Biochemistry 5-6: Complement System Regulation And Deficiency Disorders Flashcards
List the 3 pathways of activation of complements?
1- the classical pathway.
2- the alternative pathway.
3- the MB lectin pathway.
List the 4 types of complement deficiencies?
1- components of activation pathway.
2- control proteins: soluble control proteins, membrane regulatory proteins.
3- complement receptors deficiencies.
4- acquired deficiencies.
List the components that my get defected in a deficiency of components of activation pathways?
C1q, C1r, C1s, C4, C2, C3, MBL, D, B, C5, C6, C7, C8, C9.
List the components that my get defected in a deficiency of soluble control proteins?
C1 inhibitor, Factor I, Factor H, C4b binding protein, S protein.
List the components that my get defected in a deficiency of membrane regulatory proteins?
CD55 (DAF), MCP CD46, CD59, HRF/C8bp.
List the components that my get defected in a deficiency of complement receptors?
C1q receptor, CR1 (CD35), CR2 (CD21), CR3 (CD11b/CD18), CR4 (CD11c - CD18).
List clinical manifestations in complement deficiencies?
1- increased susceptibility to infections: with systemic course - bacteremia + meningitis.
- S.pneumoniae, S.pyogenes, H.influenzae (early components, defect in opsonization).
- Neisseria meningitidis (defect in terminal components).
2- autoimmune disorders: defective immune complex clearance.
3- angioedema.
List ways to test for complement deficiencies (laboratory testing)?
1- CH50.
2- AH50.
3- plasma C3 and C4 levels.
4- other tests:
- C5a, C3a, Bb..
- tissue deposition of complement (immunofluorescence).
What is CH50 testing used for?
Detecting a deficiency of the classical pathway.
Assesses the ability of the test serum to lyse sheep erythrocytes optimally sensitized with rabbit antibody.
What is AH50 testing used for?
Measure the total alternative pathway (lysis of unsensitized rabbit RBCs).
What is plasma C3 and C4 levels testing used for?
Measured in nephelometric immunoassays.
Helpful in following patients.
What is CH50 testing sensitive to?
Sensitive to reduction, absence and/or inactivity of any component of the pathway.
What does the CH50 test?
Tests the functional capability of serum complement components of the classical pathway to lyse sheep RBCS, pre-coated with rabbit anti-sheep RBC antibody (hemolysin).
List the results for CH50 and what do they mean?
When antibody-coated SRBC are incubated with test serum, the classical pathway of complement is activated and hemolysis results.
- if a complement is absent, the CH50 level will be zero; if one or more components of the classical pathway are decreased, the CH50 will be decreased.
List the clinical manifestations of complement component deficiencies?
- rare.
- individuals have a variety of clinical presentations.
- individuals are susceptible to infection.
- other are susceptible to immune complex-mediated syndromes ( SLE, glomerulonephritis, dermatomyositis, anaphylactoid purpura, and vasculitis).
- others have angioedema.
- in rare instances, patients may even be asymptomatic.
List the 7 classifications of complement component deficiencies?
1- inherited classical pathway deficiencies.
2- inherited mannose-binding lectin pathway deficiencies.
3- inherited alternative pathway deficiencies.
4- C3 and late-acting components deficiencies.
5- inherited deficiencies of complement inhibitor proteins: autosomal recessive, autosomal dominant (C1 inhibitor deficiency), X-linked (properdin deficiency).
6- complement receptor 1, 2 or 3 deficiency.
7- acquired deficiencies of complement components.
Defects in the early components of the classical pathway do not lead to overwhelming infection, why?
Because the MBL and alternative pathways can bypass these defects.
A deficiency of the early components of complements results in what?
Results in poor clearance of immune complexes resulting in increased immune complex disease.
List the complement proteins, defects, and diseases associated with inherited classical pathway deficiencies?
Complement proteins: C1q, C1r, C1s, C4, C2.
Defect: impaired solubilization of immune complexes; poor immunoregulation.
Diseases associated: autoimmune disease (SLE), may be severe; infections with encapsulated organisms.
What is systemic lupus erythematous (SLE)?
- autoimmune disorder characterized by multi system inflammation with the generation of autoantibodies.
- autoimmune reactions directed against constituents of cell nucleus, DNA.
- antibody response related to B and T cell hyperactivity.
List the dermatological manifestations that may arise with SLE?
1- Malar rash: butterfly-shaped red rash over the checks below the eyes and across the bridge of the nose, may be flat or a raised rash, made worse by sun exposure.
2- Discoid lupus: red, raised patches with scaling of the overlying skin.
3- Vasculitis skin lesion.
4- swan neck deformity.
What happens in a C1q deficiency?
SLE, SLE like syndrome, chronic rash-vasculitis, septicemia and meningitis.
What happens in a C2 deficiency?
- 10-30% of individuals present with an SLE-like illness.
- usually no infection, but they are prone to recurrent pyogenic infections (particularly due to encapsulated bacteria).
- associated with IgG subclass deficiency.
- other diseases associated include polymyositis, glomerulonephritis, Hodgkin lymphoma, vasculitis and Henoch-schonlein purpura.
List the complement proteins, defects, and diseases associated with inherited mannose-binding lectin pathway deficiencies?
Complement protein: MBL, MASP.
Defect: impaired first line defense against microbes.
Diseases associated: repeated infections; accelerated course of SLE and RA reported.