immuno_mod2_ms1

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

INNATE IMMEDIATE PHASE

LATENCY (HIDING)

INVADE SENSORY NEURONS WHICH EXPRESS RELATIVELEY LOW LEVELS OF MHC, THUS AVOID CTLs

OTHER HIDING PATHOGEN IS 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

EARLY INDUCIBLE PHASE

RESISTANCE TO LYSOSOMAL DAMAGE - INHIBITION OF O₂ DEPENDENT KILLING

CATALASE BREAKS DOWN RESPIRATORY BURST PRODUCT, H₂O_2, 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

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

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)

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

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

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

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

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

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

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

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

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

DECREASED EXPRESSION OF MCH CLASS I

PREVENTS TAP ASSOCIATION WITH TAPSIN

HIV AND CMV ALSO DECREASE MCH

HIDING (INSIDE T LYMPHS AND MACROs) HIV

LATENCY (HERPES)

INHIBIT COMPLEMENT- BARRIERS (LONG CHAIN POLYSACCHARIDES), SIALIC ACID, M PROTEIN

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

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

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

ANTIGEN (HARMLESS IN MOST INDIVIDUALS) THAT STIMULATES ALLERGIC RESPONSES IN ATOPICS

ESP (IgE ASSOCIATED ALLERGY)

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)

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

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

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)

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

• 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

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

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

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

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

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

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

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

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

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.

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.

IMMUNODEFICIENCY

DEFECTIVE INTEGRIN (CD18)

AFFECT ABILITY OF LEUKS TO MOVE FROM BLOOD TO SITE OF INFECTION

IMMUNODIFICIENCY

DEFECTIVE SUPEROXIDE PRODUCTION AFFECTING ABILITY OF PHAGS TO DESTROY INGESTED BACTERIA

INABILITY TO REDUCE NITROBLUE TETRAZOLIUM DYE (TEST)

O2 + NADPH OXIDASE --> SUPEROXIDE (O2-)

COMPLEMENT ~2-4%

PHAG ~15%

• B CELL ~50%
• NORM CIRCULATING B CELLS ~20-30%

T CELL ~30-40%

• 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

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

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

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

CELL MEDIATED IMMUNODEFICIENCY

SELECTIVE DYSFUNTION ASSOCIATED WITH CANDIDA (YEAST) INFECTIONS

OTHER T CELL FUNCTIONS NORMAL

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

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

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

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

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

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

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

AUTOIMMUNE

INDUCTIVE EFFECT UNKNOWN

MIXED Ab AND CELL-MEDIATED RESPONSES PROBABLY INVOLVING TYPE II & IV HS

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

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

AUTOIMMUNE

TYPE II HS AGAINST COLLOGEN TYPE IV OF BM OF RENAL GLOMERULI, AND LESSER EXTENT PULMONARY ALVEOLI

AUTOIMMUNE

ACUTE IDIOPATHIC POLYNEURITIS

PERIPHERAL NERVE DEMYLINATION

AUTOIMMUNE DISEASE

HYPOTHYROIDISM

ANTI-THYROGLOBULIN; ANTI-THYROID EPITHELIUM

AUTOIMMUNE

ADRENAL GLANDS

ANTI-ADRENAL CELL MEMBRANES; LYMPH/MONO CORTICAL INFILTRATION

AUTOIMMUNE

SALIVARY GLANDS

GLANDULAR INFLAMMATION

AUTOIMMUNE

PLATELETS OR MEGAKARYOCYTES

PLATELET DESTRUCTION/ ABNORMAL BLEEDING

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.

AUTOIMMUNE

INTESTINAL GRANULOMATOUS DISEASE

MUCOSAL MEMBRANE OF TERMINAL ILEUM

MUCOSAL ULCERATION; OBSTRUCTIVE GRANULOMA

AUTOIMMUNE

HEART

MYOCARDITIS; SCARRING OF HEART VALVES

AUTOIMMUNE

EPIDERMIS

BLISTERING OF SKIN

AUTOIMMUNE

INITIALLY JOINTS

SPREAD TO CARTILAGE AND NEIGHBORING BONE AND MUSCLE

IMMUNE COMPLEX DISEASE IN SYNOVIUM, RF AGAINST IgG PROMINENT

INFLAMMATORY CELLS NOTED

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

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

CLASS I (ABC) TARGETS FOR CTLs

CLASS II (DP,DQ,DR) TARGETS FOR CD4+