Lecture 5 - Innate Immunity II

Question 0

What are the 4 stages of the complement system?

Answer 0

Initiation
Formation of C3 convertase (C3b)
Formation of C5 convertase (C3b/C4b/C2a)
Formation of MAC complex

Question 1

What are the 3 activation pathways of the complement system?

Answer 1

Classical, Alternative, Lectin

Question 2

What does the complement system cooperate with?

Answer 2

blood coagulation pathway and kinin-killikrein system

Question 3

What antibodies initiate the classical pathway, how many interactions are they, and what portion of the molecule do they interact with?

Answer 3

IgM (pentamer) IgG
2 interactions
tail (Fc) portion

Question 4

What makes up the C3 convertase complex in the classical and lectin pathways and what do they bind to?

Answer 4

C4b/C2a

bind Fc and Mannose respectively

Question 5

What makes up the C3 convertase complex in the Alt. pathway?

Answer 5

C3b/Bb (B factor)

Question 6

what is the function of C3b and C3a?

Answer 6

C3b serves as an opsonin to promote phagocytosis

C3a acts a chemoattractant for neutrophils

Question 7

what does C5a do?

Answer 7

very strong chemoattractant for neutrophils that changes the permeability of blood vessels

Question 8

What makes up the MAC complex and what does it do when activated?

Answer 8

C6,7,8,9

causes lysis of cells

Question 9

What is in high [ ] in the blood? what does it mean if the ration is low?

Answer 9

C3 and C4

it means utilization is faster than the synthesis

Question 10

what happens once C1q detects Abs?

Answer 10

C1q binds Fc portion of IgM and activate C1r and C1s

Question 11

What begins the lectin pathway and what is it similar in structure to?

Answer 11

MBL (hexametric), similar to C1q

Question 12

what does MBL activate?

Answer 12

MASP1 and MASP2

Question 13

What does Ficolin bind to and what does it activate?

Answer 13

binds to N-acetylglucosamine

activates MASP1 and MASP2

Question 14

What are collectins and what 3 types are there?

Answer 14

trimeric, soluble effector molecules with a lectin head

MBL, SP-A, SP-D

Question 15

What is MBL, what does it bind to, what does it do, and what are low levels associated with?

Answer 15

it is a soluble PRR, binds carbs, enhances phagocytosis, low levels = increased susceptibility to infections

Question 16

what do SP-A and SP-D do and what can they inhibit?

Answer 16

act as opsonins, directly activate macrophages, may increase apoptosis

inhibit bacterial growth

Question 17

What are ficolins, what is their structure like, what do they bind to, and what do they activate?

Answer 17

plasma/humoral proteins of the innate immune system, have a fibrinogen-type crd, bind to N-acetylglucosamine and LPA (+), activate LP through MASPs

Question 18

how is the alternative pathway initiated? what inhibits this pathway in mammalian surface cells?

Answer 18

spontaneously, when C3 recognizes LPS

DAF

Question 19

What are the 3 complement effector functions?

Answer 19

inflammation: C5a, C3a
phagocytosis: C3b
MAC: microbe lysis

Question 20

What are the 4 inflammatory effects of complement? whats the highest potency?

Answer 20

smooth muscle contraction, inc permeability of blood vessels, degranulation of basophils, chemotaxis
Some Indians Don’t Clean

C5

Question 21

C3b is a complement receptor on macrophages which signal what?

Answer 21

inflammation (cytokines, IL-1, IL-6, TNF) and killing of microbes (ROS and NO)

Question 22

what is TGF-Beta

Answer 22

chemoattractant, remodeler and activator of fibroblasts and CT for scar tissue

Question 23

What is present in local inflammation?

Answer 23

endothelial cells, chemokines, IL-1, IL-6, TNF

Question 24

What is systemic protective effects are characteristic of the brain, liver, and bone marrow

Answer 24

IL-1 --> fever IL-6 --> acute phase proteins TNF, IL-1, IL-6 --> leukocyte production

Question 25

TNF can cause pathological abnormalities systemically which lead to what and include what?

Answer 25

septic shock Dec. cardiac function, thrombosis and capillary leak, insulin resistance

Question 26

acute phase proteins are pentraxins. what are the major ones, what do they recognize and what can they activate and how?

Answer 26

CRP and SAP which can INC x1000 during infection and are normally low recognize phosphorylCholine and phosphatidylethanolamine act. classical pathway by binding C1q

Question 27

what acute phase proteins may have dramatic INC in [ ]?

Answer 27

CRP, SAP, MBL, a1-acid glycoprotein

Question 28

what are the 2 type I interferons and what are they produced by?

Answer 28

IFN-alpha and IFN-beta | produced by virus-infected cells

Question 29

what do they activate in unaffected cells and infected cells?

Answer 29

JAK-STAT | CTL-mediated killing

Question 30

what is needed for an immune response and proliferation of lymphocytes?

Answer 30

2 signals, one from Ag recognition for activation of lymphocytes one from innate immune responses to microbes