Transcript 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.