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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
Where are CR2/CD21 found?
B Cells, FDC
26
Where are CR3, CD11b/CD18 integrin found?
Myeloid Leukocytes.
27
Where are CR4, CD11c/CD18 integrin found?
Myeloid Leukocytes.
28
What happens in the complement terminal pathway?
C5 activation by Alternative C5 convertase | Stimulation/Recruitment of C5b triggers Membrane Attack Complex formation
29
What is the membrane attack complex?
Combination of C5b, C6-8, and C9 which for pores in pathogen surfaces.
30
Role of C5 in MAC?
Initiation
31
Role of C9 in MAC?
Forms a membrane spanning pore that disrupts the cell's integrity and can result in cell death
32
How is MAC regulated in humans?
CD59
33
How does CD59 work?
CD59 binds to the C5b678 complex and prevents recruitment of C9 to form the porn
34
CD59 = CI Factor ____
5
35
Molecular cause of paroxysmal nocturnal hemoglobinuria
Missing CD55 or 59 from somatic mutation in gene - PIGA
36
Inheritance pattern of paroxysmal nocturnal hemoglobinuria
X-linked
37
Loss of CD55 (DAF) causes....
Inability to prevent complement activation | Extravascular hemolysis --> Anemia
38
Loss of CD59 causes....
Intravascular hemolyiss --> Anemia/Free Hb | Free Hb --> NO-scavenging, Fatigue, Esophageal spasms, Thrombosis
39
Paroxysmal nocturnal hemoglobinuria treatment?
Bone Marrow Transplant | Eculizumab
40
What is Eculizumab
Humanized Anti-C5 antibody | Prevents activation of C5 by C5 convertase
41
Name the two types of C3 convertase
Classical -- C2a:C4b | Alternative -- Bb:C3b
42
Describe classical pathway activation
CR1 binds C-reactive protein or antibody on pathogen surface
43
What happens in the classical pathway following C1 binding
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
T of F. A single IgG can activate the classical pathway
False. Multiple IgG are required for C1q to bind
45
Significance of the binding structure of the complement pathway?
Allows for amplification on the pathogen surface
46
Which antibodies are really good are fixing complement?
IgM, IgG3
47
Which antibodies are really bad at activating the complement pathway?
IgD, IgG4, and IgE
48
CR1 binds to... | What cells have it?
C3b Macrophages, Neutrophils, RBCs Also -- FDC, Glomerular Podocytes
49
Function of CR1?
Phagocytosis | Clearance of Immune Complexes
50
CR2 binds to... | What cells have it?
C3d Follicular DC B Cells
51
Function of CR2?
Antigen Trapping | B Cell Activation
52
CR3 binds to... | What cells have it?
iC3b | Macrophages, Neutrophils
53
Function of CR3
Phagocytosis
54
CR4 binds to... | What cells have it?
iC3b | Macrophages, Neutrophils
55
Function of CR4
Phagocytosis
56
Role of erythrocyte CR1?
Prevents the body from being overrun with immune complexes
57
List the Complement system anaphylatoxins in order of Potency
C5a > C3a > C4a
58
Effects of complement anaphylactoxins
Vasodilation, Inc. Vasc. permeability Smooth musc. contraction Mast cell degranulation Chemotaxis of neutrophils
59
Absence of C4A leads to...
Increased susceptibility to systemic lupus erthematosus
60
Absence of C4b leads to...
Increased susceptibility to infections
61
Describe the Lectin pathway.
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
Molecular cause of Hereditary Angioneurotic Edema?
Deficiency of Functional C1 Inhibitor
63
Inheritance pattern of Hereditary Angioneurotic Edema
Autosomal Dominant
64
Effects of Hereditary Angioneurotic Edema?
Increased bradykinin, decreased C4, C2 Recurrent Edema in Skin, GI, UG, and Larynx Ab pain, pelvic pain, suffocation
65
What is a C2 kinin?
A vasoactive peptide generated by clevage of the C2b fragment by plasmin

Immunology Test #2 (8 decks)

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