First Concepts.
WOB is Optimal
Two key medical concepts,
autoimmunity and the self, cloud
reasoning and spread confusion.
Autoimmune disease
An autoimmune disease, e.
g., Grave's disease, Myasthenia gravis, or aplastic anemia, arises when the immune response of the body is directed against its own tissues. Here
this view is unacceptable since WOB is optimal
and does not commit suicide. If a phenomenon appears to be self destructive,
we simply do not understand its real
meaning. Indeed, autoimmune
diseases are the most obscure in medicine.
Self and non-self
In order to become autoimmune
and turn immunity against itself the immune system has to distinguish
between its self (auto) and non-self (hetero). These fundamental concepts of immunology are as obscure as the philosopher's
stone of the alchemists. The knowledge of the self is innate, yet
the organism grows and produces new substances (antigens), like milk
casein during lactation, which is regarded as self, otherwise it would
be destroyed.
Gut flora
What about our gut flora, which deserves to be recognized as a non-self?
Gut bacteria continually cross the mucous membrane into our body by
a process called translocation. By this means the immune system samples
gut flora antigens, and creates
against them antibodies. However, it does not attack them, otherwise we would be sick like when typhoid crosses the mucosa.
Think of the herpes virus which slumbers peacefully in the nervous system
like other self-cells. Once in a while it is awakened by a slight fever,
turns into a non-self and creates blisters. Or, the myriad of provirus
sequences in the genome. Are they self or non-self?
Dendritic cell
These and other examples indicate that the self concept is useless.
The immune system may apply other criteria to decide when to attack.
Like danger, favored by Polly Matzinger and Ephraim
Fuchs (1): "If we forget about self for the moment and
step sideways to look at the other side of the equations above, we find
it possible to ask a different question,
namely "how does the immune system decide whether to
respond or not?" I have conjectured
that it might respond to danger,
not to non-self."
Whenever a cell dies, a dendritic cell becomes activated,
captures normal and viral
antigens from its neighborhood up-regulates MHC molecules, loses Fc
receptors, and travels to the local lymph node, where it presents the
captured antigens to passing T cells.
A T-cell needs two signals to be activated: a normal cell antigen and the antigen
of the invader. If it faces only the first, it dies. In other words,
T-cells recognize antigens
of all cells in the body, and attack only dying cells. This attractive theory is generally ignored, and immunologists
continue preoccupying themselves with the self.
Necrosis
WOB is unaware of danger and cannot sense an incoming death.
The sense of danger is an attribute of the mind,
which it transmits to
WOB. Matzinger's hypothesis ought to be
modified slightly. WOB senses only necrosis. The immune system is activated only when a dendritic
cell samples two antigens, that of a necrotic cell and of an invade
, whereupon WOB activates the process
of inflammation.
We ought to distinguish
between immune activation and inflammation. The
immune system continually surveys antigens in the body. When
detecting cell death (necrosis) it removes the debris by local means
(apoptosis). In an extensive necrosis it initiates
inflammation whose task is to clean up dead cells and repair the
damage. Since no foreign antigens are involved,
it will be called sterile
necrosis. Like following a myocardial
infarction, when inflammation removes dead muscle and replaces it with
a scar. Or following ovulation when the empty follicle gradually dies
(atresia).
In a non sterile necrosis, activated T-cells kill the cell and its invader, whereupon inflammation
is initiated. By themselves T-cells or the immune system, do not initiate
inflammation. Necrosis initiates it. Translocated
bacteria activate T-cells only when causing necrosis, like in typhoid.
By themselves T-cells or the immune system do not initiate destructive
autoimmunity.
Tumor
According to medicine, a tumor arises during a random error
(mutation) of the genome.
From its very beginning the tumor belongs to the realm of the
non-self, and yet the immune system does not attack it. According
to the theory of Immunological Surveillance
by F.M.Burnet, immune system
continually eliminates mutated cells, yet some succeed to sneak through
its surveillance and cause
cancer. Two errors cause cancer, an error in the genome and one
in immunological surveillance, which we cannot accept. WOB does not
err only theories do.
Matzinger has yet a different view: "A newly arising tumor cell may express antigens not expressed
by its normal tissue mates, but this is not enough to alert the immune
system. There is no intrinsic difference between a rapidly dividing
tumor cell and a rapidly dividing hematopoietic cell". . . "Consequently, as it grows, any tumor unable to deliver
signal-Two should induce deletion of tumor specific T cells". (1)
Instead of concluding that immune system does not regard tumor as a
threat, Matzinger proposes means to convince dendritic cells to deliver
signal -Two and "convince" T-cells that the tumor is dangerous.
Patient suffering
Hitherto all attempts to immunize the host against his tumor have
failed. Nevertheless, immunologists conduct clinical trials in which
this flawed reasoning is applied to patients which endure painful treatments. Tumor
immunization fails even in laboratory animals with genuine tumors.
Nevertheless scientists rush to immunize patients. Since host cannot
be immunized against his tumor they conjured up the tumor associated
antigen, against which patients are immunized. Since this antigen
is tissue specific and not tumor specific antibodies actually harm the
tissue itself.
Medicine ought to realize that the tumor is part of the self.
It proceeds through two phases: Compensation
and decompensation.. During the first it causes no harm. During decompensation it impinges upon
other processes. The expanding tumor compresses capillaries and deprives
the tissue from its blood supply. This is when cancer requires treatment.
References
Polly Matzinger THE REAL FUNCTION OF THE IMMUNE SYSTEM or TOLERANCE AND THE FOUR D's (danger, death, destruction and distress) http://cmmg.biosci.wayne.edu/asg/polly.html