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DESCRIBE THE 3 PHASES OF HOST DEFENCE
INNATE IMMUNITY (IMMEDIATE: 0-4 HRS). INVOLVES COMPLEMENT
EARLY INDUCED (EARLY: 4HRS TO 4DAYS). INVOLVES PHAGOCYTOSIS
ADAPTIVE (LATE: 4+ DAYS). INVOLVES T & B CELLS AND CLONAL EXPANSION
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HERPES SIMPLEX
INNATE IMMEDIATE PHASE
LATENCY (HIDING)
INVADE SENSORY NEURONS WHICH EXPRESS RELATIVELEY LOW LEVELS OF MHC, THUS AVOID CTLs
OTHER HIDING PATHOGEN IS HIV
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HIV
IMMEDIATE INNATE PHASE
HIDING
INSERT INTO HOST DNA (PRIMARILY T LYMPHS AND MACROPHAGES)
OTHER HIDING PATHOGEN IS HERPES SIMPLEX
ALSO DECREASES MHC I AND B-2 MICROGLOBULIN TRANSCRIPTION
BLOCKS TAP AND INCREASES MHC I TURNOVER THROUGH ENDOCYTOSIS
LITTLE IMPACT ON HLA-C&E FOR PROTECTION AGAINST NK CELLS
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LIPOPOLYSACCARIDE (LPS) AND LIPOTEICHOIC ACID (LTA)
2 POTENT COMPLEMENT ACTIVATORS
GRAM-NEGATIVE LPS AND GRAM POSITIVE LTA
BACTERIA HAVE EVOLVED SEVERAL MECHANISMS FOR AVOIDING ACTIVATION OF COMPLEMENT BY LPS AND LTA
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SALMONELLA AND E. COLI
IMMEDIATE INNATE PHASE
BLOCK COMPLEMENT (C3b)
O-ANTIGENS COMPOSED OF LONG CHAIN POLYSACCHARIDES CREATING A THICK WALL OF "SMOOTH STRAINS"
NEISSERIA GONORRHEAE AND STREP PYROGENES ALSO BLOCK COMPLEMENT
DOWNSIDE IS LONG POLYSACCHARIDE CHAINS ARE HIGHLY IMMUNOGENIC
SALMONELLA ALSO RESISTANT TO LYSOSOMAL DAMAGE (EARLY INDUCIBLE PHASE) PhoQ-PhoP
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NEISSERIA GONORRHEAE (IMMEDIATE INNATE)
IMMEDIATE INNATE PHASE
BLOCK COMPLEMENT
SIALIC ACID IS ASSOCIATED WITH OLIGOSACCHARIDES OF HOST AND INHIBITS COMPLEMENT
N. GONORRHEAE ATTACHES SIALIC ACID TO LPS (NOW LIPOOLIGOSACCARIDE (LOS))
SALMONELLA, E. COLI, AND STREP PYROGENES ALSO BLOCK COMPLEMENT
N. GONORRHEA ALSO SHOWS ANTIGENIC DIVERSITY IN LATE PHASE
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STREP PYROGENES (IMMEDIATE)
BLOCKS COMPLEMENT AND PHAGOCYTOSIS
PROTEIN M BINDS HOST FACTOR H WHICH DESTROYS C3b
C3b INVOLVED IN OPSONIZATION AND ALSO PART OF C5 CONVERTASE THAT FORMS MAC
SALMONELLA, E. COLI, AND N. GONORRHEAE ALSO BLOCK COMPLEMENT
PHAGO CHEMOTAXIS IN EARLY INDUCED PHASE
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HOST REGULATORS OF COMPLEMENT (6)
FACTOR H: COENZYME ALONG WITH FACTOR I THAT INHIBITS C3b BY ACTIVATING ENZYME THAT CLEAVES. ALSO INACTIVATES ALTERNATE PATHWAY BY DISSOCIATING Bb FROM THE C3bBb COMPLEX
C4bBb: COFACTOR IN CLEAVAGE OF C4b BY FACTOR I, INHIBITING FROM INTERACTING WITH C2a IN FORMING C3 CONVERTASE
COMLEMENT RECEPTOR TYPE 1 (CR1) AND MEMBRANE COFACTOR PROTEIN (MCP): BOTH COFACTORS FOR FACTOR I CLEAVAGE OF C4b AND C3b
DECAY ACCELERATING FACTOR (DAF): BINDS C3 CONVERTASE IN BOTH CLASSICAL AND ALT PATHWAYS CAUSING DISASSOCIATION OF CONVERTASE COMPLEX
CD59: INVIBITS MAC FORMATION BY INTERFERING WITH DEPOSITION OF C9 MOLECULES
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STAPH. AUREUS (BARRIER)
EARLY INDUCIBLE
PROTECTIVE BARRIER
GENERATES WALL OF FIBRIN THAT STOPS LEUKOCYTES. PRODUCES COAGULASE WHICH ACTIVATES PROTHROMBIN --> THROMBIN --> FIBRINOGEN --> FIBRIN
PRODUCES STAPHYLOKINASE WHICH DIGESTS FIBRIN SO STAPH AUREUS CAN ESCAPE
STREP PNEUMONIAE ALSO MAKES BARRIER
STAPH AUREUSCAN CAN RESIST LYSOSOMAL DAMAGE IN EARLY INDICIBLE PHASE AND MISDIRECT IMMUNE RESPONSE AND INTERFERE IN Ab FUNCTION IN LATE PHASE
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STREP PNEUMONIAE (EARLY INDUCIBLE)
EARLY INDUCED PHASE
PROTECTIVE BARRIER
CAN MAKE 90 DIFFERENT POLYSACCHARIDES THAT MAKE THICK SLIMY WALL "CAPSULE" THAT INHIBITS PHAGOCYTOSIS
POLYSACCHARIDES ARE IMMUNOGENIC AND WILL EVENTUALLY STIMULATE OPSONINS
BASIS OF RECENTLY DEVELOPED PNEUM VACCINES
STAPH AUREUS ALSO MAKE BARRIERS
STREP PNEUM ALSO SHOWS ANTIGEN DIVERSITY IN LATE PHASE
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STREP PYOGENES (EARLY INDUCED)
PHAGOCYTE CHEMOTAXIS
PRODUCES C5a PEPTIDASE THAT CLEAVES POTENT LEUKOCYTE CHEMOATTRACTANT C5a
C5a AND C3a ARE ANAPHYLOTOXINS WHICH ATTRACT LEUKOCYTES AND INCREASE VASCULAR PERMEABILITY
INHIBITS COMPLEMENT IN IMMEDIATE INNATE PHASE
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PANTON-VALENTINE LEUKOCIDIN (PVL) IN STAPH AUREUS
EARLY INDUCIBLE PHASE
KILLING PHAGOCYTES
PVL IS PORE-FORMING CYTOTOXIN ASSOCIATED WITH INCREASED VIRULENCE
PRESENT IN MAJORITY OF COMMUNITY-ASSOCIATED MRSA (CA-MRSA)
YERSINIA PESTIS ALSO PHAGOCYTE KILLER
STAPH AUREUS ALSO USES PROTECTIVE BARRIER IN EARLY INDUCIBLE STAGE
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YERSINIA PESTIS
EARLY INDUCIBLE PHASE
KILLING PHAGOCYTES
YERSINIA OUTER PROTEINS (YOPs) B/D FORMS PORES IN CELL MEMBRANES OF HOST MACROPHAGES AND LINKED TO CELL LYSIS
YOP J INJECTED INTO CYTOPLASM OF HOST CELLS VIA TYPE III (NEEDLE) SECRETION SYSTEM. YOP J INTERFERES WITH SIGNALING PATHWAYS REQUIRED FOR VARIOUS PHAGOCYTIC ACTIVITIES, ACTIVATION OF CYTOKINE GENES, AND CAN TRIGGER APOPTOSIS
PVL IN STAPH AUREUS ALSO A PHAGOCYTE KILLER
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LEGIONELLA PNEUMOPHILIA
EARLY INDUCIBLE PHASE
INHIBITS PHAGO/LYSOSOME FUSION
CREATES ABNORMAL ENDOSOME IN ALVEOLAR MACROPHAGES
ERROR IN SIGNALING BETWEEN C3 ON BACTERIAL SURFACE BINDS AND RECEPTORS CR1 AND CR3 ON PHAG CELL CAUSES ABNORMAL COILING OF PSEUDOPOD AROUND BACTERIUM
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MYCOBACTERIUM TUBERCULOSIS
EARLY INDUCIBLE PHASE
RESISTANCE TO LYSOSOMAL DAMAGE - HYDROPHOBIC SHIELD
SOME INHIBITION OF PHAGO/LYSOSOMAL FUSION
THICK WAXY HYDROPHOBIC CELL WALL COMPONENTS, MAINLY MYCOLIC ACIDS, PREVENT DEGRADATION
CAN FORM GRANULOMAS
BACILLUS ANTHRACIS, SALMONELLA, AND STAPH AUREUS ALSO HAVE RESISTANCE
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BACILLUS ANTHRACIS
EARLY INDUCIBLE PHASE
RESISTANCE TO LYSOSOMAL DAMAGE
UNNATURAL ISOMERIC D-CONFIGURATION OF POLY D-GLUTAMATE CAPSULE NOT RECOGNIZED BY CONVENTIONAL PROTEASES OF THE LYSOSOMES
MYCO TUBERCULOSIS, SALMONELLA, AND STAPH AUREUS ALSO RESIST LYSOSOMAL DAMAGE
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SALMONELLA (EARLY INDECIBLE PHASE)
RESISTANCE TO LYSOSOMAL DAMAGE - ALTERED SUSEPTIBILITY TO ANTI MICROBIAL PEPTIDES
GENETIC SENSING SYSTEM PhoP-PhoQ REGULON
PhoQ SENSES PHAGO/LYSO FUSION BY PRESENCE OF CATIONIC ANTI-MICROBIAL PEPTIDES (DEFENSINS) AND DROP IN Mg++. CATIONIC ANTI-MICROBIAL PEPTIDES BIND IONICALLY TO NEGATIVE PHOS GROUPS OF LPSs RESULTING IN PORE FORMATION ON BACTERIA
PhoP TRANSCRIPTIONAL ACTIVATOR FOR MULTIPLE GENES (30+) THAT INTERFERE WITH VARIOUS DESTRUCTIVE PROCESSES IN PHAGOCYTES, INCLUDING THE CHANGE OF LPSs THAT PREVENT IT FROM BEING TARGETED BY ANTI-MICROBIAL PEPTIDES, REDUCED CYTOKINE RESPONSES, AND DECREASED ANTIGEN PRESENTATION.
MYCO TUBERCULOSIS, BACILLUS ANTHRACIS, AND STAPH AUREUS ALSO HAVE RESISTANCE TO LYSOSOMAL DAMAGE
SALMONELLA ALSO INHIBITS COMPLEMENT PATHWAY (IMMEDIATE INNATE PHASE)
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STAPH AUREUS (LYSOSOMAL RESISTANCE)
EARLY INDUCIBLE PHASE
RESISTANCE TO LYSOSOMAL DAMAGE - INHIBITION OF O2 DEPENDENT KILLING
CATALASE BREAKS DOWN RESPIRATORY BURST PRODUCT, H2O2, INTO WATER AND OXYGEN
MYCO TUBERCULOSIS, BACILLUS ANTHRACIS, AND SALMONELLA ALSO RESISTANT TO LYSOSOMAL DAMAGE
STAPH AUREUS ALSO HAS PROTECTIVE BARRIER IN EARLY INDUCIBLE PHASE AND CAN MISDIRECT IMMUNE RESPONSES AND INTERFERE WITH Ab FUNCTION IN LATE PHASE
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LISTERIA MONOCYTOGENES
EARLY INDUCIBLE PHASE
ESCAPE FROM LYSOSOME
PORE-FORMING HEMOLYSIN (LISTERIOLYSIN O) AND 2 FORMS OF PHOSPHOLIPASE C
ONCE LYSED FROM LYSOSOME, INTERACTS WITH HOST ACTIN CYTOSKELETAL SYSTEM USING ACTIN-BASED MOTILITY AND ESCAPES INTO ADJACENT CELLS
INDUCES OWN MOVEMENT THROUGH ACTIN POLYMERIZATION WHICH PROTECTS FROM Ab AND EXTRACELLULAR ENVIRONMENT
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STAPH AUREUS (IMMUNE RESPONSE)
LATE PHASE
MISDIRECTING IMMUNE RESPONSE - DEPLETION OF ANTIGEN-SPECIFIC T CELLS
PRODUCES SUPERANTIGENS THAT ACTIVATE LARGE # OF T CELLS WITH PRO-INFLAMMATORY CAPABILITIES (TH1 & TH17). ALSO IL-2, IFN-g, IL-1, AND TNF-a
RESPONSES ARE POLYCLONAL AND INVOLVE 20-40% OF ALL CD4+ T CELLS LEADING TO TOXIC SHOCK SYNDROME
MAY DRIVE T CELL ARM OF IMMUNE RESPONSE TO PARALYSIS (DEPLETION)
MYCO LEPRAE ALSO MISDIRECTS IMMUNE RESPONSES
STAPH AUREUS HAS PROTECTIVE BARRIER AND RESISTANCE TO LYSOSOMAL DAMAGE (EARLY INDUCIBLE)
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MYCOBACTERIUM LEPRAE
LATE PHASE
MISDIRECTING IMMUNE RESPONSE - SKEWING TH1 TH2 BALANCE
2 FORMS: LEPROMATOUS LEPROSY ASSOCIATED WITH FULMINATE SYSTEMIC SPREAD FO PATHOGEN. HIGH TH2 BUT NO TH1, ABSENCE OF CELL-MEDIATED IMMUNITY WHICH IS NEEDED.
TUBERCULOID LEPROSY ASSOCIATED WITH RESTRICTED SPREAD AND PROMINEMT CELL-MEDIATED IMMUNITY (HIGH TH1). GRANULOMAS AND NORMAL Ab SERUM LEVELS
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TREPONEMA PALLIDUM
LATE PHASE
HOST-PARASITE MIMICRY
AGENT OF SYPHILIS BINDS TO HOST FIBRONECTIN RECEPTORS, OF WHICH THERE ARE MANY
FIBRONECTIN SERVES AS BRIDGE THAT ALLOWS PATHOGEN TO BIND AND COLONIZE HOST TISSUES
COATED IN FIBRONECTIN ALSO CLOAKS TREPONEMA PALLIDUM FROM HOST IMMUNE SYSTEM
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STAPH AUREUS (ANTIBODY FUNCTION)
LATE PHASE
INTERFERENCE OF Ab FUNCTION - NEUTRALIZATION OF OPSONIZING Ab
STAPH PROTEIN A (SPA) BINDS TO IgG THROUGH ITS Fc REGION WHICH CAUSES IT TO LOSE OPSONIZING CAPABILITY
NEISSERIA MENINGITIS ALSO INTERFERES IN Ab FUNCTION
AUREUS ALSO HAS BARRIER AND LYSOSOMAL RESISTANCE IN EARLY INDUCIBLE PHASE AND MISDIRECTING IMMUNE RESPONSE IN LATE PHASE
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NEISSERIA MENINGITIS
LATE PHASE
INTERFERES IN Ab FUNCTION - IgA PROTEASE
FRAGMENTS OF IgA THAT REMAIN CONTINUE TO BIND TO PATHOGEN AND BLOCK COMPLEMENT ACTIVATING IgG Ab FROM BINDING
STAPH AUREUS ALSO INTERFERES IN Ab FUNCTION
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STREP PNEUMONIAE (LATE)
LATE PHASE
ANTIGEN DIVERSITY
EACH STRAIN (90+) CARRIES SLIGHTLY DIFFERENT POLYSACCHARIDE ANTIGENS IN THEIR CAPSULES. IMMUNITY TO ONE STRAIN STILL LEAVES INDIVIDUALS UNPROTECTED AGAINST OTHER STRAINS (SEROTYPES)
INFLUENZA, T. BRUCEI, N. GONORRHEA ALSO SHOW ANTIGENIC VARIATION
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INFLUENZA VIRUS
LATE PHASE
ANTIGENIC DIVERSITY - RNA
ANTIGENIC DRIFT = EPIDEMIC. POINT MUTATIONS (ESPECIALLY IN HEMAGGLUTININ AND NEURAMINIDASE) CAUSE EPITOPE CHANGES LEADING TO DIMINISHED ABILITY OF PREVIOUSLY EXISTING Ab TO RECOGNIZE VIRUS
ANTIGENIC SHIFT = PANDEMIC. REASSORTMENT OF GENOMIC SEGMENTS USUALLY FROM DIFFERENT SPECIES (PIGS, BIRDS)
STREP PNEUM, T. BRUCEI, AND N. GONORRHEA ALSO SHOW ANTIGENIC DIVERSITY
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TRYPANOSOMA BRUCEI
LATE PHASE
ANTIGENIC VARIATION - GENE REARRANGEMENT
AFRICAN SLEEPING SICKNESS
UNIQUE EXPRESSION SITE ONLY ALLOWS ONE VARIABLE SURFACE GLYCOPROTEIN (VSG) TO BE EXRESSED AT A TIME.
GENE CONVERSION SWITCHES OUT VSG IN EXPRESSION SITE WITH NEW ONE, CAUSING WAVES OF ANTIGENICALLY DISTINCT TRYPANOSOMES AND CYCLICAL NATURE OF THE DISEASE
STREP PNEUM, INFLUENZA, AND N. GONORRHEA ALSO HAS ANTIGENIC DIVERSITY
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NEISSERIA GONORRHEA
LATE PHASE
ANTIGENIC VARIATION
PILUS STRUCTURE ALLOWS BINDING TO HOST EPITHELIAL CELLS
NUMEROUS VARIATIONS OF PROTEIN PILIN BUT ONLY ONE EXPRESSED AT A TIME, SO ABLE TO EVADE BY CHANGING SURFACE ANTIGENS
STREP PNEUM, T. BRUCEI, INFLUENZA ALSO SHOW ANTIGENIC DIVERSITY
N. GONORRHEA ALSO BLOCKS COMPLEMENT IN IMMEDIATE INNATE PHASE
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CYTOMEGALOVIRUS (CMV)
DECREASED EXPRESSION OF MHC CLASS I
BLOCKS TAP
INCREASED TURNOVER OF MHC VIA ENDOCYTOSIS
HEAVY CHAIN MIMICRY COMPETES FOR B-2 MICROGLOBULIN
BLOCKS HLA-A,B,C BUT NOT E WHICH PROTECTS AGAINST NK CELLS
HIV & ADENOVIRUS ALSO DECREASE MHC
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ADENOVIRUS
DECREASED EXPRESSION OF MCH CLASS I
PREVENTS TAP ASSOCIATION WITH TAPSIN
HIV AND CMV ALSO DECREASE MCH
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STRATEGIES FOR EVADING IMMEDIATE INNATE PHASE
HIDING (INSIDE T LYMPHS AND MACROs) HIV
LATENCY (HERPES)
INHIBIT COMPLEMENT- BARRIERS (LONG CHAIN POLYSACCHARIDES), SIALIC ACID, M PROTEIN
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STRATAGIES FOR EVADING EARLY INDUCIBLE PHASE
EVADING PHAGOCYTOSIS - COAGULASE, POLYSACCHARIDE CAPSULE
PHAGOCYTE CHEMOTAXIS (C5a PEPTIDASE)
KILLING PHAGOCYTES (PORE-FORMING, APOPTOSIS)
INHIBIT LYSOSOME FUSION (ENDOSOME ABNORMALITY)
RESISTANCE TO LYSOSOMAL DAMAGE (HYDROPHOBIC SHIELD, D-CONFIGURATION, CATIONIC LYSO ANTI-MICRO, BREAKDOWN OF H2O2
ESCAPE PHAGOSOME
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STRATAGIES FOR EVADING LATE PHASE
MISDIRECTION OF IMMUNE RESPONSE (DEPLETION, SKEWING TH1 TH2 BALANCE)
HOST MIMICRY (FIBRONECTIN)
INTERFERENCE WITH Ab FUNCTION (NEUTRALIZATION, IgA PROTEASE)
ANTIGENIC VARIATION (SEROTYPES, ANTIGENIC DRIFT/SHIFT, GENE REARRANGEMENT)
DECREASED EXPRESSION OF MHC
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HYPERSENSITIVITY
HYPERSENSITIVITY = ALLERGY = EXAGGERATED MANIFESTATION OF NORMAL IMMUNE RESPONSE THAT:
1) EXCEED HEALTHY LIMITS OF INTENSITY AND/OR
2) DIRECTED AT TISSUES PARTICULARLY SENSITIVE TO PRODUCTS OF SUCH RESPONSIVENESS
INDIVIDUALS WITH PREDISPOSITION FOR ALLERGY ARE ATOPIC
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ALLERGEN
ANTIGEN (HARMLESS IN MOST INDIVIDUALS) THAT STIMULATES ALLERGIC RESPONSES IN ATOPICS
ESP (IgE ASSOCIATED ALLERGY)
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IMMUNE RESPONSE VS. IMMUNE REACTION
HYPERSENSITIVETY DISEASES REQUIRE SENSITIZATION INVOLVING AN IMMUNE RESPONSE THAT PRODUCES POTENTIALLY HARMFULL SOLUABLE OR CELLULAR FACTORS
PATHOLOGY WHEN THESE FACTORS COMBINE WITH AND ELICIT DAMAGE TO HOST TISSUES (IMMUNE REACTIONS)
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SENSITIZATION VS. ELICITATION
HYPERSENSITIVITY DISEASES REQUIRE INITIAL SENSITIZING EXPOSURE TO ALLERGEN, FOLLOWED BY EXPOSURES TO ALLERGEN THAT ELICIT SYMPTOMS
IN SOME CASES, SENSITIZATION PHASE MAY BE COMPLETED BEFORE ALLERGEN IS CLEARED FROM BODY, ALLOWING ELICITATION TO BEGIN DURING INITIAL ALLERGEN EXPOSURE
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TYPE 1 HS
IMMEDIATE
Ag-SPECIFIC IgE Ab
IgE-FIXED MAST CELLS, BASOPHILS, AND EOSINOPHILS DEGRANULATE TO RELEASE ACTIVE AGENTS
INITIAL EXPOSURE GENERALLY COMES BY WAY OF TRANSMUCOSAL PRESENTATION OF Ag THAT PROMOTES TH2 RESPONSE, FOLLOWED BY B-CELL ACTIVATION
Ab CAN ENTER ORAL OR RESP ROUTES AND ARE USUALLY SMALL SOLUABLE MOLECULES
IL-4 BY TH2 CELLS PROMOTE SELECTIVE SWITCHING TO IgE
Ag-SPECIFIC IgE BINDS VIA Fc REGION (TAIL DOWN) TO MAST CELLS, BASOPHILS, EOSINOPHILS THAT EXPRESS Fc-EPSILON-R1 FOUND IN MUCOSAL AND EPITHELIAL TISSUES.
Ab-SPECIFIC IgE MAY REMAIN ASSOCIATED FOR YEARS
- ex:
- RHINITIS
- ASTHMA
- VENOM REACTIONS
- FOOD ALLERGIES
- DRUG ALLERGIES
- URTICARIA (HIVES)
- ANAPHYLACTIV SHOCK
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ELICITATION OF TYPE 1 HS
CROSSLINKING OF Ag-SPECIFIC IgE PREVIOUSLY FIXED TO MAST CELLS AND OBSERVED WITHIN MINUTES OF EXPOSURE
REACTIONS VARY WITH INTENSITY DEPENDING ON DOSE AND ROUTE OF ALLERGEN EXPOSURE
SYMPTOMS RANGE FROM MINOR LOCALIZED IRRITATIONS (RHINITIS) TO SERIOUS LOCALIZED REACTIONS (ASTHMA) TO LIFE-THREATENING SYSTEMIC CIRCULATORY COLLAPSE (ANAPHYLACTIC SHOCK)
IMMEDIATE RESPONSE ACCOMPANIED BY SLOW (HOURS) ADDITIONAL WAVES OF IgE RESPONSES AND INFLAMMATORY ACTIVITIES (LATE-PHASE RESPONSE)
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DEGRANULATION
TYPE 1 HS
- CAUSES VASCULAR PERMEABILITY, INC BLOOD FLOW, DEC BLOOD PRESSURE, INC MUCOUS SECRETIONS, AND SMOOTH
- MUSCLE CONTRACTIONS
BRIDGING OF IgE TRIGGERS INFLUX OF Ca++ INTO CELL RESULTING IN 1) DEC cAMP THAT INITIATES MEMBRANE DESTABILIZAITON FOR GRANUAL RELEASE 2) MEMBRANE LIPID TURNOVER, VIA ARCHIDONIC ACID, LEUKOTRIENES AND PROSTAGLANDINS
RELEASED PRODUCTS CIRCULATING AT SIGNIFICANT LEVELS WITHIN MINUTES
- EXAMPLES:
- HISTAMINES - INC VASC PERM AND LOCAL BLOOD FLOW
- LEUKOTRIENES & PROSTAGLANDINS - SMOOTH MUSCLE CONTRACTION, INC VASC PERM AND MUCOUS SEC
- CHEMOKINES - ATTRACT LEUKOCYTES
- ENZYMES - BREAK DOWN TISSUE MATRIX PROTEINS
- CYTOKINES - INC INFLAMMATORY ACTIVITIES, INC TH2 RESPONSE, INC GROWTH AND ACTIVITIES OF EOSINOPHILS
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TYPE 1 HS SITES OF REACTIVITY
- SKIN:
- LOCALIZED WHEAL-AND-FLARE REACTIONS OBSERVED FOLLOWING LOCAL INTRACUTANEOUS EXPOSURE TO ALLERGEN (ex INSECT BITE). SKIN TESTS FOR Ag-SPECIFIC IgE HYPERSENSE MIMIC AND MEASURE THIS LOCLAIZED REACTION. URTICARIA (HIVES) IS MORE DISSEMINATED, OFTEN ASSOCIATED WITH ALLERGEN INGESTION AND MIGRATION TO SKIN
- GUT:
- CRAMPING, VOMITING, DIARRHEA DIE TO SMOOTH MUSCLE CONTRACTION. IF ALLERGEN FOUND SYSTEMICALLY, URTICARIA AND/OR ANAJPHYLAXIS CAN OCCUR
- LUNGS:
- ALLERGIC RHINITIS ASSOCIATED WITH NASOPHARYNX AND UPPER AIRWAY. MORE SERIOUS REACTIONS OCCUR FOLLOWING ACTIVATION OF MAST CELLS OR THE SUBMUCOSA OF LOWER AIRWAYS RESULTING IN ASTHMA
- SYSTEMIC:
- SIGNIFICANT EXPOSURE CAN RESULT IN CATASTROPHIC WIDESPREAD INCREASES IN VASC PERM, DEC IN BLOOD PRESSURE, AND SMOOTH MUSCLE CONTRACTION THAT CONSTRICTS AIRWAYS (WHILE SURROUNDING TISSUES SWELL DUE TO ABNORMAL SHIFTS IN FLUIDS. SYSTEMIC ANAPHYLAXIS
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TREATMENTS FOR TYPE 1 HS
AVOIDANCE
DESENSITIZATION - GIVING MULTIPLE, VERY SMALL THEN ESCALATING DOSES OF ALLERGEN WHICH SHIFT IgE TO IgG. EFFECTIVENESS HIGHLY VARIABLE, IMPERMINANT, AND MAY RESULT IN ANAPHYLAXIS
INHIBITION OF MEDIATOR RELEASE - INHIBIT CALCIUM INFLUX OR RAISE LEVELS OF cAMP
INHIBITION OF MEDIATOR EFFECTS: REVERSE TARGET TISSUE ACTIVITIES CAUSED BY MEDIATORS. EPINEPHRINE PROMOTES REFORMING OF ENDOTHELIAL TIGHT JUNCTIONS, RELAXATION OF SMOOTH MUSCLE, AND STIMULATION OF HEART. BRONCHODIALATORS AND ANTIHISTAMINES (H-RECEPTOR ANTAGONISTS. INFLAMMATORY ACTIVITIES, ESP LATE PHASE RESPONSES, CAN BE TREATED WITH ADMIN OF CORTICOSTEROIDS
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TYPE II HS SENSITIZATION
CYTOTOXIC ANTIBODY
PRODUCTION OF SPECIFIC Ab REACTIVE WITH EXTRINSIC (FOREIGN) Ag OR REACTIVE WITH INTRINSIC Ag PRODUCED BY TARGET TISSUE.
Ag STICKS NONSPECIFICALLY TO TISSUE & ABSORBED
INCOMPLLETE NEGATIVE SELECTION OF B CELLS SPECIFIC FOR SELF
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TYPE II HS ELICITATION
ONSET AND SEVERITY VARIES BASED ON KINETICS AND EXACT CHARACTERISTICS (eg SPECIFICITY, AFFINITY, ISOTYPE) OF Ab PRODUCED
SYMPTOMS CAUSED BY BINDING OF Ab (USUALLY IgG) SPECIFICALLY TO Ag-COATED HOST CELLS, FOLLOWED BY DIRECT LYSIS DUE TO COMPLEMENT ACTIVATION AND FURTHER AGGRAVATED RELEASE OF COMPLEMENT CASCADE (ANAPHLATOXINS C3a, C5a). FcR BEARING AND CR BEARING LEUKOCYTES ALSO RECRUITED TO AREA.
SMOOTH LAYER OF Ab/COMPLEMENT COATING TISSUE UNLIKE RANDOM COATING OF TYPE III
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HEMOLYTIC DISEASE OF NEWBORN
TYPE II HS
Rh- MOM HAS Rh+ BABY. BIRTH CAUSES SENSITIZATION OF MOM TO Rh+ BLOOD. IF 2ND BABY IS Rh+, MOM'S Ab (IgG) ATTACK FETAL HEMOGLOBIN CAUSING SEVERE FETAL ANEMIA.
GIVE RhoGam
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GOODPASTURE'S SYNDROME
TYPE II HS
AUTOIMMUNE DISORDER WHERE Ab BINDS TO BASEMENT MEMBRANES OF RENAL GLOMERULI (SOMETIMES PULMINARY ALVEOLI).
SPECIFIC FOR ALPH-3 CHAIN OF TYPE IV COLLAGEN.
TRIGGERS COMPLEMENT CASCADE, ACTIVATION OF MONOCYTES & NEUTROPHILS VIA Fc RECEPTORS
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TYPE III HS SENSITIZATION AND ELICITATION
IMMUNE COMPLEX DISEASE
INITIAL Ag EXPOSURE RESULTS IN ACTIVATION OF Ag-SPECIFIC B CELLS.
SPECIFIC IgG Ab REACT WITH Ag THAT IS TYPICALLY SOLUABLE AND FREELY CIRCULATING
MANY MOLECULES OF Ab BIND TO MANY MOLECULES OF Ag, FORMING CROSSLINKS RESULTING IN LARGE INSOLUABLE Ag-Ab COMPLEXES.
FcR+ AND CR+ PHAGOCYTES CANNOT HANDLE, CAUSING DEPOSITION IN/ON FILTERING ORGANS SUCH AS KIDNEYS OR AREAS RICH IN CAPILLARY BEDS SUCH AS LUNGS
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ARTHUS REACTION
TYPE III HS
INJECTION OF Ag ATTRACTS CIRCULATING IgG, FORMING IMMUNE COMPLEXES, ACTIVATING COMPLEMENT CASCADE, ATTRACTING PHAGOCYTIC CELLS (C5a), AND RESULTING IN LOCAL INFLAMMATORY RESPONSE
SERUM SICKNESS AND ADMIN OF LARGE DOSES OF DRUGS CAUSE Ag-Ab COMPLEXES
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TYPE IV HS SENSITIZATION
DELAYED TYPE (DTH)
ACTIVATION OF CD4+ TH1/17 CELLS
OCCURS OVER 10-14 DAYS WHEN SMALL Ag ASSOCIATES COVALENTLY WITH HOST MEMBRANE PROTEINS.
CD4+ ACTIVATED AGAINST Ag SUBSEQUENTLY FOCUS EFFECTOR ACTIVITIES ON HOST TISSUE TO WHICH Ag IS ATTACHED
Ag TAKEN INTO CELLS EVENTUALLY PRESENTED BY MHC I AND THEN RECOGNIZED BY CD8+ CELLS LEADING TO RELEASE OF INFLAMMATORY CYTOKINES AND LYSING OF HOST TISSUES
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TYPE IV HS ELICITATION
EXAGERATED FORM OF CELL-MEDIATED IMMUNITY (INTRACELLULAR)
Ag TAKEN INTO CELLS THEN PRESENTED BY MHC 1 ACTIVATES CD4+ AND CD8+ CELLS.
CYTOKINES INCLUDING CHEMOKINES, IFN-GAMMA, TNF-ALPHA & BETA, AND IL-3/GM-CSF RELEASED. RARELY SEE ANTIBODIES (TH2 EXTRACELLULAR)
INFLUX OF CELLS CAUSES EDEMA AND INDURATION (FIRM TO THE TOUCH) DUE TO HIGH DENSITY CELL. TYPE I SWELLING IS SOFT TO THE TOUCH DUE TO INFLAMMATION CAUSED BY FLUID.
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3 VARIANTS OF TYPE IV HS (DTH)
NOT MUTUALLY EXCLUSIVE
CONTACT HS - EPIDERMAL REACTION WITH LANGERHANS' CELL MOSTLY PRESENTING Ag TO T CELLS. INFILTRATING T CELLS MOSTLY CD4+. OCCURS WITHIN 24-48 HRS OF EXPOSURE. DO NOT CONFUSE WITH SYMPTOMS RESULTING FROM NON-IMMUNOGENIC TISSUE-DAMAGING IRRITANTS.
TUBERCULIN HS - INTRADERMAL REACTION MOSTLY BY MACROPHAGES AS Ag PRESENTERS. MONOCYTES MAKE UP 80-90% INFILTRATE WITH CD4+ OUTNUMBERING CD8+ 2-TO-1. OCCURS WITHIN 24-48 HOURS. CLASSIC ex TUBERCULIN SKIN TESTING
GRANULOMATOUS HS - CAN PROGESS FROM TUBERCULIN HS AND OCCURS SLOWLY (21-28 DAYS). PERSISTANCE OF DIFFICULT-TO-DEGRADE Ag WITHIN MACROPHAGES, INCLUDING INTRACELLULAR PATHOGENS. INORGANIC MATERIALS CAN STIMULATE, BUT DISTINGUISH DUE TO LACK OF LYMPHOCYTES. GRANULOMA FORMATION MAINLY DUE TO RECRUITMENT, PROLIF, AND ACTIVATION OF TH1 LYMPHS AT SITE OF RESPONSE. T CELLS FORM "CUFF" AROUND FUSED MACROPHAGES CALLED MULTI-NUC GIANT CELLS. EPIITHELIOID CELLS ALSO RECRUITED (RARE MACROPHAGE SECRETES TNF-ALPHA). PHYSICAL DAMAGE TO TISSUE DUE TO HIGH DENSITY CELLULAR CONTENT AND FIBROSIS OBSERVED DUE TO INC COLLAGEN SYNTH.
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LEUKOCYTE ADHESION DEFICIENCY
IMMUNODEFICIENCY
DEFECTIVE INTEGRIN (CD18)
AFFECT ABILITY OF LEUKS TO MOVE FROM BLOOD TO SITE OF INFECTION
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CHRONIC GRANULOMATOUS DISEASE
IMMUNODIFICIENCY
DEFECTIVE SUPEROXIDE PRODUCTION AFFECTING ABILITY OF PHAGS TO DESTROY INGESTED BACTERIA
INABILITY TO REDUCE NITROBLUE TETRAZOLIUM DYE (TEST)
O2 + NADPH OXIDASE --> SUPEROXIDE (O2-)
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PERCENTAGE OF IMMUNODEDICIENCY DISEASES
COMPLEMENT ~2-4%
PHAG ~15%
- B CELL ~50%
- NORM CIRCULATING B CELLS ~20-30%
T CELL ~30-40%
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ANTIBODY VS. CELL-MEDIATED IMMUNODEFICIENCY
- ANTIBODY:
- FREQUENT EXTRA-CELLULAR INFECTIONS
REDUCED SERUM Ab LEVELS; PARTICULAR ISOTYPE LEVELS
REDUCED CIRCULATING B CELLS; SURFACE Ig+ CELLS (NORM 20-30% OF LYMPHS)
REDUCED FUNCTIONAL B CELLS (TEST WILL STAPH PROTEIN A)
- CELL-MEDIATED:
- FREQUENT VIRAL, FUNGAL, AND INTRACELLULAR INFECTION
REDUCED CIRCULATING T CELLS (CD3, 4, 8)
REDUCED FUNCTIONAL T CELLS (TEST PHYTOHEMAGGLUTININ PHA)
NEGATIVE SKIN TEST Ag ASSOCIATED WITH MICROORGANISMS COMMONLY FOUND IN ENVIR
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SCID
FAMILY OF IMMUNODEFICIENCY DISORDERS (DEFECTIVE EARLY PROGENITOR CELLS
MAY FOLLOW AUTOSOMAL OR SEX LINKED PATTERS
EITHER COMPLETE ABSENCE OF T&B CELLS, OR SOME B CELLS PRESENT BUT DYSFUNCTIONAL DUE TO NO CD4 CELLS
~50% OF AUTOSOMAL DUE TO LACK OF ADA OR PURINE NUCLEOSIDE PHOSPHORYLASE (PNP)
BARE-LEUKOCYTE SYND: CLASS I OR II MHC MOLECULES CAUSE IMPAIRED DEVELOPMENT OR IMPAIRED ACTIVATION OF SUBSETS OF T CELLS (ex VARIANT CLASS I INVOLVES MUTATED TAP GENES, CAN'T PRESENT TO CD8+)
RAG DEFICIENCY
X-LINKED: DEFICIENT CYTOKINE RECEPTORS (IL2, 4, 7, 9, 15). IL7 IMPORTANT FOR EARLY PROGENITOR DEV
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AGAMMAGLOBULINEMIAS
IMMUNODEFICIENCY: B CELLS MISSING OR DYSFUNCTIONAL
MAY BE ALL B CELLS OR PARTICULAR ISOTYPE
MAY BE INDIRECT CAUSED BY FAULTY CD4+
X-LINKED CONGENITAL: BRUTON'S, DEFECTIVE TYROSINE KINASE (btk) FOR V-DJ JOINING. PRE B CELLS MAY BE PRESENT BUT SUBSEQUENT MATURATION DEFECTIVE. YOUNG BOYS
COMMON VARIABLE IMMUNODEFICIENCY (CVI): LOOKS LIKE BRUTONS BUT IN OLDER PATIENTS. EQUAL M/F SO AUTOSOMAL.
SELECTIVE IgA MOST COMMON
X-LINKED HYPER IgM SYNDROME: DEFECTIVE CD40 LIGAND ON ACTIVATED T CELLS, SO CANNOT INITIATE B CELL ISOTYPE SWITCHING (LYMPH NODES LACK GERMINAL CENTERS)
ACTIVATION INDUCED CYTIDINE DEAMINASE DEFICIENCY (AID): B CELLS WITH DEFECTIVE CLASS SWITCHING AND AFFINITY MATURATION
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DiGEORGE'S SYNDROME
IMMUNODEFICIENCY: CELL-MEDIATED
CONGENITAL THYMIC DYSPLASIA (PHARENGIAL ARCHES)
THYMUS, PARATHYROID, AORTIC ARCH, OTHER UPPER-CHEST TISSUES, DYSMORPHIC FACESE
PRE T CELLS PRESENT AND CAN BE INDUCED TO MATURATION (THERAPUTIC)
B CELLS PRESENT BUT VARIABLE FUNCTION DUE TO ABSENCE OF FUNCTIONAL T CELLS
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MUCOCUTANEOUS CANDIDAISIS
CELL MEDIATED IMMUNODEFICIENCY
SELECTIVE DYSFUNTION ASSOCIATED WITH CANDIDA (YEAST) INFECTIONS
OTHER T CELL FUNCTIONS NORMAL
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AIDS
CELL MEDIATED IMMUNODEFICIENCY
HIV USES CD4+ RECEPTORS TO ENTER CELLS (Gp120 BINDS TO CD4+ RECEPTOR)
CERTAIN CHEMOKINE RECEPTORS ACT AS CORECEPTORS (CCR5 ON T & MACRO, CXCR4 ON T ONLY)
DECREASED CD4+ (TH1,17,2), DEND CELLS, MACROPHAGES. EFFECTS BOTH ADAPTIVE & NON-ADAPTIVE
KAPOSI'S SARCOMA: INCREASED CANCER INCIDENCE
- NORM CD4 ~1200ul
- ASYMPTOMATIC HIV ~800ul
- AS OPPOR INFECTIONS BEGIN <500ul
- FULL-BLOWN AIDS <200ul
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PROBLEMS WITH T CELL CENTRAL TOLERANCE
CERTAIN SELF PEPTIDES MAY NOT BE AVAILABLE IN THYMUS FOR NEGATIVE SELECTION
- MHC MAY NOT PRESENT CERTAIN PEPTIDES EFFECTIVELY FOR NEGATIVE SELECTION
- DEPENDS ON EXACTLY WHICH MHC ALLELS AN INDIVIDUAL CARRIES
RELATIVE RISK: PROBABILITY FOR PARTICULAR AUTOIMMUNE DISEASE IN CERTAIN INDIVIDUALS DEPENDING ON CONSTELLATION OF MHC ALLELS
EPITOPE SPREADING: CRYPTIC EPITOPES -- SELF-Ag PRESENTED AT TOO LOW OF CONCENTRATIONS TO COMPLETELY ELIMINATE REACTIVITY, AND MAY BECOME PROMINENT LATER IN THE RESPONSE
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PROBLEMS WITH PERIPHERAL T CELL TOLERANCE
SEQUESTERED SELF-Ag IN IMMUNOLOGICALLY PRIVILEGED SITES ARE RELEASED INTO PERIPHERY
INAPPROPRIATE EXPRESSION OF CLASS II MHC WILL INCREASE THE PROBABILITY OF AUTOIMMUNE T CELL RESPONSIVENESS IN TH1,17, AND 2
INAPPROPRIATE EXPRESSION OF CO-STIM MOLECULES (B7, CD80/86) WILL NOT CAUSE ANERGY/APOPTOSIS IN CTLs
DYSFUNCTIONAL T-REG MAY DISTURB BALANCE OF CYTOKINES ALLOWING IMMUNOREGULATORY DYSFUNCTIONS AND EXPRESSION OF PATHOLOGICAL SELF-REACTIVITIES
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PROBLEMS WITH B CELL CENTRAL TOLERANCE
LIMITED EXPOSURE TO SELF Ag IN MARROW
SOMATIC MUTATIONS IN B CELLS ACTVATED TO FOREIGN Ag MAY CAUSE EXPRESSION OF RECEPTORS FOR Ag WITH NEW REACTIVITIES AGAINST SELF
ANTIGEN MIMICRY: SIMILARITY BETWEEN FOREIGN Ag AND SELF THAT ALLOWS IMMUNE CROSS REACTIVITY (ex RHEUMATIC FEVER/HEART DISEASE
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PROBLEMS WITH B CELL PERIPHERAL TOLERANCE
SELF Ag SEQUESTERING (ex CNS AND EYE LENS)
SPLIT TOLERANCE (2 CELL TYPES NEEDED FOR ACTIVATION) INEFFECTIVE DUE TO 1) ACTIVAGTION OF ANERGIC T CELLS OR 2) BYPASS OF T CELLS DUE TO MITOGENS/ADJUVANTS (NONSPECIFIC T-INDUCER INDEPENDENT) OR PHYSICAL LINKAGE OF FOREIGN Ag TO SELF Ag (NONSPECIFIC T-INDUCER DEPENDENT) CAUSING ACTIVATION OF DORMANT SELF-REACTIVE B CELLS
NEO-EPITOPES CREATED AS RESULT OF PARTIAL DEGRADATION OF SELF Ag DURING INJURY OR TRAUMA. SELF Ag DEFORMED AND POSSESSES FOREIGN CHARACTER
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ADCC
INVOLVED IN AUTOIMMUNITY
Ab-DEPENDENT CELL-MEDIATED CYTOTOXICITY
Fc RECEPTOR BEARING KILLER CELLS (K/NK CELLS) AND CR BEARING PHAGOS ATTACK CELLS BOUND BY SPECIFIC Ab
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AUTOIMMUNITY ANTI-RECEPTOR DISEASES
GRAVE'S DISEASE: THYROID STIM HORMONE RECEPTOR AGONIST. stimulating thyroid hormone synthesis and secretion, and thyroid growth (causing a diffusely enlarged goiter). The resulting state of hyperthyroidism can cause a dramatic constellation of neuropsychological and physical signs and symptoms, which can severely compromise the patients’ ability to maintain jobs and relationships
MYASTHENIA GRAVIS - ACh RECEPTOR AGONIST
INSULIN-DEPENDENT DIABETES MELLITUS - PANCREATIC BETA CELLS. EXCESSIVE TIREDNESS, INCREASED THIRST, POLYURIA, WEIGHT LOSS
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MULTIPLE SCLEROSIS
AUTOIMMUNE
INDUCTIVE EFFECT UNKNOWN
MIXED Ab AND CELL-MEDIATED RESPONSES PROBABLY INVOLVING TYPE II & IV HS
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RHEUMATOID ARTHRITIS
AUTOIMMUNE
MIXED Ab AND CMI EFFECTORS INVOLVING TYPE III & IV HS
PROMINENT IMMUNE COMPLEX IN JOINTS
ABNORMAL IgG PRODUCED IN SYNOVIUM, AND Ab RESPONSE IS INITIATED AGAINST ABNORMAL IgG (REFERRED TO AS RHEUMATOID FACTOR RF)
COMPLEMENT THEN STARTS DESTROYING HOST TISSUE
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SYSTEMIC LUPUS ERYTHEMATOSUS
AUTOIMMUNE
SYSTEMIC, PROMINENT ANA+/DNA REACTIVE Ab AND HEMATOPOIETIC/LYMPHOPOIETIC CELL Ab
GREATER INCIDENCE IN WOMEN OF CHILD-BEARING YEARS (SEX HORMONE INFLUENCES)
RASH, SERUM COMPLEMENT DEPLETION, KIDNEY DISEASE, LE CELLS
ATTACK ERYTHS, PLATELETS, COAGULANTS, LYMPHS, NEUTS, NEURO, DNA, IgG
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GOODPASTURE'S SYNDROME
AUTOIMMUNE
TYPE II HS AGAINST COLLOGEN TYPE IV OF BM OF RENAL GLOMERULI, AND LESSER EXTENT PULMONARY ALVEOLI
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GUILLIAN-BARRE SYNDROME
AUTOIMMUNE
ACUTE IDIOPATHIC POLYNEURITIS
PERIPHERAL NERVE DEMYLINATION
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HASHIMOTO'S DISEASE
AUTOIMMUNE DISEASE
HYPOTHYROIDISM
ANTI-THYROGLOBULIN; ANTI-THYROID EPITHELIUM
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ADDISON'S DISEASE
AUTOIMMUNE
ADRENAL GLANDS
ANTI-ADRENAL CELL MEMBRANES; LYMPH/MONO CORTICAL INFILTRATION
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SJOGREN'S SYNDROME
AUTOIMMUNE
SALIVARY GLANDS
GLANDULAR INFLAMMATION
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THROMBOCYTOPENIAS
AUTOIMMUNE
PLATELETS OR MEGAKARYOCYTES
PLATELET DESTRUCTION/ ABNORMAL BLEEDING
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CHRONIC ATROPHIC GASTRITIS; PERNICIOUS ANEMIA
GASTRIC MUCOSA
LOSS OF GASTRIC SECRETORY FUNCTION
FAILURE OF B12 ABSORPTION DUE TO LOSS OF INTRINSIC FACTOR PRODUCING CELLS (PARIETAL CELLS IN STOMACH)
water soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood.
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CROHN'S DISEASE
AUTOIMMUNE
INTESTINAL GRANULOMATOUS DISEASE
MUCOSAL MEMBRANE OF TERMINAL ILEUM
MUCOSAL ULCERATION; OBSTRUCTIVE GRANULOMA
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RHEUMATIC FEVER
AUTOIMMUNE
HEART
MYOCARDITIS; SCARRING OF HEART VALVES
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PEMPHIGUS VULGARIS
AUTOIMMUNE
EPIDERMIS
BLISTERING OF SKIN
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RHEUMATOID ARTHRITIS
AUTOIMMUNE
INITIALLY JOINTS
SPREAD TO CARTILAGE AND NEIGHBORING BONE AND MUSCLE
IMMUNE COMPLEX DISEASE IN SYNOVIUM, RF AGAINST IgG PROMINENT
INFLAMMATORY CELLS NOTED
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TRANSPLANTATION DEFINITIONS
SYNGENEIC - IDENTICAL TWINS
ALLOGENEIC - DIFFERING GENETICS BETWEEN MEMBERS OF SAME SPECIES
XENOGENEIC - MAJOR GENETIC DIFFERENCES BETWEEN DIFFERENT SPECIES
AUTOGRAFT - TISSUE GRAFTED BACK INTO ORIGINAL DONOR
ISOGRAFT - TISSUE GRAFTED BETWEEN SYNGENEIC INDIVIDUALS
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3 PHASES INVOLVED IN ALLOGRAFT REJECTION
RECOGNITION PHASE - APCs TAKE UP GRAFT Ag AND PRESENT. Ag REACTIVE LYMPHS ACTIVATED, AND VASCULARIZATION HELPS ACTIVATE CIRCULATING LYMPHS. EARLY RESPONSE MAINLY BY CD4+ CELLS
PROLIFERATION AND DIFFERENTIATION PHASE - CD4+ CELLS & MACROPHAGS MEDIATE T & B CELLS. EFFECTOR T CELLS LEAVE LYMPH NODE AND REACH GRAFT THROUGH BLOOD
DESTRUCTIVE PHASE - CTLs PRIMARY FORCE IN GRAFT REJECTION. CYTOLYSIS INVOLVES BINDING, MOVING CYTOPLASMIC GRANULES (CONTAIN PERFORIN) AND GRANZYMES ADJACENT TO TARGET CELL. ACTIVATED B CELLS BECOME PLASMA CELLS AND THEIR Ab INTERACT WITH COMPLEMENT AND ADCC
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MHC IN GRAFT REJECTION
CLASS I (ABC) TARGETS FOR CTLs
CLASS II (DP,DQ,DR) TARGETS FOR CD4+
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