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Phar 503 > Cytokines > Flashcards

Cytokines Flashcards

1
Q

What are cytokines

A

chemical messengers within the immune system

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2
Q

T/F: Cytokines are made in advance and stored

A

False: Rapidly synthesized and secreted after stimulation, brief self limited with a short half life

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3
Q

What are two factors that regulate cytokines

A

quantity produced and cytokine receptors that are present

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4
Q

What the cytokine exceptions that do not change gene expression resulting in new functions or proliferation

A

Chemokines, Tumor necrosis Factor (TNF)

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5
Q

What are cytokine functions

A

regulate proliferation, differentiation, and function of immune cells, participate in the inflammatory response, regulate neuronal hematopoietic and embryonic development development

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6
Q

T/F: Cytokines can be autocrine, paracrine, and endocrine

A

True

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7
Q

What are properties of cytokines

A

Pleiotropy, redundancy, synergy

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8
Q

Pleiotropy

A

one cytokine can act on multiple cell types differently

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9
Q

Redundancy

A

multiple cytokines have the same effect and use same signaling subunits

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10
Q

synergy

A

cytokines work together to cause a change

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11
Q

What are the functional classifications of cytokines

A

Mediators and regulators of innate immunity, mediators and regulators of adaptive immunity, stimulators of hematopoiesis, chemokines

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12
Q

What produces innate immunity cytokines

A

mononuclear phagocytes (dendritic cells and macrophages) but also endothelial and epithelial cells

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13
Q

What are the major cytokines for innate immunity

A

TNF-alpha, IL-1,IL-12,IL-10, Interferon (IFN-alpha and IFN-beta), chemokines

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14
Q

What is a main property of TNF-alpha

A

Induces inflammation in an effort to limit spread of infection (usually gram negative bacteria and other microbes)

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15
Q

What are the biologic actions of TNF-alpha at low quantities

A

neutrophil activation leads to higher chemokine procution, endothelial cells secrete chemokines and adhesion molecules, apoptosis of some cells

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16
Q

What is the ultimate effects of TNF-alpha in lower quantities

A

increase vascular permeability, redness swelling, and inflammation

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17
Q

What are the biologic actions of TNF-alpha at moderate quantities

A

Hypothalmus produces fever, hepatocytes produce actue phase proteins, bone marrow leukocyte production is increased

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18
Q

What are the biologic actions of TNF-alpha at high quantities

A

the heart has low output due to inhibition of myocardial contractility (hypotension), decreased systemic vascular resistance and loss of anticoagulant properties, hypoglycemia due high use of glucose by muscles and no glucose replacement by liver

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19
Q

What is the biologic activity of IL-1 at low concentrations, high concentrations

A

local inflammation (adhession molecules expressed by endothelial cells), fevers metabolic changes and acute phase proteins are secreted

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20
Q

What functions IL-1 has with TNF-alpha to cause change in endothelial cells

A

leaky to fluid allowing influx of plasma containing antibodies complement proteins and etc., sticky for leukocytes

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21
Q

How does IL-1 differ from TNF-alpha

A

Cannot cause cell apoptosis, Cannot cause shock by itself, Binds different receptor but produces similar effect

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22
Q

What is the most important function of IL-12

A

Stimulate differentiation of Thelper cell into IFN-gamma producting T helper 1 cells, Enhances cytolytic function of activated CD8+ t cells (lysis of infected cells)

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23
Q

What does secretion of IFN-gamma cause

A

macrophage activation: killing of phagocytosed microbes

24
Q

Which cytokine inhibits cellular immunity in favor of humoral response

A

IL-10

25
Q

What is the biological activites of IL 10

A

Inhibits production of IL-12 and TNF-alpha by activated macrophages, inhibit expression of costimulators and MHC by macrophages

26
Q

What is the role of interferons

A

Interfere with viral replication causing prevention of virus spreading through the tissue

27
Q

T/F: Interferon synthesis is in response to double stranded RNA found

A

True

28
Q

What are the two interferon structured groups, what are each produced by

A

IFN-alpha/leukocytes, IFN-beta/fibroblast

29
Q

T/F: IFN-alpha and INF-beta do not bind the same receotor and illicit different biologic responses

A

False: Both type 1 interferons bind the same receptor and illicit similar biologic responses

30
Q

What are the functions of Type 1 interferons

A

induce resistance to viral replicalication in all cells, increase MHC 1 expression and antigen presentation all cells, activate dendritic cells and macropages, activate NK cells to kill virus-infected cells

31
Q

What are the major cytokines for adaptive immunity

A

IL-2, IL-4, and IL-5, IFN-gamma, TGF-beta

32
Q

What is the major function IL-2

A

growth factor for antigen-stimulated T cells, responsible for T cell clonal expansion after antigen recognition

33
Q

What is the major biological activity of IL-2

A

T cell, B cell and NK cell prolifeations through promoting the cell cycle

34
Q

What is the negative feedback IL-2 has

A

At high IL-2 induce apoptotic death of antigen activated T cells

35
Q

What is the biological activity for IL-4

A

Major stimulus for T helper 2 cells differentiation from T helper 0 cells leading to B cells, antagonizes the macrophage activating effects of IFN-gamma leading to inhibited cell mediated immunity, major stimulus for IgE antibody class switching

36
Q

What is biologic activity of IL-5

A

Major stimulus for B cell differentiation and class swithing, activates eosinophils to destroy parasites opsonized by IgE

37
Q

What is the type 2 interferon

A

IFN-gamma

38
Q

What does IFN-gamma cause in macrohphages, B cells, Naive CD4+ T cells, and APCs

A

macrophage activation leading to increased microbicidal activity, isotype to opsonizing antibodies, development of T helper 1 cells, increased MHC expression and antigen presentation

39
Q

What does IFN-gamma inhibit

A

Inhibits proliferation of T helper 2 cells

40
Q

What is the main biologic action of TGF-beta

A

Inhibits adaptive immunity

41
Q

How does TGF-beta inhibit adaptive immunity

A

Inhibit T cell proliferation and effector function, Inhibit b cell proliferation, promotes IgA isotype switching in activated B cells, inhibits macrophages

42
Q

What are the two main roles of cytokines in B cell differentiation and antibody response

A

Provide amplification mechanisms by augmenting B cell proliferation and differentiation, determine the type of antibody produced by promoting class switching

43
Q

What produces stimulators of hematopoiesis and what are the fucntions of these stimulators

A

produced by bone marrow stomal cells, leukiocytes and other cells, promote differentiationand expansion of bone marrow progenitor cells

44
Q

What are examples of stimulators of heamtopoiesis

A

Stem Cell Factor, Colony-stimulating factors, Thrombopoietin, erythropoietin

45
Q

T/F: Chemokines Allow movement against gradient and hard to regulate

A

True

46
Q

What are the five major families of cytokine receptors

A

TNF receptor, Class 1 cytokine receptor Hematopoietin, Class 2 cytokinereceptor interferon, Ig superfamily receptor, chemokine receptor

47
Q

What causes redundancy and antagonism exhibited by cytokines

A

sharing of signal transduction molecules

48
Q

IL-2 receptor is made up of what subunits, what are the functions

A

alpha (binding component), Beta and gamma (signal transduction component)

49
Q

What are the three types of forms for IL-2 receptor

A

low, medium, and high affinity (changes in subunits present causes the change in affinity)

50
Q

What is the cytokine signal trnasduction in IL-2 receptor

A

binding of cytokine causes activation of JAK, activated JAK phosphorylate receptor sites and create docking , sites for STAT molecules, after binding to the receptor STATs are phosporylated and dimerize to translocate into the nucleus and act as transcription factors for target genes

51
Q

What cytokine receptor is the most commonly used by cytokines

A

Cytokine 1

52
Q

What is X-Linked Scid

A

Inability to transmit the cytokine signal increasing susceptibility to infections

53
Q

What is toxic shock syndrome

A

Superantigen causes massive polyclonal antibody production as well as extremely high levels of inflammatory cytokines TNF-alpha and IL-1 causing a cytokine storm

54
Q

What is bacterial septic shock

A

Bacterial LPS causes over stimulation causes mass cytokine production from macrophages as well as extremely high levels of inflammatory cytokines TNF-alpha and IL-2 causing a cytokine storm

55
Q

What causes each shock, which is fatal

A

Enterotoxin derived from gram positive bacteria (toxic shock syndrome), Endotoxins derived from gram negative (bacterial septic shock), bacterial septic shock

56
Q

What the mechanisms for cytokine antagonists/inhibitors

A

Proteins produced by cells to locally regulate cytokine activity as a receptor antagonist, cytokine biding domain enzymatically cleaved from cell surface

57
Q

T/F: IFN-alpha will only be induced by virally infected cells

A

True

Phar 503 (25 decks)

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