Vitamin D and Immunity - T Cells
The importance of vitamin D in immune defence mechanisms in the human and why sunlight and vitamin are not important in furry nocturnal mammals.
Immunity involves defence processes against infection and learning from the experience so that on a second occasion the process will be more rapid.
We must remember that we are only 10% human. We are composed of about 100 trillion cells, but only 10 trillion are human: the other 90 trillion are bacterial. When we die these take over and we decompose. The “life force” prevents this during life and there are several defence mechanisms in place. These also prevent infection from external organisms (infection by bacteria normally resident on are in the body are call “nosocomial”).
The main physical barriers include the integrity of the skin, the mucus and the cilia on the respiratory tract, and the acidity of the stomach. We then have metabolical processes within the tissues, should there be invasion by bacteria.
The important first-line action is by lymphocytes, found in lymph glands, and lymphoid tissues such as the tonsils. It is important to recognise the two types of lymphocytes: B cells and T cells. The have different evolutionary and embryological origins and functions.
B cells originate in the embryonic Bursa of Fabriccius. They are concerned with the production of antibodies.
T cells originate embryologically in the thymus and they are concerned with tissue immunity. It is the T cells that are the subject of this review. Vitamin D in its activated form 1,25(OH)2D is an important co-factor, combining with the genetically encoded vitamin D receptor (VDR).
T cells that have never been exposed to a bacterial or viral antigen are described as “naive”. They have not yet learned to respond to infection, but when they have they are described as “antigen-primed”. The process is much more rapid when antigen-primed, by a factor of 50.
Pathway 1
1. The T cell receptor (TCR) recognises the antigen, followed by:
2. Lck activation,
3. Zap70 activation,
4. PLC?1 activation
(low level in human),
5. MAPK cascades,
6. production of transcription factors,
7. gene expression,
8. cytokine production and release,
9. cell-cycle entry -> proliferation of T cells.
Alternative pathway 2, with vitamin D effect:
1. The T cell receptor (TCR) recognises the antigen, followed by:
2. Lck activation,
3. Zap70 activation,
4. MAPK p38 cascades,
5. production of transcription factors,
6. gene expression,
including VDR activation,
7. VDR combines with 1,25(OH)2D and translocates to the nucleus,
8. Vitamin D-responsive elements activate gene encoding PLC?1 ,
9. PLC?1 up-regulation x75,
- cytokine production and release,
- cell-cycle entry -> explosive proliferation of T cells.
An important observation is that in the human naive T cells, the PLC?1
is low level. Vitamin D in its fully activated for 1,25(OH)2D combine with VDR to activate the PLC?1 gene. When PLC?1 activity is enhanced by a factor of 75, T cells undergo explosive proliferation and defence mechanisms are brought into action, with cytokine release (pathway 2).
On the other hand mice have a high level of PLC?1 in naive T cells, and therefore the T cell proliferation is as in pathway 1. Vitamin D is not necessary.
This explains why furry nocturnal animals are able to survive in the absence of sunlight and with minimal vitamin D.
Further reading (not for the feint-hearted):
von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Ødum N, Geisler C.
Vitamin D controls T cell antigen receptor signaling and activation in human T cells.
Nature Immunology 2010; 11: 344-350.
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