In this essay we will discuss about:- 1. Meaning of Immunology 2. History of Immunology 3. Scope.
Essay on the Meaning of Immunology:
In the process of evolution, the body of organisms has developed the property of distinguishing “self” and “nonself”, the “self” is accepted and “nonself” is rejected or degraded. For the rejection or degradation of “nonself”, organisms’ body has evolved a remarkably versatile defence system called immune system that operates via various mechanisms, which are collectively grouped under the name immunity or resistance (defence).
The immunity or resistance (defence) is therefore the insusceptibility of the body to the effect of “nonself’ factors like pathogenic microorganisms and their toxins and other kinds of foreign substances. The latin term immunis, meaning “exempt” is the source of the term immunity, the English world. The branch of biology that deals with immunity or resistance is called immunology.
The immunity operation by the immune system of organism’s body against the “nonself” is called immune response, which can be considered to perform two interrelated functions: recognition and response. Recognition is highly specific and distinguishes one foreign pathogen from the other.
Furthermore, it discriminates between foreign molecules and the body’s own cells and molecules. Response, however, is of two types: effector response and memory response. When a foreign pathogen is recognised, the immune system of the body recruits a variety of cells and molecules to neutralize and eliminate the invader.
This response is called effector response. In memory response, the immune system retains a memory of its encounter with an invader so that a second encounter with the same invader sometime later evokes a faster and more intense immune response.
Two fundamentally different types of immunity (immune response) operate in the body against microbial pathogens and other foreign substances, which are:
(i) Innate (nonspecific or natural) immunity and
(ii) Acquired (specific or adaptive) immunity.
The innate immunity includes general mechanisms inherited as part of the innate structure and function of each vertebrate, and acts as a first line of defence.
This immunity lacks immunological memory, i.e., it operates to the same extent each time a microbial pathogen or foreign substance is encountered by the vertebrate host. Contrary to it, the acquired immunity is a more highly evolved system of specific responses that recognize and selectively eliminate specific microbial pathogens and foreign substances.
Moreover, the acquired immunity retains memory of its first encounter with foreign invaders and improves on repeated exposure to them. Substances that are recognised by the immune system as ‘foreign’ and provoke immune responses are referred to as antigens.
The antigens cause specific cells to generate special type of proteins called antibodies (immunoglobulins), which bind to and inactivate the antigen. In addition to the specific cells that generate antibodies, there are other cells of immune system that destroy the foreign invaders.
The above mentioned two immunities (innate and acquired) usually work together to provide a high degree of protection for vertebrates. In some circumstances, however, the immune system of the body fails in providing protection because of some deficiency in its components.
At other times, it becomes an aggressor and turns its awesome powers against its own host resulting in immune disorders (malfunctions). Hypersensitivities (allergies), autoimmune diseases, immunodeficiencies, and transplantation (tissue) rejection are such immune disorders.
Essay on the History of Immunology:
Following is a summarized and lucic account of the achievements which are considered to be the milestones in the development of immunology.
Immunology is claimed to have emerged out of some observations in the ancient past. The ancient people observed that individuals who had recovered from certain infectious disease were not attacked by the same disease again, i.e., they became immune to the disease.
Another important observation dates back to 430 BC when Thucydides, the great historian of the Peloponnesian War, wrote that only those individuals who had recovered from the plague would not contract the disease a second time, and could nurse the plague patients. Thucydides’s observation is perhaps the earliest written reference to the phenomenon of immunity.
The first recorded attempts to induce immunity deliberately were made by Chinese and Turks in the 15th century. They either inhaled the dried crusts derived from small pox pustules or inserted them into small cuts in the skin (this technique is called variolation).
Lady M.W. Montagu, the wife of the British ambassador to Constantinople, observed in 1718 that there were positive effects of the technique of variolation applied on to the native population. She also applied this technique on her own children and found the positive results.
Development of Vaccination:
The technique of variolation was significantly improved by Edward Jenner, an English physician, in 1798. He was intrigued by the fact that milkmaids, who had contracted the mild disease cowpox, became immune to the dreaded smallpox. Jenner reported to the Royal Society in London the value of immunization with cowpox as a means of protecting against smallpox; a clear case of vaccination.
Thus, he did on the basis of the fact that when he inoculated a 8-year old boy, James Phipps, with cowpox content, the boy escaped from smallpox infection. Jenner’s explanation regarding cowpox vaccination against smallpox established the scientific credibility of vaccination to prevent disease and was accepted by the scientists and physicians of the time.
Jenner, therefore, is credited to have developed the “first vaccine” from cowpox. Jenner’s technique of inoculating with cowpox to protect against smallpox spread rapidly throughout Europe. But unfortunately, it took about a century before this technique was applied to other diseases.
Recognition of Immunology as a Science:
Immunology got recognition as a science in 1880 when the world witnessed a spate of progress brought about by the work of Louis Pasteur, who was studying with cholera bacterium, Pasteur had succeeded in culturing this bacterium, and had shown that chickens developed cholera when the cultured bacteria were injected into them.
Once he used an old culture for injection into some chickens, which fell ill but, to Pasteur’s surprise, they recovered. He subsequently injected these chickens again with freshly cultured bacteria, but these chickens were protected from cholera.
Pasteur speculated that aging had weakened the virulence of cholera bacterium, and that such attenuated pathogens could be used for inoculation. Pasteur used the term “vaccine” for the attenuated strain in recognition of the work of Jenner with cowpox; the term “vaccine” is derived from the Latin world ‘vacca , meaning “cow”.
Pasteur’s experiment with cholera bacterium represents a case of serendipity, which so often happens in science. In fact, Pasteur did not plan the above experiment, but he had to use the ‘old’ bacterial culture because he had been away on summer vacation, and he had to reinoculate the same chickens because his supply of fresh chickens was limited.
But this does not lessen the contribution of Pasteur; it only highlights as to how a genius exploits a chance observation to the best possible extent. Subsequently, Pasteur extended these findings to other diseases like anthrax disease of sheep; he vaccinated sheep with heat-attenuated anthrax bacillus (Bacillus anthracis).
In 1885, Pasteur administered a series of attenuated rabies virus preparations to a boy, Joseph Meister, who was repeatedly beaten by a mad dog. The boy survived and later became the custodian of Pasteur Institute. The latter was established in 1888 and became the professional centre for work in immunology.
Discovery of Phagocytosis and Cell-Mediated Immunity:
In 1883, a Russian scientist Elie Metchnikoff while studding infection of the common water-flea (Daphnia) by a fungus demonstrated that certain white blood cells, which he termed phagocytes, were able to ingest (phagocytose) microbial pathogens and other foreign substances. This was the first demonstration of the process of phagocytosis.
Moreover, noting that these phagocytic cells were more active in immunized animal and contribute to its immune state, Metchnikoff hypothesized that cells were the major effector of immunity and gave the concept of cell-mediated immunity.
Discovery of Humoral Immunity:
Von Behring and Kitasato demonstrated in 1890 that serum (the liquid, non-cellular component of coagulated blood) from animals previously immunized to diphtheria could make unimmunized animals immune to the disease when it was administered to the latter.
Since it was a discovery which showed that the immunity was mediated by non-cellular body fluids (known at the time as humors), the door of humoral immunity was opened.
For this discovery, Behring was awarded Nobel prize in 1901. Humoral immunity, however, was fully confirmed only during 1930s mainly through the efforts of Elvin Kabat and other workers who demonstrated that a fraction of scrum called gamma-globulin (now called immunoglobulin or antibodies) was found responsible for immunity acquired following immunization.
Controversy over Cell-Mediated and Humoral Immunity:
A great deal of controversy developed between the supporters of cell-mediated immunity and of humoral immunity. Achievements in the field of humoral immunity occurred lastly in comparison to cell-mediated immunity, and this helped emergence of controversy. But, later, the reasons were un-curtained.
Studies with serum took advantage of the ready availability of blood and established biochemical techniques, whereas it was difficult to study the activities of immune cells before the development of tissue culture techniques. This is why the information about cell-mediated immunity lagged behind informations about humoral immunity.
Cell-Mediated and Humoral Immunity Co-exist:
The controversy regarding the roles of cell-mediated and humoral immunities prolonged for some decades and, finally, came to an end in 1940s and 1950s when the two systems were found to be interrelated and necessary for the immune response. This became possible mainly by the contributions of Merill Chase, Bruce Glick and others.
During 1940s, Merill Chase successfully transferred immunity against tuberculosis-organism by transferring white blood cells between guinea pigs. This demonstration lighted again the interests in cellular- immunity.
The identification of lymphocytes as the cells responsible for both cell-mediated and humoral immunity during 1950s by using tissue culture techniques, and the existence of two types of lymphocytes (B lymphocytes and T lymphocytes) demonstrated by Bruce Glick were the major breakthrough in solving the controversy. B. Glick advocated that B lymphocytes are involved in humoral immunity, whereas T lymphocytes play role in cell-mediated immunity.
Immunity also Reacts to Non-pathogenic Substances:
Jules Bordet demonstrated around 1900 that the immunity also reacts to non-pathogenic substances such as red blood cells from other species. Serum taken from an animal inoculated previously with non-pathogenic material reacts with the latter in a specific manner, and this reactivity could be passed to other animals by transferring serum from the first.
Karl Landsteiner and others demonstrated that inoculating an animal with almost any organic chemical induces production of antibodies that would react specifically to the chemical.
These demonstrations made clear that the antibodies possess ability for an almost unlimited range of reactivity. Also, Landsteiner discovered ABO blood groups which was used for successful blood transfusions in humans. This sensational discovery won Landsteiner a Nobel prize in 1930.
Concept of Selective Theory:
In 1900, Paul Ehrlich proposed the concept of selective theory. He demonstrated that cells in the blood expressed a variety of receptors on their surface, which he called “side-chain receptors”. Ehrlich explained that the receptors react specifically with pathogenic agents and inactivate them.
In addition, such an interaction induces the cell to produce and release more receptors with the same specificity. He also proposed that the specificity of the receptor was determined before its exposure to the antigen, and the antigen selected the appropriate receptor.
Clonal Selection Theory:
The selective theory of Ehrlich was proved to be essentially correct by experimental data of Niels Jerne, David Talmadge, and E. Macfarlane Burnet collected during 1950s. But, these workers refined the selective theory and named it clonal selection theory.
Clonal selection theory explains that when an individual lymphocyte binds to an antigen on its specific receptor site, the binding activates the lymphocyte causing it to proliferate into a clone of cells that have the same immunologic specificity as the parent cell. The clonal selection theory has been further refined and is now accepted as the underlying paradigm of modern immunology.
Clonal selection theory has been widely accepted and in recognition Burnet was awarded Nobel prize in 1960, which he shared with Sir Peter Medawar. Twenty four years later in 1984, Niels Jerne was also awarded the Nobel prize for his contributions, which led to the discovery of clonal expansion concept and evaluation of the idiotype network in the regulation of immune responses.
Structure of Antibody:
In their pioneer work, Rodney R. Porter and Gerald M. Edelman demonstrated through enzyme cleavage experiments that the four polypeptide chains of antibody (immunoglobulin) molecule can be cleaved into three pieces, i.e., two antibody fragments (Fab) and one crystallisable fragment (Fc).
For this contribution. Porter and Edelman were awarded the Nobel prize in 1972. Subsequently, Wu and Kabat demonstrated in 1970 that there occur hypervariable regions in the antibody molecule.
Major Histocompatibility Complex (MHC):
Peter Gorer in the mid 1930s developed the concept that the rejection of foreign tissue takes place due to an immune response to cell-surface molecules; the molecules now called histocompatibility antigens. During these studies, Gorer identified four groups of genes, designated I through IV, that encoded blood-cell antigens.
Gorer and Snell carried out the work in 1940s and 1950s and demonstrated that antigens encoded by the genes in the group designated II participated in the rejection of transplanted tumors and other tissue. Snell called these genes as histocompatibility genes.
Although Gorer died before his contributions were recognised fully, Snell was awarded the Nobel prize in 1980 for this landmark contribution along-with Dausset and Benacerraf who worked on human leucocyte antigen (HLA) complexes.
Technique of Somatic Hybridization:
A major breakthrough was witnessed in 1975, when George Kohler and Ceaser Milstein demonstrated a technique of somatic hybridization and used it to produce immunologically homogenous monoclonal antibodies. Monoclonal antibody producing technique popularized by the name hybridoma technology. Kohler and Milstein were awarded the Nobel prize in 1984 for their brilliant contribution.
The above mentioned important historical contributions led rapid progress in immunology, which became instrumental in developing various fields of medical microbiology such as organ and tissue transplantation, vaccinology, and molecular biology, However (Table 41.1) lists the workers who have received Nobel prize for their significant contributions to immunology.
Essay on the Scope of Immunology:
Our knowledge of the immunological processes underlying the reactions of the body to infectious agents, to tumours, and to transplanted tissues and organs has advanced remarkably by using modern techniques, including those developed by biochemists and molecular biologists.
These techniques have enabled the identification of genes coding for molecules like the T-cell receptor and MHC molecules. The genes coding for immunologically important molecules have been cloned and relatively large amounts of pure recombinant proteins have been produced.
It is now possible to culture many different cell types in vitro and to clone these cells so that a population with an identical genetic makeup is obtained.
Many different strains of inbred mice, including ‘knock-out’ and ‘knock-in’ mice, have been developed for the investigations of cellular interactions, gene inactivation’s, etc. The role of a number of gene products has been elucidated by producing transgenic animals and studying the effect of the introduced genes.
Immunologists have developed many new techniques, including novel ways of producing a homogeneous immunoglobulin preparation, viz., monoclonal antibody, by using impure antigens. The development of these strictly defined reagents revolutionalized immunoassays and detection systems that employ antibodies.
Their potential in the treatment of infectious diseases, cancer patients, organ transplants, etc. is being actively investigated and a number of clinical trials have been performed. In addition to antibodies, other immunologically important molecules have been produced and are being developed as therapeutic agents.
The introduction of flow cytometry has revolutionized the analysis of cell populations and the use of polymerase chain reaction has increased the sensitivity of the detection of microorganisms.
The interplay between cells and molecules of the immune system is extremely complex. We are only now beginning to understand the intricacies of immune recognition. Some molecules appear to have many different functions depending on their location or the presence of other molecules.
The possibility of harnessing these powerful reagents to aid the elimination of not only pathogenic microorganisms, but also cancer cells is being actively pursued.
The ability to predict the minimum structures that can induce protective immunity will allow the development of more effective and safer vaccines. It may also become possible to develop novel ways of treating autoimmune diseases, allergic conditions and tumours, and to develop new strategies to reduce transplant rejection.
Thus it can be seen that immunity in its original meaning, referring to resistance to infections by means of a specific immune response, is only one activity of a complex system in animals.
The total activity of the cellular system is concerned with mechanisms for preserving the integrity of the individual with far-reaching implications in embryology, genetics, cell biology, tumour biology and many non-infectious disease processes.