Antibody Structure & Formation IgG IgA IgE Autoantibodies ANA p-anca Isotype

Antibody, also known as Immunoglobulin (Ig), is produced by active B-Cells called plasma cells. Antibodies have a variable region that recognizes specific characteristics on pathogens called epitopes or antigens. Each Plasma Cell makes antibodies that are directed against a single antigen. Antibody can be secreted as free floating antibody or be bound to the plasma cell membrane to act as the B-Cell Receptor.

Antibodies are the most important part of Humoral Immunity and act via multiple different mechanisms. Antibodies can have a direct effect on pathogens by coating the pathogen so that it cannot interact with cells. However, antibodies primary work via their interactions with other immunologic processes. Antibodies “tag” pathogens so that they can be more easily recognized by other immune processes. The variable region of the antibody binds to the pathogen while the constant portion of the antibody interacts with NK cells, macrophages, and complement. The Constant Region (Fc) can:
Bind to C1 and trigger the complement cascade.
Bind to Fc receptors on macrophages which in turn increases the phagocytosis and removal of the pathogen. This process is called Opsonization.
Interact with NK Cells which can cause direct damage to the pathogen via the release of perforins and granzymes. This is called Antibody-Dependent Cell-Mediated Cytotoxicity.

Antibody has a Y shape and is made up of 2 heavy chains and 2 light chains. Antibody is broken down into 2 main regions, the constant region and the variable region. The variable region (Fv) of the antibody is present at the “tip” of the antibody and has 2 separate places where antigen can bind. The Fv is made up of part of the light chains and part of the heavy chains. The Constant Region (Fc) is the “stem” of the antibody and is primarily made up of the heavy chain. The Constant Region doesn’t vary much within isotype groups while the variable regions can have infinite variability. It needs to be able to “match” whatever antigen it is targeted against.

There are 5 different types of heavy chain. Each type of heavy chain is consistent within a subgroup of antibodies called an isotype. The different isotype groups are IgA, IgE, IgM, IgG and IgD (which is low yield for step 1). Each isotype has unique characteristics and actions.
• IgM = is the first type of antibody produced following the exposure to any antigen and can be thought of as “Basic” antibody. It’s activation is Helper T-Cell Independent and therefore can be triggered by exposure to peptide or carbohydrate antigens.
• IgG = is the main antibody found in the blood. It requires interaction with Helper T-Cells (Helper T-Cell Dependent Activation) and therefore can only be formed in response to a peptide antigen in a host with functioning T-Cells (i.e. not in somebody with a severe T-Cell Immunodeficiency like AIDs or Hyper IgM Syndrome). IgG is the only isotype that can cross the placenta to the fetus.
• IgA = forms Mucosal Immunity and protects the bodies orifices. Found in mucus, tears, saliva, and breast milk. Prevents the entry of pathogens into the GI, urogenital, and respiratory tracts.
• IgE = Bound to the membrane of Mast Cells. Plays a role in acute inflammation and Type I Hypersensitivity (Anaphylaxis). When multiple membrane bound IgE molecules bind allergens and aggregate/cross-link, they cause the release of histamine.

Isotype Switching, or Class Switching, is the process by which plasma cells change the class/isotype of the antibody they produce.
Antibodies are supposed to be directed at pathogens. When antibodies are directed at the body’s own cells, the antibody is called an Autoantibody and they cause autoimmune diseases. There are laboratory tests available to detect these autoantibodies and the results can be used to help diagnose these conditions.
Insert autoantibodies
Derivative of “hand finger thumb thumbs up” available at… via Public Domain