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Host Defense Exam 1 > Compliment > Flashcards

Compliment Flashcards

1
Q

What are the three effects of the products generated by the compliment components

A

1) Recruit inflammatory cells
2) Opsonize microbial pathogens and immune complexes to make them more recognizable by the immune system
3) Kill microbial pathogens through MAC

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2
Q

The classical pathway is activated by what?

A

Antigen:antibody complexes

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3
Q

The Lectin pathway is activated by what?

A

Lectin binding to pathogen surfaces

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4
Q

The Alternative pathway is activated by what?

A

pathogen surfaces

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5
Q

What component of the classical pathway recognizes the antibody:antigen complex? What is it binding?

A

C1: binds to the Fc portion of the antibody molecule

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6
Q

Why does C1 not bind to soluble unbound antibody?

A

The binding of the antibody to antigen induces a conformational change in the antibody constant region. This exposes a site on the Fc portion that can be bound by C1

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7
Q

How many globular heads make up C1?

A

6

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8
Q

How many globular heads of C1 must be bound to antibody?

A

At least 2: this means that two Fc portions need to be within close molecular proximity of each other on the antigenic surface

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9
Q

What is the chain of events that occurs within the C1 complex following binding to two or more globular heads?

A

C1q binds to the Fc regions, C1r undergoes a conformational switch and becomes enzymatically active and cleaves C1s, which after cleavage is enzymatically active as well

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10
Q

Differentiate activation of C1 binding to IgG vs IgM

A

IgG: monomer, therefore there must be a higher density of IgG on the antigen in order to activate C1

IgM: pentameric, therefore can always activate C1 by itself

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11
Q

Which protein initiates the lectin pathway?

A

Mannose-binding lectin and ficolins recognize and bind carbohydrates on pathogen surfaces

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12
Q

What does ficolin bind?

A

oligosaccharides containing acetylated sugars

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13
Q

What does MBL bind?

A

mannose, fucose and other complex carbohydrates

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14
Q

What are the two serine proteases physically associated with MBL/ficolin that are analogous to C1r and C1s?

A

MASP-1 and MASP-2

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15
Q

Activated C1qrs or MBL/ficolin activated MASP1 and MASP2 cleave what?

A

C4 is cleaved into C4a and C4b,

C4b fragments then bind C2

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16
Q

How is C2 cleaved?

A

C2 is cleaved by C1s (or MASP-1/MASP-2) into C2a and C2b.

C2a combines with the C4b on the cell surface to form the C4b2a complex

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17
Q

What is another name for C4b2a? What is its purpose?

A

C4b2a is a C3 convertase, capable of cleaving C3 into C3b and C3a. 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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18
Q

What is the purpose of producing C3b?

A

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

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19
Q

What is the C5 convertase?

A

C4b2a3b is the C5 convertase. It produces C5a and C5b.

C5a is a soluble inflammatory mediator, and C5b is a capable of complexing with other components

20
Q

Describe the MAC

A

C5b binds to C6 and C7
C8 binds the complex and inserts into the membrane
1-16 molecules of C9 bind to form a pore in the membrane

21
Q

MAC complexes are more effective at what class of bacteria

A

Gram negative, because they don’t have much of a cell wall_

22
Q

What is required for the activation of the alternative pathway?

A

The activation of the alternative pathway depends on slow hydrolysis of C3, which spontaneously occurs in the plasma

23
Q

What is the C3 convertase of the alternative pathway?

A

Hydrolyzed C3 (that occurred spontaneously in the plasma) can bind Factor B, and the resulting C3Bb complex is a C3 convertase that can generate additional molecules of C3b

24
Q

C3b binds factor B, allowing for cleavage by what? What is formed?

A

Factor D. This forms C3bBb

25
Q

What is necessary for stabilization of C3bBb?

A

Factor P (properdin)

26
Q

What is another name for C3bBb?

A

C3 convertase of the alternative pathway

27
Q

What is the C5 convertase of the alternative pathway?

A

C3bBbC3b

28
Q

Why is C5 convertase the last step in the compliment pathway?

A

Because the formation of C5b is necessary for initiation of MAC complex formation

29
Q

Can viruses be eliminated via the MAC?

A

Certain viruses with a membrane coat can be lysed via MAC

30
Q

Phagocytes, including neutrophils and macrophages, carry receptors for what opsonin?

A

C3b.

When an antigenic particle is coated with C3b, C3b assists in the adherence and ultimate ingestion of the particle by the phagocytic cells

31
Q

What is the receptor against C3b called?

A

CR1

32
Q

The removal of antigen-antibody complexes from the circulation depends on what compliment component? How does this occur?

A

C3b

Via C3b, antigen-antibody complexes bind to complement receptors on circulating red blood cells. As the RBC passes through the spleen and liver, the coated complexes are stripped off the RBCs by resident phagocytes

33
Q

What compliment component is important for chemotaxis of neutrophils, eosinophils, basophils and monocytes to the site of infection?

A

C5a

34
Q

Which compliment components are capable of binding to specific receptors on mast cell and basophils?

A

C3a, C4a and C5a

35
Q

How does C3a, C4a and C5a lead to vascular changes?

A

They bind specific receptors on mast cells and basophils which cause them to release histamine, which leads in increased vascular permeability

Because of this, they are called anaphylatoxins

36
Q

What protein is important for the inhibition of C1? How does it work?

A

C1INH (C1 inhibitor)

It inhibits C1 by dissociating C1r and C1s from the C1 complex

37
Q

Name 5 inhibitors of the C3 convertase

A 
Decay-accelerating factor (DAF)
C4 binding protein (C4BP)
Compliment receptor 1 (CR1)
Membrane cofactor protein (MCP)
Factor I (I)
38
Q

What three things inhibit C5 convertase?

A 
Factor I (I)
Factor H (H)
Compliment receptor 1 (CR1)
39
Q

What factor prevents the assembly of the MAC?

A

CD59

40
Q

Deficiencies in the initiation of the classical pathway leads to what disease?

A

Immune-complex disease

41
Q

Deficiencies in the lectin pathway leads to what diseases?

A

Bacterial infections, primarily in childhood

42
Q

Deficiencies in the alternative pathway leads to what diseases?

A

Infection with pyogenic bacteria and Neisseria spp, but no immune-complex disease

43
Q

Deficiencies in C3b deposition leads to what diseases?

A

Infection with pyogenic bacteria and Neisseria spp.

Sometimes immune complex disease

44
Q

Deficiencies in the membrane attack components leads to what disease?

A

Infection with neisseria spp. only

45
Q

What disease is caused by a deficiency of C1 INH?

A

Hereditary Angioneurotic Edema (The lady with the blown up face)

46
Q

Failure in CD59 ( inhibitor of MAC formation) leads to what disease?

A

Paroxysmal Nocturnal Hemoglobinuria –> red blood cell lysis

47
Q

A deficiency of the early components of complement results in poor clearance of immune complexes resulting in what disease?

A

Immune complex disease

Host Defense Exam 1 (12 decks)

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