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(#09-03)

Immunology:

ch 7 p 37

Prevention and treatment of disease depend not only on how we protect ourselves from, but also on how we defend ourselves against invaders such as Viruses.

Some Viruses persist in the body of the infected person for months or years, even though AntiBodies against the particular Virus are also present. There are several well known examples of persistent Viral Infections in humans.

One is the Virus of the common cold sore, the Herpies Simplex [HSV]. A closely related Virus to herpies is called CytoMegaloVirus ("big cell"), because the Virus produces a large body in the infected cells called an inclusion body.

These Viral inclusion bodies occur in herpies and in certain cells when infected by the regular Measles Virus, Rubella.

p 39

The Immune Systems of the body are responsible for checking the destructive ability of Viruses, and on occasion may even be responsible for some of the manifestations of an infection.

The way the Immune System stops Viral Infections is related to the way the Virus spreads in the body. A Virus spreads from one cell to another when cells are multiplying or dividing.

The first type of spread is usually stopped by AntiBodies in the blood called "Humoral" AntiBodies. These AntiBodies attach themselves to the Viruses and destroy them. This attachment forms what the Immunologists now call a Virus-AntiBody-Complex.

Humoral AntiBodies neutralize the Virus by covering the surface and thus preventing its attachment to cells. The straighforward neutralization of Virus particles sometimes occurs with the aid of a substance called Complement.

Another mechanism of Cellular Immunity consists of inflammatory cells such as Lymphocytes and Plasma Cells which prevent Viruses from fusing, thus interfering with their spread.

Certain immune Lymphocytes exude a toxin called LymphoToxin and also Interferon, a protein substance which prevents a Virus from multiplying and thus prevents other cells from becoming infected.

Interferon may protect a very large number of cells in a certain organ such as the liver or the Brain.

Certain cells in the body make Interferon much better than other cells and agents such as Viruses or bacteria stimulate or induce the production of interferon by cells. The mchanism is called "Cell-Mediated" Immune Response.

It is still an unanswered question as to why in the presence of the various Immune Systems of the body, Viruses can remain hidden, persisting in certain cells and continuing to damage them.

In some instances Viruses infect the cells of the Immune System, such as in leukemia, and thus depress the Immune Response of the individual. This depression of the Immune Response is referred to as binding or interfering with AntiViral AntiBody.

p 40

The next important questions to be answered are:

  1. Can effective means such as vaccines be developed to prevent or to control persistent infections?

  2. Is there any way to cure persons once they become chronically infected? Certainly one approach to prevention is to induce or encourage the production of interferon. A second possibilty is to stimulate the Immune Responses of the body to combat infection.

The cells in the Immune System of the body begin their development in the liver, during the life of the baby before birth.

These basic cells then operate through the Thymus Gland to produce certain types of Lymphocytes known as T-Cells and some of them operate through the Bone Marrow and produce another type of Immune Cell known as the B-Lymphocyte.

This B-Cell may become a Plasma Cell, which lives only a day or two; but plays a very important role in the Immune System of the body, making it possible for us to defend ourselves against invading Viruses which cause disease.

The AntiBodies formed in the body do not help us recover from an infection, but they do prevent getting the disease a second or a third time. The main role of the Immune System is prevention.

The cells which develop from the Thymus and Bone Marrow play a very important role, in combating infection and ridding the body of certain infections.

When the body lacks the ability to defend itself, rare deficiency diseases result. Because the body lacks Immune AntiBodies And Immune Cells which are needed to keep us well.

When we are deficient in certain immune mechanisms, we suffer from infectious diseases; which can be fatal in the individual, who lacks the ability of defense through the Immune Systems.

p 41

We must think of treatment in terms of prevention. Smallpox PolioMyelitis and Measles can be prevented, by inoculation of a safe and modified form of the Virus.

Thereby, inducing the production of AntiBodies which do not cure disease but prevent infection by the specific infecting agent or Virus.

Although the possibilty of treatment of MS by encouraging and stimulating the Immune Mechanisms is under intensive study and research the best treatment at present is prevention.

The fact that many patients with MS related to Viral infections which have become chronic or persistent have periods of feeling better and of actually improving to the point of partial recovery if not complete suggests that direct treatment is a reality.

This event is referred to as a remission or a ceasing of the symptoms and these periods may last for months and even years.

They lend hope to the fact that Immune Systems can be encouraged and induced to produce a period of recovery or a remission. Research which can stimulate Immune Responses is the direct attack against chronic Viral Infections, which is at the threshold of medical practice.

One of the first agents to be discovered and developed is Transfer Factor (TR). To create TR a donor must be found whose blood has a natural Immune Response to the subject's disease.

The acceptable donor will spend approximately four hours while all the blood in his body is processed to "seperate out" TR. The donor's blood flows into a cell separator - a centrifuge device where the red blood cells settle to the bottom, the Plasma rises to the top, and the white blood cells stay near the center.

The white cells are siphoned out and frozen, turning them into white powder. This powder containing TR, can be injected into the patient suffering with the specific disease or infection to increase resistance to the illness.

p 42

Patients with MS may have a Viral infection affecting the Brain, since these patients have a measured difference in their Immune Response to Measles leading researchers to suspect that MS may be an ongoing Measles Virus infection. This suggests therapy using Immune Response agents, i.e., Transfer Factor.

BCG (Bacillus Calmette-Gerin) is a bacterial substance considered to increase Cellular Immunity. It may also cause some undesirable side effects. Another chemical substance that stimulates Cellular Immunity without serious side effects is an agent called Levamisole.

This drug boosts Cellular Immunity particularly if Cell-mediated Immunity is depressed. Spitler found that Levamisole helped to control recurrent infections with Herpes Viruses. It is truly an AntiViral agent.

Reports in the medical literature record favorable results from the use of Levamisole in Herpes Virus infections, Influenza and Hepatitis.

Levamisole restores immune functions particularly in cells involved in Cell-mediated Immune reactions. Levamisole has been used sucessfully in several diseases of humans, including recurrent and chronic infections.

Recent Research On Multiple Sclerosis:

ch 8
p43

In a paper concerned with Genetic factors in MS, several diseases were discussed; but only in Multiple Sclerosis was a strong association of Lymphocyte determinants observed.

The authors reported that in patients with MS an increased frequency of HL-A3 and HL-A7 types were observed, confirming findings that had previously been observed in several other laboratories.

The influence of the Genetic factors on the clinical course of the disease had been analyzed, and only among patients who carry the HL-A7 or the LD-7 Genetic determinants, were rapidly developing disease observed.

p 44

These investigators found an association between the occurrence of high Measles' AntiBodies in MS patients who carry HL-A3, 7 and/or W18. Suggesting that Genetic factors contribute to the control of AntiBody production.

No conclusion was reached as little is known about the components of the Measles Virus involved in this activity.

These authors did state that the Leukocyte migration test (MIF) was the rationale behind the treatment of MS patients with Transfer Factor (TR), the substance which normalizes the reactivity.

Finally, it was evident from their studies that the LD-7A is a Genetic determinant which occurs in 60% to 70% of patients with MS, and this when compared to 16% in normal individuals provides some insight into Genetic factors in Multiple Sclerosis.

The second group of investigators reported Immunologic factors as they relate to the Genetics of DeMyelinating disease.

The authors agreed with previously outlined report that HL-A3 and HL-A7 types are over-represented in MS, when compared to control populations and they also agreed that LD-7A is strikingly over-represented in Multiple Sclerosis.

Measles AntiBodies tend to be higher in MS patients than in controls but persons who bear HL-A3 have higher Measles AntiBody titers than those who do not, whether or not they have MS. Measles AntiBody titers were higher in the Serum of patients with MS than in those individuals with LD-7A, and also higher in brothers and sisters.

A third report analyzed HL-A in nine families in which at least two individuals had MS. Although inconclusive, it suggested that differences in exposure to enviromental factors such as Measles Virus may explain why not all individuals with the Genetic susceptibility develope the disease.

It is possible that immune deficiency is why some individuals are more susceptible than others to common childhood illnesses. Also the occurrence of Measles late in childhood might increase the likelihood of acquiring Multiple Sclerosis.

p 45

The difficulties of evaluating any form of treatment were emphasized. A theoretical basis for attacking the Genetic relationship in MS was cited since HL-A studies have shown a dominance of the 7A type and its correlation with progression of disease.

Another study found a selective cellular suppression to Measles Virus was present in patients with Multiple Sclerosis. It was this selective suppression which prompted the investigation of TR and the ability of cells in the body and in the test tube to react to Measles Virus.

The authors selected individuals who exhibited a high degree of reactivity to Measles Virus and these individuals provided the TR used in their study.

Fifteen patients were studied and eleven developed significantly higher values to Measles Virus following the use of TR. The majority of these patients exhibited an increased response to Measles Virus. Increased migration values continued for six weeks following the injection of TR.

The last paper in this series was a further study of immunity in patients with MS. Serum from patients with MS inhibited the immune release in Lymphocytes from patients with Measles-infected cells. This data suggests the Lymphocyte killer function in patients with Multiple Sclerosis.

A recently published report on visna, a chronic inflammatory DeMyelinating in the CNS of sheep, throws further light on the problem of how a Virus is able to persist in the host and become a "slow Virus".

This Virus produces a severe crippling DeMyelinating disease in sheep; however there is no evidence that it has any counterpart disease in human beings.

p 46

Another recent report showed mouse tissue culture cells were markedly inhibted in their growth when exposed to Brain and spleen tissues from patients with MS.

First these researchers tested samples from ten cases of MS and found a reduction in the total cells in their cultures treated with Brain material from seventy-one MS patients and samples from forty-five non MS patients.

These cultures showed a reduction in the yield from the MS material when compared to control material.

The presence of the agent responsible for the decrease was not limited to the Brain and Spleen tissue from the patients but also found in the Serum and CerebroSpinal Fluid and in Kidney tissue and in Lymph Nodes from MS patients.

It was concluded that the cause of the reduction in the cell yields was high in the mice treated with MS material, but no response was observed in samples from the non-MS patients.

The Virus-like agent found in association with MS patients is small and similar in size to the Scrapie agent. An important difference is that the effect produced by this agent can be neutralozed by Sera from MS patients; while no such neutralization has been detected in Scrapie.

This research represents an important milestone in MS and offers hope in the search for answers.

p 47

A report on the relationship between Measles Virus AntiBodies and OligoClonal Immune globulin (IgG) in CerebroSpinal fluid (CSF) in patients with MS shows: Measles Virus AntiBody occurred in the Serum and CSF of 80% of patients with MS.

Several methods to study Measles AntiBodies in the Serum and Spinal fluid were used to compare patients with MS and with SSPE. These authors concluded that in the patients with SSPE the IgG represents an OligoClonal IgG response to a high level of AntiBody against the Measles Virus.

Studies with the electron microscope were presented with pictures of tissue culture cells infected with the SSPE Virus and Measles Virus. Brain material from patients dying with MS were studied and changes similar to those initally reported in 1972 by John Prineas.

The structural changes were much like those found previously in association with cells proved to be infected with the Measles Virus. The intertwined Measles Virus tubules fill the nucleus of all cells.

_________________________
Continued_in_(#09-04)




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