(#08-03)

They infect us by getting inside our cells, taking over the cell's own protein machinery, making the cell produce more of them instead of the protein or compounds it usually makes.

Eventually, the Virus kills the cell and then moves on to infect its neighbors. AntiBodies can be made against some Viruses to prevent them from getting into the cells in the first place.

But the majority of Viruses infect us by travelling internally from cell to cell; they never expose themselves to our Humoral defenses. Our Cellular Defenses evolved against these IntraCellular enemies.

During Viral infections a messanger Lymphocyte will eventually come into contact with a Viral-infected cell. Such a cell is so sick that even its surface structure is changed; the configuration of proteins making up its outer membrane becomes slightly different.

The circulating Lymphocyte picks up this Antigen and returns to the T-Cell area of the nearest Lymph Node, touching a T-Cell causes it to transform itself into an incipent killer Lymphocyte.

This seeks out a Virally infected cell and couples with the Antigen on its surface, thereby triggering its internal protein-killing machinery. Coupling with the infected cell is the chemical switch that transmutes the T-Cell into a killer cell.

Chemical compounds form within the Lymphocyte, which pass from it into the infected cell, kill the Virus; stop the Viral spread and thus give our body the chance to regenerate itself.

Recently, subpopulations of T-Cells have been identified. Called Regulator Cells:
• They comprise the Effector or Killer Cells that directly attack foreign subvstances;
• Helper Cells that assist other kinds of Immune System cells;
• Suppressor Cells that "turn off" overreactions to specific Antigens;
• NonSpecific Suppressor Cells that turn off reactions to almost everthing.

These last react indiscriminately and so, theoretically, could put the body out of action altogether. We do not know how Suppressor Cells exert their inhibitory influence over the Immune System; it might be through direct contact or via a soluble substance they release.

It is suspected, however, that while most of the Lymphocyte population in humans decrease with age, Suppressor Cell activity does not; in fact, it seems to increase - rather a nasty thought.

By 1965, it was obvious that our Immune System is one reason for our survival as a species.

Who could doubt that our AntiBodies, our Granulocytes and Macrophages, our Complement and Properdin, were responsible for our bodily protection and continued existance?

But often the same mechanism for defense can be complicating and hazardous because the reaction which is set up starts off a chain called HyperSensitivity reactions.

A baby fed cow's milk that's full of foreign proteins may develop just such a reaction. The infant produces a reactive protein(s) which reacts back with the foreign substance specifically.

An infant may carry in his Serum a very high titer of AntiBodies against the proteins in cow's milk. If so, then the infant is allergic; he has an altered reactivity to milk which he did not have before getting these AntiBodies.

Another kind of complication is seen in the strange disease that often followed injections - prior to the discovery of antibiotics - of horse Serum containing AntiBodies against human disease causing Bacteria.

Some of those who received a second shot, even if they recovered from their infection, developed fever and joint pains within a fortnight; a few showed blood and protein in their urine; some even had skin rashes.

A third injection could kill the person, and a number did die from the disease that was named, appropriately, Serum Sickness.

Long after the Serum injections ceased, investigations on rabbits continued in an effort to find the cause of the puzzling disease associated with them. The disease only occurred after the second injection of protein.

The first provoked the production of AntiBodies by the rabbit's Immune System.

Their blood showed a marked increase in circulating AntiBodies specific for Serum. Within hours after the second injection, there was a gigantic increase in AntiBody levels and with it, the beginning of disease.

A terrifying bodily reaction followed a third injection; almost instantaneously the animals' lungs filled with fluid, their inflammed vessels burst open and bleed, their hearts dilated, their Kidneys turned white, and minutes later the animals were dead.

Not every rabbit injected was affected in this way. All received the same quantity, yet not all developed Serum sickness.

The mystery was compounded by the fact that the survivors were those whose Immune Systems, for some odd reason, did not produce vast amounts of AntiBodies against the injected matter.

The conclusion forced on the incredulous investigators was that the disease was caused by the rabbits' own AntiBodies produced against the proteins which were mistakenly read as foreign.

If the circulating Antigen-AntiBody complex got stuck in the Kidneys, the rabbit acquired Kidney Disease; if they were deposited in the joints, there was joint disease; in the skin, skin rashes. If they were deposited all over, death quickly ensued.

Serum Sickness is the first documented example of an AutoImmune Disease; that is, one in which the individual's Immune System makes AntiBodies against its own tissues.

But what caused the production of these AntiBodies? What were they made for? Against? Again, a kind of chain reaction occurred: AntiBodies were made by the recipient against the "foreign" cells of the injected substance.

However, their surfaces, although somewhat changed, were still so similar in structure to the surfaces of the recipient's own normal cells, that the AntiBodies produced to counter the invader cross-reacted with them as well.

In short, the AntiBodies attacked the foreign cells and the normal cellular constituents of the recipient's body, causing disease.

Clearly, we are capable of making AntiBodies or, more accurately, AutoAntiBodies against ourselves. Powerful as our Immune System is in protecting us, it can be just as relentless in pursuing our destruction.

Not only does our Immune System protect us from outside invaders; it also mounts guard against those inside as well. It is a system which performs the dual function of surveillance and destruction.

Our body, we know, is always replacing itself; for every cell that is lost or worn out, a new one exactly like it takes its place. Simple mechanical errors of replication, or mutations, are bound to occur, probably more than we realise.

But our Immune System recognizes and destroys them, before they can grow and divide. This internal control is as crucial to our survival, as our ability to fend off outside attackers.

Sometimes, though, the functions of the Immune System apparently can be hideously deranged and the two most dreaded modern diseases, Multiple Sclerosis and at least some of the Cancers, are regarded as exemplifing aberations of our life-preserving force.

On the other hand Multiple Sclerosis is commonly regarded as an AutoImmune Disease or, more properly, as one with an Immunologic basis in which Lynphocytes, for one reason or another, have become sensitised to Brain and mount an attack on that organ.

However, it is likely that something more than a defective Immune Response is involved in both MS and Cancer - the Genetic constitution of the individual.

p114

Strange AntiBodies have been found in the Serum of MSers', AutoAntiBodies that seem to be made against parts of the patients' own Brain. Why are these AntiBodies produced?

What, after approximately twenty years of life, causes the MSer's own Brain tissue suddenly to be read as foreign and attacked by his own Immune System?

Whatever the Etiology of MS proves to be, it is probable that Immunologic processes play some part in the evolution of the clinical picture.

Their possible involvement is usually discussed in terms of two major concepts: Immune deviation and AutoImmunity. The former characterizes a failure of the Immune System to react to certain Antigens, combined with a normal or often excessive production of AntiBodies.

This condition is common to another disease of the Central Nervous System SSP - (Subacute Sclerosing PanEncephalitis), where a chronic Measles Virus infection is combined with an inadequate Immune Response to Measles Antigens and high titres of AntiMeasles AntiBodies.

There is evidence that in MS, something similar occurs. Various Measles AntiBodies produced locally within the Brain, have been found in the CerebroSpinal Fluid, as well as specific AntiBodies against certain components of Measles Virus.

Since there are no reported cases of recurring Measles - one attack supposedly gives life-long immunity - the Virus must lie dormant in the Brain from the time of the original attack.

The initial Immune failure permitting the Virus to escape, could be due to altered PUFA membrane concentrations which affect the Lymphocyte response to the Measles Virus.

The enevelope of the Virus represents a modified segment of the cell surface membrane, and an infection fuses with it.

Changes in membrane composition might lead to alteration or masking of the antigenicity of the Virus or to modification of the cell-Virus interaction.

The body's Immune System obviously destroys most of the original invading Measles Virus, but some getting into a few of the blood cells, are able - for unknown reasons - to hide there and survive.

During this dormant period the body ignores them, or else after the initial childhood attack the hidden Viruses are so adequately shielded from the body's defenses that the Immune System is never able to reach them.

When they begin to grow in the cells where they have been harboured for so long, perhaps in the wake of stress, the immune system responds.

In an effort to destroy the growing Virus - or at least to isolate them and prevent them from infecting other cells - the infected Brain is subjected to a massive Immune Reaction.

Which is so powerful that both infected and normal cells in the area of battle are destroyed together. In most cases an Immune Response is life saving.

But unlike other cells, a Brain cell once destroyed is destroyed forever: Virus or Immune Reaction, when a Brain cell begins to degenerate it is gone and can never be replaced.

In the case of a Viral Brain disease, the body's own defenses once brought into play only add to the Neurological destruction being caused by the Virus.

Recognising this, efforts have been made to restore the appropriate immune response to the Measles Virus, using Transfer Factor, which is a form of ImmunoPotentiation Therapy.

On the other hand, primary DeMyelination may be the result of AutoImmune destruction of autologous Meylin.

There are, in the blood of some MSers', Lymphocytes that are sensitised to Myelin Basic Protein; in these cases, there is a possibility that an AutoImmune type of DeMyelination is taking place.

But it is also possible that the proportion of cells sensitised to Myelin Basic Protein is very low and their contribution to the DeMyelination occurs as a result of an AutoImmune process, even if the initiating Antigen is removed, the AutoImmune DeMyelination is likely to be Progressive.

Indeed this process may underlie the Progressive course of the disease from the very onset seen in a small minority - 10% - of cases.

An alternative possibility is that Myelin is damaged as a nonspecific consequence of a Specific Cell-Mediated Immune Reaction occurring to an Antigen in the vicinity of a nerve.

In this situation it would be possible for a wide variety of different agents to provoke primary DeMyelination simply as a consequence of Cell-Mediated Immune reactivity in their neighberhood.

In other words, Myelin is damaged as a nonspecific consequence of a specific delayed-type HyperSensitivity reaction directed at a nonnervous tissue Antigen.

The mechanism of "bystander" DeMyelination is not unlike that involved in hay fever.

In this bystander-type Immune Disease the tissue of the allergic person are injured because they are near the destructive chemical reaction of the Immune Response.

In hay fever the Antigen is not a foreign circulating protein as it is in Serum sickness, but pollen grain. Our Immune System goes after these as if they were alive. But since they are not they cannot be killed.

They just stay on the surfaces, where the body blindly throws more and more IgA AntiBodies, more and more Complement, more and more Lymphocytes at them.

The whole area surrounding the pollen grains - the Bronchus, the lining of the eyes, the mucous membranes of the nose - becomes the battlefield.

The chemical mediators (Histamine, Serotonin) released by the AntiBody reaction pulverise the normal cells - Innocent Bystanders - on which the pollen sit.

They stay where they are while the cells around them are damaged by the chemical mediators, becoming swollen and keeping us miserable, unable to breathe or to see normally.

AntiHistamines do not remove the pollen grains or prevent our AntiBodies coupling with them. All they do is interfere with the effect of the chemical mediators secondary to the Immune Reaction.

They stop the swelling of the normal tissues, the mucous production, the inflammation and the itching that is the result of the Immune Response. The pollen grains may still be there, the AntiBodies still produced, but injury to the surrounding tissues is reduced.

If hay fever is not as deadly an Immune Complex Disease as Serum Sickness, it's because the Immune Reactions that occur in the sufferer are restricted to the surface of the body, not to deeper organs.

But the skin and the Central Nervous System have the same origin - EctoDerm. Therefore, it is not unreasonable to assume, that both are subject to similar reactions to Antigens.

A study of Cell-Mediated DeMyelination showed that, irrespective of the Antigen used, DeMyelination took place. Whatever was injected into vitreous to bring in the sensitised cells, caused extensive DeMyelination.

Primary DeMyelination to sensitisation by Brain specific Antigen, as well as the indifferent type, suggests that the same kind of lesion can be induced by any Antigen eliciting a Cell-Mediated Immune Response.

These findings are important in interpreting the lesions of MS, because similar changes will be observed when cells are "called in" as a result of immunisation to Brain constituents, or to Virus, in fact to any other Antigen which finds its way to the Brain and induce a delayed type of hypersensitivity reaction.

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The mechanism of Cell-Mediated Myelin damage is unclear. The delayed-type HyperSensitivity reactions demonstrated lead to a MonoNuclear Cell invasion of adjacent Myelinated nerves with consequent primary DeMyelination.

This reaction is not necessarily directed against an endogenous Myelin Antigen - Myelin Basic Protein; instead its target may be an exogenous Antigen, one of enviromental origin, introduced into the vicinity of the Myelinated fibers.

This bystander effect suggests that soluble factors released by activated Lymphocytes either attack the Myelin directly or through recruitment of accessory cells such as Macrophages.

This seems to be the most plausible explanation since cells specifically sensitised to Myelin, or AntiMyelin AntiBodies, are absent during the course of this reaction.

The exposure of Lymphocytes to influenza and certain other common Viruses may greatly influence their response to Antigens not only do cells from those exposed to banal Viral Infections develop unusual reactivity, but they appear to be on edge in the sense that they undergo "spontaneous" transformation to a greater degree than normally.

Such irritability if the cells may persist for some weeks and may occur in the presence of an influenza epidemic even when the person concerned hasn't suffered obvious clinical infection.

It is clear, that any Antigen finding its way into the CNS and then attracting cells, could cause both primary and secondary DeMyelination.

Those Antigens that, without great difficulty, can find their way to the CNS are allergens and Viruses, and perhaps we need to distinguish between infective MS (which is probably preceeded by inflammatory changes) and allergic metabolic MS (which may or may not occur in the absence of inflammatory cells).

If the PathoGenesis of MS is indeed Immune-mediated, our problem is two-fold: the sensitised cell seeking an Antigen in the Myelin or in its Myelinating cell which somehow, nust be denied access to the Brain, or disarmed locally; and the specific Antigen these cells look for in the Brain.

Apart from the few instances where Lymphocytes are sensitised to Myelin Basic Protein, we have to assume that the cells are attracted into the Brain by an Antigen not yet identified.

If this Antigen is a Virus, it is highly unlikely that DeMyelination in MS is a direct result of its cytopathic affect on Myelinated cells, because there are no pathologic changes in the Oligodendroglia or Myelin before the arrival of a cellular infiltrate, ie. Macrophages.

(Myelination occurs in two phases: a phase of OligodendroGlial proliferation followed by the manufacture of lipid containing Myelin sheaths by the established Oligodendroglia or Glial Cells.)

ImmunoSuppresive therapy, also seems to indicate that Virus-induced OligoPathic DeMyelination is not operative in MS. Besides, the life-long nature of MS generally, its long periods of health interspersed with unpredictable exacerbations, is not what would be expected from an acute infectious illness, Viral, Bacterial or fungal.

Also autopsy examinations of MSers' Brains usually show a kind of tissue destruction different from that caused by any known Viral diaease.

Thus, if a Virus is the source of attraction of the cells it is unlikely to be harmful as long as the host's Immune System does not launch an attack on it. What does the harm is not the Virus but the adverse effect of a hyperacute reaction between Virus and Immune System.

What causes DeMyelination, then is not the invader Virus or Allergen, but the interaction between sensitised cells and Antigens. Put another way, DeMyelination is the result of an Allergic Reaction that depends on an Antigen coupling with the susceptible cell.

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Continued_In_(#08-4)