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Transcript
Question bank –MHC-5
Q1 Explain briefly the fallowing :
a. The major histocompatibility complex (MHC).
The major histocompatibility complex (MHC) is a large genetic complex glycoprotein's
with multiple loci. The MHC loci encode two major classes of membrane-bound
glycoprotein's: class I and class II MHC molecules. TH cells generally recognize antigen
combined with class II molecules, whereas TC cells generally recognize antigen combined
with class I molecules. Class III MHC antigens constitute early complement proteins C4 and
C2.Other inflammatory proteins, e.g.tumour necrosis factor (TNF), are encoded in adjacent
areas.
b. The major histocompatibility complex (MHC) classes and their biological
function
The MHC loci encode two major classes of membrane-bound glycoprotein's: class
I and class II MHC molecules. TH cells generally recognize antigen combined with
class II molecules, whereas TC cells generally recognize antigen combined with class
I molecules. Class III MHC antigens constitute early complement proteins C4 and
C2.Other inflammatory proteins, e.g.tumour necrosis factor (TNF), are encoded in
adjacent areas.
c. MHC molecules biological function.
MHC molecules function act as antigen-recognition molecules, but they do not possess the
fine specificity for antigen characteristic of antibodies and T-cell receptors. Rather, each
MHC molecule can bind to a spectrum of antigenic peptides derived from the intracellular
degradation of antigen molecules. In both class I and class II MHC molecules the distal
regions (farthest from the membrane) of different alleles display wide variation in their
amino acid sequences.
d. The role of MHC molecules in antigen recognition by T cells.
The role of MHC molecules in antigen recognition by T cells.
(a) Class I MHC molecules are expressed on nearly all nucleated cells.
(b) Class II MHC molecules are expressed only on antigen presenting cells. T cells
that recognize only antigenic peptides displayed with a class II MHC molecule
generally function as T helper (TH) cells. T cells that recognize only antigenic
peptides displayed with a class I MHC molecule generally function as T cytotoxic
(TC) cells.
e. Biological mechanism of MHC.
Complex Antigens Are Degraded (Processed) and displayed (Presented) with MHC
Molecules on the Cell Surface. In order for a foreign protein antigen to be recognized by a T
cell, it must be degraded into small antigenic peptides that form complexes with class I or
class II MHC molecules. This conversion of proteins into MHC-associated peptide
fragments is called antigen processing and presentation. Whether a particular antigen will
be processed and presented together with class I MHC or class II MHC molecules appears to
be determined by the route that the antigen takes to enter a cell.
f. Class III MHC.
Class III MHC antigens constitute early complement proteins C4 and C2.Other
inflammatory proteins, e.g.tumour necrosis factor (TNF), are encoded in adjacent areas
g. Class II MHC biological mechanism.
Exogenous antigen is produced outside of the host cell and enters the cell by
Endocytosis or Phagocytosis. Antigen presenting cells (macrophages, dendritic
cells, and B cells) degrade ingested exogenous antigen into peptide fragments within
the endocytic processing pathway.
Experiments suggest that class II MHC molecules are expressed within the endocytic
processing pathway and those peptides produced by degradation of antigen in this
pathway bind to the cleft within the class II MHC molecules. The MHC molecules
bearing the peptide are then exported to the cell surface. Since expression of class II
MHC molecules is limited to antigen-presenting cells, presentation of exogenous
peptide–class II MHC complexes is limited to these cells. T cells displaying CD4
recognize antigen combined with class II MHC molecules and thus are said to be
class II MHC restricted. These cells generally function as T helper cells. Antigen
Selection of Lymphocytes Causes Clonal Expansion. A mature immunocompetent
animal contains a large number of antigen-reactive clones of T and B lymphocyte.
g. Class I MHC biological mechanism.
Endogenous antigen is produced within the host cell itself. Two common examples
are viral proteins synthesized within virus-infected host cells and unique proteins
synthesized by cancerous cells. Endogenous antigens are degraded Into peptide fragments
that bind to class I MHC molecules within the endoplasmic reticulum. The peptide–class I
MHC is then transported to the cell membrane. Since all nucleated cells express class I
MHC molecules, all cells producing endogenous antigen use this route to process the antigen.
T cells displaying CD8 recognize antigen associated with class I MHC molecules and
thus are said to be class I MHC restricted. These cytotoxic T cells attack and kill cells
displaying the antigen–MHC class I complexes for which their receptors are specific.
h. HLA (human leukocyte antigen):
Major histocompatibility complex of humans. The complex occupies segment of1.52.0 centiMorgans of the short arm of chromosome 6. The HLA complex contains
genes that encode class I histocompatibility molecules (HLA-A,HLA-B ,HLA-C and
HL A-E) , Class II histocompatibility molecules ,HLA-D, and Class III molecules
(C2, C4,factor B and P-450 cytochrome (21-hydroxylase). The genes encoding tumor
necrosis factors alpha and beta are located between the class III genes and HLA-B.
Most of the genes in the HLA complex are highly polymorphic.
i. The immunologic role of MHC.
The MHC typically contains genes encoding class I histocompatibility molecules and class
II histocompatibility molecules, which are important for
1- the growth and differentiation of B and T lymphocytes.
2- Antigens presentation.
3- Cytotoxicity.
4- Graft rejection and mixed lymphocyte reactions.
l.