-Individual, unique differences between antibodies of different antigen binding specificities
-Each persons serum will contain millions of differet idiotypes
-Both heavy and light chains contribute to the antibody idiotype
The T lymphocyte antigen receptor:
-T lymphocytes also specifically recognize antigen but do not synthesize Ig molecules
-They express a surface bound T cell antignen receptor
-The TCR shares several characteristics with the Ig’s
-Associated with the receptor is the CD3 molecule (for intracellular signaling)
-All TCRs have a domain structure similar to antibody light chans: both have a variable domain with
hypervariable loops and one constant domain
-TCR is noncovalently linked to the CD3 molecule. Engagement of TCR by antigen stimulates CD3 to
transmit biochemical signals into the cell interior
-T cell receptos also have isotypes.
-Most common isotype is the alpha/beta TCR
-The gamma/delta TCR is another isotype
-The gamma/delta subtype is most often found on the skin and on mucosal surfaces
-CD8 cells recognize antigens on Class I
-CD4 cells recognize molecules presented on Class II
Immune recognition / Class restruction / MHC restriction:
-CD8 natural killer cells can only recognize antigen presented on class I molecules
-CD4 helper T cells only recognize antigen presented on class II molecules
-Ex: macrophage east bacteria, chops bacteria up, and presents it to T helper cell
-If it is presented on MHC class II, a CD4 helper T cell must bind
-Ex: a fibroblast infected with a virus presents the peptide on a class I molecule. The binding T cell
will be CD8 THE LYMPHOID SYSTEM:
-Organizaton
-Primary lymphoid organs are the anatomical locations in which lymphocytes develop
-Primary organs are bone marrow and the thymus
-Secondary lymphoid organs are places where lymphoid tissues differentiate
-Secondary organs are in the gut, lymph nodes, and spleen
-Pre B cells, immature B cells, and mature B cells are found in the bone marrow ANOTHER REVIEW: (inappropriately juxtaposed) -IL1: proinflammatory, comes from macrophages
-IL2: T cell signal to B cell to induce further division, proliferation. May be autostimulator. Activates NK cells.
-IL3: In bone marrow, stimulates bone marrow stem cells, myeloid line
-IL4: From T cell, induces B cell to class switch to IgE
-IL5: If T cell releases IL-5, then the B cell will switch to IgA
-IL8: comes from macrophages and is chemotactic
-IL-7: important for lymph cell development
-IL3: in bone marrow, important for myeloid cell development
-cd21: A B cell marker to which EBV binds
-cd40: A B cell marker necessary for class switching
-cd28: Expressed by T helper cells and most CD8 T cells. This is a costimulatory molecure needed for T cell activation. Binds
B7 on a B cell, macrophage, or dendritic cell
-cd2 Expressed by ALL T cells and mediates adherence to other cells by LFA3
-cd3 Expressed by All T cells, mediates TCR associated signal transduction molecules
-Lymph node cortex: place for B cells
-Lymph node paracortex: place for T cells Cellular adhesion molecule definitions:
-Include CD2 and LFA3 moleculesthat aid in helper T cell interactions
-ICAM molecules mediate leukocyte migration
-ICAM 1,2,3 and bind to LFA-1 and mediate migration to inflammatory sites
-Selectins to light binding to endothelial cell surface B Cell Development and Differentiation:
-B lymphocytes differentiate from precursors in the bone marrow
-B cells leave the bone marrow with full ability to recognize and respond to antigen
-Light chains have a variable and constant region (lambda)
-Kappa light chains have a variable and constant region
-heavy chains have a variable and constant region
-Through the rearrangement of genes, B cells develop from the precursors into plasma cells
-The purpose of these adhesion molecules is to move T cells and neutrophils to specific sites
-Cd2 and LFA3 molecules mediate T cell adhesion and movement
-Cd40 ligands are found on activated T helper cells. This molecule binds to the cd40 receptor on B cells
and is essential for isotype switiching.
TOLERANCE:
-Absence of specific immune responses in an otherwise fully immunocompetentperson
-Unresponsiveness can be autotolerance or specifically induced acquired tolerance MAJOR HISTOCOMPATIBILITY COMPLEX -Highly polymorphic genes endocding the proteins that regulate immune responses
-Genes inclide the class I and class II cell surface proteins
-Class III genes encode some complement molecules and cytokines
-Class I molecules are HLA A, B,C
-Class II molecules are HLA DP, DQ, and HLA-DR
HLA GENE CLASS I ANTIGENS
-Class I glycoproteins are on the surface of all nucleates cells and platelets
-Necessary for antigen recognition by CD8 cells
-Genes come from chromosome 6
-All class I molecutes share common structures
-An alpha heavy chain
-A light B chain called B2 microglobulin
-Proteins synthesized in cell cytosol are routinely degraded by proteases
-Protiens from viruses, bacteria, parasites, or neoantigens formed by tomr cells are often expressed on class I
-Ability of CD8 t cell to recognize antigen depends on association of antien with class I protein
-Target cell destroyed by NK cell
HLA GENE CLASS II ANTIGENS
-Expressed on a more restricted set of cells including the antigen presenting cells
-Dendritic, langerhans, activated macrophages, B cells, activated T cells bind EXOGENOUS peptide epitopes that
have been endocytosed and processed; this is necessary for CD4 recognition
-Class II proteins only found on cells of the immune system
-Class II MHC genes include HLA DR, DQ, and DP.
-Codominantly expressed and highly pleomorphic
-MHC class II does not have B2 microglobulin
-Cells use peroxides and other enzymes to destroy bacteria
-Helper T cells signal B cells to produce IgM
-B cells then differentiate and class switch to appropriate isotype
-A word about antigenicity: -Proteins of low molecular weight
-Foreignness: phylogenic distance, normally will not recognize, “self” (selected in thymus)
-Chemistry: certain degree of complexity required
-The portion of the antigen that binds to the antibody is the antigenic determinate or epitope IMMUNOLOGY WRAP UP: -T cells can stimulate itself
-IL2 is proinflammatory, it can stimulate both B and T cells
-Isotype switching involves cytokines described in above table
T CELL HELPER SUBSETS -T helper 1 cells: involved in DTH reactions. Involved in stimulus of CD8 cells. Cell mediated immunity
-Gamma interferon from T helper 1 inhibits T helper 2 cells
-If fighting a specific pathogen, you can turn off cell regulated immunity
-Cross regulation can help turn off the cell mediated immunity response
-T helper 2 cells help produce antibody by stimulating B cell division