Circulating leucocytes can be subdivided into several groups characterized on morphology, cell surface markers and biological function. There are two families of molecular structures on the cell surface called clusters of differentiation and adhesion molecules . The biological function of many of the CD molecules is now known and knowledge of their presence is very useful in identifying specific leucocyte subpopulations. Adhesion molecules facilitate many biological activities, particularly those involved in cell-all recognition. Their functions include cellular activation, cytokine release, capture and ‘rolling’ of leucocytes along the endothelial cell lining of blood vessels and extravasation. There is an overlap between these two families and certain adhesion molecules have also been assigned CD numbers.
Lymphocytes are spherical cells, approximately 10 tun in diameter with a prominent nucleus of densely packed nuclear chromatin. There are two main populations, the T and B lymphocytes.
T cells T cells have two principal functions, and are divided into:
HELPER/INDUCER CELLS enhance certain immune responses. They receive antigen from specialized presenting cells and initiate or reinforce antibody production, natural killer cell and cytotoxic responses, mainly by the production of the lymphokines interferon- y, interleukin-2 and interleukin-4. T-helper cells can be distinguished by the presence of the CD4 protein on their surface.
CYTOTOXIC/SUPPRESSOR CELLS which can kill another cell. This kind of response is used in dealing with virus infections and cancer cells. The suppressor cell can down-regulate immune responses at an appropriate time. It may function by releasing soluble factors or messenger molecules which act on the B lymphocytes to reduce their output of antibodies. The cytotoxic/suppressor lymphocyte can be recognized by the presence of the CD8 cell surface molecule.
B cells These cells produce antibody and comprise approximately 25% of the lymphocyte population. B lymphocytes capable of producing a specific antibody to a given antigen are rapidly encouraged to multiply by a mechanism called clonal expansion (Fig. 2.16). In this process, once a E cell !->~S been exposed to a specific antigen (which it recognizes through immunoglobulin molecules located in the cell membrane), and in L.e presence of cytokines (interleukins 1-6 and B-cell growth factors), it is activated and divides. Following this expansion step, B lymphocytes differentiate to become plasma cells which produce large amounts of antibody. Morphologically, plasma cells are distinguished by a cytoplasm containing large amounts of endoplasmic reticulum (Fig. 2.1Sb). The plasma cell has a relatively short half-life and is ‘terminally differentiated’, i.e. after it has fulfilled its antibody producing function it dies. Following the death of these cells, the expanded B cell population shrinks back to its original 51Ze,although some remain as memory cells. As well as surface immunoglobulin, B lymphocytes can be distinguished by the presence of the CD 19 and CD20 molecules.
ANTIBODY MOLECULES (IMMUNOGLOBULINS)
Antibodies are serum glycoproteins that are produced as a highly specific response to an antigenic challenge.
Two HEAVY CHAINS (each with four domains).
Two LIGHT CHAINS (either K or A polypeptides, each with two domains).
VARIABLE ‘V’ DOMAINS which have great variation in amino acid sequence between immunoglobulins, and have short segments of hypervariable regions.
FAB (FRAGMENT ANTIGEN BINDING). Antigen binding occurs where the loops bearing the hypervariable regions of the light and heavy chains come together in space. The conformational structure of the binding site determines the ‘goodness of fit’ or affinity/avidity of any particular antibody for an antigen.
CONSTANT “C’ DOMAINS in which the amino acid sequences are relatively conserved.
Fc (FRAGMENT CRYSTALLINE) is formed from constant domains and regulates the effector functions including binding to cell surface receptors and complement fixation), leading to elimination of the bound antigen.
ISOTYPES. These are determined by the type of heavy chain and define the immunoglobulin class (IgG, A, M, D or E).
ALLOTYPES are a result of different allelic forms of K and ,\ light chains, and ‘Yand a heavy chains. These are inherited as autosomal co-dominants, and have disease associations.
IDIOTYPES are markers found in the hypervariable region and are associated with the antigen-binding site. The idiotype is antigenic and can be defined by serological techniques.
THE HINGE REGION gives flexibility to the antibody molecule, allowing ease of binding to antigen and cellsurface receptors.