USMLE Immunology-Interleukins responsible for IgG class switching?

[Estranged]

Kaplan mentions that IFN-γ is responsible for class switching to IgG while Fa 2016 (pg200) mentions that IL 4 is responsible for both IgG and IgE class switching. Which one is more accurate? Any insight is appreciated.

---

Members don't see this ad.

 

[PugsAndHugs]

I always though IFN-y was released by Th1 cells to stimulate macrophages AND inhibit the Th2 response (which is to class switch).

 

[cellsaver]

IL-4 is responsible for increasing isotype switching to IgE, B cell growth, Th2 cell differentiation
IL-5 is responsible for increasing isotype switching to IgA, differentiation of eosinophils
IFN-g is responsible for increasing intracellular killing by macrophages, MHC Class I & II expression and Th1 cell differentiation

UWorld is your best friend. Don't trust FA nor Kaplan.
Do searches on UW using keyword feature

 

[Estranged]

PugsandHugs I thought the same too. But I was really confused with FA and to make matters worse I ran into a question from kaplan q book today about the immune response that takes pace in lepromatous leprosy. It mentions that these patients present with over production of IL4 IL5 IL6 IL10 IL13 and TGF β (this is a Th2 response). And then the question is: what characteristic of the lepromatous form is predicted based on this fact? And the correct answer Hypergammaglobulinemia.
If ifn-γ is responsible for class switching to IgG then hypergamma globulinemia should be associated with a Th1 response right? Im confused now🙁

 

[Event_Horizon]

PugsandHugs I thought the same too. But I was really confused with FA and to make matters worse I ran into a question from kaplan q book today about the immune response that takes pace in lepromatous leprosy. It mentions that these patients present with over production of IL4 IL5 IL6 IL10 IL13 and TGF β (this is a Th2 response). And then the question is: what characteristic of the lepromatous form is predicted based on this fact? And the correct answer Hyper -gamma-globulinemia.
If ifn-γ is responsible for class switching to IgG then hypergamma globulinemia should be associated with a Th1 response right? Im confused now🙁

Gamma-globulin does not refer to IFN-gamma, but to the gamma peak that occurs in a serum protein electrophoresis. A significant portion of immunoglobulins of the blood are what create this peak.

 

[Estranged]

Gamma-globulin does not refer to IFN-gamma, but to the gamma peak that occurs in a serum protein electrophoresis. A significant portion of immunoglobulins of the blood are what create this peak.

I know that hypergammaglobulinemia refers to elevated gamma globulins (antibodies being the most significant) and not IFN-gamma. 🙂 I think my question was not very clear. According to many sources lepromatous leprosy is associated with high IgG in the serum. I thought that high levels of IgG are associated with Th1 response generally speaking, while Th2 is associated with high IgA or IgE ( maybe i m wrong here and this is why i ;m getting confused). But then again according to this question in lepromatous leprosy there is Th2 response mainly, so why do we see high IgG in a Th2 response and not in Th1 if Ifn -gamma is responsible for IgG class switching? ( I thought Ifn-gamma released from Th1 -> IgG class switch-Th2 inhibition ->so Th1 response=high IgG. Correct me ifi'm wrong here. If on the other hand FA is correct and Il4 is responsible for IgG switvhing then yes, Th2=high IgG. Which brings back the original question: Which interleukin is responsible for IgG class switching. ) I don't know if this makes sense.

 

[Event_Horizon]

I know that hypergammaglobulinemia refers to elevated gamma globulins (antibodies being the most significant) and not IFN-gamma. 🙂 I think my question was not very clear. According to many sources lepromatous leprosy is associated with high IgG in the serum. I thought that high levels of IgG are associated with Th1 response generally speaking, while Th2 is associated with high IgA or IgE ( maybe i m wrong here and this is why i ;m getting confused). But then again according to this question in lepromatous leprosy there is Th2 response mainly, so why do we see high IgG in a Th2 response and not in Th1 if Ifn -gamma is responsible for IgG class switching? ( I thought Ifn-gamma released from Th1 -> IgG class switch-Th2 inhibition ->so Th1 response=high IgG. Correct me ifi'm wrong here.) I don't know if this makes sense.

Ah, forgive me. I don't think that you are false in saying that INF-gamma initiates some IgG production from plasma cells, but humoral immunity is definitely not the function major of the Th1 response. It is primarily cellular mediated immunity with CD8+ cells and macrophages, driven by major inflammatory cytokines like INF-gamma. The Th2 response is the primary pathway for humoral immunity with CD4+ cells initiating major class switching in B-cells to produce various immunoglobulins, driven by major cytokines like IL-4, IL-5, and IL-10.

At least that is how I learned it.

 

[Estranged]

Ah, forgive me. I don't think that you are false in saying that INF-gamma initiates some IgG production from plasma cells, but humoral immunity is definitely not the function major of the Th1 response. It is primarily cellular mediated immunity with CD8+ cells and macrophages, driven by major inflammatory cytokines like INF-gamma. The Th2 response is the primary pathway for humoral immunity with CD4+ cells initiating major class switching in B-cells to produce various immunoglobulins, driven by major cytokines like IL-4, IL-5, and IL-10.

At least that is how I learned it.

I see your point. So you are suggesting that IgG production can be present in both Th1 and Th2 responses right? Maybe both Ifn-gamma and Il4 can initiate IgG class switching.

 

[Event_Horizon]

I see your point. So you are suggesting that IgG production can be present in both Th1 and Th2 responses right? Maybe both Ifn-gamma and Il4 can initiate IgG class switching.

No, I don't believe IFN-gamma can cause IgG class switching. I think it may stimulate some plasma cells to secrete IgG. Immunoglobulin class switching is definitely driven by IL-4/IL-5 in the Th2 response. I just crosschecked with my 2017 version of FA and the cytokine page says nothing of IFN-gamma causing class switching, only that it promotes macrophage/NK-cell function and MHC expression, and suppresses the Th2 response.

 

[Estranged]

ok so perhaps Kaplan is wrong ( pg 63/2016 " IFN-γ enhances isotype switching to IgG"). FA 2016 says exactly the same with what you quoted fro Fa 2017.
Thanks for your responses anyway. 🙂

 

[Estranged]

I did a little research and found this table. So it seems that Il4 stimulates IgG1 and IgG4 class switch while Ifn-gamma stimulates IgG1. I crosschecked with "how the immune system works" by Lauren Sompayrac (amazing book btw) and it must be correct. 😀

 

[sab3156]

It seems that both IL-4 and IFN-g are responsible for class switching to IgG... but the question remains, is either one a more potent inducer of the class switching? FA says IL-4 is responsible, and doesn't mention anything about IFN-g, even though they both do induce the class switching. Imagine if you were to get a question about isotype switching to IgG, and two separate answer choices had to do with IFN-g and IL-4... -_-