As per danger hypo, ischaemic damage[during organ transplantation ] is making immune cel aware of danger and prompting them to produce antibody [against graft ]
Questn :- Wat happens in Ischaemic heartDisease [myocardial infarction ]? there is ischaemic damage but no antibody [macrophage neutrophophil come but no antibody ]is produced against the heart of dat IHD patient
Why immune cel not attack the new latctating breast acc to danger hypo and query on this
To xplain why new lactating breast is not rejected matzinger's hypo assert the following:-
“ Why do mammalian mothers not reject their fetuses or attack their
newly lactating breasts, which produce milk proteins that were not part of earlier “self”? To answer some of these questions, I proposed
the Danger model, which suggests that the immune system is more concerned with damage than with foreignness, and is called
into action by alarm signals from injured tissues, rather than by the recognition of nonself”
Now at dis d query arise
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Why do mammal attack their newly growing sperm if their blood testis barrier break [mumps inducedOrchitis] ?
another query
Experiment-1 :- If breast milk from a lady is subcutaneous injected into a second lady , then there is immune reaction in second lady.
Experiment-2 :-- But upon sc injection of her own milk in 1st lady , there is no immune reaction.
But if SNS model is wrong , and as milk [of 1st lady ] is causing no danger in 2nd lady…… so immune reaction in 2nd lady against milk of 1st lady should have never occurred.
[ Fact that milk protein is actually not a danger molecule in human body is proved from experiment-2 above]
Acordng to matzinger's danger pathway [model ] the cause of transplant rejection has been xplained as this
"Foreign entities that are not associated with
microbes include transplants and fetuses. Why
should the former be rejected and the latter not?
Although the INS model would suggest that
neither should be rejected because they are not
associated with microbial stimulators, and the
old SNS models would suggest that both should
be rejected because they are nonself, the Danger
model suggests that healthy fetuses should
not be rejected because they do not send alarm
signals. Transplants, however, cannot be performed
without surgical and/or ischemic damage.
Thus, to induce the acceptance of transplants
without lifelong immunosuppression, we
should mimic the body’s own way of inducing
tolerance, i.e., by blocking the endogenous
alarm and/or costimulatory signals"
My query
In a breast reconstructn surgey in a lady using muscle flap from her own latissimus dorsi muscle
Or
inCABG , VEIN graft in a patient from his own long sapphenous vein
Surgical damage occurs but no immune rejection does occur. Why so ?
PATHOGENESIS OF AUTOIMMUNE DISORDER
MYSTERY IN PATHOGENESIS OF AUTOIMMUNE DISORDER
why does rheumatic carditis[RHD ] occur?
According to SelfNon Self model - Reason is Cross reaction with streptococcal M protein to which fetus is not exposed
Question - The entire antigenic epitope is always there in[heart ] valve .... so why suddenly antibody is created only when this antigen is presented by streptcocci? In other words since the antigenic epitopes of Strepto M and cardiac myosin are same [almost ] , so the antigenic epitope of strepto M-protein had been exposed to the humanFetus in his foetal life in form of cardiac myosin. I refer this argument henceforth as argument 1 .
Why is it occurring only in 3-16 yr age? Why only 3% patients of Strepto infection have RHD ..? This shows that there is not only a mechanical stereotype antigen antibody reaction in this but something apart
Danger pathway of matzinger xplain : “For autoimmunity, the Danger model offers
a unique suggestion that would not arise
from the SNS or the INS models. Starting
with the view that “bad” death or cell stress
can elicit an immune response, the model
suggests that some autoimmune diseases may
be caused by mutations in genes governing
the normal physiological death and clearance
processes, or by environmental pathogens or
toxins that cause cellular stress or death. In
these cases, the immune system is not at fault;
it is doing its job of responding to alarm
signals (but, in these cases, to the detriment
of the host).’’
Danger Model [of matzinger ] explains Streptococci is danger to body. So in Strepto infection , if body thinks that there is enough danger , then anti Strepto M-protein [and anti cardiac ] Ab is created. Now it follows that in people of 3-16 yr age and only 3 % of such people .. the body thinks that Strepto infection is a sufficient danger
Why so? What is the danger pathway that is fulfilled only in these handful people ?
Now if anyway i accept that danger impulse is coming because Strepto is causing cell lysis .. then question appears : When recombinant or extracted M protein of streptococcus is injected into lewis rat, then too there is RHD. Why so ? there is no cell destructn here because no live Streptococci hav been introduced into the rat
If i accept that danger impulse is coming just because the epitope is of an external organism [keeping in mind argument 1 ] then following query come
[I] When O positive [Rh positive ] blood from a donour is injected into an O positive recipient ..then there is no anti Rh antibody in the recipient. Why so ? Here also the Rh antigen is from an external organism viz donour
[II] we accept that antibody of blood group [like anti B and anti A ] do appear in blood of an infant for first time due to reaction with some alimentary tract bacterial antigens. It follows that our alimentary canal has bacteria that express both A and B antigens. Now let us take a A blood group subject. In his alimentary tract there is bacteria that express A antigens that are "cross reacting " with hiss group A RBCs. The situation is equal to Streptococci expressing protein "cross reacting " with cardiac valve. But we dont hear autoimmune disease of this type . Why so ?
Why semen doesnt act like foreign body to women?
some1 asked this to me overOrkutComm
Fetus [the product of semen ]that iz xpressing the antigen of father ..is in the placenta. Placenta is a immunopreviledged site which is coated wid sialic acid or like [can"t recapitulate sorry ] which is not foreign to mother. Inside this coat is the fetus ..wid its paternal / own antigen hidden. Now blood from mom does not direct come to fetus. Only plasma come ..not any blood cell. So the fetal body do not evoke immunity inside placenta
But acc to matzinger hypoth , as fetus or sperm is not doing any harm to mom , so no antibody elicits. But i dont agree to disHypothesis. My frnd also asks not to write it.So plz overlook dis atpresent
Now why sperm is not directly killed inside uterus? everyday men eat millions of foreign proteins,every day hundreds of foreign antigens are entering respiratory pathAndNoseBut there is no immune reactivity. If hen\duck egg protein is injected intra muscular or iv ...there ud b immunity. But upon eating , when the protein encounter oral and esophagus mucosa [ before digestion in stomach, though stomach digestion does not reduce or stop antigenicity of that egg protein ] .... then there shud b strong antibody productn. ButIt DoesNot Occur. Becos mucosal imunity is different. Here sumtime a Th2 response [not Th 1 ] result in suppressor B .... which causes suppression of imunity. Same is there in uterine endometrium. Besides spermatozoa hav sialic acid coat probably which hides the antigen
Then life of sperm is 2days. it mayNotAFFORD enough time for the increase of antibody level to a titre .... that too with factorsListed above .. to kill all million of sperms
Yes if u test blood of a lady [having sexual intercourse ] .. ab for sperm UD SURE be FOUND
And other point is continued low dose exposure 2 a foreign protein ie semen[without adjuvant ] causes peripheral imune tolerance in the corresponding lady partner .
And still sumtime imune activity occur against sperm. SeminalAntign acts as immunogen and that is the cause of many eclampsia.Several studies have investigated the strongly decreased incidence of pre-eclampsia in women who had received blood transfusions from their partner, those with long, preceding histories of sex without barrier contraceptives, and in women who had been regularly performing oral sex, with one study concluding that "induction of allogeneic tolerance to the paternal HLA molecules of the fetus may be crucial. Data collected strongly suggests that exposure, and especially oral exposure to soluble HLA from semen can lead to transplantation tolerance."
# Bonney EA (December 2007). "Preeclampsia: a view through the danger model". Journal of Reproductive Immunology 76 (1-2): 68–74. doi:10.1016/j.jri.2007.03.006. PMID 17482268.
# Koelman CA, Coumans AB, Nijman HW, Doxiadis II, Dekker GA, Claas FH (March 2000). "Correlation between oral sex and a low incidence of preeclampsia: a role for soluble HLA in seminal fluid?". Journal of Reproductive Immunology 46 (2): 155–66. doi:10.1016/S0165-0378(99)00062-5. PMID 10706945
# Johansson M, Bromfield JJ, Jasper MJ, Robertson SA (June 2004). "Semen activates the female immune response during early pregnancy in mice". Immunology 112 (2): 290–300. doi:10.1111/j.1365-2567.2004.01876.x. PMID 15147572
