Immunology - B cells and immunoglobulins

Antigenic determinants - Types

3 types of determinants: This is what makes Ig different. Isotypic: Determined by heavy chains (mu, delta, etc.). GENERAL type based on the heavy chain. Allotypic: Something in the Ig molecule that has been genetically given to offspring by the parents -- specifics that make the Igs slightly different from another person's Ig even if it is for the same pathogen. Subtle differences based on the genetics of the parents. Idiotypic: Specific differences within one Ig molecule that occurred just as it was being produced. Based on subtle differences between individuals.

B cell receptors

AKA immunoglobulins: Either secreted free into blood or attached to a cell. Have a Y-shaped appearance. Have variable and constant regions. Composed of heavy and light chains. Heavy chain component determines the lass of antibody - there are 5 heavy chain constant regions present in the heavy chain. Hinge region: Allows for better binding to an antigen. Allows for a tighter fit because it can move/bend. Antibodies assume shape more complementary to the epitope of the antigen. Binding induces conformation changes in antigen, antibody, or both.

Studies of antibodies - Fc and Fab fragments

Antibodies are digested with protease/papain to get two parts -- Fc and Fab. A sample is done and gel electrophoresis separates the molecules based on weight into bands (two bands in this case). Antigen was then added to each group (Fc and Fab) to see which would bind -- Fab does the antigen binding and not Fc. This is how they could tell where binding occurs. Benefits to this: Allows us to manipulate the situation and can be used for diagnostic testing if we know what binds to the antigen.

Antigenic determinants (1)

Antibodies can become antigens, aka immunogen. Rabbits in research: Rabbits are injected with antigen, rabbit makes immunoglobulin (humoral response) -- this is called anti-antigen (antibody). Serum is taken from the rabbit, Ig is concentrated and injected into another rabbit -- get anti-anti antigen (or anti-antibody) -- this is an antibody, but against the one produced by the FIRST rabbit. IMMUNOGLOBULIN CAN BECOME AN EFFECTIVE ANTIGEN - TCRs CANNOT.

Constant region domains

B cells express different classes of immunoglobulins at different stages of development. Immature B cells (have not seen antigen yet): Express IgM. Mature B cells (still before antigen activation): Express IgD and IgM. Secreted immunoglobulins: Will not see these Ig before contact with antigen -- IgE, IgA, IgG.

Isotype and variable region

Isotype: Refers to a class of antibody on a B cell receptor. T cells do not have classes. Isotype classes: mu, delta, gamma, epsilon, alpha. Variable region: This is where the antigen binds and what makes immunoglobulins different.

Immunoglobulin classes - IgG

Most abundant. A SECRETED molecule. Can opsonize. Can also assist natural killer cells in their killing. Involved in neutralizing viruses: As a free molecule it binds to viruses and removes them from circulation so they cannot infect cells. Differ in size at the hinge region. Can cross placenta in some species and also found in colostrum. SECRETED, BUT CAN BECOME MEMBRANE BOUND.

B cell maturation

Resting B cells have their membranes bound with immunoglobulin -- this Ig NEVER leaves the cell. Encounter with antigen: Bacteria or other antigen is encountered, which stimulates the B cell. Stimulated B cell gives rise to antibody-secreting plasma cells: Plasma cells then secrete antibody. Clonal division: Before clonally dividing, B cells can have antigen on their surface, but it may not be the Ig directed at that specific antigen.

Immunoglobulin classes - IgE

SMALLEST amount of all isotypes, but important. Often found bound to mast cells. SECRETED, BUT CAN BECOME MEMBRANE BOUND. Main role: Allergic reactions and an antiparasitic. VERY strong inflammatory response -- antigen binds to two different IgEs, which causes degranulation and then histamine is released as a result.

Immunoglobulin classes - IgA

Small percentage of Igs. Main role: Neutralization of infectious organisms before they infect the cell; found esp. in respiratory tract or GI and prevent the antigen from entering and causing destruction. Found in mucus and associated with epithelial membranes. Can also be secreted into milk, saliva, and tears. SECRETED, BUT CAN BECOME MEMBRANE BOUND. Produced by plasma cells more than ANY other type of Ig even though it does not exist in the highest percentage of Ig -- this is because of the area that IgA is present in (areas of mucosal attack by antigens, which are common, so they need to be produced a lot).

Immunoglobulin classes - IgM

Small percentage of Igs. Sit on the surface of membrane B cells. Found on pre B lymphs (naive). MEMBRANE BOUND. First line of response: First immunoglobulin that sees an antigen; this meeting causes change in B cell from naive to lymphoblast, then to plasma cell. Role in immune response: Even though it is membrane bound it can help with complement activity, agglutination of RBCs, and also a minor help in neutralizing viruses.

Immunoglobulin classes - IgD

VERY small amount. Found on naive B lymph cell membranes and also ones that become plasma cells; MEMBRANE BOUND. Activates B cells, but has no other known function.