Complement Deficiency

Question 1

What are the three biological effects of complement?

Answer 1

Lysis, Opsonization, and danger signaling

Question 2

What complement component is chemotaxis for neutrophils?

Answer 2

C5a, probably works on mast cells to

Question 3

What complement components are important for opsonophagocytosis?

Answer 3

C3b and iC3b

-bind directly to microbes

Question 4

What are the danger signals of complement?

Answer 4

C3a, C4a, and C5a

Question 5

What is responsible for the clearance of immune complexes?

Answer 5

C3a and iC3b, also important is the CR1 receptor

Question 6

How would complement co-activate a B cell?

Answer 6

CR2 is expressed on B cells and will respond to C3d on the surface of microbes. requires cross linking with BCR

Question 7

What does the C1 inhibitor stop?

Answer 7

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

Question 8

What will an anaphylatoxin inhibitor do?

Answer 8

It will degrade the danger signals C3a, C4a, and C5a preventing peptide mediators of inflammation and phagocyte recruitment

Question 9

What will S protein do?

Answer 9

S protein blocks insertion of C5b6789 into host cell membranes. Prevents the MAC complex from working.

Question 10

What are the inflammatory mediators that can cause cutaneous swelling?

Answer 10

Histamine and Bradykinin

-vasodilation and vascular permeability

Question 11

What do allergic reactions require?

Answer 11

A trigger to set of the reaction.

-lack of one can be indication of something else at play

Question 12

What is the significant that affected skin is not pruritic?

Answer 12

Means the cause is probably not histamine driven

Question 13

Why would epinephrine, diphehydramine, famotidine and prednisone provide no releif to a patient with angioedema?

Answer 13

If these provide no releif it means the angioedema is not histamine drive. Must look for other factors at play

Question 14

When is tryptase produced?

Answer 14

Produced by mast cells in resposne to hypersensitivity reactions, elevated in allergic angioedema

Question 15

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?

Answer 15

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

Question 16

What is the cause of hereditary angioedema?

Answer 16

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

Question 18

What are the 4 types of angioedema and their defining factor?

Answer 18

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

Question 19

How to you treat hereditary angioedema?

Answer 19

• 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

Question 20

On a coagulation panel pt has high PT, INR, aPTT, and low fibrinogen? Whats going on

Answer 20

This is DIC

Question 21

Recurrent infections of gram negative Neisseria Meningitis? What are you suspecting?

Answer 21

Complement deficiency. But what type?

Question 22

A CH50 is undetectable, what does that mean?

Answer 22

CH50 is a measure of the classical pathway and indication for a complement defiency

Question 23

What does Factor I do?

Answer 23

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.

Question 24

What is C2 cleaved into that causes edema?

Answer 24

C2 Kinin, a peptide that alters vascular permeability

Question 25

What seperates heretidary angioedemas from other angioedemas?

Answer 25

This is driven by bradykinin, where allergic angioedemas are driven by histamine.