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80 Cards in this Set
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examples of HS diseases
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Lupus, rheumatoid arthritis, scleroderma, Sjogren's syndrome, myasthenia gravis
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HS disease
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usually referred to as autoimmune diseases; usually two or more types of HS reactions causing damage to tissues
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HS reaction
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a pathologic process that results from specific interactions between antigens (either exogenous or endogenous) and humoral antibodies or lymphocytes
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HS Reaction (2nd definition)
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a condition in which the body's defenses react with exaggerated or innappropriate immune responses to what is or what is percieved to be a foreign substance, often causing severe inflammation
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Tyle 1 HS reaction
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IgE-mediated reactions
allergy anaphylaxis |
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when you have an allergic reaction to something, is it your first time being exposed to the allergen?
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No, it is at least the 2nd or the nth time
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CD4+ T-lymphocytes
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get excited into making cytokines, IL-4 and IL-5
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Cytokines IL-4 and IL-5
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cause two things to happen:
- mast cell growth - production of IgE antibodies from B lymphocytes |
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IgE antibodies
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attach themselves to mast cells; now mast cells are "primed" to initate an IgE-mediated allergic reaction next time you come in contact with the allergen
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2nd or nth time coming into contact with the allergen
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millions of copies of the allergen cause IgE crosslinking of all adjactent IgE antibodies.
This causes DEGRANULATION of the mast cells, releasing HISTAMINE |
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Preformed primary mediator of inflammation
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Histamine
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Histamine (Actions)
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-vasodilation
-smooth muscle contraction -increased mucous production -capillary and venule leakiness |
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smooth muscle contraction caused by histamine during allergic asthma
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Histamine causes bronchoconstriction, resulting in dyspnea and shortness of breath
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Smooth muscle contraction caused by histamine if the allergen was an ingested food/drug
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histamine would cause smooth muscles contraction of the intestines -- abdominal cramping and diarrhea
could also cause urticaria (hives) |
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Early Phase/Initial response in Type 1 HS reactions
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crosslinking of IgE antibodies, causing degranulation and release of Histamine from granule cells
occurs within 5-30 mins after exposure |
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Secondary mediators of inflammation
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Prostaglandins and Leukotrienes (eicosanoids?)
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Activation of Phospholipase A2
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produces Arachidonic Acid within the mast cell
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Arachidonic acid
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cyclooxygenase pathway: produces prostaglandinds
5-lipoxygenase pthwy: produces leukotrienes |
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prostaglandins and leukotrienes
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cause worse: fever, pain, vasodilation, increased mucous production and vascular leakiness
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leukotrienes
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are several THOUSAND times more vasodilatory and bronchospasmogenic than histamine
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Late phase response
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occurs 2-8 hours after exposure in about 1/2 of all Type 1 HS reactions
- Prostaglandin and leukotriend production -release of cytokines |
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cytokienes IL-1,4,5,6 and TNF
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together with leukotriene B4, cause CHEMOTACTIC RECRUITMENT AND ACTIVATION OF INFLAMMATORY CELLS (eosinos, etc)--->cause epithelial cell damage (usually muscosal)
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epithelial cell damage (usually mucosal) is caused by?
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inflammatory cells (eosinos etc) that are chemotactically recruited and activated by Cytokines IL-1,4,5,6, TNF and Leukotriene B4)
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Type 1 localized reactions
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1. on skin (urticaria)
2. in nose (conjunctiva, bronchioes) *atopy - genetically susceptibility to localized type 1 reactions. Atopic patients have higher IgE levels in plasma and are prone to "atopic diseases" (allergic rhinitis and conjunctivitis; asthma, urticaria, and food allergies) |
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what causes urticaria?
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food
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what causes conjunctiva and bronchioles (allergic rxns in nose)?
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zillions of allergens we're exposed to ..... pets, pollens, etc
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Atopy
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the genetic susceptibility to localized Type 1 reactions.
Atopic patients have higher IgE levels in plasma nad are more liely to have: allergic rhinitis or conjunctivitis asthma urticaria food allergies |
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Atopic diseases
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allergic rhinitis and conjunctivities
asthma urticaria food allergies |
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atopic patients
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have higher IgE levels in plasma
are more prone to atopic diseases (asthma, urticaria, food allergies, etc) |
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Systemic Type 1 reactions!!
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foods or drugs taken:
orally (peanuts, penicillin) given I.m. (penicillin) s.c. (bee stings, insect bites) i.v. (antiserum) CAN CAUSE ANAPHYLAXIS WITHIN MINUTES |
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Anaphylaxis
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-itching, hives, skin erythema
-bronchospasm and increased mucus=Bad SOB -G.I. Spasm= cramps, vommitting, diarrhea -Global vasodilation --> anaphylaxis shock--> could be fatal! |
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drug used to treat mast cell degranulation adn histamine RELEASE
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mast cell stabilizers
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drugs used to treat the actions of histamine
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antihistamine (benadryl, claritin)
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drugs used to treat bronchospasm
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bronchodilators
-Beta2 agonists -anticholinergics |
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drug used to prevent the production of arachidonic acid by phospholipase A2
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Steroids : Nasal, PO, Inhaled
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Drugs used to prevent the production of prostaglandins by cyclooxygenase
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PA NSAIDs
-advil (ibuprofen) |
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action of leukotrienes
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Leukotriene receptor blockers
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Late phase release of cytokines IL1,4,5,6, TNF
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Steroids: Nasal, PO, Inhaled
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ANaphylaxis
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3 drug combo:
Antihistamine (Benadryl): to stop early phase respone Steroid (methylprednisone): to stop late phase respone Epinephrine: Vasoconstriction, bronchodilation, and to stimulate the heart |
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Vasoconstriction (drugs)
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alpha 1 receptor
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Bronchodilation (drugs)
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Beta 2 receptors
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Heart Stimulation (drugs)
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Beta 1 receptors
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Type 2 HS reactions
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3 subtypes.
1. Antibody-Dependent Cell-Mediated Cytotoxicity 2. Complement-dependent reactions 3. Antibody-Mediated Cellular Dysfunction |
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antibody dependent cell mediated cytotoxicity (ADCC)
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IgG antibodies attach to target cell antigen at ANTIGEN BINDING REGION
-a neutrophil, NK cell, macrophage or eosinophil attaches the Fc portion of the Ab, which causes lysing of the cell via lysosomal enzyme or cytokine release and/or oxygen free radical attack |
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what portion of the antibody attaches to the target antigen cell in ADCC?
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the antigen binding region
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What portion of the antibody does the natural killer cell, eosinophil, macrophage or neutrophil attach to?
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the fc region
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what types of cells that have the receptors for the Fc portion of the antibody in ADCC type 2 sensitivity reactions?
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neutrophils
NK cells macrophages eosinophils |
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ADCC
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type 2 hypersensitivity reaction
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classic example of ADCC
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involed IgE attachment to parasites, which are then killed by eosinophil attachment to the Fc portion of IgE
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What kind of cell attaches to the Fc portion of IgE in IgE attachment of Parasites (an example of ADCC HS reaction)
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eosinophil
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what is eosinophilia or Increased serum IgE indicative of??
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allergies or allergic infection (from parasites, etc)
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specific example of parasite- induced eosinophilia
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Visceral Larva Migrans
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Explain visceral larva migrans
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a common intestinal parasite of cats and dogs winds up in the mouth of a child-->eggs hatch in intestines, and penetrate wall-->larvae distributed EVERYWHERe (liver, heart, lung, eye, CNS, etc)
--reccurent/chronic fever cough, wheezing, recurrent pneumonia rash eye lesions hepat and/or splenomegaly |
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A child has a recurrent/chronic cough, hepatomegaly, rash, chronic fever and eye lesions. What are these symptoms of?
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Visceral Larva Migrans
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Labs for visceral migrans larva
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increased Serum IgE levels (several times NL)
and elevated white cound due to eosinophilia (>60%) |
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Complement dependent reactions
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1. direct (osmotic) lysis
or 2. opsonization and phagocytosis |
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transfusion reactions
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complement dependent type 2 HS reaction
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erythroblastosis fetalis
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complement dependent type 2 HS reaciton
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autoimmune hemolytic anemia
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complement dependent type 2 HS reaction
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opsonization and phagocytosis
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complement depend type 2 HS reaction
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direct (osmotic) lysis
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complement dependent type 2 HS reaction
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Anitbody mediated cellular dysfunction
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attachment of one's own Ab to "self antigens" on cell surfaces doesn't cause death of the cell, or even damage, per se, but instead causes dysfunction of those cells without also causing inflammation
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examples of Antibody mediated cellular dysfunction
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graves disease
myashenia gravis |
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Myasthenia gravis
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Antibody mediated cellular dysfunction (Type 2 HS reaction)
auto-antibodies attache to ACETYLCHOLINE RECEPTORS on the pre-synaptic side of hte neuromuscular junction and effectively BLOCK THE ATTACHMETN OF ACH--> DECREASED NEUROTRANSMISSION and EASY FATIGUABILITY (not necessarily weakness) |
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Grave's Disease
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Antibody-Mediated Cellular dysfuntion type 2 HS reaction
auto-antibodies attach to the thyroid stimulating hormone (TSH) receptors and stimulate overproduction of the thyroid hormones -->hyperthyroidism |
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Type 3 HS reactions
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immune-complex-mediated
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immune complexes
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formed by attachement of antigen-to-antibody-antigen and os on,
form righti n circulating blood and then attach to VASCULAR ENDOTHELIUM and wreak havoc in vascular beds surrounding the tissue |
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how do IC cause problems?
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they activate complement
and Neutrophils and other granulocytes are attracted by both ICs and activated complement |
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what is the primary step towards tissue/cell damage?
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IC-inducted complement activation
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"badboy complement fragments"
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C3A and C5A
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C3A and C5A
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anaphylatoxins: increase vascular permeability, permitting entry of ICs and anaphylatoxins into tissues..
also, chemotactic for PMN (polymorphonuclear leukocytes), which also emigrate into the tissue, attempting to phagocytise the ICsand in doing so, they realease downright tissue-injurious substances |
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PMNs
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polymorphonuclear leukocytes
-neutrophils, eosinophils and basophils. -emigrate into the tissue ,try to phagocytised ICs and in doing so, become activated and release a small arsenal of inflammatory and tissue-injurious substances (prostaglandins, oxygen free radicals and lysosomal enzymes) |
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What do PMNs release?
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prostaglandins
other chemical junk oxygen free radicals lysosomal enzymes(able to destory collagen, elastin, cartilage and basement membranes) |
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antigens that form ICs with one's own antibodies that are exogenous
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can be exogenous bacteria, viruses or protein sera
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antigens that form ICs with one's own antibodies that are endogenous
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cell nuclear components, such as DNA
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Common sites at which deposition of ICs and complement activation and tissue/cell injury occurs
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-small blood vessels-->vasculitis-->ischemia
-skin-->urticaria and rashes -joins-->rheumatoid arthritis and lupus -kidney-->glomerulonephritis -lung and kidney-->goodpasture syndrome |
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Mircothrombi
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cause local ischemia or infarct and related cell injury and/or death.
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Ics also cause microthrombi by
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causing both platelet aggregation and activation of HAGEMAN FACTOR, which in turn starts the COAGULATION PATHWAY
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hageman factor
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produced by ICs producing microthrombi
hageman factor starts the coagulation pathway |
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systemic lupus erythematosus (SLE)
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chonronic antigenemia causes chromic production of ICs and the related vascular and organ problems
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