Cells Of Immune System

Immunology CELLS OF IMMUNE SYSTEM MAJOR CELLS OF IMMUNE SYSTEM The immune system is made of four major kinds of cells: • lymphocytes - produce antibodies • T lymphocytes - cooperate with B cells and produce cytokines • Macrophages • Natural killer (NK) cells - non-specific hunter-killers The B and T lymphocytes are two groups of nonphagocytic, morphologically indistinguishable, but functionally different lymphocytes. However, there are certain features that are common to B and T cells like; B and T lymphocytes recirculate around the body from blood to tissues and back again into circulation, Each lymphocyte has individual receptor in its plasma membrane to enable it to recognise a particular antigen which confers specificity, On getting stimulated with specific antigen these lymphocytes undergo clonal proliferation and They show property of memory giving rise to a faster and bigger immune response on re-challenge with the same antigen. B Lymphocytes B line stem cells are present in the bone marrow and are the source of pre-B cells which on maturation become precursors of plasma cells. The antibodies are produced by stimulated plasma cells. In an adult approximately 30% of the lymphocytes circulating in the blood can be identified as B cells on the basis of their surface Ig markers. Their distribution in various important organs / tissues is as under: Peripheral blood 15-30% Lymph nodes 20% Bone marrow 75% Thymus 10% Tonsillar lymphocytes 50% Splenic lymphocytes 50% Activation of B-cells: Each B cell carries the genetic instruction to produce antibody of unique antigen specificity as a membrane receptor. On getting stimulated mature B cells differentiate into antibody secreting plasma cells. T Lymphocytes T cells, just like B cells they also originate from precursor cells of the bone marrow but mature in the thymus. Several subsets of the T cells arise during this maturation process, each becoming focussed upon a specific function. Thymus, lymph nodes and peripheral blood are rich in T lymphocytes. Their distribution is as under: · Peripheral blood 55-75% · Lymph nodes 75% · Bone marrow 10% · Thymus 75% Functions of T Cells include: T cells mediate cell-mediated immunity (CMI) through the production of cytokines, T cells can directly act on and destroy virus infected cells, tumour and foreign cells (cytotoxic action) and T cells act as regulatory cells that modulate the activity of other T cells, macrophages or B cells, regulation can be in the form of help or suppression.

Nomenclature of T Lymphocytes With the help of monoclonal antibodies various types of T cells have been identified which indicate presence of different physicochemical structures on the surface of these cells. WHO has suggested a terminology for T cells in which abbreviation CD is to be used. CD refers to cluster of differentiation. At present the numbering system for CD is equivalent to T so that CD4 cells are T4 whereas CD8 cells are T8 cells. The purification of T lymphocytes has revealed that there are three major functional subsets of these cells. · Helper T cells (help B cells and other T cells to multiply into large clones) · Cytotoxic T cells (responsible for killing virus-infected cells) · Delayed type hypersensitivity T cells (act by releasing macrophage chemotaxin and macrophage migration inhibition factor) Natural Killer (NK) Cells The NK cells are large granular lymphocytes (LGL) and constitute around 3% of the peripheral lymphocytes. They are: · More granular cytoplasm than B or T cells · Non-phagocytic · Nonadherent to surfaces · Destroy target cells without prior training · IL-2 receptors present · Activated by IL-2 and IFN Macrophages Macrophages circulate in blood as monocytes and get rooted to some tissues as tissue macrophages. These are not antigen specific and hence also called as accessory cells of immune system. They playa key role in CMI and produce various lymphokines, enzymes and factors that are involved in reorganization and repair following tissue damage. Cytoklnes Cytokines are a class of nonantibody molecules that are produced by many different cells, immune and nonimmune, in a highly regulated manner. They exert different biologic effects which change the behaviour and function of many cells that are needed in immune response. Cytokines are usually low molecular weight glycoproteins that are biochemically distinct. The antigen-independent activity of cytokines is directed mainly towards those cells which have specific receptors for these on their surfaces. These cells are:

Interferons (IFN) Interferons are a set of proteins which are released by virus infected cells in vivo and which react with uninfected cells so as to render them resistant to infection with viruses. Around 20 human interferons have been characterized. General Characteristics of Interferons • These are a family of glycoproteins • These do not have any direct action on viruses • Their activity is not virus specific. Interferon induced by one virus is effective against many other viruses • These are usually species specific • The production of interferons is augmented at elevated temperatures such as 40°C • Steroids and high oxygen tension depress the synthesis of interferons • Synthesis of interferons begins within one hour of induction and takes around 12 hours to reach its maximum activity • These are sensitive to the action of proteolytic enzymes but resist destruction by nucleases and lipases • Interferons are resistant to heat at 56°C for upto 60 minutes • These are nondialysable • Interferons do not get sedimented even if these are centrifuged at 100,000 g for several hours • Antisera against three types of interferons are now available and with their help it has been shown that the three types are antigenically distinct. Types of Interferons These belong to three antigenically and chemically distinct types, known as alpha, beta and gamma. The gamma interferon is not induced by viral infection but is continuously produced by lymphocytes following stimulation with mitogens and hence is also one of the lymphokines. None of the interferons can be produced in the virus infected cell cultures. Interferon Inducers Most RNA viruses are good interferon inducers and with the exception of pox viruses all DNA viruses are poor interferon inducers. Other than infectious viruses followings are the interferon inducers. Mechanism of Action of Interferons It is now believed that interferons belong to the family of 'non-classical hormones' which cannot only inhibit the viral replication but also modulate the immune system and may act as anti-tumour agent. Interferon binds to specific receptors on the plasma membrane thus inducing the production of three enzymes: 1. 2-5 A synthetase 2. RNase L (endoribonuclease) 3. Protein kinase. By various mechanisms these three enzymes inhibit the protein synthesis in interferon treated virus infected cells. Interferons also activate T lymphocytes, macrophages and NK cells in the immediate vicinity of virus infected cell to develop their cytotoxic potential. These effector cells not only destroy the target but on coming in contact with viral antigen on the surface of cells, get stimulated to produce more interferons. This cascade effect greatly amplifies the lytic arm of the immune response. Biological Effects of Interferons I. Induction of resistance to viral infections II. Induction of resistance to some of other intracellular microbial infections such as malaria, toxoplasmosis III. Inhibition of growth of tumour cells IV. Increased expression of MHC antigens on surfaces V. Enhanced cytotoxic effects of NK, K and T cells. Recombinant interferon is now extensively used in therapy of chronic hepatitis due to hepatitis C virus. Local application in high doses has shown some promise in infections with herpes virus

keratitis and respiratory viruses as well as genital warts.