Test 2: Complement System Flashcards

1
Q

Functions of complement system?

A
  • lysis of target cell
  • opsonization
  • activation of inflammatory response
  • clearance of immune complexes
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2
Q

Classical Pathway different than Alternative or Lectin because…

A

Classical is the only one that is antibody dependent

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3
Q

Initiation of Classical Pathway

A

C1q binds to Fc region of Ab/Ag complex

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4
Q

What Ab typically starts the classical pathway and why?

A

IgM because of its large size–pentamer

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5
Q

Formation of classical recognition unit

A

Attachment of C1q activates C1r (two of them) then C1s–>C1qrs

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6
Q

Formation of classical activation unit

A
  • Recognition unit splits C4 then C2–>C4b2a

- this unit will split C3–>C4b2a3b=C5 convertase

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7
Q

What is the major component of the complement system?

A

C3

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8
Q

Formation of Membrane Attack Complex

A

C5 convertase splits C5–>C5b

-this attracts 67and 8–>C5b678 which will attract polymerized C9= C5b6789

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9
Q

What are the 2 major mechanisms of the MAC?

A
  1. Direct destruction of cell wall; creates pores/holes in cell
  2. Indirect: MAC changes lipid structure of antigen which disrupts the osmolarity–>lysis
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10
Q

Stimulants of Alternative pathway?

A

bacterial cell wall components, fungi, viruses, parasites, immune complexes, RBCs, and polymers

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11
Q

Major difference between classical and alternative pathways?

A

Recognition unit…No C1, C2, or C4

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12
Q

Initiation of Alternative pathway?

A

C3 spontaneously hydrolyzes–>C3b fragment will attach to foreign surface

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13
Q

Components of alternative pathway

A

C3b, Factor B, Factor D and Properdin

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14
Q

continuation of alternative pathway after C3b?

A

Factor B binds to C3b and is cleaved by Factor D–>C3bBb=C3 convertase
-Properdin binds and stabilizes C3 convertase and hydrolyzes more C3–>C3bBbC3b–>activation of C5 convertase–>MAC

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15
Q

Mannose Binding Lectin (MBL) pathway difference with classical?

A

Recognition unit is different: MBL+ MASP1 MASP2 and MASP3

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16
Q

What binds C1r2s2 so that it dissociates from C1q?

A

C1 inhibitor

17
Q

What blocks association of C4b and C2a?

A

C4b-binding protein, complement receptor type I, or membrane cofactor protein (MCP)

18
Q

What cleaves inhibitor bound C4b?

A

Factor I, makes them ineffective

19
Q

In alternative pathway, what prevents binding of C3b and Factor B?

A

CR1, MCP, or factor H

20
Q

What cleaves inhibitor bound C3b?

A

Factor I, makes it ineffective

21
Q

What dissociates C3 convertase?

A

C4bBP, CR1, factor H, and DAF

22
Q

What prevents insertion of MAC into membrane?

A

S protein

23
Q

What prevents assembly of poly-C9 and blocks formation of MAC?

A

HRF and MIRL

24
Q

Importance of CR1 receptor?

A

mediates transport of immune complexes to liver/spleen to clean the circulation

25
Q

What are anaphylatoxins and examples of them?

A

They are involved in vascular permeability to allow for better exchange of cells to amplify immune response; C3a, C4a, and C5a

26
Q

What are chemotaxins and examples of them?

A

They attract immune system–recruit PMNs and macrophages; C5a

27
Q

What are Opsonins and examples of them?

A

Helps with opsonization for phagocytes; C4b, C3b, and iC3b

28
Q

Bacteria that can resist lysis?

A

Gram positive bacteria, nucleated cells, or tumor cells

29
Q

How are viruses neutralized?

A

Typically via classical pathway. (enveloped viruses can be lysed); causes aggregation so they cant infect host and are more vulnerable to phagocytes

30
Q

What is paroxysmal Nocturnal Hemoglobinuria (PNH)?

A

Lack of DAF

31
Q

What are ways to test the complement system?

A

immunologic assays, assays for classical and alt pathways, and Complement fixation testing

32
Q

Complement Fixation Testing?

A

Add known antigen to patient serum with complement and Sheep RBC

  • If patient has the antibody for that antigen they will form complexes and complement will bind to that
  • If antibody not present in serum, complement will attach to the sheep RBC and cause it to lyse–>fluid turns red