Defence System of Body; Role of Leucocytes

Body Immunity: Animal body is always exposed to harmful invaders like viruses, bacterial fungi and animal parasites, and to toxic substances which either enter into the body from outside (e.g., poison injected by poisonous animals), or are produced by the invaders, or are formed in the body itself by diseased tissues. The body ahs an inherent ability to resist all invaders and toxins that tend to damage the tissues. This ability is called immunity. It is studied under the branch called immunology. Immunity is of two types – Innate and acquired.

Innate Immunity

It is the general defense of body, including the following four mechanisms:

(1)        Phagocytosis of invaders by leucocytes and tissue macrophages.

(2)        Destruction of micro-organisms swallowed with food by the HCI of gastric juice and by digestive enzymes.

(3)        Resistance of skin to invading micro-organisms.

(4)        Destruction of invaders and toxins in the blood itself by certain defensive compounds such as lysozymes, properdin, basic polypetides an naturally occurring antibodies, which are always present in the blood plasma.

This innate immunity makes human body resistant to certain animal diseases such as hog cholera, cattle plague, dysentery, etc. On the other hand, it makes animal bodies resistant to certain severe human diseases such as poliomyelitis, mumps, measles, syphilis, human cholera, etc.

            Phagocytic System of Defense: Under this defense system invading micro-organisms are ingested and destroyed by leucocytes of blood and macrophages of connective tissues. As mentioned before, both leucocytes and macrophages are amoeboid and mobile units of the defense system of body.

            The leucocytes can move against bloodstream. They can also squeeze through pores of thin capillary walls to wander about in the tissues (Fig.). This phenomenon is termed diapedesis. In the tissue fluid, the leucocytes engulf invaders, debris of broken cells and inert foreign particles by means of pseudopodia. This process is called phagocytosis (Gr., phagein = to eat). It was discovered and named by Metchnikoff (1892 – winner of 1908 Nobel Prize) Neutrophils and monocytes are the most potent phagocytes. Neutrophils can perform phagocytosis in circulating blood itself. Monocytes do so only in tissue fluids, where they first enlarge and transform into large and powerful macrophages (=scavenger cells). The latter are capable of engulfing larger and more numerous particles than can be engulfed by neutrophils.

Fig.         Diapedesis of WBCs and relation of blood, lymph and tussue fluid

Within the cytoplasm of phagocytes, phagocytized particles remain in membrane-bound phagosomes. Lysosomes of the phagocytes fuse with phagosomes and pour their hydrolytic enzymes into them. The phagosomes are, then, called digestive vesicles. The phagocytized particles are eventually digested by these enzymes.

            Monocytes which become macrophages and the macrophages of connective tissues themselves comprise the so-called mononuclear phagocytic or reticuloendothelial or tissue macrophage defense system (Aschoff, 1924).

Inflammation: It is complex of sequential changes in tissues under innate immunity occurring in response to injury which may be caused by viruses, bacteria heat, toxic chemicals, etc., or by physical or other factors. The damaged tissue liberates vasodilators such as histamine, bradykinin and serotonin. These substances increase the local blood flow by dilating arterioles and arterial capillaries and also the permeability of venous capillaries. A large quantity of plasma fluids with some proteins such as fibrinogen, therefore, leak from capillaries into the affected tissue. The tissue, therefore, becomes red, warm and swollen due to accumulation of fluid (=local edema). This is called inflammation. The extracellular and lymphatic fluids clot around the inflamed tissue (=walling off) to prevent the spread of injury to adjacent tissue. Macrophages, already present in the tissue, start phagoyctizing the invaders and debris of broke tissue cells. These, thus, function as the constituents of the “first line of defense” in innate immunity. Next, certain substances, released by the inflamed tissue into the blood-stream, induce the blood neutrophils to migrate and collect inenormous number at the site of inflammation. These, thus, from the constituent of the “second line of defense”. Thereafter, blood monocytes migrate into the tissue and transform into macrophages, acting for in last stages of inflammation and help in removal of debris.

In the above process of defense, a large number of neutrophils and macrophages are destroyed. The debris of broken and disintegrating invaders, tissue cells, neutrophils and macrophages forms a creamy paste, called pus. Usually, the pus collects in a pus cavity which may open and empty itself at body surface, or into some internal cavity. If the pus cavity remains closed, the pus is autolyzed and absorbed by surrounding healthy tissues.

Acquired, Adaptive or Specific Immunity

This is the ability of body to develop special defense against extremely powerful invaders and toxins which may cause serious and even fatal diseases. It is of two basic types – humoral and cellular (= lymphocytic). In humoral immunity, the body develops circulating antibodies which are globulins (=immunoglobulin or gamma globulins), capable of attacking invader micro-organism or toxins. In cellular immunity, on the other hand, the body produces a large number of specifically sensitized lymphocytes which attach to and destroy specific invaders.

Antigens: Each type of toxin and an invading organism contains certain large molecules (of 8000 or more molecular weight) of one or more specific chemical compounds which are generally proteins, large polysaccharides, or lipoproteins. These compounds elicit an immune response in an animal body, and are, therefore, called antigens. Drugs, certain chemical constituents in the dust, industrial affluent and poisons of certain plants and animals which elicit immune responses also act as antigens. Transplantations of tissues and organs from one person to another generally fail, because the specific proteins of the donor which differ from those of the recipient act as antigens and induce immune reactions in latter’s body.

Role of lymphocytes and lymphoid system: Humoral and cellular immunity is the product of body’s lymphoid tissues (lymph nodes and nodules, spleen, thymus, gastrointestinal submucosa, bone marrow, tonsils, etc.). Lymphocytes present in lymphoid tissues play the major role in acquired immunity responses. All lymphocytes are originally derived, in late embryo, from certain pluripotent haemopoietic mesodermal stem cells, which occur initially in yolk sac, later in embryonic liver and spleen and finally settle in bone marrow. In bone marrow after birth, these proliferate and differentiate into “T” and “B” types (T-lymphocytes or T-cells and B-lymphocytes or B-cells) for cellular and humoral immunity respectively. Those responsible for cellular immunity (“T” type) first migrate to thymus gland where these again proliferate and are “programmed”, i.e., sensitized to recognize specific invaders or antigens (Fig.). Those lymphocytes which are responsible for humoral immunity (“B” type) first migrate to some yet unknown organ or tissue (most probably bone marrow) for sensitization. Sensitization of all lymphocytes occurs shortly before birth and for a few months after birth. Sensitized lymphocytes first circulate freely in blood for a few hours and then, settle in lymphoid tissues.

Fig.         Sensitization of lymphocytes for immunity

A some invader or toxin enters the body, the lymphocytes which have already been sensitized to recognize it and are present in lymphoid organs, rapidly proliferate to increase enormously in number. For humoral immunity, most of the progenies of the specific ‘B’ lymphocytes transform into larger cells called plasmocytes or plasma cells which, then, produce the specific antibody and release it into the lymph and blood for throughout the body. Rest of the daughter lymphocytes remain stored in the lymphoid organs as “memory cells” for future is sponses. The circulating antibodies, either destroy the antigen or invader by dissolving it, or simply destroy its poisonous effect (=detoxification) or combine with it to form a precipitate or a complex which causes inflammation. In cellular immunity, the “T” lymphocytes already “committed” for specific invaders or antigens actively proliferate, producing numerous “cytotoxic” or “killer” lymphocytes. The latter migrate into the blood to destroy the concerned antigen or invader by first phagocytizing it and then destroying it by their contained antibodies. It is believed that “T’ and “B” lymphocytes and tissue macrophages co-operate in combating invaders and toxins, in all immune reactions.

Humoral immunity protects the body from fast-occurring diseases like cold, influenza, tetanus, measles, smallpox, cholera, etc., while cellular immunity provides protection from slowly and gradually progressing diseases like tuberculosis, cancer, leprosy, etc.

Autoimmune diseases: Sometimes some tissue of the body itself starts releasing some abnormal substance which may act as an antigen. “T’ and “B’ lymphocytes specific to his antigen react and start destroying the tissue. This is called an autoimmune disease. For example, rheumatic fever is caused by autoimmunity developed against tissues of heart and joints. Similarly, glomerulonephritis is autoimmunity against basement membrane of glomeruli. In Hashimoto’s disease, the thyroid gland is destroyed by autoimmunity.

Vaccination: This process has been used since long to develop and improve acquired immunity against specific diseases. A person can be vaccinated by injecting dead pathogenic organisms that are no longer capable of causing the disease. But which still have their chemical antigens intact so that the specific “T” or “B” lymphocytes are sensitized. This type of vaccination is used to protect the body against typhoid fever, diphtheria, whooping cough and many other types of bacterial diseases. Also, immunity can be achieved against toxins that have been already treated with chemicals to destroy their toxic nature but not their antigens. This procedure is used in vaccinating against tetanus, botulism, etc. Finally, a person can also be vaccinated with live, but attenuated pathogens. The latter are either grown in special culture media, or are passed through a series of laboratory animals until they have mutated enough to become incapable of causing the disease, but still carry the specific antigens. Such vaccination is used against poliomyelitis, yellow fever, smallpox, measles and many other types of viral diseases.

Active and Passive immunity: Both, innate and acquired immunities of body come under active immunity, because these involve phagocytization and chemical inactivation or destruction of antigens and pathogens. A temporary immunity can be created in the body even without the attack of concerned pathogens or antigens. This is done by infusing antibodies, sensitized lymphocytes, or both from some other person or animal which has been actively immunized against the pathogen or antigen. These infused antibodies, or sensitized lymphocytes last for a few days or weeks and keep the body safe against possible attack of specific pathogens or antigens. This is passive immunity.

Allergy: This is an important side effect of immunity. Sometimes, repeated doses of an antigen in the form of a drug, cosmetic or household chemicals cause formation, in the body, of a very large amount of antibodies or a large number of sensitized lymphocytes. A subsequent does of a high concentration of such an antigen causes widespread cellular or humoral immune reaction in a number of tissues or even in the whole body. The antigen-antibody complex precipitates the tissues. Hence, there is extensive invasion of tissues by macrophages, causing vide spread inflammation, edema and destruction of small blood vessels, or widespread skin eruptions. This reaction is called allergy. It can occur in any person. Some persons have inherited ‘genetic allergic tendency’. This is phenotypically expressed in the formation of some antibody in an abnormal quantity. Whenever the body is exposed to the scientific antigen, allergic reaction occurs.