Complement

Question 1

C1-4 deficiency

Answer 1

Autoimmune type things- SLE

alternative pathway takes over

Question 2

C3 deficiency

Answer 2

key in both classical and alternative
serious recurrent pyogenic infections
GN, immune complex disease

Question 3

C5-8 deficiency

Answer 3

increase susceptibility to neisseria (mening and gonococcal infections) as cannot lyse these cells

Question 4

Deficiency of C1 esterase inhibitor

Answer 4

hereditaty angioedema
AD condition
unregulated activity of C1s, C1r, Complement cascades. BRADYKININ RELEASE 
nausea, vomiting, choking
Can treat with C1 inhibitor concentrates
STeroids to prevent sometimes
Often FH angioedema
NO URTICARIA

Question 5

Deficiency CD55 and CD59 due to glycophosphatidyl inositol linkages not working

Answer 5

PNH

Question 6

Three pathways

Answer 6

classical - Ag Ab complexes on pathogen surface espec IgM, IgG, CRP, C1q, also INNATE immune system via CRP and lipoteichoic acid on gram+ bacteria
- C1 ro C4

alternative - pathogen surfaces themselves- MAIN pathway. Also IgA immune complexes, polysacharides, C3 nephritic factor
-C3+ properdin

mannose binding lectin- sugar mannose on pathogen surfaces bind MBL and ficolins 1-3

Question 7

3 functions of complement

Answer 7

Opsonise- most important (C3b)
Lyse via MAC
Peptide mediators of inflammation and chemo-attraction- C3a, C5a, C4a

Question 8

C3a,C5a

Answer 8

peptide mediators of inflammation, recruit phagocytes

Question 9

C3b

Answer 9

opsonise

Question 10

C5b, C7-9

Answer 10

MAC formation

Question 11

Best test for exclusion of hereditary angioedema is

Answer 11

C1 inhibitor function

ALL types reduced

Question 12

If looks like C1 inhibitor deficiency but C4 levels normal?

Answer 12

Could be type 2- dysfunctional rather than reduced quantity of inhibitor. C1 inhibitor levels also normal or increased

Question 13

What is the type of hered angioedema where it is nothing to do with complement?

Answer 13

Factor XII gain of function mutation
ostrogen related
only in women

Question 14

What are the acquired types of c1 esterase def?

Answer 14

Autoimmune- ab against the inhibitor (C1 inh level normal)
Consumption- with B cell lymphoprolif disorders

In these the C1q level is low- normal in hereditary forms

Question 15

Acute tx hered angioedema?

Answer 15

life threatening- replace C1 IH protein
bradykinin 2 receptor antagonist- Icatibant

ADRENALINE AND ANTIHIST DO NOT WORK

Question 16

preventative tx angioedema?

Answer 16

anabolic steroids like danazol
tranexamic acid
Replace

In acquired form can use CS, immunosupression, treat underlying disease.

Question 17

Gain function mutation in factor H, I, MCP, C3, B of alternative pathway?

Answer 17

Atypical HUS

Question 18

Eculizumab

Answer 18

Monoclonal Ab against C5a- rol ein PNH and aHUS