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Immunology: Th1/Th2 vs cellular/humoral responses

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Immunology: Th1/Th2 vs cellular/humoral responses

Postby jacobsherman » Mon Nov 01, 2010 12:27 pm

Hi,

I'm having some trouble getting these distinctions clear in my mind. Could someone please help me to understand the difference(s) between these two distinctions:
  • Th1 vs Th2 responses
  • Cellular vs humoral responses

Let me try to explain what seems unclear. I understand a "cellular" response to involve increased T cell activity, especially CD8+ cytotoxic T cells, but also 'helper' CD4+ T cells which enhance the activity of CD8+ T cells. I understand a "humoral" response to involve increased B cell activity, especially plasma cells and, therefore, increased production of antibodies. B cells also receive 'help' from CD4+ T cells. This is where the difference between the two distinctions becomes unclear to me. CD4+ T cells that help CD8+ T cells are referred to as Th1 cells, correct? CD4+ T cells that help B cells are referred to as Th2 cells, correct? Or do Th2 cells merely self-promote CD4+ cells?
My confusion leads me to think that the two types of distinction listed above are very similar i.e. that a Th1 response is very much related to a cellular response and that a Th2 response is very much related to a humoral response. I'd be very grateful if someone could confirm this or explain where I'm going wrong.

Two related questions:
  • Is there an actual direct protective effect of CD4+ T cells or do they only protect by providing help to CD8+ T cells and B cells?
  • I realise that there are Ig molecules that are defined as more Th1 and those that are defined as more Th2 but I don't understand why this is.

I hope I have been clear about the things which are... unclear to me! I look forward to someone helping me out!

Thanks in advance for your time,

Jacob
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Postby biohazard » Tue Nov 02, 2010 9:35 am

As far as I can tell, you have understood the things quite well.

About the direct CD4+ effect: There is no such direct CD4+ response as there is with CD8+ T cells, B cells, or cells of the innate immune system. CD4+ cells function by strenghtening or regulating the response of other immune cells. CD4+ cells themselves depend on the so-called antigen presenting cells (APCs) that collect antigens from their environment and display it to the CD4+ cells. These cells include dendritic cells, macrophages and B cells.

About the Ig molecules: Th1 and Th2 responses are pretty much determined by the cytokines the Th cells secrete. For example, Th1 cytokines, such as IFN-g, tend to promote IgG-based responses that are, for example, protective from allergy. Thus, healthy persons tend to mount Th1-biased immune responses towards harmless allergens, whilst atopic persons have Th2-deviated (cytokines such as IL4) responses that promote IgE formation. IgE, in turn, binds to basophils and mast cells and when an allergen is bound by its specific IgE, it cross-links the FceRI receptors on surface of the basophil and causes the release of substances that cause the allergic symptoms.

Physiologically, Th1 responses are thought to be important for defence against microbes and Th2 against multicellular parasites. The low number of parasitic infections in modern Western world is thought to be one reason for the increase in the prevalence of allergy. However, the precise roles of the different types of responses are still not fully understood and it is quite likely that many other Th responses and T cell subsets wait to be recognized.

Different Th responses do not exclusively target just one cell type (e.g. B cells), but have wider effect on many types of immune cells. The outcome of any given response is a sum of many factors and usually includes cytokines from many cell types and cell-cell interactions between different cells.
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Re: Immunology: Th1/Th2 vs cellular/humoral responses

Postby jacobsherman » Tue Nov 02, 2010 11:48 am

I don't know who you are, biohazard, but I really hope you are a teacher of some kind. That was an incredibly clear and structured explanation. Thank you - I am finally comfortable with these definitions which have eluded me for ages!
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Postby biohazard » Wed Nov 03, 2010 9:50 am

Why, thank you :)

I actually do some teaching; I teach microbiology and immunology to medical students a few months in a year. I hope they feel my explanations good enough as well (admittedly, they quite often look like they just didn't understand anything :P)

Most of my time goes to research, though!
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Re: Immunology: Th1/Th2 vs cellular/humoral responses

Postby jonmoulton » Wed Nov 03, 2010 3:17 pm

Looks like the story of the role of immunoglobulins is in revision.

Donna L. Mallery, William A. McEwan, Susanna R. Bidgood, Greg J. Towers, Chris M. Johnson, and Leo C. James

Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21)

PNAS published ahead of print November 2, 2010, doi:10.1073/pnas.1014074107

Open access:
http://www.pnas.org/content/early/2010/ ... 7.abstract
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Postby biohazard » Thu Nov 04, 2010 7:27 am

Now, that was something new to me indeed. Thanks for the link, jonmoulton!
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Re: Immunology: Th1/Th2 vs cellular/humoral responses

Postby jonmoulton » Thu Nov 04, 2010 4:00 pm

You're very welcome -- that paper challenged my mental model and I thought you'd find it tasty too.
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Re: Immunology: Th1/Th2 vs cellular/humoral responses

Postby arma9eddon » Wed Aug 24, 2011 8:07 pm

The field of immunology is a slippery one to get a grasp on. I like to remind myself that just prior to the discovery of T cells, an eminent immunologist of the time proclaimed at a symposium for the field that they now knew all of the parts of the immune system, it was just a matter of mopping up some details. Here we are talking about Th1, Th1, Th17, Treg etc.

TRIM21 was a very interesting discovery and I look forward to reading about detailed functional analysis in the future.

My point, however, is that I would like to respectfully disagree with biohazard's assessment that CD4+ T cells are not direct effectors in the way a classical CD8+ T cell is thought to be. This was certainly the long-held theory, but not so recent observations have cast confusion onto that neat package. Various groups have indeed described CTL-like function in CD4+ cells. (here is a random reference: ucp.php?mode=activate&u=70785&k=2MS6YGSIGU)

The fact that T cell classifications are still not rock-solid will no doubt be of little surprise to biohazard since based, on reading his very helpful summary of Th cells, biohazard certainly understands the evolving nature of immunological discovery and debate.

Cheers,
J
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Re: Immunology: Th1/Th2 vs cellular/humoral responses

Postby biohazard » Thu Aug 25, 2011 9:52 am

arma9eddon wrote:The field of immunology is a slippery one to get a grasp on. I like to remind myself that just prior to the discovery of T cells, an eminent immunologist of the time proclaimed at a symposium for the field that they now knew all of the parts of the immune system, it was just a matter of mopping up some details. Here we are talking about Th1, Th1, Th17, Treg etc.

TRIM21 was a very interesting discovery and I look forward to reading about detailed functional analysis in the future.

My point, however, is that I would like to respectfully disagree with biohazard's assessment that CD4+ T cells are not direct effectors in the way a classical CD8+ T cell is thought to be. This was certainly the long-held theory, but not so recent observations have cast confusion onto that neat package. Various groups have indeed described CTL-like function in CD4+ cells. (here is a random reference: ucp.php?mode=activate&u=70785&k=2MS6YGSIGU)

The fact that T cell classifications are still not rock-solid will no doubt be of little surprise to biohazard since based, on reading his very helpful summary of Th cells, biohazard certainly understands the evolving nature of immunological discovery and debate.

Cheers,
J


Indeed, I am not surprised about anything when it comes to the field of immunology - new things are discovered every day and old theories get abandoned or remodeled along the way. Thus it is often very difficult to explain these things in any kind of simplified manner as there are exceptions after exceptions everywhere and unknown pathways and previously unknown cell types, and new functions are found for "old" cells all the time.

I know that CD4+ cells engage in lots of cell-to-cell interaction when working with other cells of the immune system and I'm not too surprised if some "direct" mechanism of action has been described that does something else than regulates or controls. Unfortunately I was not able to open the link in your post so I could not take a better look at what that was all about.

Perhaps you could check the link to the reference when you have time and I will take a look at it after I return from my brief holiday. Anyways, thank you for pointing out that I have missed this kind of detail.
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Postby Aiyaya » Wed Aug 31, 2011 2:05 am

This is where the difference between the two distinctions becomes unclear to me. CD4+ T cells that help CD8+ T cells are referred to as Th1 cells, correct? CD4+ T cells that help B cells are referred to as Th2 cells..

(links removed ~ Admin)
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Postby biohazard » Thu Sep 08, 2011 10:00 am

Th1/Th2 division is mainly based on the cytokines they produce and they do not exclusively help just one certain cell type. Th1 cells produce cytokines (such as IFN-g) that generally promote cell-mediated immunity, including CD8+ T cells and Th2 cytokines (e.g. IL-4) promote humoral responses / B cell function.

However, this division is simplified since many more cytokines are produced by both helper T cell subsets, and there is overlap in cytokine production and function of different helper T cell subsets.
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