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Veterinary Dermatology > Cytokines - Fadok REF 2023 > Flashcards

Cytokines - Fadok REF 2023 Flashcards

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Dermatology Board Prep flashcards
1
Q

What are cytokines and what are their main purposes?

A

Small molecular weight proteins. Responsible for growth, differentiation, and survival (or death) of cells in tissues. Also have effector functions.

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2
Q

What are chemokines and why are they called this?

A

Small subset of cytokines that are involved in chemotaxis via production of a gradient.

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3
Q

How to chemokines call cells into tissues?

A

Via a concentration gradient of the chemokines which attract the cells to the area.

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4
Q

Understand difference between Cytokines and hormones in terms of targets, redundency, circulation, and influence

A

Hormones have many targets and are produced by few cells. CKs are produced by many cells and have few targets. CKs have high redundency, hromones have low redundency (backups). CKs rarely circulate in blood stream but hormones DO. CK influence locally whereas hormones influence widespread.

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5
Q

Paracrine definition

A

CK impacts a cell in the immediate surrounding of where it is produced.

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6
Q

How can CKs act in an endocrine action?

A

They get into circulation and affect a distance cell such as with inflammatory systemic diseases.

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7
Q

which CK does intracrine signaling?

A

pro-IL1alpha. It is intracellular until n-terminus is cleaved off. It can act as transcription factor for upregulation for nf-kappab and AP-1 (transcription factors for inflammation).

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8
Q

What can pro-IL1alpha cause increased CK secretion of?

A

IL6, 1L18

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9
Q

What keeps CKs restricted to local sites or overall impact controlled? (Multiple factors are involved)

A

Produced by cells next to target cells (the producing cell is near target cell), small amounts are produced, directional release, receptor endocytosis, and CKs bind to extracellular matrix. quenching in circulation by soluble receptors, natural antagonists. CKs are usually not stored pre-formed (must be synthesized by gene transcription). CKs are usually short-lived (mRNA is short-lived). they are produced as-needed. Some must be processed after production.

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10
Q

Why is restriction of CK to local area critical?

A

High levels of circulating proinflammatory CK can lead to cytokine storms (killer in toxic shock syndrome, influensa, severe malaise in food poisoning and post viral encephalopaties).

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11
Q

What is pleotrophy?

A

One cytokine can have multiple activities.

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12
Q

What does IFN-gamma do?

A

B cell differentiation, activates T cells, activates granulocytes, endothelial cell activation, increased NK cell activity.

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13
Q

Who produces IFN-gamma?

A

Th cells - Tc, NK cells; and macrophages

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14
Q

What is redundency in CKs?

A

Multiple CKs have the same or similar activities.

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15
Q

What are functions of IL1, IL6, TNF-alpha

A

liver - acute phase proteins –> activate complement - many other functions - see list

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16
Q

IFN-gamma inhibits which tpe of t cells, Th1 or Th2?

A

Th2

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17
Q

IL4 inhibitis which type of cells, Th1 or Th2

A

Th1

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18
Q

TGFbeta activates ______ but deactivates ______ (cell type).

A

activates monocytes, deactivates macrophages.

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19
Q

Th1 makes which CKs

A

IFN-gamma, TNFalpha, LT

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20
Q

Th1 cells affect which types of pathogens

A

viral and intracellular pathogens

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21
Q

Th2 cells make which CKs

A

IL5,4,13,31

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22
Q

Th2 cells affect which types of pathogens or conditions

A

allergy, parasites

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23
Q

Th17 cells affect which types of pathogens

A

inflammation/inflammatory conditions, extracellular pathogens

24
Q

Th17 makes which cytokines

A

IL17, IL22, (il6, TNFalpha)

25
Q

T helper cells are also called _______ T cells

A

Effector T cells

26
Q

Th9 cells induced by which CKs?

A

IL4, TGFbeta

27
Q

Th9 cells repressed by which CKs

A

IFN-GAMMA

28
Q

Function of Th9 cells

A

chronic inflammation (perpetuate it), food allergy??

29
Q

Th9 cells make which CKs

A

IL9,10

30
Q

Th22 cells function

A
31
Q

Th follicular cell function

A

LIves in lymph nodes, regulate b cells, important in long term humoral immunity, help pump up the amount of Ig that is produced.

32
Q

Naive T cell can turn into which cell types depending on the CK it is exposed to?

A

Th BCL6, Th9, Treg, Th2, Th1, Th17, others

33
Q

What tells the T cell what to do

A

APCs.

34
Q

What type of dendritic cells are made in allergic skin compared to normal skin

A

Allergic skin - DC2. Normal skin - DC1.

35
Q

What CKs do allergic skin dendritic cells make?

A

IL4, IL5, IL10

36
Q

Which CKs activate langerhans to become TH2 promoting in the allergic epidermis?

A

IL33, IL24, TSLP

37
Q

What is IL8 for?

A

Neutrophil activation, stim neutrophils to make factors to promote Th2 and Th22 cells

38
Q

What type of langerhans promote allergic response?

A

type 2

39
Q

What are skin alarmins and list their functions?

A

Cytokines that stim type 2 response; functions: activate dendritic cells to go to the lymph nodes, activate innate lymphoid cells to secrete IL4 and Il13

40
Q

How do steroids work in AD?

A
41
Q

What is the glucocorticoid receptor and where is it located?

A

cytoplasmic/cytosolic receptor (located INSIDE of the cells)

42
Q

How does CSA work?

A
43
Q

What molecule does CSA bind?

A

Cyclophilin, which inhibits calcinurin; present in almost every cell.

44
Q

Why does it take several weeks for CSA to work?

A

Because it decreases production of cytokines which takes time, including IL2

45
Q

How does Oclacitinib work?

A

Binds to Janus kinase. It still dimerizes, but inhibits phosphorylation and so there is no production of cytokines.

46
Q

What molecule does Apqoeul bind to?

A
47
Q

Know the steps of the janus kinase signaling pathway from when the cytokine binds the receptor until the stimulation of itch and inflammation.

A
48
Q

MOA of cytopoint

A

Neutralizes only IL-31 before binding to its receptor.

49
Q

Most common organism involved in post grooming furunculosis?

A

Pseudomonas aeruginosa.

50
Q

What are members of the IL6 family

A

IL31, oncostatin M, cardiotropin, IL6, IL11, leukemia inhibitor factors

51
Q

What are the roles of the IL6 family of CKs?

A

neuronal growth, bone metabolism, heart development, immune regulation, T cell differentiation.

52
Q

Which cells mainly secrete IL31

A

Th2 memory CD4+ CLA+ cells; also macrophages, mastocytes, dendritic cells, eos, and basophils

53
Q

What is the format of the IL31 receptor

A

complex heterodimer formed by the IL31RA (alpha) and the oncostatinMbeta receptor (OMSR)

54
Q

Which part of the IL31R does IL31 bind to?

A

The alpha subunit

55
Q

What is the cascade that happens after IL31 binds to its receptor?

A

Binding of IL-31 to this receptor results in the phosphorylation of a triple intracellular cascade:

(a) Janus kinase 1 and 2 (JAK1/JAK2), together with their signal transducer and activator of transcription factors 1, 3, and 5 (STAT1, STAT3, andSTAT5) (3 to a greater extent than 1 and 5)

(b) the protein kinase B pathway (PI3K/AKT) –> PI3K + AKT

(c) SPH-2 –> the mitogen-activated protein kinase pathway (MAPK)

56
Q

Which cells express the IL31R receptor

A

epithelial, neuronal, and immune cells,such as keratinocytes, fibroblasts, dendritic cells, masto-cytes, macrophages, basophils, and eosinophils, as well as peripheral neurons and dorsal root ganglia

57
Q

CP study folder - Baldrich article for more questions

A

Veterinary Dermatology (4 decks)

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