Immunology can be defined as a study of the mechanisms which are responsible for resistance to infection. Although these same mechanisms may occasionally also be responsible for the production of disease symptoms. Until a few decades ago immunology was closely intermingled, and almost synonymous with microbiology and infectious disease medicine although nowadays it is a major independent discipline.
Written records from over 2,500 years ago reveal an awareness that persons who recover from certain diseases cannot contract them again. For example, one of the earliest accounts of immunity comes from China, where they not only noticed that people who recovered from smallpox were resistant to reinfection, but also that the various epidemics varied in their severity - one year being usually fatal and other years being much milder. Chinese physicians therefore deliberately infected healthy people with material (crusts or fluid) taken from cases of mild smallpox, thus rendering them resistant during the serious epidemics. Although this practice was introduced to Europe in the early 1700's it was at best a risky procedure, since people occasionally died from these "mild" infections! It was not until 1796 that Edward Jenner, an English country physician, put into practice a well known countryside observation that the beauty of milk maids was often due to the fact that they rarely contracted smallpox since they almost invariably caught cowpox which made them immune to smallpox. This procedure was the first example of vaccination (from Vacca which is the latin for cow), a term later coined by Louis Pasteur in honor of Jenners contribution to include any procedure which induces immunity. Nowadays vaccination is synonymous with immunization.
The next major step towards an understanding of immunology was not possible until the late 1800's when Pasteur in France, and Koch in Germany demonstrated how microbes cause disease. The initial studies on vaccination using a defined microbe were made in Pasteur's laboratory where they were working on Chicken Cholera (Pasteurella aviseptica). Pasteur, on returning from holiday, tried to use an old culture of the bacilli, only to discover that it was apparently ineffective in producing the disease. Being a careful person (or maybe mean!!) he tried to reuse the animals with a fresh isolate of the microbe, and discovered that the old "attenuated" culture had induced immunity in the chickens to challenge with the virulent organisms. This finding may have prompted Pasteur to make his famous epigram that "chance favors only the prepared mind". Pasteur later extended these findings to Anthrax and finally to Rabies, which after experiments in animals was given to a small boy who survived and became the gate keeper of the Pasteur Institute!
In 1883 a Russian, Eli Metchnikoff first demonstrated the role of phagocytic cells in the immune process. Again like the discovery of Pasteur, it occurred while he was on holiday (actually he was unemployed, since he had resigned from his job!) Metchnikoff was a Zoologist, and since he was on holiday near the sea he decided to examine some starfish larvae that he found. He pushed a splinter of wood into one of the animals and was surprised to see that many phagocytic cells surrounded the "foreign object". His subsequent investigations elucidated much of the basic role of phagocytic cells in dealing with infections. Much of Metchnikoff`s work was carried out at the Pasteur Institute where Roux and Yersin had isolated a toxin from diphtheria bacilli which was responsible for many of the symptoms of this disease.
The next major step forward was in the discovery (initially by Von Behring in Robert Kochs laboratory in Berlin) that immunity could be passively transferred using serum taken from a previously immunized animal. This serum component became known as antibodies. The next step was the discovery that antibodies could not only protect an individual from infection, but could directly lyse (in vitro) bacteria cultures such as cholera . Soon afterwards two other phenomena of antibacterial serum were demonstrated, precipitation and agglutination. These discoveries soon lead to the development of serotherapy where serum from horses immunized with organism such as diphtheria and tetanus would cure people if administered soon after the infection developed. In 1899 Bordet discovered that immune serum contained two components, a heat stable one that had the activity of agglutination and precipitation (the antibody activity), and a heat labile one that was responsible for bacterial lysis (later known as complement). At the beginning of the 1900's Landsteiner demonstrated that antibodies could not only be produced against complex organism and proteins but also against simple organic chemical such as diamino benzene sulphonate.
The development of these two different approaches to immunity, the cells of Metchnikoff, and the antibodies of the German investigators lead to considerable controversy as to which was the most important in immunity. This question was largely settled in the early 1900's when it became clear that both cellular and humoral factors were involved in immune protection, and that immune serum could also act together with phagocytic cells to increase phagocytosis (opsonization).
Between 1903 and 1910 the role of histamine in the phenomena of anaphylaxis was elucidated, initially by Riche and Portier, and later by Dale and his colleagues. Up until the late 1940's the actual substance responsible for antibody activity was not known until the development of electrophoretic protein separation techniques by Tiselius in 1939. He demonstrated that the gamma globulin fraction of serum increased in concentration following immunization and that antibody activity was confined to this fraction.
The next 50 years saw the development and expansion of immunology into the major discipline it is today
The immune system is a fully integrated physiological system which is found in all multicellular animals but is best developed in vertebrates, and in particular mammals and birds. When a disease causing organism gets into the body, two distinct, but interrelated branches of the immune system are active, the non- specific immune response and the specific immune response. Both of these systems are physiological mechanisms give the animal the ability to recognize materials as foreign to itself, and to neutralize, eliminate or metabolize them.
The immune system has developed frm the physiological mechanisms that have evolved to cope with a multicellular existence. The primary functions of maintaining homeostatasis by removal of dead and effete cells and debris by continous surveillance has been adapted and developed for defence against infection.
The immune system, like all physiological systems, is affected by a variety of major modifying factors:
This type of immunity is present throughout most of the metazoa, and probably represents the earliest development of protection against disease causing organism and foreign bodies. Non-specific immune response can be mediated either by humoral factors, mainly proteins present in body fluids, or by phagocytic cells such as coelomocytes and polymorphonuclear leukocytes. This type of immunity plays a vital part in combatting disease and major defects in non-specific immunity usually result in fatal, overwhelming disease. A characteristic feature of non-specific immunity is that it requires no prior exposure to the organism to be effective.
Physical and Biochemical Barriers
Keratinised skin provides a good physical barrier to many microorganisms thereby preventing entry. Howerver, a few specialised pathogens such as hook worm have developed mechanisms for penetrating this barrier. In addition pathogens transmitted by biting vectors are able to gain entry to the body.
The surface of the skin normally has an acid pH and a high salt concentration discouraging most of the pathogens. There are also a variety of antimicrobial components secreted in sebum
Cilia and Mucus provide a physical barrier on the more susceptible mucus membranes preventing pathogens from attaching to cell surfaces
There are a variety of body secretions - eg Spermine in semen, acid in gastric secretions and lysozyme in tears which are active antimicrobials.
Once a pathogen has managed to colonise part of the body then humoral and cellular effector mechanisms come into play
Non-Specific Humoral Components
Complement - A very important cascade of enzymes which induce a variety of immunological functions including inflammation, opsonisation and pathogen lysis
Natural antibody - Even though an individual may not have meet a pathogen before many of the epitopes on the surface of pathogens are also found on commensal gut flora or as components of food. These cross-reacting antibodies are able to inactivate, opsonise and activate the complement pathway
Acute Phase Proteins -
Non-Specific Celular Components
Granulocytes:
Polymorphonuclear cells produced in the bone marrow from a myeloid stem cell
Neutrophils - Adult humans produce about a million neutrophils a second which although many circulate in the blood (70% of the toal white blood cell count) most can be found attached to the cells lining the capillaries. Neutrophils circulate in the blood for 3 or four days and then migrate out into the tissues where they die witn a day or so. These cells are highly phagocytic and can kill pathogens by a variety of oxygen dependent and independent mechanisms
Eosinophils - Peripheral blood normally contains less than 1% of these cells unless the individual is atopic or has a high parasitic worm burden. Although phagocytic these cells are efficient at exocytosis and are able to dammage large organisms such as schistosomulae by releasing toxic components onto a pathogens surface.
Mediator Cells:
Basophils -
Mast Cells -
Mononuclear cells:
Macrophages -
Natural Killer cells -
The principal characteristic of this type of immunity is that it is not only specific to particular components of pathogens or antigen, but displays an enhanced response the second and subsequent times it comes into contact with the same organism. This memory capability is what makes the specific immune system so effective in dealing with many infectious agents. As in the non- specific branch of the immune response, specific immunity is mediated by both humoral and cellular responses. The antibody fraction of gamma globulins is responsible for humoral immunity and deals with infectious agents via a variety of methods such as agglutination, precipitation, neutralization, and in&127; conjunction with complement, lysis. Certain types of immunoglobulin are specialized for particular functions such as lysis or protection at mucosal surfaces. Antibodies may also collaborate in destroying disease causing organisms with lymphocytes and macrophage which are the cells responsible for the cellular arm of the specific immune response. Both of these types of cells are able to destroy pathogens by a variety of cellular mechanisms including cytotoxicity, cytostasis, and by lymphocyte activation of macrophages which are then able to phagocytosis and kill ingested organisms. The lymphocytes, particularly those that have been "educated" by the thymus gland (T cells) play a central role in coordinating the entire specific and non-specific immune responses. The second important group of lymphocytes are the B lymphopcytes which are responsible for producing antibodies, these are derived from the bursa of Fabricius (only in birds) or its equivalent in mammals (the foetal liver, the bone marrow and the mucosal assiciated lymphoid tissue).
Evasion of the Immune Response
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Humber@UEL.AC.UK
©David Humber 1996 - Last Modified: Tuesday, October 13th 1998 at 09:20 PM