Immunology (Antigen and Major Histocompatibility Complex).pptx

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1. Antigen Ace John Felix S. de la Cruz, RMT, MD, DPSP

2. Definition of Terms Antigen substance that is specifically recognized by the adaptive immune system. Immunogen substance capable of causing an adaptive response. Stimulate immune response Major Histocompatibility Complex (MHC) responsible for presenting either endogenous or exogenous antigens

3. Factors Influencing the Immune Response Biology of the host Age, health status and genetics. The way in which the host encounters the antigen Route of exposure and dosage of antigen. Nature of the antigen

4. Traits of Antigens and Immunogens Macromolecular size at least 10,000 daltons ( Da ) to be recognized by the immune system. more than 100,000 Da – most effective immunogen . Foreignness un-relatedness to the host. plant protein is a better immunogen for an animal than is material from a related animal

5. Traits of Antigens and Immunogens Chemical composition and Molecular complexity Proteins > Polysaccharides, nucleic acids and Lipids Synthetic polymers ( Nylon and Teflon)-used in making artificial heart valves and elbow replacements. Ability to be processed and presented within MHC molecules

6. Epitope Part of an immunogen , called the “antigenic determinant”. Precise molecular shapes or configurations recognized by B cells, or the peptide sequences detected by T cells. Large molecules may contain numerous epitopes .

7. Epitope Linear epitopes sequential amino acids on a single polypeptide chain. Can be identified by B and T lymphocytes Conformational epitopes result from the folding of one or more polypeptide chains. Identified by only B Lymphocytes

8. Epitope

9. Haptens Non-immunogenic by itself but is able to form new antigenic determinants when combined with a larger carrier molecule. Due to its size, it is incapable of antibody-mediated precipitation or agglutination. eg . Catechols from poison ivy plant and drugs like penicillin

10. Adjuvant Substances delivered simultaneously with antigen for the purpose of potentiating, or enhancing, the immune response . stimulates innate immune receptors, such as Toll-like receptors, that detect the presence of infection or danger . works by preventing antigen from diffusing away from a site of inoculation . Used in vaccines like recombinant protein antigens (except live attenuated or killed microbes ). eg . Mineral (Aluminum or phosphate) and Lipids ( monophosphoryl Lipid A or synthetic Lipid A) adjuvants

11. Relationship of Antigens to the Host Autoantigens antigens that belong to the host. Don’t evoke immune response on normal circumstances. Alloantigens Antigens from other members of the host’s species. capable of eliciting an immune response . Heteroantigens Antigens from other species, such as animals, plants, or microorganisms. Heterophile antigens - unrelated plants or animals which are either identical or closely related in structure with the antigen of interest leading to cross-react ion.

12. Major Histocompatibility Complex Old name “ Human Leukocyte Antigen ” (HLA). initially identified by their antigenicity in the context of organ transplantation, their main immune function is to serve as carriers of peptide antigens for recognition by T cells. found on all nucleated cells in the body.

13. Genes Coding for MHC Molecules (HLA Antigens) encoded by the most polymorphic gene system found in humans. Inherited as haplotype from each parent. short arm of chromosome 6 divided into three categories or classes.

14. Three Categories/Classes of MHC Class I genes : three different locations or loci, termed A, B, and C. Class II genes : situated in the D region, and there are several different loci, known as DR, DQ, and DP. Class III genes code for the complement proteins, C4a, C4b, C2, and B, as well as cytokines such as tumor necrosis factor (TNF)

15. Class I Class II Class III involved in antigen recognition by T cells secreted proteins that have an immune function Expressed on cell surface Not expressed on cell surfaces Endogenous Antigens Exogenous Antigens N/A All nucleated Cells . Lymphocytes and myeloid cells > liver , neural cells, muscle cells, and sperm. All Antigen Presenting cells ( Macrophages) N/A

16. Structure of Class I and Class II MHC Molecules MHC Class I MHC Class II

17. Role of Class I and II MHC Molecules in the Immune Response Antigen presentation peptide fragments derived from degraded proteins are transported to the plasma membrane, allowing recognition by T lymphocytes. MHC have evolved to deal with two distinct types of infections: those that attack cells from the outside (such as bacteria) those that attack from the inside (viruses and other intracellular pathogens) Class I : watchdogs of viral, tumor, and intracellular parasitic antigens that are synthesized within the cell. Class II : help mount an immune response to bacterial infections or other pathogens usually found outside of cells.

18. MHC Class I and Class II Peptide Presentation Pathway

19. MHC Class I Peptide Presentation Pathway ( Endogenous Pathway)

20. MHC Class II Peptide Presentation Pathway ( Exogenous Pathway)

21. Clinical Significance of MHC Modern transplant HLA testing Lessen if not prevent graft rejection. Inheritance of certain HLA types may predispose individual to development of autoimmunity.

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