The Generation of Specific Immunity
Antibody structure! Antibodies classified by specificity (antigen, binding site) and class (general structure, function)! Differences in variable regions produce different specificities; differences in constant regions produce different classes of antibodies! Survey of effective antigens suggests that thousands of antibodies are possible
Antibody formation Multiple exposures to antigen induce a memory response IgG IgM IgM (blue) (red)
Questions...! Why is there a memory response?! With so many antibodies, why are there none that react with one s own proteins?! Where do all the specific binding sites come from?! How is the genetic information for that many proteins stored?! How and why does the type of immunoglobulin change after reinnoculation?! How are antibodies induced by the presence of antigen?
There are several types of lymphocytes involved in the immune response (B for bone) (T for thymus)
Clonal selection Why is there a memory response?! Lymphocyte stem cells (B cells and others) differentiate to become potential antibody producing cells, each capable of producing one antibody (of random specificity).! Presence of antigen stimulates cell division of the cell(s) that make antibodies that react with that antigen to produce a clone of antibody producing cells.! Once stimulated, there are more of the clone ready to be re-stimulated thus the memory response. With so many antibodies, why are there none that react with one s own proteins?! Early in the beginning of stem cell differentiation, clones that produce anti-self antibodies are removed.
Stimulation of a B cell clone involves a membrane-localized binding site
How do the large number of specific binding sites arise? How is the genetic information for that many proteins stored?! Antibody genes come from diverse combinations of gene parts! B-cell maturation joins V (variable), D (diversity) and J (joining) segments to form variable region of gene, connected to C (constant) region! Thus, each clone has a different variable (VDJ) region and produces a protein with a different specificity
! B-cell maturation joins V (variable), D (diversity) and J (segments) to form variable region of gene, connected to C (constant) region! After transcription in a plasma cell, RNA splicing joins the VDJ region to the constant region
How and why does the type of immunoglobulin change after reinnoculation? Class switching changes the constant region
How are antibodies induced by the presence of antigen? Antigen-presenting cells and T Cells MHC and antigen presentation! Class II MHC (major histocompatibility complex): antibody-like membrane protein! MHCs in different clones: different specificities! Alpha and ß chains with binding sites! Constant region anchors molecule to plasma membrane! Macrophages with Class II MHC take up antigen and break it into pieces; display pieces on MHC on surface.
MHC and antigen presentation! Alpha and ß chains with binding sites! Constant region anchors molecule to plasma membrane (Looks the same on a macrophage)
MHC and antigen presentation! Macrophages with Class II MHC take up antigen and break it into pieces! Display pieces on MHC on surface.! Present antigen pieces to T H cells
Macrophage activates T H cell
T H cells stimulate B cells to become plasma cells
Cellular immunity: all cells display internal antigens on their surface through Class I MHC proteins
T C (cytotoxic) cells recognize foreign antigens Foreign (non-self: skin grafts, virus-infected cells, some cancerous cells) Self: T cells removed during embryogenesis
T C cells kill the cells with foreign antigens
Summary! T and B lymphocytes, and the MHC and immunoglobulin gene systems, work together to protect the vertebrate body from a) bacterial, fungal, and protist infections, b) viral infections, and c) cancerous changes in cells.! Development of the immune system involves changes in gene activity (and even gene structure) in clones of cells! Development of the immune system also involves responses to exogenous influences (antigens) and signal cascades! Major new principle: cells change their genetic information (in random fashion) as a part of development; use selection to choose the useful information (Darwinian development!)! Does this occur in any other organ system? No evidence, but maybe in the brain?