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36 Cards in this Set
- Front
- Back
What is complement?
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Series of heat sens. proteins circulated in serum tissue fluids except urine and CSF.
-help antibody-antigen complex to mediate immune response. -invovled in both innate and adaptive immune response |
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Where is complement synthesized?
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In liver; appear in fetal circ during 1st trimester.
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how is complement activated?
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Sequentially by Ag-Ab complex or endotoxin. Mediator of antibody response to downstream target cell for phagocytosis or cell mediated response
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Inactivation?
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Inhibitors in plasma (short lived)
-when its overwhelming its controlled to maintain homeostasis. |
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Biological function
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Responsible for certain aspects of immune inflammatory response, can be either beneficial or harmful to host.
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Classical Pathway basics
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-Specific acquired (adaptive) immunity initiated by antibody
-Complement is activated by Ag-Ab complex (IgM or IgG) -Fc portion of the antibody form a binding site for C1q. -Downstream : C1q, r, s, C4 (beginning of rxn), C2, C3, C5-C9 (numerical order) -Property (factor P) is not invovled. |
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3 stages of classical pathway
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1. recognition stage
- C1q act as the recognition element - It binds to Fc portion of IgM or IgG - The activated C1 molecule can cleave many C4 molec. 2) Activation stage: The complement components C4, C2, C3, C5, C6, C7, C8, C9 participate in that order 3) Membrane attack stage: Complement components C5, C6, C7, C8, C9 participate where cell membrane damage and cell lysis occur |
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Alternative pathway
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Involves Properdin system (Factor P)
-Activated by bacterial endotoxin, polysaccharide, and immune complex of IgA -starts at C3 then C5-C9 activation cascade. more or less nonspecific, no antigen antibody binding. -early components of complement (C1, C4, C2) are by passed -considered first line defense |
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Lectin pathway MBL-MASP
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-very potent, high affinity to bind sugars on bacterial cell wall.
-homologous to classical but with mannose-binding lectin (MBL) instead of C1q. -activated by binding MBL to mannose on bacterial surface, that activates MBL associated serine protease (MASP) that can then activate C4 and C2. -bind together to form C3 convertase as in classical pathway -not antibody dependent -deficinet in MBL increase infections during early childhood. |
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What's the central step to all the pathways?
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C3 convertase needed to convert inactive to active form.
The intiation is the distinctive part that you should keep in mind. |
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Cytolysis - biological effect of complement
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-activated complement proteins polymerize on cell surfaces of bact or erythrocyte to form pores in its membrane and cuase excess water to move in.
-Osmotic lysis occurs. |
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Opsonization
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target Ag for immune response
-binding of complement proteins C3b to surfaces of foreign organisms or particles -Phago cells express spec. receptors for opsonins when bound to C3b can promote phagocytosis. -binding of antigen to phagocytes is greatly enhanced w/ opsonin coating. |
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Inflammatory response - biological effects of complement
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-small frags. released during complement act have sev. inflammt. actions
-C5a: chemotactic (attracts neutrophils and macro + activates them). -C3,4,5: anaphylatoxins : degranulation of mast cells + release His + other inflammatory mediators by activating endothelial cells or phagocytes. |
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Immune Complex Clearance
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-C3b facil. binding of immune complex to erythrocytes and enhance removal by liver + spleen.
-binds erythrocytes to blood vessels, and become targets for phagocytosis. -C3 deficiency: immunocomplex disease. |
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Enhancement of antibody production
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-C3b binds to receptors CR2 on B cell - increases Ab production.
-Pyogenic infection in those who are C3b deficient. |
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Side effects - self destructive
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-if complement is activated systemically on a large scale (Gram-bacilli)
-activated by an autoimmune response to host cells |
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Features of hypersensitivity reactions
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-over rxn of normal immune sys to env antigens
-same substance or allergen can trigger multiple systems or categories of hypersensitivity. -undesirable (damaging, discomfort producing + something fatal) -require pre-sens. immune state of host -divided into 4 types: type 1-4 based on mech involved and time taken for rxn. |
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List 4 hypersensitivity rxn
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Type I: classical immediate
Type II: cytotoxic Type III: immune complex mediated (soluble, no cells involved) Type IV: delayed or cell mediated |
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Determinant factors of hypersens. rxns
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-chemical nature of allergen
-route involved in sensitization (inhalation, ingestion, injection) -physiological state of individual/genetic potential |
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Describe Immediate hypersensitivity
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-common among pop in developed countries
-prereq: need prior sens to antigen -binding of antigen to antigen spec IgE on mast cells -relase of mediators (histamine, leukotrienes, prostaglandins, platelets activating factor, and serotonin) |
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What is the typical response to type 1 hypersens. rxns?
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-smooth muscle contraction and bronchial spasm
Increased capillary permeability and edema Vasodilatation and urticaria [hives]. Hives are a consequence of vasodilation. Excessive mucus production Allergic rhinitis [hay fever] running nose Diarrhea or vomiting |
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Describe the difference between systemic and local form of type 1 hypersensitivity rxns..
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Systemic: anaphylaixs - more severe
-Exp to allergen to which a person is previously sensitized -Allergens: penicillin, anesthetics, insect venom -Treatment: corticosteroid injection, Epi, anti-His Local form- atopic allergy -Exposure to allergens produce IgE -includes inhalants, foods, contactants, drugs -strong familial predispo. to atopic allergy IgE - faster response here |
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Type II - cytotoxic
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-onset is within minutes to an hour
-multiple organs may be effected -antigens normally endogenous -Haptens (exogenous chem) may also trigger - drug induced hemolytic anemia, granulocytopenia + thrombocytopenia -mediated by Ab IgM or IgG + complement -phagocytes and K cells may also play a role (Antibody dependent cell cytotoxicity) |
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mechanism of cytolysis in endogenous way
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blood proteins initiate a series of enzymatic reactions
„fixing‟ of complement fragments to antigen-antibody complex on cell surface tagging it for destruction |
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Mechanism of cytolysis in exogenous way
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allergens trigger the classical complement pathway
antibody binds to specific antigen recruitment of inflammatory cells opsonization phagocytosis |
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Antibody dependent cellular cytotoxicity (ADCC)
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Antibody coated
cells killed by NK, macrophages, neutrophils and eosinophils that possess Fc receptors |
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What are some examples of Type 2 rxns?
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-Blood transfusion rxn due to ABO incomp.
-Rh incomptability (Hemolytic disease of newborn) -SLE -Graves's disease: non-cytotoxic type II -Graft rejection cytotoxic rxns (Ab vs. graft) -Drug rxn - Penicillin, quinine |
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Type 3 immune complex mediated
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-Rxn can be general or organic spec - involves skin, kidney, lung, blood vessel, joints.
-antigen can be exogenous or endogenous -mediated by soluble immune complexes** -rxn can take hrs or days after exposure to antigen |
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Action of immune complex in Type 3
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Soluble Ag in blood bound to soluble IgG
Formation of Ag-Ab immune complex of different sizes Ag: - exogenous (bacterial, viral or parasite) - endogenous (autoimmunity: e.g., SLE). Ab: mostly IgG class, although IgM may also be involved. Deposit into small blood vessels, joints, and glomeruli Acute inflammatory reactions Tissue and organ damage In some cases, immune complexes become deposited in walls of small blood vessels in alveoli Acute alveolar contraction and anaphylaxis ** not sure where the immune complex will end up because its soluble and circulates. |
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What are some examples of Type 3?
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Arthus reaction (local, e.g. diabetic patients receiving insulin
subcutaneously) Serum sickness (systemic, injection of large doses of foreign serum Post-streptococcal glomerulonephritis (associated with infective endocarditis) Hypersensitive pneumonitis (farmer lung, immune complexes deposition in lung after repeated inhalation of dust , mould spores) Autoimmune diseases (e.g. SLE, rheumatoid arthritis) |
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What makes type 3 unique from the others?
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Soluble antigen
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Type 4 - cell mediated hypersens.
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Also known as delayed type hypersensitivity.
The classical example of this hypersensitivity is tuberculin (Montoux) reaction which peaks 48 hours after the injection of antigen (PPD or old tuberculin). The lesion is characterized by induration and erythema. Caused by products of antigen-specific effector T cells. T cells undergo blastogenesis and cellular division to produce reactive cells. Usually takes 24 – 48 hours. |
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What does tissue damage result from?
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-No his or chemically related sub. relased
-usually due to products of activated macrophages -Infectious disease mostly: TB, leprosy, blastomycosis, histoplasmosis, toxoplasmosis, lesihmaniasis -Granuloma formed - i. Intracellular organisms resist destruction by macrophage ii. Persistent antigen stimulate local DTH reaction iii. Release of cytokines leads to accumulation of macrophages*** iv. Give rise to epithelial and giant cell granuloma |
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Test for Type 4- tuberculin
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Tuberculin test (PPD)
-measurement of induration -below 10 mm means negative result. delayed response that is part of type 4. |
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Diagnosis of hypersensitivity
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1) History taking for determining the allergen involved
2) Skin tests (for type I): Intra-dermal injection of battery of different allergens A wheal and flare (erythema) develop at the site of allergen to which the person is allergic 3) Determination of total serum Ig level 4) Determination of specific Ig levels to specific antigens |
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Management of hypersensitivty reactions
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1) Avoidance of specific allergen responsible for condition
2) Hyposensitization (allergen-specific immunotherapy): Injection gradually increasing doses of extract of allergen to desensitize the immune system. - Production of Ig G blocking antibody which binds allergen and prevent combination with Ig E - It may induce T cell tolerance - Routes: subcutaneous, intralymphatic, sublingual, transcutaneous 3) Drug Therapy: corticosteroids injection, epinephrine, antihistamines |