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HDID Block 1 > Adaptive cytokines > Flashcards

Adaptive cytokines Flashcards

1
Q

Describe the function of the following “adaptive” cytokines

IL2

IFN-y

IL4

IL5

IL 13

IL17

IL21

A

IL2 - two is for T cell proliferation (Tregs**)

IFN-y - activates macrophages (lets interfere and activate these #macrophages)

IL4 - B cell proliferation and class switching to IgE

IL5 - B cell proliferation and (class switching to IgA)

IL13 - same as IL4

IL17 - acute inflammation (when you’re 17, your life is lit)

Il21 - Tfh cell differentiation + B cell activation

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2
Q

The subtypes of IL17 involved in adaptive immunity are ___ and ___

A

IL17a and IL17f

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3
Q

Which subtype of Th cell is responsible for activating B cells so they become high rate Ab producers?

A

Thf (T follicular helper cells) are for necessary for B cell activation so they become high rate Ab producers

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4
Q

The differentiation of Th2 cells is induced by IL2 and IL4, and the Th2 cells themselves secrete which cytokines (3 of them)?

A

IL4

IL5

IL13

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5
Q

Th17 cells secrete IL22 and what 2 IL17 subtypes?

A

IL17a and IL17f

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6
Q

Which cytokines induce Th17 proliferation?

A

TGF-Beta

IL1

IL6

IL23

**you beta have my 6.23 cents. Sorry bruh, I gave it to 7-teenagers **

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7
Q

IFN-y and ___ promote Th1 differentation

A

IL12

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8
Q

Tregs are induced by __ and __

A

TGF-B and IL2

**its beta 2 regulate than to go out of control**

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9
Q

IFNy signaling leads to a response against (intracellular/extracellular) bacterial pathogens and viruses

INFy also helps (CD4+/CD8+) T cells and induces IgG __ and __ subtypes

Too much IFNy can result in ___

A

see image below

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10
Q

Il4, 5 and 13 all have responses against what type of pathogen?

They also activate B cells to class switch to IgG1, __ and __

When these are expressed in an uncontrolled manner, this can result in what kind of diseases?

A

see below

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11
Q

IL22, IL17a and IL17f elicit responses against (intracellular/extracellular) pathogens

The innate cell induced by the action of these is the ___

Which antibodies are later made following release of these cytokines?

Too much of these can result in which types of conditions?

A

see below

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12
Q

Which cytokines/cytokine receptors make up the common gamma subfamily?

A

IL2 (2 is literally the best even number out there)

IL4 (4 is a multiple of 2)

IL7 (7 is God’s # of perfection)

IL9 (9 was a semi-weird age)

IL15 (15 was a very weird age)

IL21 (21 was when it all started to go downhill)

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13
Q

T/F: If there’s a mutation in the gamma subunit, you’ll lose responsiveness to all 6 IL2 receptor subfamily cytokines

A

True indeed.Mutation in common Y chain: you lose signaling through all these receptors >> causes X linked SCID

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14
Q

The IL2 receptor family signals through which pathway?

A

Jak/Stat pathway

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15
Q

There are 2 types of IL2 receptor, namely the ___ and ___ receptors

Which one is made of IL2 receptor a, b and y chains, and which one has only the b and y chains?

A

High affinity and intermediate affinity receptor

High affinity IL2R receptor: has a, b and y chains; can bind very low IL2 levels and have a response; T regs are very responsive to low levels of IL2

Intermediate affinity IL2R: only has b and y; needs more IL2 in order to elicit a response. Memory CD8+ T cells + NK cells are responsive thru the intermediate receptor

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16
Q

Why do Tregs respond very well to low levels of IL2?

A

T regs are very responsive to low levels of IL2 because at basal levels, they express high levels of IL2Ralpha, making them very responsive to low IL2 levels via the high affinity receptor

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17
Q

CD8+ T cells and NK cells are responsive thru the intermediate receptor because why?

A

Memory CD8+ T cells + NK cells are responsive thru the intermediate receptor because, in the case of CD8+ cells, they express high levels of IL2Rbeta

18
Q

What is the difference between the Type I and Type II IL4 receptors?

Which other cytokine can bind the Type II receptor?

If you lose the type I receptor, what happens?

A

The Type II IL4 receptor binds to IL4ralpha + IL13ralpha to elicit a response

If there’s a mutation in the common gamma chain, you’ll lose signaling through the Type I receptor but you can still signal thru the Type II receptor if the cells express the IL3Ralpha chain

The IL13 receptor is the same IL-4Ralpha + IL13Ralpha1 subunit, so IL13 actually binds the IL-13Ralpha1 subunit first, then there’s dimerization with the IL4Ralpha subunit

**note that both receptor types also signal through JAK/STAT signaling**

19
Q

The GM-CSF receptor subfamily shares a common __ subunit. thru which pathway do these receptors signal?

GMCSF, ___ and ___ are all cytokines with receptors in this family

A

Beta subunit

Jak/Stat signaling

GMCSF, IL3 and IL5

20
Q

The receptor for IL17 (a and f) is made up of which 2 chains?

The IL17Ra chain is shared by other IL17 receptors, including the receptor for___ *which is NOT made by Th17 cells*

Thru which signaling pathway do the Il17 receptors work?

A

IL17 a and f function as dimers (aa, af, and ff)

The receptor for IL17 consists of 2 chains (IL17R a and c)

The IL17Ra chain is shared by other IL17 receptors, including the receptor for IL17C *which is NOT made by Th17 cells*

**note that receptors for IL17 signal through the NF-Kb pathway**

21
Q

Where in the RES are naive B and T cells activated?

Where is this organ do either of these reside?

A

In the #lymph node

B cells live in the lymphoid follicles, and T cells go to the paracortical zone (T cell zone) – the localization for both is determined by specific chemokines

22
Q

What are the functions of CXCR1 and 2?

A

CXCR1 and CXCR2 are both involved in neutrophil recruitment

23
Q

Which CXCR is involved in T cell recruitment and binds CXCL9, 10 and 11?

A

CXCR3 is involved in T cell recruitment

24
Q

Which chemokine receptor is involved in mixed lymphocyte recruitment and is a co-receptor for HIV?

A

CXCR4 is involved in mixed lymphocyte recruitment and is an HIV co-receptor, as is CCR5 (CCL4)

25
Q

___ is involved in lymphocyte migration to follicles (ligand = CXCL13)

A

CXCR5 is involved in lymphocyte migration to follicles (ligand = CXCL13)

26
Q

Which chemokine has CCL4 or 5 ligand and is involved in recruitment of T cells, DCs, monocytes and NK cells?

A

CCR5: recruitment of T cells, DCs, monocytes and NK cells (CCL4 or 5 ligand)

27
Q

What is the role and ligand of CCR7?

A

CCR7: lymphocyte and DC migration into T cell zone of lymph nodes (ligand = CCL19/21)

28
Q

How does the drug Xeljanz work?

A

Xeljanz is a #jak inhibitor (note that all the drugs that end in -ib- are Jak inhibitors)

29
Q

The antibodies Lebrikizumab and Dupilumab work against which chemokine receptors?

A

Lebrikizumab: anti-IL13

Dupilumab: anti IL4Ralpha

**Lebrikizumab has almost 13 letters

Dupilumab ain’t 4 alpha**

30
Q

Describe (again) the JAK/STAT signaling pathway that most cytokines signal thru

Name the members of the JAK family

A

see image below

31
Q

Ruxolitinib aka jakafi is a ___ inhibitor and is used to treat polycythemia vera and myelofibrosis

A

Jak1/Jak2 inhibitor

**my boy Jakafi’s been dating Rux (pronounced Ruth) and she takes lit(tle) nibs (like rude comments) at people**

32
Q

A JAK 3 inhibitor used to treat RA, psoriasis and UC is ___,aka Xeljanz

A

Tofacitinib (has 3 i’s in it for JAK 3, tofa ne arthritis shuwa)

33
Q

___ is a Jak1 inhibitor used to treat canine AD and pruritus

A

Oclatinib/Apoquel

**my dog Ocla got canine AD and pruritus so we had to give him apoquel**

34
Q

Olumiant/Baricitinib is a JAK1/JAK2 inhibitor used to treat___

A

rheumatoid arthritis

*that dude used to be the #1 bari-sta at the starbucks but he has RA now so after taking olumiant, he’s down to #2*

35
Q

Inrebis/Fedratinib is a ___ inhibitor used to treat myelofibrosis

A

JAK2 inhibitor

36
Q

Upadacitinib, aka ___ is a JAK 1 inhibitor used to treat RA

A

Upada gotta a fancy watch. The label is called Rinvoq

37
Q

What is the mechanism of action of Pitrakinra (targets IL4ralpha)?

A

Pitrakinra: mutant IL4 (mutations in tyrosine 124 and arginine 121) such that it can bind to the IL4 receptor alpha but it can’t dimerize with the common gamma chain

38
Q

What is the mechanism of action of dupilumab?

A

Dupilumab: Ab binds to epitope on IL4Ralpha that’s important for dimerization so the receptor can’t form a functional Type I or Type II receptor

39
Q

Mepolizumab and benralizumab target which cytokine/cytokine receptor?

A

Mepolizumab targets IL-5, and benralizumab targets IL-5Ralpha

** the M in both antibodies makes you think of IgM which is a pentamer so both target 5. Mepo = IL5 cytokine, benra = benRECEPTOR**

40
Q

Secukinumab and ixekizumab block which IL17?

Brodalumab blocks which IL17 receptor chain?

A

Secukinumab and ixekizumab block IL17a (so it’ll block the IL17a homodimers and heterodimers but it WON’T block IL17f)

Brodalumab blocks the IL17Ralpha chain, so all the receptors chains that form a dimer with that will be blocked by that Ab (think brodalumab is broad)

41
Q

The side effects of IL17/IL17 receptor alpha targeting include neutropenia and ___ infections. Some unexpected side effects include ___ and suicidal ideation/behavior

A

The side effects of IL17/IL17 receptor alpha targeting include neutropenia and Candida infections. Some unexpected side effects include flares/IBD induction and suicidal ideation/behavior

42
Q

What are the functions/mechanisms of the IL2 cytokine complex molecules SB46 and NARA1?

A

S4B6 interacts with IL2 and releases IL2 such that it prefers the high affinity receptor (which, you will recall promotes Tregs)

NARA1 interacts with human IL2 on a different epitope (blocks the ability of CD25 aka the alpha subunit to interact with IL2) so that promotes interaction with the intermediate affinity receptor (recall again that this is highly expressed on CD8+ T cells and NK cells who engage in anti tumor killing)

HDID Block 1 (12 decks)

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