Immunoglobulins (Ig) are also known as antibodies and they have molecular weights between 160000 and 970000 (Guyton, 2006, p. 443). They are key components of the vertebrate immune system and are a part of the humoral immune system, forming the base of the B-Cell. Igs function in cell-cell recognition as well as structural organization and regulation of musucle (Harpaz, Chothia, 2004). All Igs are made up of a light and a heavy polypeptide chain, usually two of each, but they may contain many more (Guyton, 2006, p. 443). They contain discrete domains of approximately 100 amino acids that are divided into categories based on function and size (Barclay, 2003). Igs have two domains, V and C. The V domain is variable and contains antigen-binding properties and the C domain is constant and responsible for effector functions and establishes the molecules diffusivity, adherence, and other biological functions (Barclay, 2003). The variable portion is different for each Ig and is the portion that attaches to an antigen. Igs are “Y” shaped molecules with the C domain making up the stem, and the V domain making up the tips of the molecule (Guyton, 2006, p. 443).
There are five principle classes of antibodies, IgM, IgG, IgA, IgD, and IgE. Approximately 75% of the antibodies present in the body are of the IgG type; they are bivalent. IgM is formed in large numbers during the primary response to an infection and have 10 binding sites which makes them very effective at protecting the body against invaders. IgE is usually only found in small quantities in the healthy individual but is known to be involved in allergies (Guyton, 2006, p. 444).
An antigen and the variable portion of the Ig is held together by hydrophobic bonding, hydrogen bonding, ionic attraction, and van der Waals forces. The mechanisms by which an antibody attempts to inactivate an invading agent are: agglutination, precipitation, neutralization, and lysis. The direct action of an antibody is usually not strong enough to repel the invader. However, the binding of the antibody to the antigen then invokes the complement system to continue the attack on the invader. The complement system is composed of approximately twenty proteins that are normally present in the plasma. There are three pathways that the complement system can take to combat an invasion, the classic pathway, alternative pathway, and the mannose-binding lectin pathway (Guyton, 2006, p. 445). Thus, the Igs are key players in the coordinated response to a microbial invasion of a host.
Dysfunctions of Igs can take many forms, including, autoimmunity, hypersensitivity, transplant rejection, immune deficiency, or amyloidosis (Robbins, 2009, p.185). Recent research has even implicated the B-Cell and immunoglobulins in the formation of solid tumors (Gunderson, Coussens, 2013).
Hypersensitivities are divided into four types, and Igs are responsible for mediating for the first three types, allergy, cytotoxic, and immune complex diseases. The etiologies of these dysfunctions are not entirely clear, but genetics and environmental factors are believed to be equally culpable. Candidates for the environmental etiology of the problem include infectious disease in childhood, pollution, dietary changes, and exposure to allergens too early amyloidosis (Robbins, 2009, p.190). Furthermore, a key finding in allergic forms of hypersensitivity is the rearrangements of heavy chains in Igs, without variable regions (Akdis, 2008). Finally, an interesting finding is that those with frequent helminthic infections do not get allergies. It is believed this is linked to the regulatory function that B-Cells and their immunoglobulins exert on the repertoire of defense cells (Hussaarts, et al., 2011)
Autoimmunity is thought to be caused by the interplay of genetics and the environment as well. Autoimmune diseases in which the Igs feature a starring role are Grave’s disease, Hashimoto’s thyroiditis, myasthenia gravis, and systemic lupus erythematosus. Many theories have been postulated as to the nature of autoimmunity but none are particularly convincing save for the genetic links. Clearly however, autoimmunity results from a failure of immunological tolerance. Normally auto-reactive antibodies are destroyed in the bone marrow before they are released into the circulation, however in autoimmunity, this clearly does not happen amyloidosis (Robbins, 2009, p. 209)..
Transplant rejection is not a failure of the immune system as such. It is a proper response of the immune system in the presence of a foreign body, however, that foreign body is particularly beneficial to the host. The immunoglobulin binds to the cells of the transplanted tissue as soon as it’s recognized as being different from the host, and this initiates a complement cascade attempting to destroy the donated tissue. This effect can be mitigated against with drugs such as steroids amyloidosis (Robbins, 2009, p.226).
Immune deficiencies, including hypogammaglobulinemia and agammaglobulinemia are caused by a lack of immunoglobulins in the diseased individual. Hypogammaglobulinemia means that there is a deficiency of one or more types of antibodies, whereas agammaglobulinemia means that there is a deficiency state of all types of autoantibodies. These diseases can be primary or secondary, and are usually the cause of severe infections that a normal healthy individual would be able to fight off amyloidosis (Robbins, 2009, p.233).
Light chain amyloidosis occurs when the antibodies produce abnormal proteins. The abnormal proteins bind together and produce deposits in various organs throughout the body. The build up of amyloid in an organ will produce organ specific symptoms and diagnosis can only be made with a biopsy of the affected organ amyloidosis (Robbins, 2009, p.249).
Immunoglobulins are key components of a healthy persons immune response. However, sometimes the immune responses are too sensitive, too strong, to weak, or otherwise disordered. When this occurs catastrophic consequences may occur as the body begins to either fight itself or is unable to repel an invading creature. Without immunoglobulins organisms would succumb to a painful death of bacteria eating organs and tissues.
References:
Akdis, C.A. (2008). New insights into mechanisms of immunoregulation in 2007.
Barclay, N.A. (2003). Membrane proteins with immunoglobulin-like domains - a master
superfamily of interaction molecules. Seminars in Immunlogy 15, 215-223. doi:10.1016/S1044-5323(03)00047-2
Gunderson, A.J., Coussens, L.M. (2013). B Cells and their mediators as targets for
therapy in solid tumors. Experimental Cell Research. http://dx.doi.org/10.1016/j.yexcr.2013.03.005
Guyton, A.C., Hall, J.E. (2006). Resistance of the Body to Infections: II. Immunity and
Allergy. Textbook of Medical Physiology (11th ed.) (pp. 443-450). Philadelphia: Elsevier Saunders
Harpaz, Y., Chothia, C. (1994). Many of the Immunoglobulin Superfamily Domains in
Cell Adhesion Molecules and Surface Receptors Belong to a New Structural Set Which is Close to that Containing Variable Domains. Journal of Molecular Biology. 238: 528-539
Hussaarts, L., van der Vlugt, E.P.M. Yazdanbaksh, M., Smits, H.H. (2011). Regulatory
B-Cell induction by helminthes: Implications for allergic disease. Journal of Allergy and Clinical Immunology 128(4), 733-739. doi:10.1016/j.jaci.2011.05.012
Kumar, V., Abbas, A.K., Aster, J.C., Fausto, N. (2009). Diseases of the Immune System.
Robbins and Cotran Pathologic Basis of Disease (8th ed.) (pp. 184-259). Philadelphia: Elsevier Saunders
