antibody can get cross-reactivity with molecules closely resembling the inducing antigen
Hapten
an antigen which is too small to generate an immune response by itself (incomplete antigen)
incomplete antigens need to be coupled to carrier molecules to elicit antibody formation
Immunogen
an antigen which can generate an immune response by itself (complete antigen)
Epitopes
segments on immunogen which are recognized by the antibody
Conformational
or Discontinuous Epitopes several epitopes that are located on one protein which become immunogenic upon protein folding
Continuous
or Linear Epitopes no folding needed, the epitopes are recognized as complete on their own
Isotypes
subdivisons common to all individuals such as the five H chain classes and the two L chain types
Allotypes
inherited small, functionally insignificant, structural differences, especially in the constant portion of the antibody
Mendelian genetic polymorphisms
Idiotypes
the distinctiveness of each antibody molecules own combining site when the site is itself used as an antigen and antibodies are elicited against it (anti-antibodies)
Immunoglobulins
Antibody molecules have a basic four-chain structural unit composed of two larger or H (heavy) polypeptide chains and two smaller or L (light) chains. The unit has two identical combining sites for antigen (bivalent). Each H-L pair contributes one combining site.
The arms of the antibody are called the fab region (fragment antigen binding), and the body of the antigen is called Fc region (the fragment crystallizable). These regions are connected by disulfide bonds, and the arms of the antibody rotate freely around the disulfide hinge region connecting the two heavy chains (ball and socket). The chains are composed of antiparallel
b -pleated sheets. These proteins are heterogeneous with respect to charge, antigen binding affinity, and idiotype.
The tips of both the variable heavy chain (VH) and variable light chains (VL) have hypervariable regions that are responsible for the the ability of the antibody to bind such a large array of antigens. These complimentarity determining regions (CDRs) work together to determine the final antigen specificity. Other than these CDRs the rest of the antibody is fairly invariant in structure. V regions account for heterogeneity of immunoglobulins
Interactions between an antibody and an antigen are reversible non-covalent interactions (electrostatic, H-bonds, van der Waal forces, hydrophobic forces).
Multiple myeloma
(tumor of bones) neoplastic disorder of plasma cells in which a single clone has become malignant. Therefore serum pool goes from heterogeneous to homogeneous. L chains are made in excess and are secreted in urine Þ Bence-Jones proteins
Structure and Function of Immunoglobulins
Light Chain two types (different N-terminus, same C-terminus) either can combine with any heavy chain class
kappa light chains (
k)
lambda light chains (
l)
Heavy Chain
five types (mnemonic "GAMED") each type represents differences in constant regions of heavy chains
IgG
150 kDa, prominent in secondary response. Most abundant Ig in serum. Only Ig that can cross placenta.
IgA
Prominent in secretions. Most abundant Ig we synthesize (dont confuse with IgG which is most abundant in serum). Produced in Lamina Propria; transported across epithelium by Transcytosis. Prevent attachment of bacteria/toxins to epithelial cell and absorption of foreign stuff. Are also secreted in breast milk and threby transferred to gut of newborn where provide protection from newly encountered bacteria until infant can synthesize own protective antibodies
IgM
900 kDa, prominent in antibody response. Mostly found in blood, and though it has a low affinity it binds many sites on the antigen thus increasing its functional affinity. First made in evolution and immune response. 10 potential binding sites
IgE
Prominent in worm infestations and allergies. Binds to Fc receptors on mast cells and basophils causing them to release inflammatory substances (i.e. histamine). Can give rise to classic allergies.
IgD
Receptor on B-lymphocytes. Found in small amounts in serum.
Monoclonal Antibodies
Plasma Cells which make only one type of antibody.
These are prepared by combining immortalized myeloma plasma cells (i.e. cancerous plasma cells) with normal antibody secreting plasma cells (from spleen). The hybrid result will be a plasma cell which creates only one type of antibody, infinitely. This is a useful research technique.