CELLS& ORGANS OF IMMUNE MECHANISM.

1. CELLS& ORGANS OF IMMUNE MECHANISM. Origin & structure.

3. IMMUNE CELLS. Fetal liver -------------yolk cells Blood cell precursors. Stem cells reside in bone marrow. Erythroid, myeloid& lymphoid series.

5. Lymphocyte populations. • T-Lymphocytes (cytotoxic &helper T-cells). • Precursors differentiate in the thymus. • B –Lymphocytes develop in the bone marrow,gut associated lymphoid tissue,spleen and lymph nodes. • The ratio of T to B cells is approximately 3:1.

6. T-Cells. • Constitute 65-80% of circulating small lymphocytes. • Life span is long(months-years). • Some (40%) develop in the gut associated lymphoid tissue(GALT)instead of thymus. • Precursors differentiate in the thymus mainly.

7. THYMIC EDUCATION. • CLONAL DELETION (by apoptosis) • Negative selection self tolerance.

8. THYMIC EDUCATION. • Positive selection for T cells that react well with self reacting antigens. • T cells are produced that are selected to react with both foreign Ag and self MHC proteins.

9. Role of T-cell receptors. • During their passage through the thymus double +ve cells synthesize a highly specific antigen receptor (TCR). • The genes that encode the receptor are variable, diversity & joining genes that rearrange and are responsible for the ability of the T-cells to recognize millions of different antigens.

10. Formation of immunocompetent T cells. • T-cell precursors differentiate into immunocompetent T-cells within the thymus. • In the initial stage they differentiate into Double positive cells(both CD4&CD8proteins). • Later they express only one type of antigen receptor&contain either CD4 orCD8 type of receptor,depending on which type of cell they come into contact.

11. Differentiation of immunocompetent cells. • The cells that come into contact with cells bearing class 1MHC protein,differentiate into CD8 +ve,while those that come into contact with class2MHC proteins differentiate into CD4+ cells. • The double positive cells are located in the cortex while the single positive cells are located in the medulla.

14. MHC PROTEINS • Class 1 MHC PROTEINS • These are glycoproteins found on the surface of virtually all nucleated cells. • The complete class 1 protein is highly polymorphic. • The polymorphism of these molecules is important in the recognition of self and nonself.

15. If these molecules were more similar, our ability to accept foreign grafts would be correspondingly improved. • The molecule also has a constant region where the CD8 protein of the cytotoxic T cells binds.

16. Class 11 MHC PROTEINS • These are glycoproteins found on the surface of certain cells, including macrophages, B cells, dendritic cells of the spleen, and Langerhans cells of the skin. • Like class 1 proteins, they have a hypervariable region that provides much of the polymorphism. They also have a constant region where the CD4 proteins of helper T cell binds.

19. BIOLOGIC IMPORTANCE OF MHC • The ability of T cells to recognize antigen is dependent on association of the antigen with either class 1 or class 11 proteins. • Cytotoxic T cells respond to antigen in association with class 1 MHC proteins. • Helper T cells recognize class 11 proteins. • This requirement to recognize antigen in association with a “self” MHC protein is called MHC restriction

21. MHC genes and proteins are also important in two other medical contexts. • Many autoimmune disease occur in people who carry certain MHC genes. • Success of organ transplant is in large part determined by the compatibility of MHC genes of the donor and recipient.

22. Antigen-Antibody Reactions • Reactions of antigens with antibodies are highly specific. • Because of the great specificity, reactions between antigens and antibodies are suitable for identifying one by using the other. • This is the basis of serologic reactions.

24. The results of many immunologic tests are expressed as a titer, which is defined as the highest dilution of the specimen e.g. Serum that gives a positive reaction in the test serum. • A patients serum with an antibody titer of, for example, 1/64 contains more antibodies, i.e. • Is a higher titer than a serum with a titer for example 1/4.

25. Medical importance of serologic (antibody-based ) tests • Diagnosis of infectious diseases. • Diagnosis of autoimmune diseases. • Typing of tissue and blood before transplantation.

26. Types Of Diagnostic Tests • Agglutination In this test the antigen is particulate (eg, bacteria and red blood cells) Antibody because it is divalent or multivalent , cross-links the antigenically multivalent particles and forms a lattice work, and clumping (agglutination) can be seen. eg. ABO blood group test is agglutination

34. Precipitation (Precipitin) • In this test the antigen is in solution. • The antibody cross-links antigen molecules in variable proportions, and aggregates (precipitates) form. • In this test the antigen is in solution. The antibody cross-links antigen molecules in variable proportions, and aggregates precipitates form

38. Radioimmunoassay (RIA) • This method is used for quantitation of antigens or haptens that can be radioactively labeled. • It is based on the competition for specific antibody between the labeled (known) and the unlabeled (unknown) concentration of material.

40. Enzyme-Linked Immunosorbent Assay (ELISA) • This method can be used for quantization of either antigens or antibodies in patient specimens. It is based on covalently linking an enzyme to a known antigen or antibody, reacting the enzyme linked material with the patients specimen, and then assaying for enzyme activity by adding the substrate of the enzyme.