By Dr Ananya Mandal, MD
Antibodies play an important role in the immune system. The immunoglobulins present on the B-lymphocyte surface send in signals to the cytoplasmic and nuclear electors. These also deliver the antigen to the cell where it can be destroyed, processed and returned to the cell surface to be presented by MHC class II molecules to antigen-speciﬁc T helper cells.
The T lymphocytes in turn send signals to the B cells for them to mature and recognize the antigens and create antibodies targeted specifically against it.
Humoral immune response
Antibodies secreted by B lymphocytes are responsible for the humoral immune response. The humoral immune system helps in destroying external pathogens and prevents spread of intracellular infections. This immune system also protects against toxins.
Different functions of different parts of the antibody
The two structural portions of the antibody, i.e. the variable (Fab) and the constant (Fc) fragments, impart distinct biological functions.
These functions are outlined as follows:
Antigen recognition – One of the major functions of the Fab region is antigen recognition. The immune system generates large number of antibodies that can recognize virtually all possible antigens present in pathogens and their products. These may be on invading microbes such as bacteria, viruses, and parasites as well as environmental antigens. Antibodies can be produced against all types of molecules including carbohydrates, nucleic acids and phospholipids but are best suited to bind against a protein.
Neutralization of pathogens – Once the antibodies recognize the antigens the binding occurs outside the cell. This is where most of the bacteria and bacterial toxins are found. The binding prevents the access of the pathogen into the cells and prevents infection or destruction of host cells. Antibodies also block the binding of the bacteria to host cells by binding to cell-surface proteins. Antibodies protect similarly from viral infections as well.
Antibodies are the first line of defence - IgM antibodies have a pentameric structure and are rapidly generated in blood. They can bind to multivalent antigens, such as bacterial cell wall polysaccharides. This is because each IgM pentamer has 10 antigen-binding sites. This enhances its strength and ability to bind to antigens. IgM antibodies are also elective in complement activation. IgG also helps in opsonization and complement activation. IgG diffuses into the tissues and binds to toxins rapidly. IgG can thus neutralize foreign antigens and protect epithelial cells from infectious agents acting as first line of defence.
Fc-mediated effector functions:
Activation of effector cells – Through their Fc fragments, antibodies can activate accessory elector cells. These include phagocytic cells like macrophages and neutrophils, T cells like natural killer cells, and eosinophils and mast cells. Each of these cells has a receptor for the Fc fragment. Thus these cells can identify an Fc fragment and eliminate the pathogens.
Complement binding – Once bound to the antigen there is formation of antigen–antibody complexes. This further activates a complex set of reactions called the complement cascade. Complements are series of plasma proteins that help in release of chemical mediators from mast cells (mast cell degranulation), phagocytosis (eating up of bacterial and microbial cells by macrophages) and cell lysis (breaking down or bursting of the invading cells). Complement activation begins when the C1q molecule binds to antibody molecules attached to the surface of a pathogen and triggers the classical pathway of complement activation. The main functions of the complements are to enable phagocytes to destroy bacteria that they would otherwise not recognize. Neither complement nor phagocytes are speciﬁc for the pathogen but the antibodies are.
Opsonization – Those microbes that replicate outside cells are removed by an interaction of the Fc part with speciﬁc receptors on the surface of elector cells. The antibodies coat the surface of the pathogen and allow binding of their Fc domains to Fc receptors present on elector cells. The macrophages and neutrophils then engulf the pathogen and internalize the microbe causing its destruction.
Antibody-mediated hypersensitivity or allergic reactions
Antibodies function in the body as a double-edged sword. With one edge they protect the body from microbes and with the other they can cause severe allergic reactions to relatively harmless proteins and other molecules present in food, environment, medicines etc.
IgE is the most important mediator of hypersensitivity or allergic reactions. When it binds to multivalent antigens there is activation of the mast cell, which releases chemical mediators stored in granules and capable of mediating local inﬂammatory reactions. This is called mast cell degranulation.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)