Immuno - Immune Responses (Acute-phase reactants & Complement)

Question 1

What is complement?

Answer 1

System of interacting proteins that play a role in innate immunity and inflammation.

Question 2

What is MAC, and what does it defend against?

Answer 2

Membrane attack complex (MAC) of complement defends against gram-negative bacteria

Question 3

What are the pathways for complement activation? What mediates each pathway?

Answer 3

(1) Classic pathway - IgM or IgM mediated (Think: “GM makes CLASSIC cars”) (2) Alternative pathway - microbe surface molecules (3) Lectin pathway - mannose or other sugars on microbe surafce

Question 4

What is the function of C3b?

Answer 4

C3b - opsonization (Think: “C3B Binds Bacteria”)

Question 5

What major function does C3a have? What other 2 complement products share that function?

Answer 5

C3a, C4a, C5a - anaphlaxis (Think: “C3A & C5A = Anaphylaxis”)

Question 6

What is the function of C5a (distinct from C3a)?

Answer 6

C5a - neutrophil chemotaxis

Question 7

Which complement proteins are involved in cytolysis by MAC?

Answer 7

C5b-9

Question 8

What are the 2 primary opsonins in bacterial defense? Which of these also helps to clear immune complexes?

Answer 8

C3b and IgG are the two primary opsonins in bacterial defense; C3b also helps clear immune complexes.

Question 9

What prevents complement activation on self cells?

Answer 9

Decay-accelerating factor (DAF, aka CD55) and C1 esterase inhibitor help prevent complement activation on self cells (e.g., RBC)

Question 10

Draw the complement cascade, including the Alternative pathway, Lectin pathway, and Classical pathway, with all ultimately leading to lysis/cytotoxicity.

Answer 10

See p. 204 in First Aid 2014 for image at bottom of page

Question 11

In general, what mediates the activation of the classic complement pathway?

Answer 11

Antigen-antibody complexes

Question 12

In general, what mediates the activation of the alternative complement pathway?

Answer 12

Spontaneous and microbial surfaces

Question 13

In general, what mediates the activation of the lectin complement pathway?

Answer 13

Microbial surfaces (e.g., mannose)

Question 14

What are 4 examples of complement disorders?

Answer 14

(1) C1 esterase inhibitor deficiency (2) C3 deficiency (3) C5-C9 deficiency (4) DAF (GPI anchored enzyme deficiency)

Question 15

What condition does C1 esterase inhibitor deficiency cause?

Answer 15

C1 esterase inhibitor deficiency –> hereditary angioedema;

Question 16

What medication is contraindicated for C1 esterase inhibitor deficiency?

Answer 16

C1 esterase inhibitor deficiency –> ACE inhibitors are contraindicated

Question 17

What condition does C3 deficiency cause?

Answer 17

C3 deficiency –> severe, recurrent pyogenic sinus and respiratory tract infections

Question 18

What increased risk does C3 deficiency pose?

Answer 18

C3 deficiency –> increased susceptibility to type III hypersensitivity reactions

Question 19

What condition do C5-C9 deficiences cause?

Answer 19

C5-C9 deficiencies –> recurrent Neisseria bacteria

Question 20

What conditions does DAF (GPI anchored enzyme) deficiency cause?

Answer 20

DAF (GPI anchored enzyme) deficiency –> complement-mediated lysis of RBC’s and paroxysmal nocturnal hemoglobinuria (PNH).

Question 21

What is the definition of acute-phase reactants? What produces them? In what general contexts are they produced?

Answer 21

Factors whose serum concentrations change significantly in response to inflammation; produced by the liver in both acute and chronic inflammatory states

Question 22

Name 4 cytokines that induce the production of acute-phase reactants.

Answer 22

Induced by IL-6, IL-1, TNF-alpha, and IFN-gamma

Question 23

What are 5 positive (upregulated) acute-phase reactants?

Answer 23

(1) Serum amyloid A (2) C-reactive protein (3) Ferritin (4) Fibrinogen (5) Hepcidin

Question 24

What are 2 negative (downregulated) acute-phase reactants?

Answer 24

(1) Albumin (2) Transferrin

Question 25

What can result from prolonged elevation of serum amyloid A?

Answer 25

Prolonged elevation can lead to amyloidosis

Question 26

What major function does C-reactive protein play? How is it used clinically?

Answer 26

Opsonin; Fixes complement and facilitates phagocytosis. Measured clinically as a sign of ongoing inflammation.

Question 27

What is the function of Ferritin?

Answer 27

Binds and sequesters iron to inhibit microbial iron scavenging

Question 28

What kind of factor is Fibrinogen? What major role does it play? With what does it correlate clinically?

Answer 28

Coagulation factor; promotes endothelial repair; Correlates with ESR

Question 29

What role does Hepcidin play? What clinical condition does it cause as a result?

Answer 29

Prevents release of iron bound by ferritin => anemia of chronic disease

Question 30

What happens to albumin levels in the context of inflammation, and why?

Answer 30

Reduction conserves amino acids for positive reactants

Question 31

What role does Transferrin play?

Answer 31

Internalized by macrophages to sequester iron