND NONSPECIFIC IMMUNITY • PRODUCED BY A VARIETY OF CELLS • STIMULATES T HELPER CELLS INPRESENCE OF ANTIGEN • ATTRACTS PHAGOCYTES IN INFLAMMATORY RESPONSE • STIMULATES HYPOTHALAMUS AND CAUSES FEVER – ENDOGENOUS PYROGEN CHEMOKINES • PARACRINE • LOW WEIGHT MOLECULES • MEDIATES INFLAMMATORY RESPONSE • INDUCES MIGRATION OF WHICHT BLOOD CELLS INTO INFECTED OR DAMAGED AREAS TUMOR NECROSIS FACTOR ALPHA • ONE OF THE MAJOR CYTOKINES THAT MEDIATES THE HOST RESPONSE TO GRAM NEGATIVE BACTERIA • RELEASED BY MONONUCLEAR PHAGOCYTES – DUE TO STIMULATION OF LIPOPOLYSACCHARIDE ACTIONS OF TUMOR NECROSIS FACTOR ALPHA • STIMULATES AN INCREASE IN B CELLS • INITIATES LEUKOCYTE ADHERANCE TO VASCULAR ENDOTHELIUM • STIMULATES OTHER MONONUCLEAR PHAGOCYTES TO SECRETE INTERLEUKINS 1, 6 OR 8 • STIMULATES THE HYPOTHALMUS TO INDUCE FEVER – ACTS AS AN ENDOGENOUS PYROGEN • IS CYTOTOXIC TO TUMOR CELLS TUMOR NECROSIS CHEMOKINES AND INTERLEUKIN 1 ROLE IN EXTRAVASATION INTERFERON GAMMA • PRODUCED BY – T HELPER CELLS, CYTOTOXIC CELLS AND NATURAL KILLER CELLS • AMPLIFIES ACTIVATION OF T HELPER CELLS • INCREASES THE EXPRESSION OF MHC MOLECULES • PROMOTES DIFFERENTIATION OF BOTH T AND B CELLS • REGULATES THE RELEASE OF Ig FROM CELLS • PROMOTES MATURATION OF CYTOTOXIC T CELLS • INDUCES ANTIVIRAL STATE • ACTIVATES MACROPHAGES, NEUTROPHILS AND NATURAL KILLER CELLS MIGRATION INHIBITION FACTOR • • • • PRODUCED BY MACROPHAGES ACTIVATES MACROPHAGES PREVENTS MIGRATION FROM SITE SECRETION INDUCED BY TUMOR NECROSIS FACTOR, LIPOPOLYSACCHARIDES AND OTHER FACTORS INTERLEUKIN 2 • PRODUCED BY HELPER T CELLS – FOR SHORT PERIOD AFTER ACTIVATION BY ANTIGEN • MEDIATES THE ACTIVATION, GROWTH AND DIFFERENTIATION OF MATURE LYMPHOCYTES • TRIGGERS THE POLIFERATION OF T HELPER AND CYTOTOXIC T CELLS • CAN INDUCE THE SYNTHESIS OF INTERFERON – INDIRECTLY ACTIVATES NATURAL KILLER CELLS • STIMULATES THE GROWTH OF CERTAIN B CELLS • HAS BEEN USED AGAINST CERTAIN CANCERS – RENAL CELL CARCINOMA – MALIGNANT MELANOMA INTERLEUKIN 3 • COLONY STIMULATING FACTOR • STIMULATES PROLIFERATION OF STEM CELLS IN BONE MARROW • INFLUENCES DIFFERENTIATION OF BONE MARROW CELLS – MAST CELLS, MACROPHAGES AND GRANULOCYTES INTERLEUKIN 8 • CHEMOATTRACTANT FOR PHAGOCYTES AND OTHER IMMUNE CELLS TO SITE OF INFLAMMATION • ALSO CALLED NEUTROPHIL ACTIVATING FACTOR • SECRETED BY A VARIETY OF CELLS • CONSIDERED A CHEMOKINE • PRIMARILY MEDIATE THE ACTIVATION AND MIGRATION OF NEUTROPHILS INTO THE TISSUES FROM BLOOD STREAM INTERLEUKIN 10 • SECRETED BY T HELPER 2 CELLS AND T REGULATOR CELLS • INTERFERS WITH THE ACTIVATION OF T HELPER 1 CELLS • INHIBITS CYTOKINE PRODUCTIN BY MACROPHAGES • MAINLY PLAYS AN ANTIINFLAMMATOR ROLE INTERLEUKIN 12 • INVOLVED IN THE DIFFERENTIATION OF T HELPER CELLS – T HELPER 1 REPONSE • ENHANCES CYTOTOXIC ACTIVITY OF NATURAL KILLER CELLS AND CYTOTOXIC T LYMPHOCYTES • BLOCKS THE FORMATION OF NEW BLOOD VESSELS BY INDUCING THE PRODUCTION OF INTERFERON GAMMA T CELL BIOLOGY RESPOND TO MHC MARKERS MHC MOLECULES • FOUND ON ALL NUCLEATED CELLS • ALSO CALLED HUMAN LEUKOCYTE ANTIGENS (HLAs) • CLASS I • CLASS II • CLASS III – ASSOCIATED WITH COMPLEMENT SYSTEM CLASS I & II MHC STRUCTURE • TWO PROTEIN CHAIN • GROOVE INTO WHICH PEPTIDE MOLECULES CAN BE INSERTED – WHICH MAY OF MAY NOT CAUSE A IMMUNE RESPONSE SOURCES OF MHC CLASS I & II ANTIGEN PROCESSING ENDOGENOUS VS EXOGENOUS CLASS I MHC MOLECULES • ENDOGENOUS ANTIGENS • PEPTIDES THAT ORIGINATE IN THE CYTOSOL • PEPTIDES AND MHC CLASS I COMBINE • CARRIED TO PLASMA MEMBRANE • DISPLAYED TO PASSING CD 8+ CELLS CELLS ARE CONSTANTLY TAKING INVENTORY OF ITS CELLULAR PRODUCTS • PROTEOSOMES CHOP OF VARIOUS PROTEINS IN CELL INTO PEPTIDE EPITOPES – SERIES OF PEPTIDES – APPROIMATELY 8-10 AMINO ACIDS LONG EXAMPLES OF ENDOGENOUS ANTIGENS • PRODUCED WITHIN CELLS OF THE BODY. – VIRAL PROTEINS PRODUCED DURING VIRAL REPLICATION – PROTEINS PRODUCED BY INTRACELLULAR BACTERIA SUCH AS RICKETTSIAS AND CHLAMYDIAS DURING THEIR REPLICATION – PROTEINS THAT HAVE ESCAPED INTO THE CYTOSOL FROM THE PHAGOSOME OF PHAGOCYTES SUCH AS ANTIGEN-PRESENTING CELLS – TUMOR ANTIGENS PRODUCED BY CANCER CELLS – SELF PEPTIDES FROM HUMAN CELL PROTEINS. PROTEINS THAT HAVE ESCAPED INTO THE CYTOSOL FROM THE PHAGOSOME OF PHAGOCYTES SUCH AS ANTIGENPRESENTING CELLS CLASS II MHC MOLECULES • EXOGENOUS ANTIGEN • BROUGHT INTO ANTIGEN PRESENTING CELL BY ENDOCYTOSIS • DIGEST IN PHAGOLYSOSOME • FRAGMENTS COMBINE WITH PREFORMED MHC CLASS II • DISPLAYED ON PLASMA MEMBRANE • RECOGNIZED BY CD4 + CELLS FORMATION OF MHC CLASS II • EXAMPLES – – – – – BACTERIA FREE VIRUSSE YEASTS PROTOZOA TOINS CLASSES OF MHC MOLECULES • • • • A, B, C, AND D CLASS I--A, B AND C CLASS II-- D GROUP MHC MOLECULES ARE ALSO INVOLVED IN SUSCEPTIBILITY T PARTICULAR INFECTIOUS AND NONINFECTIOUS DISEASES T CELLS • SECRETE CYTOKINES • ATTACK VIRUS INFECTED CELLS • ATTACK HOST CELLS WITH INTRACELLULAR PARASITES • ATTACK CANCER CELLS • CELL MEDIATED IMMUNITY T CELLS • MADE IMMUNOCOMPETENT IN FETAL THYMUS • FOUND IN BLOOD AND LYMPH SYSTEM TYPES OF T CELLS T HELPER, CTYOTOXIC T CELLS AND REGULATOR CD 4 T HELPER CELLS • DO NOT DIRECTLY KILL THE CELL • CAN ENLARGE AND DIVIDE – INCREASES NUMBER OF T4 CELLS • CAN SECRETE CYTOKINES – INHIBITS PATHOGEN – RECRUIT OTHER CELLS • T HELPER 1, T HELPER 2 AND T HELPER 0 T HELPER CELLS • Th 1 – RECOGNIZE ANTIGEN PRESENTED BY MACROPHAGES – INITIATE CELL MEDIATED IMMUNITY – PRODUCE IL-2, INTERFERON GAMMA, LYMPHOTOXIN, AND TUMOR NECOSIS FACTOR BETA • PROLIFERATION OF T 8 LYMPHOCYTES • DIFFERENTIATION INTO CYTOTOXIC T LYMPHOCYTES • ACTIVATION OF CYTOTOXIC T LYMPHOCYTES • ACTIVATION OF NATURAL KILLER CELLS • PROLIFERATION OF T 4 LYMPHOCYTES T HELPER CELLS • T HELPER 2 • RESPOND TO ANTIGENS PRESENTED BY B LYMPHOCYTES (AS ANTIGEN PRESENTING CELLS) • PRODUCE INTERLEUKINS 2, 4, 5, 10 AND 13 – – – – – STIMULATE ANTIBODY PRODUCTION STIMULATE DIFFERENTIATION INTO PLASMA CELLS ENABLE CLASS SWITCHING ACTIVATE EOSINOPHILS AND INCREASE IgE • TO FIGHT HELMINTHS AND ARTHROPODS T HELPER CELLS • BALANCE BETWEEN T HELPER 1 AND T HELPER 2 PLAYS A ROLE IN HOW WELL THE CELL FIGHTS CERTAIN INFECTIONS T REGULATOR CELLS • FORMERLY KNOWN AS SUPPRESSOR T CELLS • MAY OR MAY NOT EXIST • THEIR FUNCTION IS TO SUPRESS THE ACTIVITY OF OTHER T CELLS ACTIVATION OF T HELPER CELLS • NEED ANTIGEN PRESENTING CELLS DISPLAYING TYPE II MHC MARKERS • T HELPER CELLS ARE CLASS II RESTRICTED – ONLY INTERACT WITH CELLS PRESENTING CLASS MHC II MOLECULES • B CELLS, DENDRITIC CELLS, AND MACROPHAGES ANIMATION OF T 4 HELPER CELLS ACTIVATION ANIMATION OF THE EFFECTS OF INTERLEUKIN 2 ACTIVATION OF CYTOTOXIC T CELLS • NEED ANTIGEN PRESENTING CELLS DISPLAYING TYPE I MHC MARKERS – CD8 CYTOTOXIC CELLS ARE CLASS I RESTRICTED • ONLY RESPOND TO CLASS I MHC MARKERS ANIMATION OF CD8 CYTOTOXIC T CELL ACTIVATION • COMBINATION OF T CELL RECEPTOR AND CD8 MARKERS WITH MHC CLASS I MARKERS ON MACROPHAGE ACTIVATE CYTOTOXIC T CELL AND LEADS TO ITS DIFFERENTIATION INTO A CYTOTOXIC T LYMPHOCYTE EFFECTS OF INTERLEUKIN 2 SECRETED BY HELPER T CELLS ON ACTIVATED CYTOTOXIC T CELLS • ONCE ACTIVATED SIGNALS AND CYTOKINES FROM T HELPER 1 CELLS WILL LEAD TO PROLIFERATION OF CD8 CELLS AND THEIR DIFFERENTIATION INTO CYTOTOXIC T LYMPHOCYTES • CYTOTOXIC T CELLS DO NOT DISPLAY INTERLEUKIN 2 RECEPTORS UNTIL THEY ARE ACTIVATED – ONLY CYTOTOXIC T LYMPHOCYTES CAN KILL OTHER CELLS • NIAVE CYTOTOXIC T CELLS CANNOT ANIMATION OF ACTIVATED CYTOXIC T CELL PROLIFERATION ANIMATION OF DIFFERENTIATION INTO CYTOTOXIC T LYMPHOCYTES CYTOTOXIC T LYMPHOCYTES THEN TRAVEL THROUGHOUT THE BODY BINDING TO INFECTED CELLS • THEY ONLY BIND TO THOSE CELLS THAT DISPLAY A MHC CLASS I MARKER WITH THE SAME ANTIGEN THEY ARE SPECIFIC FOR • THEY BIND TO THE MHC CLASS I MARKER AND RELEASE PERFORIN, GRANZYMES AND CHEMOKINES THAT TRIGGER EITHER LYSIS OR APOPTOSIS APOPTOSIS OTHER ACTIVITIES OF T HELPER CELLS T HELPER 1 CELLS ALSO ACTIVATE MACROPHAGES • BINDING OF MACROPHAGE TO T HELPER 1 CAUSES SECRETION INTERFERON GAMMA BY T HELPER 1 CELLS • INTERFERON BINDS TO RECEPTORS ON MACROPHAGE • INTERFERON GAMMA ACTIVATES MACROPHAGE – PRODUCES MORE HYDROLYTIC ENZYMES IN LYSOSOME – PRODUCES MORE NITIC OXID – PRODUCES MORE TOXIC OXYGEN RADICALS T HELPER CELLS ALSO ACTIVATE NATURAL KILLER CELLS • IL-2 AND IFN GAMMA PRODUCED BY T helper 1 CELLS ACTIVATE NATURAL KILLER CELLS AQUIRED IMMUNE TOLERANCE • TOLERANCE INDUCTION • BODY’S ABILITY TO MAKE ANTIBODIES AGAINST NONSELF ANTIGENS WHILE TOLERATING SELF ANTIGENS • ESTABLISHED EARLY IN EMBRYONIC LIFE NULL CELLS • LACK SPECIFIC SURFACE MARKERS • NATURAL KILLER CELLS • PART OF NOSPECIFIC IMMMITY NATURAL KILLER CELLS • • • • • • SMALL POPULATION NONSPECIFIC NULL CELLS DESTROY TUMORS VIRUS INFECTE CELLS FUNGI, BACTERI, PROTOZOA, AND HELMINTHS • IMMUNE SURVEILLANCE HOW NATURAL KILLER CELLS WORK • ACTIVATED BY INTERFERONS AND INTERLEUKIN 2 • CALCIUM DEPENDENT SEQUENCE • INSERT PERFORIN 1 INTO TARGET • RELEASE LYSOSOMAL SECRETIONS – CAUSES LYSIS OR APOPTOSIS INTERACTION OF A NATURAL KILLER CELL WITH A NORMAL BODY CELL INTERACTION OF A NATURAL KILLER CELL WITH A CELL NOT DISPLAYING MHC CLASS I MARKERS APOPTOSIS • PROGRAMED CELLULAR DEATH NATURAL KILLER CELLS INTERACTIONS ARE PART OF NONSPECIFIC IMMUNITY SUPERANTIGENS • BACTERIAL PROTEINS • STIMULATE IMMUNES SYSTEM MORE EXTENSIVELY • NONSPECIFICALLY STIMULATE T CELLS • INDUCE MASSIVE CYTOKINE PRODUCTION HYPERSENSITIVITIES • • • • ALLERGIES EXAGGERATED IMMUNE RESPONSE IMMEDIATE OR DELAYED MAIN DIFFERENCE IN HOW IMMUNE SYSTEM RESPONDS TYPE I ANAPHYLACTIC HYPERSENSITIVITY • IgE ANTIBODY • MAY BE HEREDITARY DISPOSITION • IgE BINDS TO BASOPHIL AND MAST CELLS • T DEPENDENT IMMUNITY • SUBSEQUENT EXPOSURE WILL CAUSE MAST CELLS AND BASOPHILS TO DEGRANULATE SYSTEMIC ANAPHYLAXIS • LARGE MAST CELL DEGRANULATION IN SHORT TIME • SMOOTH MUSCLE CONSTRICTION IN BRONCHIOLES • ARTERIOLE DILATION • INCREASED VASCULAR PERMEABILITY CAUSE OF DEATH • • • • REDUCED VENOUS RETURN REDUCED BLOOD PRESSURE CIRCULATORY SHOCK ASPHYXIATION POSSIBLE CAUSES • DRUGS • ANTISERA • INSECT VENOM LOCALIZED ANAPHYLAXIS • • • • ATOPIC ALLERGIC RHINITIS BRONCHIAL ASTHMA FOOD ALLERGIES PREVENTING TYPE I RESPONSES • REPLACE IgE RESPONSE WITH IgG RESPONSE • SERIES OF ALLERGEN SHOTES • EFFECTIVE ABOUT 65 TO 75% WITH INHALED ALLERGENS TYPE II CYTOTOXIC HYPERSENSITIVITIES • DESTRUCTION OF HOST CELLS • LYSIS OR TOXIC MEDIATORS • ANTIBODY MEDIATED CELLMEDIATED CYTOTOXICITY • IgG OR IgM • DIRECTED AGAINST TISSUES OR CELL SURFACES • INTERACT WITH COMPLEMENT EXAMPLES • BLOOD TRANSFUSIONS WITH WRONG BLOOD TYPE (ABO) • HEMOLYTIC DISEASE OF THE NEWBORN • DRUG INDUCED HEMOLYTIC ANEMIA DRUGS THAT CAN INTIATE A TYPE II HYPERSENSITIVITY • PENICILLIN • QUINIDINE • METHYLDOPA TYPE III IMMUNE COMPLEX HYPERSENSITIVITY • FORMATION OF IMMUNE COMPLEXES • NORMALLY REMOVED BY RETICULOENDOTHELIAL SYSTEM • EXCESS MAY ACCUMULATE • ACTIVATES COMPLEMENT EXAMPLES OF TYPE III HYPERSENSITIVITIES • SERUM SICKNESS • DRUG REACTIONS • POSTSTREPTOCOCCAL GLOMERULONEPHRITIS • SYSTEMIC LUPUS ERYTHEMATOSUS • RHEUMATOID ARTHRITIS • GOODPASTURE’S SYNDROME • FARMERS LUNG ASPERGILLOSIS GLOMERULAR NEPHRITIS TYPE IV CELL MEDIATED HYPERSENSITIVITY • • • • T CELL MEDIATED USUALLY TAKES DAYS TO OCCUR MEDIATED BY CYTOKINES CAUSES EXTENSIVE TISSUE DAMAGE EXAMPLES OF TYPE IV • INTRACELLULAR PARASITE MYCOBACTERIUM • TB TEST • SOME AUTOIMMUNE DISEASE • CONTACT DERMATITIS • KILLING OF CANCER CELLS • TRANSPLANT REJECTION AUTOIMMUNE DISORDERS • FAILURE TO RECOGNIZE SELF ANTIGENS AUTOIMMUNITY VS AUTOIMMUNE DISORDER FACTORS THAT AFFECT AUTOIMMUNE DISORDERS • • • • VIRUSES GENETICS ENDOCRINE SYSTEM PSYCHONEUROIMMUNOLOGICAL MORE COMMON IN OLDER PEOPLE TRANSPLANT REJECTION • ISOGRAFTS • ALLOGRAFTS • XENOGRAFTS MECHANISMS OF TISSUE REJECTION • T CELL IMMUNITY IS ACTIVATED • CYTOTOXIC T CELLS KILL TISSUES • T HELPER CELLS RELEASE CYTOKINES • NATURAL KILLER CELLS ALSO INVOLVED IMPORTANCE OF MHC MARKERS • CLASS I MHC MARKERS • 77 MHC MOLECULES CODED FOR BY FOUR GENES • ATTEMPT TO MAKE AS CLOSE A MATCH AS POSSIBLE CYCLOSPORIN. TACROLIMUS AND OTHER DRUGS GIVEN TO SUPPRESS T CELL IMMUNITY IMMUNODEFICIENCIES PRIMARY/CONGENITAL VS SECONDARY/ACQUIRED PRIMARY/CONGENITAL IMMUNODEFICIENCY • CHRONIC GRANULOMATUS DISEASE • COMMON VARIABLE HYPOGAMMOGLOBULEREMIA • DI GEORGE’S SYNDROME • SEVERE COMBINE IMMUNODEFICIENCY DISEASE CHRONIC GRANULOMATOSUS DISEASE • RECURRENT INFECTIONS • DEVELOPMENT OF INFLAMMATORY CELLS – IN LYMPH NODES, LUNGS, BONES AND SKIN • INHERITED LACK OF NADPH OXIDASE IN NEUTROPHILS – THEY ARE UNABLE TO KILL INGESTED MICROBES Di GEORGE’S SYNDROME • THYMUS FAILS TO DEVELOP • NO T CELL IMMUNITY – CELL MEDIATED – T DEPENDENT HUMORAL IMMUNITY • GENERALLY DIE OF VIRAL INFECTION BRUTON-TYPE AGAMMAGLOBULEMAI • INHERITED DEFECT USUALLY INHERITED BY BOYS • CANNOT MAKE ANTIBODIES • SUFFER RECURRENT BACTERIAL INFECTIONS • DO HAVE CELL MEDIATED IMMUNITY • IMMUNOGLOBULIN DEFICIENCIES USUALLY OCCUR IN ONLY ONE Ig CLASS – IgA IS MOST COMMON SEVERE COMBINED IMMUNODEFICIENCY DISEASE • SCIDs • NEITHER B OR T CELLS ARE PRODUCED • BOY IN THE BUBBLE SECONDARY IMMUNODEFICIENCIES • • • • • • • ACQUIRED AFTER BIRTH CANCER STRESS DIABETES MALNUTRITION CERTAIN ENVIRONMENTAL TOXINS HIV