(Transcribed from Dr. Laville’s lecture, 18 Feb 2000 by Brian Buschman)
Return to Semester One Goodies
Return to The Unofficial Ross Page
Immunoglobulins (antibodies) are the body’s first line of defense against a foreign invader. Immunoglobulins (Ig) are made up of four peptide chains, two heavy chains and two light chains. All the chains have two types of regions, variable and constant. The light chains have one variable and one constant region and the heavy chains one variable and three constant regions. The constant regions are constant between all immunoglobulins of the same class but the variable regions differ in each different antibody (Ab) for the sake of recognizing different antigens (Ag).
Antibodies as a whole can be divided into two regions by special cleavage enzymes:
1) Fab that is the region that contains both the light chain and part of the heavy chain and binds to the Ag.
2) Fc that is the region that is composed of only part of the heavy chain and binds to the receptor on phagocytotic cells.
Immunoglobulins belong to one of five major types identified as IgA, IgG, IgM, IgD and IgE. They all have light chains that belong to one of two classes, k or l. Each type of immunoglobulin has heavy chain classes specific for it identified as a, g, m, d and e. The heavy chain classes of IgA, IgM and IgG have more then one class which are identified by the Greek letter and a number (a 1, a 2, a 3).
The liver makes most plasma proteins but immunoglobulins are one exception that are made by cells derived from lymphocytes and are degraded by the liver.
Lymphocytes differentiate into T-lymphocytes and B-lymphocytes. The T-lymphocytes will be discussed in the lecture on the immune response. B-lymphocytes become B-cells that produce one specific type of Ab which stick to the B-cell plasma membrane. T-helper cells assist in the binding of an Ag to the B-cell bound Ab. When an Ag is bound via Ab to the B-cell it will differentiate into both plasma cells and B-memory cells. Plasma cells are able to switch classes during Ab production to be able to produce Abs of different classes. Memory cells will stick around to quickly activate the immune response in infected again by the same Ag.
Each of the five different classes of Igs play a slightly different role in the immune response:
1) IgG can be found in extravascular tissue spaces. They are the antigens that can cross the placenta and they function to help neutralize toxins in the body.
2) IgA is the secretory Ab that protects body surfaces. It is the Ig that is passed from mother to child through breast milk.
3) IgM protects the blood stream, as it is the largest (being a pentamer) of the Igs. It’s the blood’s first line of defense and it functions in bacterial lysis.
4) IgE is bound to Fc receptors of mast cells to function in immediate hypersensitivity reactions. It induces degranulation of mast cells to promote them to produce factors such as histamine, leukotriene, etc.
5) IgD have an unknown function.
Certain disease states will cause the rise of specific classes of antigens. Analysis of the serum levels of various Igs can be diagnostic for certain classes of diseases.
1) IgG will rise in the presence of autoimmune diseases such as active hepatitis and SLE.
2) IgA will rise in response to diseases of the respiratory (TB, bronchiectasis) and intestinal tract (Crohn’s disease).
3) IgM will rise with biliary cirrhosis, haemoprotozoan infections (malaria), some acute viral infections (viral hepatitis) and at birth with interuterine infections.
4) IgG, IgA and IgM will all rise with chronic bacterial infections and AIDS.
5) IgE rises with allergy (type 1 hypersensitivity and secondary to immunodeficiency and immunosuppression) and in direct response to infections.
Monoclonal response – When B-cells are activated they usually differentiate into multiple clones (polyclonal response) to produce multiple antibodies of different classes. In this case B-cell malignancy leads to a monoclonal response.
Bence-Jones Protein (BJP) is the name for an excess of light chains produced by malignant B-cells. The excess light chains are small enough to be filtered by the glomeruli of the nephron but are large enough that it breaks holes in the epithelia as it passes through. This will lead to leakage of albumin into the urine (a material that is usually too large). It is a form of renal disease and can be diagnosed by the presence of albumin and BJP in the urine.
Paraproteinemia is the increased blood viscosity. It results in poor blood flow causing retinal and cerebral thrombosis, peripheral gangrene and small hemorrhage.
Mylomatosis is the malignant proliferation of plasma cells causing disordered production and degradation of Ig.
Waldenstrom’s macroglobulinemia involved malignant B-cells and has similar symptoms as hyperviscosity.
Return to Semester One Goodies
Return to The Unofficial Ross Page