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Immunology 436 > Chapter 12 Cytokines > Flashcards

Chapter 12 Cytokines Flashcards

1
Q

Which cells produce cytokines? Function?

A

All cells of innate and acquired immune system. They function as chemical messengers of the immune system. You can compare them to hormones of the endocrine system

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2
Q

General properties of cytokines?

A

-Polypeptides
-Communicate between cells at low concentrations of 10^-10 to 10^-5
-Bind specific receptors to exert effect
-Short half life of HOURS
-Pleiotropic: affect variety of cell types
-Redundant: have similar functions in different cells
-Rarely act alone, but are additive, synergistic, and antagonistic

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3
Q

What does it mean for cytokines to be additive, synergistic, or antagonistic?

A

Additive = effects directly sum
Synergistic = amplify signal together (2+2=6)
Antagonistic = one cytokine inhibits another

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4
Q

What does autocrine mean?

A

Cell secretes cytokine that exerts effect on self

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5
Q

What does paracrine mean?

A

Cell secretes cytokines that act on near-by cells

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6
Q

What does endocrine mean?

A

Cell secretes cytokines (hormones) that have systemic effect, travel to a completely different location

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7
Q

Cytokines impact cell ______.

A

Proliferation

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8
Q

Which cells express functional cytokine receptors?

A

Only cells stimulated by antigen, meaning that cytokines act only on Ag-activated lymphocytes

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9
Q

How does the body ensure immune specificity?

A
  1. Cytokines only act on Ag-stimulated cells
  2. Cell-cell contact required for stimulated cells (APC and Th)
  3. Limited action due to short half-life
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10
Q

Example of pleiotropy involving IL-4?

A

Activated Th cell secretes IL-4, which causes the proliferation of B, T, and mast cells. B cells are also activated and differentiated

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11
Q

What are Th0 cells?

A

They are naive T cells that differentiate into Th1 or Th2 cells

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12
Q

What influences differentiation of Th0 cells?

A

Cytokines released by APC, NK, and mast cells

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13
Q

What does Th1 pathway do?

A

Facilitates cell-mediated immunity. Th1 cells present antigen to Tc cells

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14
Q

What does the Th2 pathway do?

A

Essential for humoral immunity. Help B cells class switch to IgE during allergic responses, defend against parasitic worms, mobilize eosinophils

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15
Q

Describe the long- vs short-term aspects of Th1 and Th2 pathways

A

Th1 = long-term
Th2 = short term

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16
Q

Function of Th17?

A

Link adaptive and innate immunity through releasing IL-17. May play role in autoimmune disease

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17
Q

Which cytokine blocks monocyte activation?

A

TGF-beta

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18
Q

What is a pyrogen?

A

Fever-inducer

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19
Q

Bacteria and viruses stimulate which cells to release which cytokines to stimulate Th1 pathway?

A

NK cells and macrophages release IL-2, IFN-gamma, and TNF-beta to make Th0 mature into Th1

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20
Q

Parasitic worms cause which cells to stimulate which cytokines to induce Th2 pathway?

A

Mast cells and NK cells make IL-4 to induce Th0 to Th2

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21
Q

List cytokines produced by Th1 cells

A

IL-2, IFN-gamma, and TNF-beta

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22
Q

Which cytokines do Th2 cells produce?

A

IL-4, IL-5, and IL-10

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23
Q

Th2 cells release which cytokine to inhibit activation of Th1?

A

IL-10

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24
Q

Th1 cells release which cytokine to inhibitor activation of Th2?

A

IFN-gamma

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25
Q

Which endogenous pyrogens (cytokines) do macrophages and neutrophils release during innate immune response?

A

IL-1, IL-6, and TNF-alpha

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26
Q

What do the pyrogenic cytokines (IL-1, IL6, and TNF-alpha) induce?

A

Acute phase proteins such as C-reactive protein (produced in liver)

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27
Q

What does CRP bind? What does it do?

A

Binds phosphorylcholine. Acts as opsonin to activate complement

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28
Q

What is the purpose of mannose-binding lectin (MBL)?

A

Opsonin for activating complement. Binds mannose on bacteria. Mimics Ab action by binding bacteria and activating complement.

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29
Q

List pro inflammatory cytokines. What do they do?

A

IL-1, IL-6 and TNF-alpha

-Cause increase vascular permeability -> inflammatory response
-induce CAM expression that bind neutrophils

30
Q

List neutrophil movement along blood vessel during inflammatory response

A
  1. Margination
  2. Rolling
  3. Adhesion
  4. Transmigration/diapedesis
  5. Chemotaxis
  6. Phagocytosis
31
Q

What is axial streaming?

A

Normal blood flow

32
Q

Describe what happens during margination

A

Capillaries dilate -> slow blood flow
Leukocytes float to periphery

33
Q

Describe rolling leukocytes

A

-tumble along epithelial surface while briefly sticking along the way

34
Q

Describe adhesion of leukocytes

A

Cytokines activate CAMs expressed on leukocytes, causing them to stick to endothelial cells of blood vessels

35
Q

Describe transmigration of leukocytes

A

Migrate between endothelial cells by diapedesis
Cross basement membrane by degrading it with collagenases

36
Q

What are interferons? Functions?

A

-Cytokines released against pathogens, tumor cells, or parasites. Named after ability to interfere with viral replication.
-Activate NK and macrophages
-Increase Ag presentation to T cells
-Promotes ability of uninfected cells to increase viral resistance

37
Q

What are chemokines? List example

A

Chemotactic cytokines
IL-8, RANTES

38
Q

Describe positive APP

A

Increasing acute phase protein production

39
Q

Describe negative APP

A

Decreasing acute phase protein concentration to save amino acids for later

40
Q

What are the amino acid patterns of chemokines?

A

CXC, CC, or CX3C at amino terminus

41
Q

How does vasodilation affect blood pressure and velocity?

A

Reduces blood pressure and velocity

42
Q

What does IL-8 do?

A

It’s a chemokine that attracts neutrophils to sites off tissue damage, and stimulates adhesion and rolling. Major player in inflammation and wound healing

43
Q

Describe RANTES

A

It’s a chemokine (CCL5) that binds receptor CCR5 on macrophages. Same receptor that HIV binds

44
Q

What is M-CSF vs G-CSF?

A

M-CSF = macrophage colony stimulating factor. Stem cell -> macrophage differentiation

G-CSF = granulocytes colony stimulating factor. Clonal growth of granulocytes

45
Q

What does GM-CSF do? What does it stand for?

A

Granulocyte macrophage colony stimulating factor.
Supports growth of both macrophages and granulocytes

46
Q

Role of IL-7?

A

Growth of lymphoid stem cells into B and T cells

47
Q

Which aa does IL-8 lack?

A

Glycine

48
Q

Role of IL-3?

A

Stimulates clonal growth of granulocytes, macrophages, megakaryocytes, eosinophils, basophils, and mast cells. Stimulates RBC production with erythropoietin

49
Q

Where is erythropoietin made?

A

Kidneys

50
Q

What therapeutic do you give to patients undergoing chemo and suffering neutropenia?

A

G-CSF

51
Q

What therapeutic do you give to a patient who underwent a bone marrow transplant? Why?

A

GM-CSF. To boost granulocytes and macrophages

52
Q

List the five families of cytokine receptors

A
  1. Ig superfamily
  2. Class I cytokine
  3. Class II cytokine
  4. TNF receptors
  5. Chemokine
53
Q

List ligands of Ig superfamily receptors

A

IL-1 and M-CSF

54
Q

List ligands of Class I cytokine receptors

A

-IL-2 through IL15, except for IL-8 and IL-10
-GM-CSF
-G-CSF

55
Q

List ligands of Class II cytokine receptors

A
  1. IFN-alpha, beta, and gamma
  2. IL-10
56
Q

List ligands of TNF receptors

A
  1. TNF-alpha and beta
  2. CD30L and CD40L
  3. Fas L
57
Q

List ligands of chemokine receptors

A
  1. IL-8
  2. RANTES
  3. MIP-1
  4. PF4
  5. MCAF
58
Q

What percent of T cell activation is normal?

A

0.001% to 0.0001%

59
Q

What percent T cells are activated during Toxic Shock Syndrome?

A

Over 20%

60
Q

What causes Toxic Shock Syndrome?

A

-S. Aureus or S. Pyogenes releases super antigen, which causes MHCII and Th to bind too tightly to each other, leading to crazy cytokine burst
-too much IL-1 and TNF-alpha -> fever, droop in blood pressure, shock, and MOF

61
Q

What does Streptococcus pneumonia do?

A

Binds platelet activating factor receptor (PAF is chemokine)

62
Q

What does Plasmodium vivax do?

A

Binds chemokine receptor called Duffy blood group

63
Q

What does T-tropic HIV bind?

A

CXCR4 on T cells

64
Q

What does M-tropic HIV bind?

A

CCR5 on macrophages

65
Q

What occurs during T cell leukemia?

A

HTLV-1 infects T cells, causing them to continuously express IL-2 and high affinity IL-2R.
Then, autocrine stimulation of infected T cells -> uncontrolled growth

66
Q

What does HTLV stand for?

A

Human T cell lymphoma virus

67
Q

Which cytokine is overproduced in neoplastic B cell myeloma?

A

IL-6

68
Q

Which cytokine is overproduced in Hodgkin’s lymphoma?

A

IL-5

69
Q

How do you reverse cellular deficiencies in chemotherapy or radiotherapy patients?

A

G-CSF or GM-CSF

70
Q

How do you treat T cell leukemia in adults?

A

Toxin-conjugated Ab bind IL-2R, which are over-expressed on cancerous T cells. Selective targeting leaves healthy T cells alone

71
Q

How do you reduce immune response to allergen?

A

Reduce Th2 response by reducing IL-4 production and switching from IgE to IgG production

72
Q

List steps of JAK-STAT cytokine receptor signaling

A
  1. Cytokine binds receptor
  2. Receptor dimerizes
  3. ATP gets cleaved
  4. JAK gets phosphorylated
  5. STAT gets phosphorylated
  6. STAT dimerizes
  7. STAT translocates to nucleus and activates gene transcription

Immunology 436 (11 decks)

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