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Immunology > Complement Activation > Flashcards

Complement Activation Flashcards

1
Q

What are the core functions of complement activation?

A

Recruit inflammatory cells (promoting inflammation).

Opsonize microbial pathogens and immune complexes (facilitating antigen clearance).

Kill microbial pathogens (via a lytic mechanism known as the membrane attack complex).

Generate an inflammatory response.

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2
Q

What are the different pathways for the activation of the complement system?

A
  • Classical Pathway
  • Lectin Pathway
  • Alternative Pathway
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3
Q

When is the classical pathway activated and when is is activated?

A

The classical pathway is activated after the immune complex formation occurs

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4
Q

What first occurs in the classical pathway?

A

C1 is the first complement component of the classical pathway which binds the exposed Fc of Ag-Ab complex

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5
Q

What makes up the C1 complex?

A

C1q
C1r
C1s

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6
Q

How is the C1qrs complex activated?

A

Activation of the C1qrs complex occurs when at least two of the C1q globular heads are simultaneously bound to antibody.

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7
Q

What happens once C1q is bound to Ab?

A

Once C1q binds Ab then C1r undergoes conformational change and becomes enzymatically active.

It cleaves C1s which then becomes activated.

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8
Q

What is the function of activated C1qrs complex?

A

Activated C1qrs after C1s cleavage will cleave C4.

The cleaved C4b fragment will bind to a cell surface (microorganism) and the C4b will bind C2.

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9
Q

What happens to C2 once it is cleaved by C4b?

A

C2 bound to C4b is cleaved by C1s which forms the C4b2a complex which remains bound to cell membrane.

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10
Q

What is the action of C4b2a?

A

It is a C3 convertase that is capable of cleaving C3 into C3b and C3a.

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11
Q

What is the function of C3 cleavage by a C3 convertase?

A

This is a major point of amplification of the pathways, since one C3 convertase can cleave up to 1000 molecules of C3.

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12
Q

What is the function of C3b, bound to the Ag surface?

A

C3b, bound to the antigenic surface, acts as a powerful opsonin and enhances the uptake of antigenic particle by phagocytes.

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13
Q

What is the function of the C4b2a3b complex that forms after C3 cleavage?

A

C4b2a3b functions as a C5 converts to cleave C5 into C5a and C5b

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14
Q

What is the function of C5a?

A

Soluble inflammatory mediator

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15
Q

What is the function of C5b?

A

Complexes with other complement and initiates the final phase of complement activation -> MAC formation.

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16
Q

Does the MAC differ by the pathway of activation?

A

NO

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17
Q

What activates the lectin pathway?

A

Mannan Binding Lectin (MBL) or ficolins (homologous to C1q) binding to mannose or other carbohydrates.

18
Q

What serine proteases are MBLs/ficolins associated with that are similar to C1r and C1s of the classical pathway?

A

MASP-1 and MASP-2

19
Q

What activates MASP-1 and MASP-2?

A

MBL/ficolin binding

20
Q

In the lectin pathway, what cleaves C4?

A

Activated MASP-1 and MASP-2 will cleave C4 and the C4b fragment will bind C2 which is cleaved by MASP-2 and forms the C4b2a complex.

The rest of the lectin pathway is identical to the classical pathway.

21
Q

How is the alternative pathway activated?

A

The alternative pathway depends upon the slow hydrolysis of C3, which spontaneously
occurs in plasma.

22
Q

What happens with hydrolyzed C3?

A

Hydrolyzed C3 will bind Factor B and form the C3 (H2O) Bb complex

23
Q

What is the function of the C3 (H2O) Bb complex?

A

The C3 (H2O) Bb complex is a C3 converts that can generate C3b

24
Q

What is the function of the C3b generated in the alternative pathway?

A

C3b binds Factor B, and Factor B is cleaved by Factor D, forming bound C3bBb.

25
Q

What is the function of C3bBb?

A

When it is bound by Factor P (properdin) which stabilizes it the C3bBb complex acts as a C3 convertase like C4b2a of the classical pathway.

26
Q

What happens when another C3b associates with C3bBb?

A

It forms C3bBbC3b which is a C5 convertase that is analogous to C4b2a3b and it cleaves C5 with C5b generating the final phase to form the Membrane Attack Complex.

27
Q

What is the function of the MAC?

A

Creates a pore in the cell membrane

28
Q

What is the function of complement proteins in opsonization?

A

Phagocytic leukocytes, including neutrophils and macrophages, carry receptors for C3b (CR1). When an antigenic particle is coated with C3b, C3b (also C4b) assists in the adherence and ultimate ingestion of the particle by the phagocytic cell. The C5a fragment also enhances phagocytosis by stimulating phagocytic cells to ingest C3b coated antigens.

29
Q

What is the function of complement proteins in clearance of immune complexes?

A

The removal of antigen-antibody complexes from the circulation depends upon C3b. Via C3b, antigen-antibody complexes bind to complement receptors on circulating red blood cells.

30
Q

What complement protein is involved in chemotaxis in inflammation and what is its function?

A

C5a is an important chemoattractant for neutrophils, eosinophils, basophils, and monocytes. The development of a C5a gradient at sites of complement activation assists in the recruitment of leukocytes to the area of antigenic challenge.

31
Q

What complement proteins are involved in vascular changes in inflammation and what is their function?

A

The fragments C3a, C4a, and C5a are capable of binding to specific receptors on mast cells and basophils, triggering granule release by these cells. The release of histamine leads to vascular changes, including increased vascular permeability. Because of this property, C3a, C4a and C5a are called anaphylatoxins.

32
Q

What inhibits complement at C1?

A

C1 INH

33
Q

What inhibits C3 convertase?

A

DAF, C4BP, CR1, MCP, Factor I

34
Q

What inhibits C5 convertase?

A

Factor H, I and CR1

35
Q

What prevents the assembly of the membrane attack complex?

A

CD59

36
Q

What prevents the assembly of the membrane attack complex?

A

CD59

37
Q

What is the result of C1/2/4 deficiency (Classical Pathway)?

A

Immune complex disease

38
Q

What is the result of MBL/MASP1/2/C2/C4 deficiency (Lectin Pathway)?

A

Childhood bacterial infections

39
Q

What is the result of Factor D and Factor P deficiency (Alternative Pathway)?

A

Infection with pyrogenic bacteria and Neisseria but no immune complex disease

40
Q

What occurs with C5-C9 deficiency?

A

Infection with Neisseria only

41
Q

What is the problem with Hereditary Angioneurotic Edema?

A

C1 INH deficiency – failure to regulate C1

resulting in fluid accumulation, epiglottal swelling.

42
Q

What is the problem with Paroxysmal Nocturnal Hemoglobinurea?

A

CD59 failure to function – lack of complement regulation leads to RBC lysis.

Immunology (25 decks)

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