CELLS& ORGANS OF IMMUNE MECHANISM.
description
Transcript of CELLS& ORGANS OF IMMUNE MECHANISM.
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 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.
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.
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 CD8 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 CD4 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
Diagnosis of infectious diseases.
Diagnosis of autoimmune diseases.
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.