Micro Test II Arcadia
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- most important component of complement
- C3
- indiv w/ deficiencies in complement susceptible to what diseases:
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1. pyogenic bacteria
2. illness involving the production of Ab's/IC's - anaphylatoxins
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potent inducers of inflammation
-C5a, C3a
-recruit inflammatory cells, activate effector mechanisms - C5a function/ effect
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activator of all cell types of the myeloid lineage (phagocytes)
-neutrophils respond chemotactically, degranulate, release free O2 rads
-inc. surface expression of adhesion molecules
-macs secret IL5+6
-basophils+ mast degran=histamine - specific immunodeficiency
- abnormalities of T + B cells (cells of adaptive immune system)
- non-specific immunodeficiency
- abnormalities in complement, phagocytes,
- primary immunodeficiency
- intrinsic defects in cells of immune system; genetic
- X-linked agammaglobulinaemia
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failure of Bcell maturation
-few or no Bcells in blood/lymphoid tissues
-no IgA, IgM, IgD, IgE - In immunodeficiency with increased IgM (HIGM)isotype, _______does not occur
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isotype switching
-Bcells cannot make the switch from IgM to IgG and IgA (mutation of CD40 ligand) - common variable immunodeficiency (CVID)
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defects in Tcell signaling to Bcells
-Bcells not defective but fail to receive signaling
-susceptible to pyogenic infec/ intestinal protozoa - transient hypogammaglobulinaemia of infancy
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in some infants IgG synthesis delayed up to 36 mo. (don't have mom's anymore)
-Bcells normal but lack CD4 TH stimulus
-susceptible to pyogenic infx - Tcell deficiency
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no Tcells or poor function = opportunistic infections
-results in Bcell deficiency since require Tcell help - severe combined immunodeficiency (SCID)
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thymus never developed
-most profound
-treatment = bone marrow transplant - causes of SCID
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1. defect on X chromosome (50%)- defective gene encodes the gamma chain of IL2 receptor- this also forms parts of IL-4,7,11,15 receps
2. other 50% due to recessive genes on other chromosomes= deficiency of ADA adenosine deaminase or PNP purine nucleoside phosphorylase - purines degredation enzymes = accum. of dATP and dGTP= toxic to lymphoid cells - MHC class II deficiency
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TH cell deficiency results
-develop. of CD4+TH cells depends on positive selection by MHCII molecules
-auto recessive
-children have recurrent gastrointestinal infx - DiGeorge anomaly
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defect in thymus embryogenesis
-Tcell deficiency variable depending upon effect on thymus
-wide eyes, low ears, upper lip shortened, cardiac malform - Wilscott-Aldrich syndrome (WAS)
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-Tcell defects and abnormal Ig levels -> small+abnormal platelets, abnormal Tcells
-eczema, pyogenic, opp infx
-X-linked - increased susceptibility to pyogenic infections caused by deficiencies of C__ and Factor __or___
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C3, factor H or I
(C3 plays a big role in opsonization)
-all inherited as auto recess - deficiencies in classical complement pathway results in development of ___
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immune complexes (ie lupus)
-complement normally dissolves immune complxes) - hereditary angineurotic edema (HAE)
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C1 inhibotor deficiency
*most important deficiency of complement
-C1 inhib responsible for dissociation of activated C1
-> swelling occurs in various parts of body
-auto dominant - chronic granulomatous disease (CGD)
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defect in ox/red pathway:
defective NADPH oxidase that catalyzes red of O2 to O2-
phagocytes incapable of forming superoxide anions (O2-)so can't kill ingested microog- they stay alive->cell med response to persistant Ag = granuloma - Leukocyte adhesion deficiency (LAD)
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complement receptor 3 (CR3) is deficient(normally binds C3b on opsonized organisms)
-severe bacterial/gastro infx - secondary immunodeficiencies examples
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chemo-toxic to Tcells
protein malnutrition- results in Tcell deficiency
diarrhea-lose Ig's
burns-lose Ig's
infections (AIDS) - proteins on HIV membrane
- gp120, gp41
- cells that carry CD4
- dendritic cells, langerhans cells, microglia of CNS
- HIV cycle
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binds gp120 to CD4
enters CD+ cell, loses coat, ssDNA copy of viral RNA made by HIV reverse transcriptase, comp strand made and integrates
when Tcell activated, HIV particles made and released by budding - effect of steroids
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dec. circ lymphocytes
dec. circ monocytes
inc. circ neutrophils
*inhibit synth of cytokines
overall= inhibition of TH cells and macrophages - cyclophosphamide
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-alkylates DNA- interferes with strand sep during repro
-B cells more affected than Tcells, dec. lymphocytes not PMN's
*good to manage auntoAb and allograft rejection - azathioprine
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fraudulent base in DNA- affects synthesis
-active only on dividing (cytostatic) dec. T+B cells, suppress NK + K cell activity - methotrexate
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analog of folic acid (essential for DNA synth)
dec. in all Ig isotypes
anti-inflam cause suppress PMN's
no effect on Tcells - cyclosporin, tacrolimus (FK506), rapamycin
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-bind to class of cytoplas proteins
-inhib Tcells and Ag presentation - iron def.
- reduced ability of neutrophils to kill bac. + fungus, impaired NK cell activ
- selenium + copper def.
- mutations in viruses= altered virulence
- vitamin A def.
- alters epith struc= increased bac binding
- vit B6 and folate def.
- reduced cell mediated immunity
- malnutrition
- decreased #s of CD4 cells, dec in opsonization
- TH2 cells...
- secrete cytokines IL13 and IL14 --> induce Bcell prolif, favor IgE production
- Type I hypersensitivity
- mast cells bind IgE via their Fc receptors, IgE induces degranulation of mast cell, releasing mediators (typical allergic rxn)
- when allergen encounters sensitized mast cell bound w/ IgE...
- cross-links surfacebound IgE-->inc. influx Ca, triggers release of PREFORMED histamine and proteases(tryptase,chymase) and NEWLY SYNTH mediators leucotrienes and prostaglandins
- 2 types of mast cells
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MMC- mucosal mast cell
CTMC- connective tissue mast cell - the skin prick test produces...
- a wheel and flare reaction
- corticosteroids
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-suppress increase in mast cell #'s
-inhibit cytokine production incl. IL13 & IL4 - sodium cromoglycate
- prevents histamine release by inhibiting calcium influx into cell
- cyclosporin A
- inhibits expression of Il2 receptors = Bcells can't proliferate
- antihistamines
- block histamine after release
- hyposensitization therapy
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-increasing doses of allergen
-increase in allergen specific IgG and suppressor Tcell (suppress IgE response) - Hyp Type II
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-Ab against own cells
-cytotoxic action by K cells or complement-mediated lysis
-ex. blood transfusions - Hyp Type III
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-immune complexes deposited in tissues
-complement activated
-PMN's attracted to deposition site
-tissue damage, inflam
ex. lupus - Hyp Type IV
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-delayed-type
-Ag-sensitized Tcells release lymphokines when encounter the Ag a 2nd time
-Tcells activating macrophages
-granulomas - difference b/t Type II and Type III?
- II is restricted to specific cells or tissues bearing the Ag, III is against soluble Ag's in the serum
- major cause of HDN
- Rhesus system
- Goodpasture's syndrome
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nephritis from Ab's to glycoprotein on glomerular basement membrane- severe necrosis of glomerulus
(type II) - Pemphigus
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blistering of skin and mucous membranes
-Ab's to a desmosome protein that forms junctions b/t epidermal cells
-breakdown of the epidermis - Myasthenia gravis
- Ab's to Ach receptors on surface of muscle membranes
- immune complexes of type III due to 3 possible causes:
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1. persistent infection/weak Ab response
2. autoimmune disease (phagocytes that remove complexes become overloaded, start to deposit)
3. inhalation of Ag material (actinomyces fungi in hay, pigeon poop - IgG produced rather than IgE) - vasoactive amines released by platelets, basophils, and mast cells cause...
- endothelial retraction = increased permeability allowing IC's to deposit on blood vessel wall
- large immune complexes removed faster or slower?
- faster because more effective at fixing complement
- IC deposition occurs where BP is ____
- high
- 3 variants of Type IV:
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1. contact hypersensitivity (poison ivy)
2. tuberculin-type (72 hrs)
3. granulomatous (21-28 days) - Leprosy
- granumolatous rxn at peripheral nerves (likes cooler areas)
- Tuberculosis
- lung- fibrosis and lesions
- Schistosomiasis
- host becomes sensitized to ova of trematode worms = granulomas
- Sarcoidosis
- tissues, lung, lymphs
- Crohn's disease
- ileum and colon
- live vaccines produce ____ and _______ immunity
- humoral, cell-mediated
- attenuation achieved by...
- mutations (large # mutations diminished virulence)
- killed vaccines produce primarily ______ immunity
- humoral
- chemicals used to inactivate pathogen
- formaldhyde = alkylating agents
- most sucessful bacterial vaccines
- inactivated toxins and toxoids
- limitation of polysaccharide vaccines
- inability to activate Th cells - activate B cells in a Tcell independent manner (not presenting Ag) = more IgM, low IgG , have to get every 4 to 5 years to boost Bcells
- recombinant antigen vaccines
- introduce gene encoding antigen of pathogen into attentuated virus or bacteria- organism serves as vector- replicates within host, expresses gene product of pathogen (also clone into yeast, ie. Hep B vx)
- DNA vaccine
- plasmid DNA encoding viral antigen injected into muscle of recipient, taken up by muscles cells and encoded protein is expressed
- anti-idiotype vaccine
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1.immunize mouse with Ag, Ab (idiotype) generated against Ag
2. immunize mouse with Ab, then anti-idiotype generated (this looks like original Ag)
3. anti-idiotype used as vaccine
-testing for HIV vaccine - living vaccine advantage
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1. Ag challenge lasts for days or weeks
2. induces it at the right site
3. contains greatest # microbial Ag's - killed vaccine disadvantage
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do not replicate in host
repeated boosters needed - adjuvants
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enhance Ab production
-aluminum salts, added to Ag
1.concentrates Ag where lymphocytes exposed to it
2. induce cytokines - commensals
- benefits from host- host does not benefit but is not harmed
- pseudomembrane colitis
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antibiotics kill normal flora of bowel
-excessive toxin released by clostridium which is normally just a minor resident --> diarrhea - characteristics of normal flora
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1. adherence to host cells (proteins, polysacch's, pili) even thru desquamation
2.production of antimicrobial substance- inhibit other competing microbes - characteristics of skin that inhibit microorganisms
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1. dryness
2. low pH (b/t 3 and 4 due to organic acids such as lactic acid)
3. inhibitory substances
(sweat glands secrete lysozyme, sebaceous secrete complex lipids that are degraded into inhibitory acids) - tears contain _____ which _____
- lyzozyme, cleaves peptidoglycan
- major cause of dental caries
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streptococcus mutans
-produces glucan that acts like cement to stick bacterial cells together - residents of adult vagina
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lactobacilli
-break down glycogen to form lactic acid - carriers
- aquried sufficient immunity but unable to eliminate pathogen from body
- adhesins
- fimbriae, pili, cell-surface structure that bind to receptors on surface of host's cells
- antiphagocytic mechanisms
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-capsules (slippery)
-fimbriae (prevent close contact)
-siderophores- compete for iron = growth factor - hyaluronidase
- breaks down hyaluronic acid= connective tissue glue = spread
- streptokinase
- activates plasmin, causes disolution of blood clots = spread
- coagulase
- coag of plasma = fibrin layer around cell= Ab doesn't recognize
- hemolysins
- breakdown RBC = iron
- enterotoxins 2 types:
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1. stim cAMP causing electrolyte imbalance= H2O flows in
2.inhibit protein synth = kills epith cells - neurotoxins
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tetanus
-spastic paralysis - block inhibitory nerve impulses so fire all the time
(botulism prevents Ach release) - pyrogenic toxins
- = superantigens --> induce secretions of TNF alpha and IL-1 = inflam, shock, death
- endotoxins
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Lipid A portion of Gram - cells
lipid A binds to macs, causing synth of TNF alpha and IL-1 - what prevents microbes from going deep into body (ie rhinovirus)
- temperature- higher temp inhibits growth inside