Cytokines Flashcards

1
Q

3 ways to categorize Immune signals

A

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

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2
Q

Germline-encoded receptors (characteristics)

A
  • 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
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3
Q

Receptors produced by somatic recombination (characteristics)

A
  • 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
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4
Q

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

A

Pattern Recognition Receptors (PRRs)

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5
Q

Example of a PRR

A

Toll-Like Receptors

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6
Q

Most well characterized PAMPs are those derived from:

A

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

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7
Q

Intracellular TLRs

A

3, 7, 8 and 9

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8
Q

Extracellular TLRs

A

1, 2, 4, 5, 6, 10

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9
Q

Principle Cell Sources of TNF

A

Macrophages, T-Cells

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10
Q

Principal cell sources of Interleukin (IL-1)

A

Macrophages, endothelial cells, some epithelial cells

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11
Q

Principal Cell sources of IL-6

A

Macrophages, endothelial cells, T-cells

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12
Q

Part 1: Pathogen Encounter (Cytokines and receptors)

A

PAMP, PPR, IL-1, IL-6, TNFα

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13
Q

Part 2: Neutrophil Influx (Cytokines and receptors)

A

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

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14
Q

G-CSF and GM-CSF

A

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

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15
Q

IL-8

A

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

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16
Q

Four families of Chemokines

A

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

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17
Q

Function of Chemokines

A

Formation of gradient to which PMNs are attracted

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18
Q

There are greater than ______ different chemokines

A

40

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19
Q

4 stages of PMN extravasation

A

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

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20
Q

Part 3 Of Immune Response

A

T-Cell activation

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21
Q

Germline genes in T-cell activation

A

MHC, CD28, CD80, CD86 (B7)

22
Q

CTLA-4

A

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

23
Q

IL-2

A

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

24
Q

Part 4: T cell differentiation into:

A

TH1 cells
TH2 cells
TReg cells

25
Q

IL12

A

Promotes Th expression of IFNγ (Th1 Pathway)

26
Q

TGFβ

A

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

27
Q

IL10

A

Promotes TReg pathway

28
Q

What happens when no APC cytokines are released

A

Th cells “default” to Th2 development

29
Q

IFNγ

A

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

30
Q

TGFβ and IL10

A

Provides autocrine signal to promote further TReg development

31
Q

IL-4 and IL-5

A

Promotes autocrine skewing towards a Th2 cell

32
Q

Th17

A

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

33
Q

What is the TReg master-regulator

A

Foxp3 (positively regulated by TFGβ)

34
Q

Therapies that alter Th cell differentiation signals

A

Alum
Ustekinumab
Helminth therapy

35
Q

Part 5:

A

B-cell activation

36
Q

Steps of B-Cell activation

A

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
Q

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

A

Complement (C3d)

38
Q

B-cell antibodies

A

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

39
Q

Part 6:

Part 7:

A

Part 6: Granulocyte degranulation

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

40
Q

FcγRI

A

Phagocytosis; activation of phagocytes - high affinity for Ig

41
Q

FcγRIIA

A

Phagocytosis; cell activation - low affinity for Ig

42
Q

FcγRIIB

A

Feedback inhibition of B-cells - low affinity for Ig

43
Q

FcγRIIIA

A

Antibody-dependent cellular cytotoxicity (ADCC)

44
Q

FcεRI

A

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

45
Q

Histamine

A

A vasoactive amine stored in the granules of mast cells

46
Q

Prostaglandin D2

A

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

47
Q

Leukotrienes

A

Made by mast cells - inflammatory mediators derived from arachidonic acid

48
Q

Part 8:

A

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

49
Q

Cytokine associated with Macrophage activation

A

IFNγ

50
Q

Cytokine associated with CD8 T cell cytotoxicity

A

Type I IFNs (IFN-α and IFN-β)

51
Q

Cytokines associated with NK cell lysis

A

IL-15

IL-18