On May 15, Kaih Bomai asked:
> 1 Does anyone know the Major histocompatibility complexes and what they
> do.
> 2 What are the stages of phagocytosis
1) The major histocompatibility complex (MHC) are involved in recognition
and presentment of antigens to T-cells. They participate in transplant
rejection, autoimmune diseases, and infection, the latter being what
they're there for. Regarding infections, there are basically two different
kinds of situations where you need to use the MHCs. One is where a cell
has been infected, say, by a virus, in which case the immune system has no
way to actually "save" the infected cell but instead will destroy it to
protect the rest of the person. Here, viral proteins are produced inside
the host ER and small peptides derived from these proteins make their way
to the surface of the cell, where proteins derived from a portion of the
MHC known as MHC Class I bind to the viral peptides and present them to
cytotoxic T-cells (CD8 cells), which lyse the infected cell.
The other situation in infection is when a macrophage or some such
cell has phagocytosed a microorganism, and now the cell will try to get
the helper (CD4) cells reactive with antigens from the microorganism to
activate. So, the microorganism is phagocytosed and brought into a
phagosome. Somehow, a different portion of the MHC (an MHC Class II
product) will accept peptides derived from the phagosome and will goto the
cell surface and present them to helper T-cells.
Their role in autoimmunity is variable and not entirely certain. They
clearly play a role, as individuals with certain MHC alleles have a
greater risk of a variety of autoimmune diseases, such as diabetes, lupus,
and Rheumatoid Arthtitis. Generally, however, it is assumed that the
T-cells are the ones with the discriminatory function -- they are the ones
who are supposed to recognize self from non-self proteins -- so the
mechanism by which certain MHC loci predispose to autoimmunity is fairly
complex.
They are also involved in transplant rejection, hence the search for
"compatible" donors of kidneys, bone marrow, etc. (Fortunately, red blood
cells lack nuclei and thus do not express MHC proteins, so you only need
to match blood donors by blood group type [A,B,AB,O}). I'm least
knowledgeable about this field, but I think the foreign MHC molecule can
itself be the antigen to which the T-cell reacts, as a foreign MHC
molecule is different but similar enough to self MHC to resemble a self
MHC plus a foreign peptide, which is precisely what T-cells are trained to
respond to.
2. The stages of phagocytosis:
(a) Margination of white blood cells (wbc) to the periphery of the blood
vessel. This is brought about by the inflammatory changes that accompany
infection, which cause a slowing of blood flow as fluid as proteins leak
through the vessel wall which has become increasingly leaky by the action
of interleukins.
(b) Rolling and Adhesion of the wbc to the vessel wall. This is in part a
consequence of margination, but it is also directly caused by molecular
mediators of inflammation, which upregulate molecules on the vessel wall
and on the wbc which cause them two be sticky.
(c) Diapedesis, or squeezing of the wbc through the vessel wall.
(d) Chemotaxis, or the process whereby the wbc directedly move in the
direction of the foreign microorganism. Various inflammatory molecules can
cause this.
(e) Phagocytosis. Here, the wbc binds the invader, engulfs it, and then,
normally, degrades it in lysosomes.
Hope this helped.
