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THE IMMUNOLOGY OF LEPROSY
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In studying the IMMUNOLOGY of Leprosy, we need to understand the leprosy patient’s ability or otherwise to resist the invasion of pathogenic organisms and, in particular - Micobacterium leprae (M. leprae), which is the germ responsible for leprosy. Only a century or more ago, there were those who thought that Leprosy was not caused by a “germ” because it was imagined to be a “Curse of God”. In fact, there are many places in the world where this superstitious concept still prevails.
In fighting disease, the body is capable of identifying any foreign organism and the defence mechanism recognises the invading germs as “Antigens” In the case of Leprosy, M.leprae is the source of the Antigens.
Actually, the body’s defence mechanism starts with the skin which is a good, protective covering. Healthy skin inhibits the entry of germs except when it is cut. The body’s fluids are mildly antiseptic, with tears, sweat and gastric juices putting up a first-line of resistance to any germs that could bring on disease. However, if the invading germs manage to break through this first-line of defence, there are several types of “Defence Cells” which are specifically designed to ingest and digest these foreign invaders. In actual fact, a battle takes place within the body as the defence cells fight against the bacteria to drive them away and this is called “Inflammation”, which may be likened to the body’s second-line of defence.
The body’s protective mechanism has two aspects - Non-Specific and Specific. In the case of the Non-specific, the large defence cells called Macrophages, through their action of “phagocytosis” (swallowing-up) sweep through the body’s blood stream to ingest and digest any foreign bodies they encounter. The macrophage looks like an amoeba and sort of flows around the germ to take it into itself, there to be dissolved by certain chemicals or enzymes. The second type of protective mechanism is specific and the body’s defence system can only “recognise” a foreign invader if it has experience in this identification of certain antigens. In lepromatous patients, their macrophages can ingest the M.leprae but cannot digest because there are no “T-Type” (“T” for Thymus, the gland which “programmes” these cells) lymphocytes to assist the macrophages to produce the needful digestive juices or enzymes. So, in the case of lepromatous leprosy, the very cells which are meant to kill off the bacilli, are actually transporting them around the body and providing an environment in which they may even be able to multiply.
TWO MAIN TYPES OF IMMUNITY:- These are (1) “Humoral Immunity” or Antibody Mediated Immunity and (2) “Cell-Mediated Immunity” (CMI). In the case of Humoral Immunity, certain chemicals (antibodies) are generated by the body when it is invaded by antigens. Why the name “Humoral”? Because these antibodies circulate in the fluids of the body which are called “Humor” .In certain types of infection, such as Diphtheria etc., the antibodies (like disinfectant) of Humoral Immunity are most effective in cleansing the system of the toxins or poisons liberated by the Diphtheria bacillus etc.. In Humoral Immunity, we see the antigens invading the body to produce antibodies. which react against the antigens to destroy them. However, while Humoral Immunity, is very effective in fighting many forms of infection, it has little positive effect against M.leprae and in fact, can cause much suffering through Erythema Nodosum Leprosum (ENL “Reaction”) which is a study in itself.
With “Cell-Mediated Immunity” (CMI), some of the invading foreign bodies and their antigens stimulate the production of certain special defence cells which mobilize to attack the antigens, at the same time establishing a severe inflammatory “reaction”. Cell-Mediated-Immunity is essential for the body’s defence against such diseases as Tuberculosis, and Leprosy. Where the antigens accumulate, these special cells - mainly lymphocytes - collect at the site and, in the case of leprosy, those sites are principally the peripheral (cooler) nerves and, more particularly, the nerve’s Schwann Cell. M.leprae has an affinity for the COOLER areas of the body and this characteristic has a bearing on the types of deformities that result from the invasion of M.leprae.
The smaller defence cells, called lymphocytes, have no phagocytic property so cannot ingest/digest the M.leprae, as can the macrophages. The role of the lymphocytes is to secrete certain chemicals which attract the larger macrophages to the site of antigen build-up and assist the macrophages to engulf and digest the M.leprae. Cell-Mediated Leprosy is the protective immunity we need against leprosy and, happily about 90% to 95% of the human race have this type of immunity in varying degrees. At one end of the “Immunological Spectrum”, these leprosy patients with a well established CMI, have the form of the disease known as “Tuberculoid” leprosy, but they may have little Humoral Immunity. At the other end of the Immunological Spectrum, Lepromatous leprosy is a complete reversal - well established Humoral Immunity but no CMI. The latter is the infectious form of leprosy.
As we can see, Immunity is stimulated by our exposure to certain germs / antigens but Immunity can also be artificially induced by our exposure to dead germs or even living germs that have been rendered non-viable or harmless. We call this “Vaccination” . When Smallpox was prevalent, all of us were vaccinated against this very contagious disease when we entered endemic areas. Those of us who worked in areas endemic to Tuberculosis were vaccinated with “BCG”. Conditions like Typhoid, Cholera, Plague etc., require their vaccines to be prepared from killed germs. We need to remember that antibodies are specific to the antigens. This means that the antibodies stimulated by a certain germ react only to that specific germ; e.g. the germs of typhoid produce antibodies which only react to those germs of Typhoid, and to no other infection. Although considerable research has been done and many trials conducted, we still do not have a really effective anti-leprosy vaccine. This remains a challenge.
Fortunately, nature has provided humans and animals with a Natural Immunity, present from birth. There are numerous diseases which affect domestic animals but which do not threaten humans. On the other hand, domestic animals are spared many of the disease from which we suffer.
Although Immunity, in most cases, helps the body’s defences against the invasion of bacteria and their antigens, there are occasions when the body reacts violently to the antigens. We call this “Lepra Reaction” - of several types - “Type 1” and “Type 2” also “ENL” - which is a study in itself .
Because only a small percentage of a community develops the disease of leprosy, even though they may come into contact with many carriers of the disease, it is obvious that humans develop a natural immunity against Leprosy.
RACIAL FACTOR IN IMMUNITY:- It is an established fact that some races or ethnic groups are more susceptible to leprosy infection than others. Paradoxically, Africans and Indians are less at risk than Europeans, Japanese or Chinese. If any in the latter three groups contract the disease, it is quite possible that they may develop the lepromatous, infectious form. This is not because of any nutritional, climatic or economic cause but due mainly to an inherent natural immunity within a particular race. A clear example of this is seen in those of the Anglo-Indian race who, though born in India, are more at risk from the serious, infectious form of “lepromatous” leprosy. .
IMMUNOLOGICAL RESPONSE AND DEFORMITY:- It may surprise many to know that the living leprosy germ is totally harmless, in that it is not “eating away” (the bacillus has no teeth!!) any fingers, toes, eyes etc., although that is the impression one may get on seeing a neglected, untreated leprosy patient in an area where there is no health education and where stigma against the disease prevails. The damage is being done not so much by the living bacilli but by the body’s strong reaction to the dead bacilli or more particularly, by the lymphatic system’s violent fighting to eliminate the antigens of the dead bacilli .
Because the bacilli are attracted to the COOLER, peripheral nerves - where they come close to the surface - such as the Ulnar nerve at the elbow, the Lateral Popliteal Nerve at the back of the knee, the Posteria Tibial at the inner ankle, the Median Nerve at the inner wrist, the Facial Nerve at the neck etc. etc.. there is a massive accumulation of lymphocytes at the site of the affected nerve and it is this build-up of defence cells that does the damage, restricting the flow of blood in the tiny blood vessels that nourish the nerves with oxygen. Where the sensory nerves are starved of oxygen (anoxia), those nerve endings are destroyed and anaesthesia results, perhaps at the tips of toes and fingers. Insensitive fingers and toes are then at risk due to cuts, burns etc.. Where the motor nerves are starved, various muscles become inoperative and different types of paralysis result such as “Dropped Foot, “Clawed Hand” , “Lagophthalmos” (eyes cannot close) , “Dropped Wrist” etc. etc.. Where the autonomic nerves are affected , the sweat and sebaceous glands may cease to function resulting in a break-down of the sweating and oiling mechanism and a consequent drying (and cracking) of the skin resulting in secondary infection. Where the hair follicle’s nerve is deprived of nourishment (oxygen) hair may cease to grow in those cooler affected areas such as the eyebrows.
Even though Tuberculoid, non-infectious patients, with strong CMI, may have so few bacilli in their bodies that they cannot be detected by ordinary microscopic means, if they are not treated, they may suffer from severe nerve damage due to the massive lymphocitic response, causing the nerves to swell 5 or more times their normal size. Sometimes the nerve sheath has to be incised to releave the pressure on the nerve’s Schwann Cells / Axon and their blood supply.
On the other hand, lepromatous, infectious patients, whose bodies may be teeming with millions of M.leprae, may suffer relatively little nerve damage (in the early stages) , because the lack of CMI means that there is no strong build-up of defence cells around the nerves.
Leprosy is a very enigmatic disease. Although it can look to be a highly contagious disease, in actual fact, as recorded in the “Guiness Book of World Records” under “D” for diseases, of all the communicable diseases, Leprosy (the tuberculoid type) is the least contagious. However, its “lepromatous” form is the most bacilliferous of all communicable bacterial diseases.
On request, more information can be given of the various “Types” of leprosy within the Immunological Spectrum, but this will suffice to cover the basic facts on the Immunology of Leprosy”
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