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29 Cards in this Set
- Front
- Back
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What is complement?
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A division of the innate immune system comprised of approximately 20 serum proteins that form a cascade to mediate direct attack, lysis, and clearance of microorganisms at the point of entry
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Where are complement proteins synthesized?
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Mainly in hepatocytes, but also in blood monocytes, tissue macrophages, and epithelial cells of the GI tract
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What are the two different pathways of the complement system?
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Classic complement pathway
Alternative complement pathway |
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What is it called the classic rather than alternative complement pathway?
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No clinical reason; the classical pathway was discovered first
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Which pathway is activated upon first exposure to a microorganism?
Why? |
Alternative complement pathway
An antibody response (which stimulates the classic complement pathway) does not mount until several weeks after exposure |
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What is common to both pathways?
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Ultimately, formation of C3b, which can either generate C5 convertase or act alone as an opsonin
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What is C5 convertase?
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Enzyme that ultimately forms the membrane attack complex (MAC), which lyses pathogens
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What are four main effects of complement, regardless of the pathway by which it was activated?
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1) Opsonization
2) Generation of inflammatory mediators and chemotaxins 3) Lysis of cells such as bacteria and tumor cells 4) Immune complex clearance |
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What is opsonization?
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Enhancement of phagocytosis by certain immunoglobulins and complement components that bind to receptors on phagocytes.
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What component of the complement system is most involved in opsonization?
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C3b
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What are the complement anaphylatoxins?
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C3a, C4a, and C5a cause degranulation of mast cells and release of mediators, including histamine, leading to local inflammation.
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Of the three (C3a, C4a, C5a), which is the most powerful anaphylatoxin?
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C5a
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What parts of the complement cascade are involved in forming the membrane attack complex?
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C5b, 6, 7, 8, 9 along with C5 convertase
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What is the mechanism of cell death via the membrane attack complex?
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Osmotic cytolysis, i.e., the cell bursts as a result of an influx of ions and water
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What are four endogenous methods of regulating the complement system?
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1) Inhibitors of the C1 protease
2) Binding of factor H to C3b and subsequent cleavage of C3b by factor I 3) Presence of decay-accelerating factor on the surface of human cells, which degrades C3 and C5 convertases 4) Regulating the availability of IgG and IgM |
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The complement system is involved in which hypersensitivity reactions?
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Types II and III
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What activates the classic complement pathway?
When? |
IgM and IgG
When they are bound to antigen and form antigen-antibody complexes IgG and IgM are known as the "complement-fixing" antibodies |
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How do these antibodies (IgM and IgG) initiate the classic complement pathway?
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The Fc region of IgM and IgG binds to and activate C1
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What components of the classic complement pathway combine to form C3 convertase?
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C4b and C2a, formed when the C1 protease cleaves C2 and C4
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What components of the classic complement pathway combine to form C5 convertase?
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C4b, C2a, and C3b
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What activates the alternative complement pathway?
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Microbial surfaces (including endotoxin) and aggregated IgA
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What components of the alternative complement pathway combine to form C3 convertase?
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C3b and Factor Bb
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What components of the alternative complement pathway combine to form C5 convertase?
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2 components of C3b with 1 component of Factor Bb
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What condition is at increased risk if a patient has a deficiency of C1 esterase inhibitor?
Why? |
Angioedema
Unrestrained production of anaphylatoxins from the complement cascade results in increased capillary permeability. |
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What condition is at increased risk if a patient has a deficiency of C2 and C4?
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Symptoms that resemble systemic lupus erythematosus and other related autoimmune diseases
Patients with systemic lupus erythematosus often have low levels of C2 and C4 |
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What other condition is associated with low levels of C2 and C4?
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Pregnancy
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What other condition is associated with low levels of C3?
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Severe, recurrent pyogenic sinus and respiratory tract infections
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What other condition is associated with low levels of C5-C8?
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Neisseria bacteremia
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What other condition is associated with low levels of decay-accelerating factor?
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Paroxysmal nocturnal hemoglobinuria, a disorder characterized by increased complement-mediated hemolysis
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