CELLS ORGANS OF IMMUNE MECHANISM Origin structure IMMUNE

CELLS& ORGANS OF IMMUNE MECHANISM. Origin & structure.

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

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.

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.

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

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.

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.

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 CD 4&CD 8 proteins). • Later they express only one type of antigen receptor&contain either CD 4 or. CD 8 type of receptor, depending on which type of cell they come into contact.

Differentiation of immunocompetent cells. • The cells that come into contact with cells bearing class 1 MHC protein, differentiate into CD 8 +ve, while those that come into contact with class 2 MHC proteins differentiate into CD 4+ cells. • The double positive cells are located in the cortex while the single positive cells are located in the medulla.

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.

• 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 CD 8 protein of the cytotoxic T cells binds.

• 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 CD 4 proteins of helper T cell binds.

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

• 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.

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.

• 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.

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

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

• 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

• 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.

• 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.