Molecular Immunology
Human Leukocyte Antigen System
The human leucocyte antigen ( HLA ) has the major importance in immune response and it is besides known as Major Histopathology Complex ( MHC ) . HLA besides plays a cardinal function in assorted clinical applications i.e. antigens organ transplant and legion diseases. The place of HLA is at the arm of chromosome 6. It is comprises of three major part that includes category I, category II and category III part.
The category I part contains three different cistrons which includes HLA-A, HLA-B and HLA-C. These cistrons encode for heavy ironss of category I molecules.
The category II part comprises of bomber parts series that includes A and B cistrons which encodes ? and ? ironss severally. DP cistron household is besides included that comprises of DPA1 and DPB1 cistron which jointly form DP molecules. DR cistron household contains individual DRA cistron and nine DRB ( DRB1 to DRB9 ) cistrons. The DRA cistron encoded ? ironss binds to assorted ? ironss that are encoded by DRB cistrons. DQ cistron household is besides a portion of category II part that is composed of DQA1 and DQB1 cistron that unite to organize DQ molecules.
The category III part is comprised of cistrons that encodes for complement system ( C2, C4, factor B ) , tumor mortification factor and hydroxylase etc. The category III part does non incorporate any cistron for HLA.
The Mendelian manner suggests that HLA haplotype are responsible from each parent for the HLA heritage. Almost all the nucleated cells expresses HLA category I molecules on their surface whereas merely B lymph cells, activated T lymph cells and antigen presenting cells ( dendritic cells, macrophages and monocytes ) expresses HLA category II molecules. The peptide adhering pockets present in HLA molecules comprises of a limited figure of aminic acids residue which determines the HLA molecules peptide adhering specificity. The adhering specificity of category I and category II HLA molecules varies and bind to different peptides.
The antigens which are synthesized within the mark cell are called endogenous antigens. These antigens are formed in response to cellular, viral or transformed induced proteins. The endogenous antigens are recognized by category I restricted T cells and binds to organize category I molecule peptide complex. This composite is so transported to the surface of mark cell and it is than able to acknowledge by CD8+ T cell receptors. The exogenic antigens are largely recognized by category II restricted T cells and are so endocytosed and so degraded by the endosomal compartments. The category II molecules besides binds to organize category II molecule peptide composite and it is so transported to the surface of the mark cell to be recognized by the CD4+ T cell receptors. The T lymph cell and HLA molecule acknowledgment is besides enhanced by some accessary molecules present in T cell receptors.
The organ transplant can be enhanced by proving of HLA system by the aid of different techniques. Complement mediated Microlymphocytotoxicity Technique is an of import technique in analysing HLA system. It provides a standard serological typewriting of category I and II antigens. Polymerase concatenation reaction ( PCR ) is used for the molecular typewriting of HLA allelomorphs. Two different PCR methods are used for molecular typewriting i.e. Sequence specific oligonucleotide investigation ( SSOP ) and Sequence specific primer method ( SSP ) . Besides, enzyme linked immunosorbent check ( ELISA ) and flow cytometry are used for HLA antibody showing.
The HLA system has the major function in organ transplant, that can be organ organ transplant or haematopoietic root cell organ transplant. The HLA system is besides involve in blood transfusion therapy where it plays a function in cross matching of blood and the constituents within. Previously HLA typewriting was besides used for parenthood testing, nevertheless, this technique has now been replaced by many other molecular techniques.
Antigen presentation and processing tracts
Two groups of T cells are involved in the ordinance of cell mediated unsusceptibility i.e. T helper cells or CD4+ T cells and Cytotoxic T cells or CD8+ T cells. The map of these cells involves the devastation and surveillance of come ining pathogens in conformity with antigen showing cells ( APCs ) . The antigens nowadays in APCs are besides combined with other molecules which are jointly known as Major Histocompatibility Complex ( MHC ) . There are two types of MHC viz. MHCI and MHC II. Both the MHC binds specifically to receptors present on Helper T cells and Cytotoxic T cells. The binding of MHC with the T cells consequences in the activation of T cells and it leads to production of antibodies, proliferation or enhance immune response if the same antigen interacts later. There are two tracts for the antigen presentation and processing.
The Endogenous Pathway
MHC category I molecules are involved in the presentation of antigen on the surface of mark cell. These antigens are formed in response to cellular, viral or transformed induced proteins. The endogenous antigens are recognized by MHC I and binds to organize category I molecule peptide complex. This composite is so transported to the surface of mark cell and it is than able to acknowledge by CD8+ T cell receptors. As the mark cell is infected by the antigen, these proteins become ubiquinated and they are presented to proteosome debasement. Proteosomes interrupt this antigen into peptides which are around nine aminic acids long. Then there comes the function of TAP protein which spans the unsmooth endoplasmic Reticulum ( ER ) membrane. TAP transport the peptides in the unsmooth endoplasmic Reticulum. The MHC I folding is regulated by chaperons and adhering Ig protein ( BiP ) which are present in ER. The TAP conveyance the peptides to the ER binds with this folded MHC I molecule and stabilising it. This MHC I molecule peptide complex is so transported to the cell surface through Golgi setup. The Cytotoxic T cells or CD8+ T cells are so able to acknowledge these molecules and turns immune response consequently.
The Exogenous Pathway
The exogenic antigens are recognized by antigen showing cells and are so endocytosed. These endocytosed proteins are so presented to category II MHC molecules and are so endocytosed and so degraded by the endosomal compartments by the action of acerb dependent peptidases. The category II MHC molecules besides binds to the exogenic antigen to organize category II molecule peptide composite and it is so transported to the surface of the mark cell to be recognized by the CD4+ T cell receptors. The peptide adhering cleft of MHC II molecule is blocked an invariant concatenation in ER, so that it can non adhere to cellular peptides or endogenous tract ‘s peptides. The MHC II molecules are transported to the cyst with the aid of this invariant concatenation. There HLA-DM which is MHC II like construction removes the cartridge holder and allows the broken peptide in the endosome to be attached. This MHC II peptide composite is so presented to the cell surface to be recognized by T assistant cells or CD4+ T cells.
