Complement Deficiency Flashcards
What are the three biological effects of complement?
Lysis, Opsonization, and danger signaling
What complement component is chemotaxis for neutrophils?
C5a, probably works on mast cells to
What complement components are important for opsonophagocytosis?
C3b and iC3b
-bind directly to microbes
What are the danger signals of complement?
C3a, C4a, and C5a
What is responsible for the clearance of immune complexes?
C3a and iC3b, also important is the CR1 receptor
How would complement co-activate a B cell?
CR2 is expressed on B cells and will respond to C3d on the surface of microbes. requires cross linking with BCR
What does the C1 inhibitor stop?
C1 inhibitor stops the classical pathway (by dissociateing C1q from C1r2s2, thus stopping the formation of C1qr2s2 the first step in the clasical pathway)
- also inhibits MASP1,2 which normally cleaves C4 and C2 that would form the lectin pathway C3 convertase C4b2b.
- MASP is MBL- associated serine proteases
What will an anaphylatoxin inhibitor do?
It will degrade the danger signals C3a, C4a, and C5a preventing peptide mediators of inflammation and phagocyte recruitment
What will S protein do?
S protein blocks insertion of C5b6789 into host cell membranes. Prevents the MAC complex from working.
What are the inflammatory mediators that can cause cutaneous swelling?
Histamine and Bradykinin
-vasodilation and vascular permeability
What do allergic reactions require?
A trigger to set of the reaction.
-lack of one can be indication of something else at play
What is the significant that affected skin is not pruritic?
Means the cause is probably not histamine driven
Why would epinephrine, diphehydramine, famotidine and prednisone provide no releif to a patient with angioedema?
If these provide no releif it means the angioedema is not histamine drive. Must look for other factors at play
When is tryptase produced?
Produced by mast cells in resposne to hypersensitivity reactions, elevated in allergic angioedema
You get a complement test and the results come back all normal except for low C4 and C2? What is going on and what else should we be concerned about? Assuming a genetic disease what do you think is the cause?
Low C4 and C2 means that complement is being activated because these are being used up.
- specifically this are the classical pathway components.
- we are not worried about other infections, becuase she has other pathways of complement that still work.
- Likely cause is a lack of C1 esterase inhibitor, so without she is getting overactivity of the classical pathway of complement
What is the cause of hereditary angioedema?
Lack of function or absence of the C1 inhibitor (C1 INH)
- Absence of C1 esterase inhibitor permits ongoing cleavage of C4 and C2 (consumption leading to low levels).
- C2b is furhter cleaved to a C2 kinin peptide which alters vascular permeability
- C1 INH also regulates the fibrinolytic and bradykinin systems, which can lead to increased vascular permeability and vasodilation,
- thus this all leads to angioedema
What are the 4 types of angioedema and their defining factor?
HAE type I is both decreased INH level and function
HAE type II is only decrease INH function
HAE III is normal INH level and function, but age of onset is much later
Acquired angioedema, usually has an underlying malignancy or autoimmune disease
How to you treat hereditary angioedema?
- Attacks are self limited 3-4 days
- Increase liver production of C1 esterase inhibitor with anabolic steroids
- replace C1 esterase with fresh frozen plasma
- Kallikrein inhibitor for acute attacks (stop edema)
- Bradykinin receptor antagonist for acute attacks (stop edema)
- NOT responsive to epinephrine, antihistamine, or steroids
On a coagulation panel pt has high PT, INR, aPTT, and low fibrinogen? Whats going on
This is DIC
Recurrent infections of gram negative Neisseria Meningitis? What are you suspecting?
Complement deficiency. But what type?
A CH50 is undetectable, what does that mean?
CH50 is a measure of the classical pathway and indication for a complement defiency
What does Factor I do?
Factor I is a regulatory compenent and is essential for cleaveing C3b and C4b into iC3b and iC4b. Thus it is a regulatory compoenent of all 3 complement pathways.
What is C2 cleaved into that causes edema?
C2 Kinin, a peptide that alters vascular permeability
What seperates heretidary angioedemas from other angioedemas?
This is driven by bradykinin, where allergic angioedemas are driven by histamine.
