Term
| What are the 3 effector functions of complement? |
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Definition
lysis
opsonization
promotion of inflammation |
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Term
What are the 3 complement pathways?
Which one involves antibody? |
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Definition
Lcetin, Classical, Alternative
Classical pathway: IgM, IgG1, IgG2, IgG3 bind C1; requires calcium |
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Term
| Which complement pathways does C1 inhibitor block? |
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Definition
Lectin pathway:blocks MBL to C4
Classical pathway: blocks C1qrs to C4 |
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Term
| What does C1 inh block in the contact activation pathway (clottin, fibrinolysis)? |
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Definition
Inactivates XII (Hageman factor) and its fragments (XIIa, XIIf)
Inhibits kallikrein
Inhibits activated factor XI
Inhibits TPA |
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Term
| Which mediator is the major cause of edema in HAE? |
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Definition
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Term
| Which complement is the principal effector of opsonization? |
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Definition
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Term
Name the 4 types of HAE syndromes.
Which is most common?
What are their features? |
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Definition
Type 1: 85% of pts. 1 gene makes no protein
Type 2: 15% of pts. 1 gene makes non-fxnal protein
Type 3: females on OCPs. C1 inh & C4 are nl. Possible causes: gain of function of Factor XII or problems with metabolizing bradykinin. Affects face more than extremities. Auto dominant
Acquired C1 inh: in pts with malignancy or autoimmunity. Monoclonal antibody to C1 inh |
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Term
Old HAE therapies:
EACA
Tranexamic acid
Impeded androgens
Name their side effects |
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Definition
EACA: myopathy, fatigue
Tranexamic acid: color blindness, liver toxicity
Danazol/Attenuated androgens: wt gain, hyperlipidemia, myopathy, liver toxicity (cancer rare), hirsutism, acne, virilization, fatique, headache, hypertension, psych problems, premature closure of epiphyses (so can't use in kids)and can't use in pregnant/lactating women. Also, should not use in prostate cancer. |
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Term
Name new HAE therapies
C1 inh (plasma:
Recombinant C1 inh:
Kallikrein inhibitor:
BK receptor type 2: |
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Definition
C1 inh (plasma: Cinryze (prophylaxis), Berinert (acute tx)
Recombinant C1 inh: Rhucin
Kallikrein inhibitor: Ecallentide, Kalbitor (Kalbitor black box warning, allergic rxns)
BK receptor type 2 antagonist: Jerinin, Icatibant |
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Term
| Dosing of Cinryze and Beriner |
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Definition
Cinryze:
1000 units 2-3 times/week (half-life is 40 hours)
Berinert: 20 U/kg for acute tx |
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Term
Mannose Binding Lectin:
Level
Frequency of defect
Risk for/types of infxns |
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Definition
Level: normally low (2 ug/ml)
30% of population has defect
Infants: predisposes to infxns
Immunocompromised hosts: aspergillus, cryptosporidia
?Rheumatologic problems |
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Term
C3Nef: C3 nephritic factor
What is it and why is it bad? |
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Definition
It's an IgG antibody found in some autoimmune diseases (inc nephritis)
Recognizes C3bBb and stabilizes it to prevent decay. As a result, more alternative pathway activation and damage. |
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Term
C3 metabolism
What do its breakdown products do? |
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Definition
C3b: binds to CD 35 on phagocytes, B cells
ICeb: binds to CD11b/CD18 and CD11c/CD18 on phagocytes and dendritic cells
C3d: binds CD21 which is only on B cells |
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Term
| Role of CD35, a complement receptor, and why is it relevant in SLE? |
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Definition
CD 35 picks up circulating immune complexes that bind complement. These are removed by liver and spleen and some CD35 is lost in the process.
Over time, SLE patients lose CD35 on their RBCs |
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Term
| Deficiency of which complement components is assoc with Neisserial infxns? |
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Definition
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Term
PNH (Paroxysmal Nocturnal Hemoglobulinuria)
1. What is it?
2. What is the defect?
3. What is the treatment? |
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Definition
1. hemolytic anemia, thrombocytopenia and neutropenia
2. Failure of synthesis of all phosphatidyl-inostiol linked membrane proteins in the bone marrow, inc CD59. The loss of CD59 and inability to limit RBC lysis leads to PNH.
3. Eculizumab, an anti-C5 MoAb. It turns off all complement steps after C5 and prevents lysis. FDA approved. |
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Term
Complement and asthma:
Evidence to support role of C3a and C5a |
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Definition
C3a & C5a are found in BAL during acute attacks
C3a induces mucus secretion
C5a induces contraction of smooth muscle and mast cell degranulation |
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Term
Complement and antibody formation
Defects in which complement pathway can be assoc with defects in antibody synthesis? |
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Definition
| Classical pathway defects are assoc with abnl antibody synthesis, germinal center foramation and memory. |
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Term
Associate the defect with the disease
CD59 MPGNII
Factor H Atypcial HUS
Factor I PNH
HELLP
Adult onset macular degen
Pyogenic infxns |
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Definition
CD59: PNH
Factor I: Atypcial HUS, HELLP, Pyogenic infxns
Factor H: MPGNII, Atypcial HUS, Adult onset macular degen |
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Term
1. If CH50=0, what defect should you consider?
2. If multiple proteins are low, is this more likely to be genetic or acquired? |
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Definition
1. Genetic defect of a numbered complement protein
2. Acquired |
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Term
| Which is more common: absence of control or numbered (complement) proteins? |
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Definition
| Absence of control proteins |
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Term
| Defects in which complement proteins are assoc with high risk for SLE? |
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Definition
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