12. Immune System. In: Encyclopedia of Life Sciences ( www ) Endogenous and Exogenous Antigen Presenting Pathways
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17. Immune Evasion Examples Mycobacteria : Inhibits phagolysosome fusion so that it survives within the phagosome Herpes simplex virus : Interferes with TAP transporter (inhibits antigen presentation) Cytomegalovirus : Inhibits proteasome activity and removal of MHC I from ER Epstein-Barr virus : Inhibits proteasome activity; produces IL-10 to inhibit macrophage activation Pox virus : Produces soluble cytokine receptors to inhibit activation of effector cells
18. Structure of Class I MHC NH 2 Alloantigenic sites CHO NH 2 COOH COOH P α1 α2 α3 β2 OH Plasma membrane Disulfide bridge Papain cleavage Cytoplasm NH 2
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20. Structure of Class II MHC Plasma membrane Cytoplasm CHO CHO CHO NH 2 NH 2 COOH COOH α1 α2 β2 β1
24. Class I polymorphism Locus Number of alleles (allotypes) HLA - A 218 HLA - B 439 HLA - C 96 There are also HLA - E, HLA - F and HLA - G Relatively few alleles
25. Class II polymorphism Locus Number of alleles (allotypes) HLA - DP A HLA - DP B 12 88 HLA - DQ A HLA - DQ B 17 42 HLA - DR A HLA - DR B1 HLA – DR B3 HLA – DR B4 HLA – DR B5 2 269 30 7 12 There are also HLA - DM and HLA - DO Relatively few alleles
34. Only mature DC activates T cells Activation/Proliferation T cell Mature DC Anergy/Apoptosis/Deletion T cell Immature DC
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37. Structure of T Cell Receptor CHO CHO CHO CHO Variable region “V” Constant region “C” Hinge “H ” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic tail + + +
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42. Interactions of Th Cell and APC LFA-3 LFA-2 LFA-1 TCR CD4 ICAM-1 Class II MHC B7-1/B7-2 (CD80/CD86 CD28 IL-1 IL-6 TNF-alpha IL-12 IL-15 TNF-beta IFN-gamma GM-CSF IL-4 T helper lymphocyte Antigen- presenting cell peptide
43. Interactions of Tc Cell and Target Cell LFA-1 TCR CD8 ICAM-1 Class I MHC LFA-3 LFA-2 T cytotoxic lymphocyte Target cell peptide
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46. HLA and disease association 87.4 37.0 10.4 13.3 15.4 9 9 9 33 26 9 79 52 87 85 B27 B27 B27 CW6 DR3 Ankylsoing spondylitis Reiter’s disease Acute anterior uveitis Psoriasis vulgaris Dermatitis herpetiformis control patients Relative risk Frequency in Associated alleles Disease
Editor's Notes
Figure 1. Professional antigen-presenting cells process intracellular and extracellular pathogens differently. In the endogenous pathway, proteins from intracellular pathogens, such as viruses, are degraded by the proteasome and the resulting peptides are shuttled into the endoplasmic reticulum (ER) by TAP proteins. These peptides are loaded onto MHC class I molecules and the complex is delivered to the cell surface, where it stimulates cytotoxic T lymphocytes (CTLs) that kill the infected cells. In contrast, extracellular pathogens are engulfed by phagosomes (exogenous pathway). Inside the phagosome, the pathogen-derived peptides are loaded directly onto MHC class II molecules, which activate helper T cells that stimulate the production of antibodies. But some peptides from extracellular antigens can also be 'presented' on MHC class I molecules. How this cross-presentation occurs has now been explained: it seems that by fusing with the ER, the phagosome gains the machinery necessary to load peptides onto MHC class I molecules. Roy, 2003 ( www )
The MHC GENE COMPLEX: The MHC complex contains a number of genes that control several antigens, most of which influence allograft rejection. These antigens (and their genes) can be divided into three major classes: class I , class II and class III . The class I and class II antigens are expressed on cells and tissues whereas as class III antigens are represented on proteins in serum and other body fluids ( e.g. C4, C2, factor B, TNF). Antigens of class III gene products have no role in graft rejection. Human MHC: Class I MHC: The class I gene complex contains three major loci , B , C and A and other undefined minor loci (Figure 1). Each major locus codes for a polypeptide, -chain that contains antigenic determinants, is polymorphic (has many alleles) and associates with -2 microglobulin ( -chain) and expressed the cell surface. Class II MHC: The class II gene complex also contains at least three loci , DP , DQ and DR ; each of these loci codes for - and one ß‑chain polypeptides which associate together to form the class II antigens . Like the class I antigens, the class II antigens are also polymorphic. DR locus may contain more than one (up to 4) functional -chain genes. Mouse MHC: The mouse MHC is located on chromosome 17. Class I MHC: It consists of two major loci , K and D . Unlike the human MHC, the mouse class I gene complex loci are not together but they are separated by class II and class III genes. Class II MHC: The class II gene complex contains two loci , A and E each of which code for one and one ß chain polypeptide, which form one class II molecule . The mouse class II gene complex is also known as the I region and the genes in this complex are referred to as Ir (immune response) genes since they control the magnitude of immune responsiveness of different mouse strains to certain antigens. Products of A and E loci are also termed IA and IE antigens , collectively known as Ia antigens .
A number of diseases have been found to occur at a higher frequency in individuals with certain MHC haplotypes. Most prominent among these are ankylosing spondylitis (B27), celiac disease (DR3), Reiter's syndrome (B27) . Other diseases associated with different specificities of the MHC are listed in Table 2. No definite reason is known for this association. However, several hypotheses have been proposed: antigenic similarity between pathogens and MHC, antigenic hypo‑ and hyper‑responsiveness controlled by the class II genes are included among them.
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