Tuesday, May 09, 2006

Hygiene Hypothesis - Part 2 - Some Immunology

Before we go further in discussing the Hygiene Hypothesis, it's necessary to know a little immunology. The basics of the immune system can be learned by reading 'Understanding the Immune System' (an online pdf published by NIH). It's a bit dated and won't go into the Hygiene Hypothesis but is still worth reading. While you are at it you can also read 'Understanding Vaccines' and 'Understanding Microbes'. These booklets have all been written for the non-scientist.

Everyone has probably heard about antibodies, produced by B cells, or humoral immunity and how they protect you against infection. That is usually the extent of most people's knowledge of immunology.I want to talk about two lesser known types of immune responses and how they tend to counter-regulate each other. These immune responses concern T cell responses or what some persons call cell-mediated immunity.

There are at least 3 kinds of T cells: Helper T cells or CD4+ T cells; Cytotoxic T cells or CD8+ T cells; and T regulatory or CD4+FoxP3+ T cells. Each has their own complex role in mediating or controlling immune responses.

CD4+ helper T cells have been divided into two types: Th1 and Th2 cells which mediate Type 1 or Type 2 cytokine responses. NOTE: both Th1 and Th2 cells help B cells make antibodies! Don't believe this crap about Th1 mediating cellular responses and Th2 mediating antibody responses. It's not that simple.

Th1 T cells usually mediate protective immune responses to intracellular pathogens. They do this by producing a cytokine called 'Interferon gamma' which activates macrophages to destroy pathogens or by 'helping' B cells make certain types of antibodies (among many other mechanisms) which also help macrophages destroy pathogens. Uncontrolled Th1 cell inflammatory responses can result in tissue or organ damage called 'immunopathology'.

Th2 T cells likely evolved in response to helminth infections. They produce a cytokine called IL-4 (interleukin 4) which is involved in mediating immune responses against worms. In some individuals, Th2 T cells also mediate allergic responses.

One important thing to be aware of is that Th1 and Th2 T cells can counter-regulate each other. Interferon-gamma produced by Th1 cells can prevent the development of Th2 cells. IL-4 produced by Th2 cells can prevent the development of Th1 cells. There is no way to tell these cells apart just by looking at them in a microscope, special techniques need to be used.

T regulatory cells, like Th1 and Th2 cells, are also CD4+ T cells but they also express FoxP3 (forkhead box P3). These cells secrete IL-10 and/or TGF-beta, molecules that can down-regulate inflammatory immune responses. Mice which lack FoxP3 expression are called scurfy and they rapidly die from multi-organ inflammation. In other words, Treg cells are necessary to regulate inflammatory immune responses.

To very much simplify:

Th1 cells mediate protection against most infectious diseases but can cause organ damage if not controlled. Th1 cells can also cause autoimmune diseases such as Type 1 diabetes, maybe multiple sclerosis, and several gastrointestinal diseases to name but a few. Th1 cells produce a cytokine that can prevent development of Th2 cells.

Th2 cells mediate protection against helminth (worm) infections and are also responsible for allergic reactions. Th2 cells produce cytokines that can prevent development of Th1 cells.

Treg cells secrete protein molecules that regulate Th1 and Th2 mediated-immune responses.


Sara said...

amazing how you can write that all out in just a few short paragraphs yet it takes us mutliple hour long lectures to learn all that :)

B-Wizz said...

That's always the case. I rememeber spending hours in O. Chem. failing to grasp topics that took hours for our Ivy League educated professor to "simplify" for us, just to wander into Plant Phys down the hall and have that professor explain it in about ten minutes.

sf00 said...

It seems like they're not Th2 cells; they're Type I NKT cells that express CD4.

sf00 said...

that are involved in asthma, was what I meant.

PCS said...

Ok, the above comments make things more complicated by bringing in antigen presentation via CD1d and invariant T cell receptors. For right now, let's keep things a bit more simple.

Sara said...

I'm enjoying the science blogs, keep them up & add more photos!! Everyone loves to see science - remember how much Kristin M. use to love coming in to see our H. poly worms :)

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