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Immunology Test #2 > The Complement System > Flashcards

The Complement System Flashcards

1
Q

What is the complement system?

A

A system of plasma proteins that mark pathogens for destruction.

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2
Q

Four functions of complement?

A

Innate Immunity (Microbial recognition)
Opsinization of pathogens
Recruitment of inflammatory cells (act as chemokines)
Lysis and Death of Pathogens (and destruction of own cells)

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3
Q

C3 is cleaved into….

List functions.

A

C3a – Recruits Phagocytes

C3b – Tags bacterium for destruction

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4
Q

Cleavage of C3 exposes ____ on C3b surface

A

Thioester Bond

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5
Q

Two possibilities following exposure of thioester bond on C3b

A
  1. Nucleophilic attack by H20 –> Soluble C3b

2. Nucleophillic attack by R-OH/R-NH2 –> C3b on surface

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6
Q

Three complement activation pathways in order of speed

A

Alternative
Lectin
Classical

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7
Q

What triggers complement activity in alternate pathway

A

Local environment generated by pathogen surface

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8
Q

What triggers complement activity in the lectin pathway?

A

Mannose binding-lectin on the pathogen surface

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9
Q

What triggers complement activity in the classical pathway

A

C-reactive protein or antibody bound to pathogen surface

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10
Q

How are complement factors produced?

A

In liver as zymogens (cleaved to become active)

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11
Q

Complement factor of highest concentration?

A

C3 is at the highest serum conc (1.2 mg/ml)

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12
Q

Describe the process of formation of alternate pathway C3 convertase

A
  1. Hydrolysis of C3 to activate
  2. Binding of B protein
  3. B cleaved to Bb by D Protein Protease
  4. Additional C3 makes soluble C3 convertase
  5. C3 hydrolyze makes into surface C3b
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13
Q

What causes hydrolysis of thioester bond in formation of alt. C3?

A

Its spontaneous

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14
Q

Explain Alternative C3 convertase amplification.

A

C3 Convertase is able to repeatedly hydrolyze present C3 molecules generating large quantities of additional C3b bound to the surface

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15
Q

List the four important regulators of the alternative pathway

A

Properdin
Factor H and Factor I
DAF
MCP

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16
Q

What does Properdin do in the alternative pathway

A

Stabilizes C3 convertase (C3bBb) on pathogen surface

Promotes Complement Activity

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17
Q

How do Factor H and Factor I influence the alternative pathway?

A

Inhibits Complement Activity
H Binds C3b and attracts Factor I
I fragments/inactivates C3b

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18
Q

How does DAF influence the alternative pathway?

A

DAF is on human cells. It disrupts C3 convertase binding on self-cell surfaces

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19
Q

How does MCP influence the alternative pathway?

A

MCP disrupts C3 convertase and attracts I Factor

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20
Q

Symptoms of Factor I deficiency?

A

Unchecked C3 activation
C3 depletion in the body
Chronic infections by encapsulated bacteria

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21
Q

Genetic inheritance of Factor I deficiency?

A

Autosomal Recessive

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22
Q

What sites in the body are especially influenced by Factor I deficiency

A
  • Recurrent infec. in URT, Ears, Skin, UT
  • Pneumonia, Meningitis, Sepsis
  • Glomerulonephritis with isolated C3 deposits
  • Rheumatoid Arthritis/Systemic lupus erythematosus
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23
Q

How does opsonization via C3b work?

A

Complement leads to C3b deposits on bacteria
CR1 on macrophage binds C3b on bacterium
Endocytosis by macrophage
Formation of phagolysosome

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24
Q

Where are CR1/CD35 found?

A

Erythrocytes, Leukocytes, Glomerular Podocytes, FDC

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25
Q

Where are CR2/CD21 found?

A

B Cells, FDC

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26
Q

Where are CR3, CD11b/CD18 integrin found?

A

Myeloid Leukocytes.

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27
Q

Where are CR4, CD11c/CD18 integrin found?

A

Myeloid Leukocytes.

28
Q

What happens in the complement terminal pathway?

A

C5 activation by Alternative C5 convertase

Stimulation/Recruitment of C5b triggers Membrane Attack Complex formation

29
Q

What is the membrane attack complex?

A

Combination of C5b, C6-8, and C9 which for pores in pathogen surfaces.

30
Q

Role of C5 in MAC?

A

Initiation

31
Q

Role of C9 in MAC?

A

Forms a membrane spanning pore that disrupts the cell’s integrity and can result in cell death

32
Q

How is MAC regulated in humans?

33
Q

How does CD59 work?

A

CD59 binds to the C5b678 complex and prevents recruitment of C9 to form the porn

34
Q

CD59 = CI Factor ____

35
Q

Molecular cause of paroxysmal nocturnal hemoglobinuria

A

Missing CD55 or 59 from somatic mutation in gene - PIGA

36
Q

Inheritance pattern of paroxysmal nocturnal hemoglobinuria

37
Q

Loss of CD55 (DAF) causes….

A

Inability to prevent complement activation

Extravascular hemolysis –> Anemia

38
Q

Loss of CD59 causes….

A

Intravascular hemolyiss –> Anemia/Free Hb

Free Hb –> NO-scavenging, Fatigue, Esophageal spasms, Thrombosis

39
Q

Paroxysmal nocturnal hemoglobinuria treatment?

A

Bone Marrow Transplant

Eculizumab

40
Q

What is Eculizumab

A

Humanized Anti-C5 antibody

Prevents activation of C5 by C5 convertase

41
Q

Name the two types of C3 convertase

A

Classical – C2a:C4b

Alternative – Bb:C3b

42
Q

Describe classical pathway activation

A

CR1 binds C-reactive protein or antibody on pathogen surface

43
Q

What happens in the classical pathway following C1 binding

A
  1. C1 catalyzes C4–>C4b and C2 –> C2a
  2. Formation of C3 convertase
  3. Hydrolysis of C3 (now its the same as alternate pathway)
44
Q

T of F. A single IgG can activate the classical pathway

A

False. Multiple IgG are required for C1q to bind

45
Q

Significance of the binding structure of the complement pathway?

A

Allows for amplification on the pathogen surface

46
Q

Which antibodies are really good are fixing complement?

47
Q

Which antibodies are really bad at activating the complement pathway?

A

IgD, IgG4, and IgE

48
Q

CR1 binds to…

What cells have it?

A

C3b
Macrophages, Neutrophils, RBCs
Also – FDC, Glomerular Podocytes

49
Q

Function of CR1?

A

Phagocytosis

Clearance of Immune Complexes

50
Q

CR2 binds to…

What cells have it?

A

C3d
Follicular DC
B Cells

51
Q

Function of CR2?

A

Antigen Trapping

B Cell Activation

52
Q

CR3 binds to…

What cells have it?

A

iC3b

Macrophages, Neutrophils

53
Q

Function of CR3

A

Phagocytosis

54
Q

CR4 binds to…

What cells have it?

A

iC3b

Macrophages, Neutrophils

55
Q

Function of CR4

A

Phagocytosis

56
Q

Role of erythrocyte CR1?

A

Prevents the body from being overrun with immune complexes

57
Q

List the Complement system anaphylatoxins in order of Potency

A

C5a > C3a > C4a

58
Q

Effects of complement anaphylactoxins

A

Vasodilation, Inc. Vasc. permeability
Smooth musc. contraction
Mast cell degranulation
Chemotaxis of neutrophils

59
Q

Absence of C4A leads to…

A

Increased susceptibility to systemic lupus erthematosus

60
Q

Absence of C4b leads to…

A

Increased susceptibility to infections

61
Q

Describe the Lectin pathway.

A

Mannose binding protein binds to bacterial surface
Activated MASP-2 cleaves C4, Some C4b on surface
MASP-2 also cleaves C2, allows C2a to bind to C4b
C2aC4b binds and cleave C3, allowing C3 binding

62
Q

Molecular cause of Hereditary Angioneurotic Edema?

A

Deficiency of Functional C1 Inhibitor

63
Q

Inheritance pattern of Hereditary Angioneurotic Edema

A

Autosomal Dominant

64
Q

Effects of Hereditary Angioneurotic Edema?

A

Increased bradykinin, decreased C4, C2
Recurrent Edema in Skin, GI, UG, and Larynx
Ab pain, pelvic pain, suffocation

65
Q

What is a C2 kinin?

A

A vasoactive peptide generated by clevage of the C2b fragment by plasmin

Immunology Test #2 (8 decks)

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