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Vet Derm Review > Immune Function > Flashcards

Immune Function Flashcards

1
Q

What function does MHC-1 have on normal cells?

A

inhibits apoptosis by NK cells

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2
Q

How can NK cells trigger apoptosis?

A

1) release perforins - form a pore to allow proteases (granzymes) to enter cell –> cytosolic capsase pathway; 2) Fas-FasLigand pathway on the surface of the cell

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3
Q

What are the 3 types of PAMP (pathogen associated molecular patterns) receptors?

A

1) Secretory: act as opsonins, binding to microbial cell walls and flagging them for activation of complement and phagocytosis
2) Endocytic receptors: mediate phagocytosis by macrophages;
3) Cell-signaling: activate intracellular pathways that lead to up-regulation of cytokines to trigger an inflammatory cascade

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4
Q

What is the function of toll-like receptors?

A

specific family of signaling pattern recognition receptors that promote inflammation and the adaptive immune response via the NF-kB cascade

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5
Q

Toll-like receptors are very similar in structure to what interleukin?

A

IL-1

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6
Q

T/F: The cardinal features of the innate immune system are rapid, non-specific, and has no memory of past events.

A

TRUE

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7
Q

What are the cardinal features of the adaptive immune system?

A

specificity, diversity, memory, specialization, self-limitation (return to homeostasis), and non-reactivity to self

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8
Q

What are the components of the innate immune system?

A

physical barrier, complement, antimicrobial peptides, cytokines, macrophages, neutrophils, NK cells

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9
Q

What are the components of the adaptive immune system?

A

antigen presenting cells, lymph nodes, T-cells, B-cells

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10
Q

What are the key mediators that link innate and adaptive immunity?

A

cytokines

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11
Q

Pleiotropy

A

one cytokine can have a different effect depending on the cell type it binds to

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12
Q

Give an example of how IL-4 exhibits pleiotropy

A

IL-4 can have both stimulatory and inhibitory effects depending on the target: 1) IL-4 stimulates class switching and IgE production in B cells, growth and differentiation factor for Th2 cells, stimulates expression of adhesion molecules on vascular endothelium, mast cell growth factor; 2) Inhibitory: counter-regulatory to IFN-gamma and down regulates IL-1, IL-6, TNF-alpha secretion by macrophages

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13
Q

Redundancy

A

multiple cytokines have the same or overlaping biological functions

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14
Q

Give an example of redundancy with B cell proliferation

A

Multiple cytokines stimulate B cell proliferation (have same function): IL-4, IL-5, IL-13

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15
Q

IL-1 and TNF-alpha both activate macrophages and in high quantities have endocrine effects such as fever and cachexia. Is this an example of Pleiotropy, Redundancy, Synergy, Antagonism, or Cascade Induction?

A

Redundancy

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16
Q

Synergy

A

two or more cytokines expressed together have greater than additive effects on a cell

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17
Q

Antagonism

A

one cytokine inhibits the action of the other

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18
Q

Cascade Induction

A

cytokine effect on a target cell that induces that cell to produce the same cytokine –> rapidly spreads to adjacent cells that also produce the same or other synergistic cytokines

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19
Q

Interleukins

A

Cytokines that regulate interactions between lymphocytes and other leukocytes

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20
Q

Interferons

A

glycoproteins that are synthesized in response to viral infections, immune stimulation or chemical stimulation - inhibit viral replication by interfering with viral RNA and protein synthesis

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21
Q

Tumor necrosis factors

A

polymeric cytokines derived from macrophages and T cells - involved in immune regulation, inflammation, and programmed cell death of some tumor cells

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22
Q

TNF-alpha, lymphotoxins, fas ligand (CD95L), CD154 (CD40L) and CD30L are all part of what cytokine family?

A

tumor necrosis factors

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23
Q

Growth factors

A

also known as colony stimulating factors - stimulate cell growth and proliferation

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24
Q

chemokines

A

small proteins that act primarily as chemotactic factors or leukocyte activators

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25
Q

Primary cytokines are part of the innate or adaptive immune system?

A

innate

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26
Q

_____ are cytokines that by themselves initiate all events required to bring about leukocyte infiltration into the tissues.

A

Primary cytokines

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27
Q

What are examples of primary cytokines?

A

IL-1, TNF-alpha, TNF-beta, IL-18

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28
Q

_____ are cytokines whose production is induced only after cellular stimulation by a primary cytokine.

A

Secondary cytokines

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29
Q

What is the main source of TNF-alpha?

A

activated macrophages

30
Q

What are the two basic responses in target cells created by TNF-alpha binding?

A

1) Gene transcription (via NF-kB pathway), 2) Apoptosis

31
Q

TNF-alpha plays a major role in leukocyte recruitment in what ways?

A

increased production and secretion of chemokines such as IL-8 and expression of adhesion molecules on the surface of vascular endothelium

32
Q

Phospholipase A2 is synethesized in response to activation of what pathway?

A

NF-kB pathway (pro-inflammatory, phospholipase A2 is the enzyme that initiates the arachadonic acid cascade)

33
Q

In high concentrations, what systemic effects can TNF-alpha have?

A

1) Fever - through induction of prostaglandin production by the hypothalamus; 2) Induction of hepatocyte-derived plasma proteins, including serum amyloid A, 3) Cachexia - appetite suppression and inhibition of lipoprotein lipase, 4) Growth factor in bone marrow - stimulates production of leukocytes, 5) Decreases myocardial contractility and vascular smooth muscle tone –> hypotension, 6) Intravascular thrombosis due to tissue factors that activate coagulation and inhibit thrombomodulin

34
Q

What is the principal mechanism by which TNF-alpha can induce apoptosis?

A

cytoplasmic caspase 8

35
Q

T/F: NF-kB activation is anti-apoptotic.

A

True - inhibits caspase-8

36
Q

T/F: IL-1 and TNF-alpha have the same function and share the same receptors.

A

False - they do have the same function in that they both stimulate the NF-kB pathway but do NOT share a receptor

37
Q

IL-1 and TNF-alpha exhibit redundancy in that they both stimulate the NF-kB pathway. What are two things that are different between the two cytokines?

A

IL-1 does NOT induce apoptosis, IL-1 has three subtypes: IL-1a, IL-1b, and IL-1RA

38
Q

IL-1a is formed by what cells? Does it require cleavage to be activated?

A

formed by keratinocytes, does not require cleavage - is formed in its active state

39
Q

IL-1b is formed through what pathway? Does it require cleavage to be activated?

A

IL-1b is synthesized in response to NF-kB gene transcription signals; DOES require cleavage to be activated

40
Q

T/F: IL-1RA does not trigger cell signal when it binds to the IL-1 receptor.

A

True - it is a competitive inhibitor of IL-1a and IL-1b

41
Q

What are the three most important cytokines of septic shock?

A

IL-1, TNF-alpha, IL-6

42
Q

When a PAMP such as LPS binds to a Toll-like receptor, what cell signal pathway is triggered?

A

NF-kB pathway, results in gene transcription of TNF-alpha and IL-1

43
Q

Why does a bad sunburn result in fever and cachexia?

A

damaged keratinocytes can release IL-1a (constitutively expressed by keratinocytes) –> results in NF-kB signaling –> transcription of TNF-alpha and more IL-1 –> TNF-alpha causes pyrexia in hypothalamus (due to prostaglandin production) and cachexia (due to inhibition of appetite and lipoprotein lipase)

44
Q

Corticosteroids promote synthesis of what inhibitor of the NF-kB pathway?

A

IkBalpha –> dimmerizes NF-kB and sequesters it in the cytoplasm, preventing translocation to the nucleus

45
Q

T/F: Corticosteroids upregulate expression of IL-1RA.

A

True - IL-1RA is a competitive receptor antagonist for iL-1 in the extracellular space

46
Q

What are two mechanisms by which corticosteroids can inhibit innate immunity?

A

1) Inhibit NF-kB signaling through synthesis of IkBalpha (inhibitor of NF-kB), 2) Upregulation of IL-1RA (competitive inhibitor of IL-1a and IL-1b)

47
Q

IL-2, IL-7, IL-12, IFN-gamma are examples of cytokines associated with what cells of the adaptive immune system?

A

Th1 helper cells

48
Q

What is the function of IL-2?

A

T-cell growth factor - upregulates T cell replication and T-cell function; triggers T-cells to move from G1 to S phase to start mitosis; induces production of Bcl-2, which is anti-apoptotic for the targeted cell; upregulates IL-2 receptors on both the origin T-cell and neighboring T-cells; principle stimulator of IFN-gamma production during responses to viral infections; Increases IgG production when it binds to B-cells; activates and promotes macrophages and NK cells

49
Q

Is IL-2 involved in the innate or adaptive immune system?

A

both!

50
Q

What genetic defect results in Severe Combined Immunodeficiency?

A

IL-2 receptor defect

51
Q

What is the function of IL-7?

A

Is a homologue for IL-2 - does everything that IL-2 does (redundancy)

52
Q

What is the principal function of IL-12?

A

promotes cytotoxic death (lethal assassin cytokine)

53
Q

How does IL-12 induce cytotoxic death?

A

Stimulates NK cells and CD8+ cytotoxic T cells; upregulates IFN-gamma production for antiviral defense; increases cell sensitivity to IL-2 and suppresses IL-4 (Th1 cytokine profile)

54
Q

What is the function of IFN-gamma? Is it a Th1 or Th2 cytokine?

A

Th1 cytokine - important for antiviral activity; enhances cytotoxic T cell mediated apoptosis of infected cells, stimulates phagocytosis by macrophages, upregulates MHC-I expression on T-cells, upregulates MHC-II expression on dendritic cells, promotes B-cell production of antigen-specific IgG; inhibits IL-4 - is a counter-regulator of Th2 lymphocyte responses, activates neutrophils, NK cell stimulator

55
Q

What are the main Th2 cytokines?

A

IL-4, IL-5, IL-10, IL-13, IL-31

56
Q

Functions of IL-4

A

Promotes IgE class switching, promotes increased IgE production by B cells, mast cell growth factor, stimulates high affinitiy IgE receptor expression on the surface of mast cells, Promotes IL-4 production and favors Th2 polarization, downregulates IL-1, IL-6, TNF-alpha, IFN gamma

57
Q

Functions of IL-13

A

IL-4 homologue - EXCEPT does not polarize to TH2

58
Q

Functions of IL-10

A

Inhibits IL-12, TNF-alpha, IFN-gamma, and MHC-II costimulation by antigen presenting cells

59
Q

Functions of IL-5

A

key growth factor for eosinophils

60
Q

Functions of IL-31

A

pruritus – triggers JAK/Stat signaling pathway, present on umyelinated C fibers in the skin; activates eosinophils and macrophages, has pro-inflammatory effects on keratinocytes

61
Q

What cytokines utilize the Jak/Stat cell signaling pathway?

A

IFN-alpha/beta/gamma; IL-2, IL-7, IL-9, IL-10, IL-12, IL-15, IL-21, GM-CSF, IL-31

62
Q

What role does IL-1 play in the innate immune system?

A

Is produced by keratinocytes (and macrophages) in response to non-specific activation (e.g. injury) – results in cascade induction for local inflammation in response to infection or injury

63
Q

What role does IL-1 play in the adaptive immune system?

A

Initiator of contact hypersensitivity and adaptive immune response to antigens exposed across the skin –> stimulates dendtritic cells, triggering them to upregulate sampling of the extracellular space, signaling them to separate from keratinocytes and migrate out of the epidermis

64
Q

What is the function of IL-6?

A

support cytokine – enhances the actions of other cytokines present in the milieu; in high concentrations has similar effects to IL-1 and TNF-alpha; also promotes IL-2 production

65
Q

IL-1 and IL-6 stimulate synthesis of what antibodies by B cells?

A

IgM

66
Q

IL-5 and IL-6 stimulate synthesis of what antibodies by B cells?

A

IgA

67
Q

What cells are the primary producers of IL-6?

A

Macrophages - in response to IL-1 or TNF-alpha activation of the NF-kB pathway

68
Q

What cells produce IL-12?

A

macrophages and dendritic cells (cells of innate immune system) - in response to activation of NF-kB pathway

69
Q

Why would a defect in IL-12 or the IL-12 receptor predispose an animal to atopic disease?

A

IL-12 promotes T-helper cells to produce a Th1 cytokine profile; Without IL-12, are polarized to Th2 and pro-allergic state

70
Q

T/F: Naïve lymphocytes home to lymph nodes and spleen rather than tissue.

A

TRUE

71
Q

What are addressins?

A

lymphocyte homing receptors expressed in tissue

72
Q

What is the function of selectins and integrins?

A

mediate slowing, rolling, and tethering (adhesion) to local capillary epithelium

Vet Derm Review (44 decks)

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