Adaptive cytokines Flashcards
Describe the function of the following “adaptive” cytokines
IL2
IFN-y
IL4
IL5
IL 13
IL17
IL21
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
The subtypes of IL17 involved in adaptive immunity are ___ and ___
IL17a and IL17f
Which subtype of Th cell is responsible for activating B cells so they become high rate Ab producers?
Thf (T follicular helper cells) are for necessary for B cell activation so they become high rate Ab producers
The differentiation of Th2 cells is induced by IL2 and IL4, and the Th2 cells themselves secrete which cytokines (3 of them)?
IL4
IL5
IL13
Th17 cells secrete IL22 and what 2 IL17 subtypes?
IL17a and IL17f
Which cytokines induce Th17 proliferation?
TGF-Beta
IL1
IL6
IL23
**you beta have my 6.23 cents. Sorry bruh, I gave it to 7-teenagers **
IFN-y and ___ promote Th1 differentation
IL12
Tregs are induced by __ and __
TGF-B and IL2
**its beta 2 regulate than to go out of control**
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 ___
see image below
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?
see below
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?
see below
Which cytokines/cytokine receptors make up the common gamma subfamily?
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)
T/F: If there’s a mutation in the gamma subunit, you’ll lose responsiveness to all 6 IL2 receptor subfamily cytokines
True indeed.Mutation in common Y chain: you lose signaling through all these receptors >> causes X linked SCID
The IL2 receptor family signals through which pathway?
Jak/Stat pathway
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?
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
Why do Tregs respond very well to low levels of IL2?
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
CD8+ T cells and NK cells are responsive thru the intermediate receptor because why?
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
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?
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**
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
Beta subunit
Jak/Stat signaling
GMCSF, IL3 and IL5
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?
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**
Where in the RES are naive B and T cells activated?
Where is this organ do either of these reside?
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
What are the functions of CXCR1 and 2?
CXCR1 and CXCR2 are both involved in neutrophil recruitment
Which CXCR is involved in T cell recruitment and binds CXCL9, 10 and 11?
CXCR3 is involved in T cell recruitment
Which chemokine receptor is involved in mixed lymphocyte recruitment and is a co-receptor for HIV?
CXCR4 is involved in mixed lymphocyte recruitment and is an HIV co-receptor, as is CCR5 (CCL4)
___ is involved in lymphocyte migration to follicles (ligand = CXCL13)
CXCR5 is involved in lymphocyte migration to follicles (ligand = CXCL13)
Which chemokine has CCL4 or 5 ligand and is involved in recruitment of T cells, DCs, monocytes and NK cells?
CCR5: recruitment of T cells, DCs, monocytes and NK cells (CCL4 or 5 ligand)
What is the role and ligand of CCR7?
CCR7: lymphocyte and DC migration into T cell zone of lymph nodes (ligand = CCL19/21)
How does the drug Xeljanz work?
Xeljanz is a #jak inhibitor (note that all the drugs that end in -ib- are Jak inhibitors)
The antibodies Lebrikizumab and Dupilumab work against which chemokine receptors?
Lebrikizumab: anti-IL13
Dupilumab: anti IL4Ralpha
**Lebrikizumab has almost 13 letters
Dupilumab ain’t 4 alpha**
Describe (again) the JAK/STAT signaling pathway that most cytokines signal thru
Name the members of the JAK family
see image below
Ruxolitinib aka jakafi is a ___ inhibitor and is used to treat polycythemia vera and myelofibrosis
Jak1/Jak2 inhibitor
**my boy Jakafi’s been dating Rux (pronounced Ruth) and she takes lit(tle) nibs (like rude comments) at people**
A JAK 3 inhibitor used to treat RA, psoriasis and UC is ___,aka Xeljanz
Tofacitinib (has 3 i’s in it for JAK 3, tofa ne arthritis shuwa)
___ is a Jak1 inhibitor used to treat canine AD and pruritus
Oclatinib/Apoquel
**my dog Ocla got canine AD and pruritus so we had to give him apoquel**
Olumiant/Baricitinib is a JAK1/JAK2 inhibitor used to treat___
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*
Inrebis/Fedratinib is a ___ inhibitor used to treat myelofibrosis
JAK2 inhibitor
Upadacitinib, aka ___ is a JAK 1 inhibitor used to treat RA
Upada gotta a fancy watch. The label is called Rinvoq
What is the mechanism of action of Pitrakinra (targets IL4ralpha)?
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
What is the mechanism of action of dupilumab?
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
Mepolizumab and benralizumab target which cytokine/cytokine receptor?
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**
Secukinumab and ixekizumab block which IL17?
Brodalumab blocks which IL17 receptor chain?
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)
The side effects of IL17/IL17 receptor alpha targeting include neutropenia and ___ infections. Some unexpected side effects include ___ and suicidal ideation/behavior
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
What are the functions/mechanisms of the IL2 cytokine complex molecules SB46 and NARA1?
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)
