Innate Immunity Part II (Lec 5)

Question 1

What are the three pathways of the complement system?

Answer 1

Classical - with antibody

Alternate - just microbial surface

Lectin - mannose binding lectin

Question 2

C3a is involved in the first step of the complement system and results in what?

Answer 2

inflammation

Question 3

C3b is involved in the second step of the complement system and results in what?

Answer 3

opsonization and phagocytocis, initiates activation of C5 and formation of C5 convertase

Question 4

C5a like C3a, results in what?

Answer 4

inflammation

Question 5

The last step in the complement system is what?

Answer 5

formation of membrane attack complex that creates holes in plasma membranes - lysis of microbe

Question 6

Complement activation involves ___ ____ in which an inactive enzyme, called a zymogen, is altered to become an active protease that cleaves the next complement protein in the cascade.

Answer 6

proteolytic cascades

Question 7

Enzymatic cascades result in ___ ____ of the amount of proteolytic products that are generated.

Answer 7

tremendous amplification

Question 8

The complement system works in cooperation with these to other proteolytic cascades

Answer 8

blood coagulation pathways

kinin-kallikrein system (vascular permeability)

Question 9

C3 convertase does what?

Answer 9

cleaves the central protein of the complement system, producing C3a and C3b

Question 10

What are collectins?

Answer 10

soluble effector molecules in the innate immune system

Question 11

What is MBL?

Answer 11

a soluble PRR that binds carbohydrates with terminal mannose and fructose and enhances phagocytosis of microbes

Question 12

Low MBL levels are associated with what?

Answer 12

increased susceptibility to a variety of infections

Question 13

What are the major functions of SP-A and SP-D collectins?

Answer 13

maintain the ability of the lungs to expand and as mediators of innate immune response, they act as opsonins, facilitating phagocytocis by alveolar macrophages

Question 14

SP-A and SP-D can directly inhibit what? Driectly activate what?

Answer 14

inhibit: bacterial growth
activate: macrophages

Question 15

What are Ficolins?

Answer 15

plasma proteins that are structurally similar to collectins but they have a fibrinogen-type carbohydrate recognition domain. they are humoral molecules of the innate immune system

Question 16

The molecular ligands of the ficolins are located on the cell walls of gram-positive or gram-negative bacteria?

Answer 16

gram-postive

Question 17

What is the function of ficolins?

Answer 17

opsonizing bacteria and activating complement system similar to MBL

Question 18

In phagocytocis, what kills the microbes?

Answer 18

reactive oxygen and nitrogen species and proteolytic enzymes

Question 19

What does activation of macrophages lead to?

Answer 19

activation of transcription factors, transcription of various genes, and the synthesis of proteins

Question 20

Macrophages are activated by what?

Answer 20

stimuli from lymphocytes such as CD40 ligand and IFN-gamma

Question 21

What is the cell source of the cytokine TNF?

Answer 21

macrophages, T cells

Question 22

What is the cell source of the cytokine IL-1?

Answer 22

macrophages, endothelial cells, some epithelial cells

Question 23

What is the cell source of chemokines?

Answer 23

macrophages, DCs, endothelial cells, T lymphocytes, fibroblasts, platelets

Question 24

What is the cell source of the cytokine IL-12?

Answer 24

DCs, macrophages

Question 25

What is the cell course of the cytokine IFN-gamma

Answer 25

NK cells, T lymphocytes

Question 26

What is the cell source of Type I IFNs?

Answer 26

IFN-alpha: DCs, macrophages | IFN-beta: fibroblasts

Question 27

TNF, IL-1, and IL-6 have multiple local and systemic ____ ___.

Answer 27

inflammatory effects

Question 28

True or False? TNF and IL-1 act locally on leukocytes and endothelium to induce acute inflammation, and both cytokines induce the expression of IL-6 from leukocytes and other cell types.

Answer 28

true

Question 29

Systemic TNF can cause the pathologic abnormalities that lead to what?

Answer 29

septic shock

Question 30

C-reactive protein (CRP) and serum amyloid P (SAP) are what type of proteins?

Answer 30

acute phase proteins from the pentraxin family

Question 31

plasma concentration of CRP and SAP are very low in healthy individuals but can increase up to how much in response to other inflammatory stimuli?

Answer 31

1000-fold

Question 32

What is the function of acute phase proteins?

Answer 32

recognize microbial structures and participate in innate immunity

Question 33

CRP and SAP recognize what? and what do they activate?

Answer 33

recognize phosphorycholine and phosphoatidylethanolamine. | activate complement by binding C1q and initiating the classical pathway

Question 34

Type I IFNs are produced by what?

Answer 34

virus infected cells, triggered in response to intracellular TLR signaling and other sensors of viral RNA

Question 35

What do Type I IFNs bind to? what do they activate

Answer 35

neighboring uninfected cells. activate JAK-STAT pathways. also bind to receptors on infected cells and induce expression of genes whose products enhance the cell's susceptibility to CTL-mediated killing

Question 36

Antigen recognition by B cells provides signal 1 for the activation of what?

Answer 36

lymphocytes

Question 37

True or False? | Molecules induced by innate immune responses to microbes provide signal 2.

Answer 37

true

Question 38

What is the target and effect of TNF?

Answer 38

``` endothelial cells: activation neutrophils: activation hypothalmus: fever liver: synthesis of acute phase proteins muscle, fat: catabolism many cell types: apoptosis ```

Question 39

What is the target and effect of IL-1?

Answer 39

endothelial cells: activation hypothalamus: fever liver: synthesis of acute phase proteins T cells: TH17 differentiation

Question 40

What is the target and effect of chemokines?

Answer 40

leukocytes: increased integrin affinity, chemotaxis, activation

Question 41

What is the target and effect of IL-12?

Answer 41

NK cells and T cells: IFN-gamma production, increased cytotoxic activity T cells: TH1 differentiation

Question 42

What is the target and effect of IFN-gamma?

Answer 42

Activation of macrophages | Stimulation of some antibody responses

Question 43

What is the target and effect of IL-10?

Answer 43

Macrophages, DCs: inhibition of IL-12 production, reduced expression of costimulators and class II MHC molecules

Question 44

What is the target and effect of IL-6?

Answer 44

Liver: synthesis of acute-phase proteins | B cells: proliferation of antibody-producing cells

Question 45

What is the target and effect of IL-15?

Answer 45

NK cells: proliferation | T cells: proliferation

Question 46

What is the target and effect of IL-18?

Answer 46

NK cells and T cells: IFN-gamma synthesis

Question 47

What is the target and function of TGF-beta?

Answer 47

inhibition of inflammation | T cells: differentiation of TH17, regulatory T cells