Download Causes of Autoimmune Diseases

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2015/10/21 ‫هديل‬.‫د‬
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Autoimmune Diseases
Immune Tolerance
T lymphocytes are capable of recognizing an unlimited number of
antigens.
● All immune and blood cells develop from multipotent hematopoietic
stem cells that originate in the bone marrow.
● Exit from BM, immature T cells undergo final maturation process in
the Thymus that "educates" them to distinguish between self and nonself antigens.
● In normal persons, the autoreactive T- cells are deleted or
inactivated.
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The process of education of T-lymphocytes to not attack the
"autoantigens" in addition to deletion or inactivation of
autoreactive cells is called “Tolerance”
Autoimmune Diseases
Autoimmune diseases arise when the induction and maintenance of
immune tolerance fails. So here our immune system will attack self
antigens.
● These diseases result in cell and tissue destruction by:
1- antigen-specific CD8 cytotoxic T cells
2- or autoantibodies (antibodies to self-proteins) and the
accompanying inflammatory process.
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Causes of Autoimmune Diseases
Exact reasons are unclear.
However ; Genetics along with environmental
factors (like hormonal influences, chemical,
physical, and certain infections) may contribute
to the tolerance failure & development of
autoimmune diseases
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SLE
Any organ in the body can be
affected
& the result is inflammation of the
skin, joints, kidneys, lung, heart,
serosal surfaces….
Like other autoimmune diseases, SLE
has a familial tendency and affects
women more than men, especially
those in the 2nd or 3rd decades of life.
Tissue Transplantation
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Grafts are divided into 4 types
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1- Auto graft: from one part of the body into another, and this graft
usually survives without the need for immunosuppression
providing that the tissue is healthy, well vascularized and there is
no infection (e.g. transplantation of the skin from one part of the body
into another).
2- Isograft: From one individual to another who is genetically
identical like the identical twin and here survival of the graft is the
role.
3- Allograft: Between two genetically non identical individuals from
the same species and here rejection of the graft is the role if
immunosuppression is not done.
4- Xenograft: transplantation from another species and here rejection
is very severe and it is unlikely for the graft to survive.
HLA system & major histocompatibility complex (MHC)
● Human leukocyte antigen (HLA) or MHC molecules, present on the
surface of cells.
● HLA system is genetically determined and this is the reason why
donor organs from relatives of the recipient are preferred over
unrelated donors.
● MHC molecules are divided into three groups:
■ MHC I and II – surface glycoproteins involved in
transplantation reaction.
■ MHC III – encode complement components system.
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Problems of Transplantation
1- Graft rejection (Host versus graft)
2- Graft versus host reaction (GVH)
Graft Rejection
● It is a complex immunologic phenomenon as responses of the host
directed against MHC on the donor graft.
● The rejection happens because the MHC (HLA) system of the donor
is different from that of the recipient so that both cell mediated
immunity and antibody response will be mounted against the
transplanted tissue.
● The major types of hypersensitivity reactions involved are types
II, III and IV.
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In renal transplantation there are (3) patterns of graft rejection:
1-Hyperacute rejection:
The recipient have antibodies to the donors HLA Ag before
transplantation.
This occurs due to previous sensitization by previous
transplantation, blood transfusion, multiple pregnancies and
infections.
In the transplanted kidney the surgeon will notice, just after vascular
anastomosis, that the kidney will become cyanosed and secretes only
few drops of bloody urine.
2-Acute rejection:
● This occurs few days after transplantation or after stoppage of the
immunosuppressive therapy.
● The rejection will lead to endothelial injury, inflammation,
thrombosis and necrosis of the transplanted tissue or organ.
3-Chronic rejection: Occurs after months-years
The main lesion here is blood vessel intimal fibrosis that leads to
ischemic glomerular injury, tubular atrophy, and shrinkage of the renal
parenchyma together with mononuclear cellular infiltration.
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Methods of increasing graft survival
1- The best results will be obtained from finding of HLA compatible
donor but unfortunately this is not available except from an identical
twin and 1:4 of brothers or sisters.
2- When the donor is not compatible we should use
immunosuppression like high doses of prednisolone or cytotoxic
therapy. Both cause non-specific immunosuppression and the patient may
suffer from opportunistic infections.
3- Now a days, antithymocytes antibodies are used.
4- Repeated blood transfusion in small doses from the same donor
before transplantation increases the success of kidney transplantation.
Graft Versus Host Disease (GVHD)
Mainly occurs in bone marrow transplantation
Before transplantation, we should destroy all the
recipient marrow by total body irradiation and
cytotoxic drugs, and this will make the patient
(recipient) immunodeficient.
After that the new bone marrow is transplanted,
its cytotoxic T- lymphocytes will attack the
recipient tissues.
The main cells involved in GVHD are CD8+ T-lymphocytes
The donor cells will attack the actively proliferating cells of the recipient
resulting in gastroenteritis (nausea & vomiting), skin rash, jaundice, etc…
End
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