Cytokines Flashcards Preview

IAHI Block 1 > Cytokines > Flashcards

Flashcards in Cytokines Deck (51):
1

3 ways to categorize Immune signals

1) Cell-contact dependent OR cell-contact independent
2) Mediated by germ-line encoded receptors OR mediated by V(D)J generated receptors
3) Pro-inflammatory OR Anti-inflammatory

2

Germline-encoded receptors (characteristics)

- The gene segments that encode the receptor are already arranged in the genome of all cells
- Each cell of the body expresses the same transcript from this gene
- Heritable

3

Receptors produced by somatic recombination (characteristics)

- The gene segments that you inherit are unarranged
- Arrangement only occurs in select lineages
- Prior to clonal expansion, each cell has a different arrangement of each gene segment, and thus each expresses a different transcript
- Sequences express are not necessarily the receptor sequences expressed in your mother and father

4

Innate lineages are activated following the interaction of pathogen associated products with __________ ___________ ___________

Pattern Recognition Receptors (PRRs)

5

Example of a PRR

Toll-Like Receptors

6

Most well characterized PAMPs are those derived from:

Bacterial and viral pathogens (least characterized are from fungal and helminth pathogens)

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Intracellular TLRs

3, 7, 8 and 9

8

Extracellular TLRs

1, 2, 4, 5, 6, 10

9

Principle Cell Sources of TNF

Macrophages, T-Cells

10

Principal cell sources of Interleukin (IL-1)

Macrophages, endothelial cells, some epithelial cells

11

Principal Cell sources of IL-6

Macrophages, endothelial cells, T-cells

12

Part 1: Pathogen Encounter (Cytokines and receptors)

PAMP, PPR, IL-1, IL-6, TNFα

13

Part 2: Neutrophil Influx (Cytokines and receptors)

IL-8, G-CSF, GM-CSF, Chemokines

14

G-CSF and GM-CSF

Granulocyte and Granulocyte-monocyte colony stimulating factor - released from Macrophages and Th cells - induce proliferation in the bone marrow

15

IL-8

Interleukin-8 - Circulating PMNs (Chemotatic - causes PMN migration toward injury)

16

Four families of Chemokines

CC chemokines: Two cys residues that are adjacent
CXC chemokines: Two cys residues separated by one amino acid
C chemokines: One cys residue
CX3C: Two cys residues separated by three amino acids

17

Function of Chemokines

Formation of gradient to which PMNs are attracted

18

There are greater than ______ different chemokines

40

19

4 stages of PMN extravasation

Stage 1: Rolling
Stage 2: Integrin activation by chemokines
Stage 3: Stable adhesion
Stage 4: Migration through endothelium

20

Part 3 Of Immune Response

T-Cell activation

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Germline genes in T-cell activation

MHC, CD28, CD80, CD86 (B7)

22

CTLA-4

Serves to negatively regulate response - competes with B7 to provide a "stop" signal through CD28

23

IL-2

A cytokine that provides autocrine, cell-contact independent, pro-proliferative feedback to the Th cell producing it

24

Part 4: T cell differentiation into:

TH1 cells
TH2 cells
TReg cells

25

IL12

Promotes Th expression of IFNγ (Th1 Pathway)

26

TGFβ

Produced by many cell types, including APCs. Promotes development of TReg cells

27

IL10

Promotes TReg pathway

28

What happens when no APC cytokines are released

Th cells "default" to Th2 development

29

IFNγ

Provides autocrine signal to promote additional Th1 gene expression
Suppresses the expression of IL-4

30

TGFβ and IL10

Provides autocrine signal to promote further TReg development

31

IL-4 and IL-5

Promotes autocrine skewing towards a Th2 cell

32

Th17

Overabundance is associated with autoimmunity; deficiency associated with susceptibility to bacterial infection
Development directed by combination of IL-6, IL-23 and TFGβ

33

What is the TReg master-regulator

Foxp3 (positively regulated by TFGβ)

34

Therapies that alter Th cell differentiation signals

Alum
Ustekinumab
Helminth therapy

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Part 5:

B-cell activation

36

Steps of B-Cell activation

B-cell recognition of native protein antigen
Receptor-mediated endocytosis of antigen
Antigen processing and presentation
T-Cell recognition of antigen
Helper T-cell is activated; expresses CD40L, secretes cytokines
B cells are activated by CD40 engagement cytokines
B-cell proliferation and differentiation

37

Signaling pathway for B-cells is enhance if _________ is bound to the antigen

Complement (C3d)

38

B-cell antibodies

IgM - Complement activation (Default antibody)
IgG - Fc receptor-dependent phagocyte responses
IgE - Immunity against helminths; mast cell degranulation
IgA - Mucosal immunity

39

Part 6:
Part 7:

Part 6: Granulocyte degranulation
Part 7: Complement cascade; phagocytosis; antibody-directed cytotoxicity (ADCC)

40

FcγRI

Phagocytosis; activation of phagocytes - high affinity for Ig

41

FcγRIIA

Phagocytosis; cell activation - low affinity for Ig

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FcγRIIB

Feedback inhibition of B-cells - low affinity for Ig

43

FcγRIIIA

Antibody-dependent cellular cytotoxicity (ADCC)

44

FcεRI

Activation of mast cells and basophils (degranulation) - High affinity for Ig (IgE)

45

Histamine

A vasoactive amine stored in the granules of mast cells

46

Prostaglandin D2

Made by mast cells; activates G-protein coupled receptors and promotes PMN chemotaxis

47

Leukotrienes

Made by mast cells - inflammatory mediators derived from arachidonic acid

48

Part 8:

Macrophage activation; CD8 T cell mediated cytotoxicity; NK cell lysis

49

Cytokine associated with Macrophage activation

IFNγ

50

Cytokine associated with CD8 T cell cytotoxicity

Type I IFNs (IFN-α and IFN-β)

51

Cytokines associated with NK cell lysis

IL-15
IL-18