Notes

HOMEOSTASIS IN THE IMMUNE SYSTEM

Discrimination between self and nonself is an important characteristic of the
immune system, and alterations in the mechanisms that normally maintain
self-tolerance can lead to a disease state called autoimmunity. Kendiliginden veya kendiliginden olmama durumu immune sistemin onemli karakteristik ozelliklerinden biridir ve isleyiste kendiliginden toleransi saglayan degisimler bizi otoimmunite adi verilen hastalikli bir duruma goturur.



Even when there is a failure in the selection processes that delete immature self-reactive
lymphocytes, the peripheral mechanisms should be able to maintain unresponsiveness to many self antigens. Seleksiyon surecinde Olgunlasmamis ve kendiliginden harekete gecen lenfositleri silen bir hata (sapma) olsa bile, peripheral mekanizma (isleyis) kendiliginden olusan antijen (antikor olusturan madde) ye karsi cevapsizliligi saglamalidir.


Autoimmunity may therefore be the result of a failure in peripheral tolerance, in which the anergy or deletion of autoreactive lymphocytes is altered. Otoimmunite, periferyal toleransta kendiliginden harekete gecen degismis (bozulmus) lenfositlerin anerji veya silinmesi durumunda ortaya cikan bir hatanin sonucu olabilir.


Encephalomyelitis and insulindependent diabetes mellitus (IDDM) are examples of autoimmune diseases due to T cell anergy breakdown. Ensefalomiyelit ve insuline bagimli seker hastaligi T hucrelerindeki anerjik kirilim, (yanlis dizilme) nin otoimmune bir rahatsizlik olusturmasina ornektir.

T cell anergy failure may occur because of abnormalities in the T cells themselves or to defects induced by inflammation, which may occur after certain infections, due to induction of tissue necrosis. T hucrelerindeki anerjik hata, t hucrelerinin kendisinde bir anormallik olmasindan ya da nekrozlu dokularin neden oldugu belli bazi enfeksiyonlarin teteiklemesiyle olusan enflamasyona bagli hatalardir.

Autoimmune diseases may also result from inappropriate cell death, for
instance, failure of activation-induced cell death. Otoimmun hastaliklar, activasyonla tetiklenmis hucre olumlerindeki hata gibi, uygunsuz hucre olumleri nedeniyle olusan hastaliklardir.

A defect in the Fas system is intimately linked to autoimmune diseases caused by the impaired removal of autoreactive lymphocytes. Fas sistemdeki herhangibir bozulma, otoreaktif lenfositlerin hatali tasinmasi sonucu olusan otoimmun hastaliklarla yakindan iliskilidir.

As already mentioned, the human autoimmune disease systemic lupus erythematosus resembles that found in lpr and gld mice, with a dysfunction of Fas or FasL, respectively (53, 54). Daha once de deginildigi gibi, insanda gozlenen systemic lupus erythematosus gibi otoimmun hastaliklar, fas ya da fasl nin fonksiyonel bozuklugu ile birlikte lpr ve gld farelerinde gozlemlenen ile benzerlikler gosterir.

Children with autoimmune lymphoproliferative syndrome (ALPS), also called Canale– Smith syndrome, have massive nonmalignant lymphadenopathy, hepatosplenomegaly, altered T cell populations, and other manifestations of systemic autoimmunity (81). Cocuklarda gozlenen ALPS ya da diger adiyla canale smith sendromu, hem karacigerin hem de dalagin buyumesi, degismis t hucresi populasyonu sistemik otoimmunitenin diger hastalik olustugunu belli eden durumlari gibi yogun miktarda malign olmayan lenfodonapati gosterirler.

The loss-of-function phenotype therefore indicates that Fas plays an important role in the regulation of the immune response and maintenance of self-tolerance. kalitimla olusan dis gorunusun fonksiyonelligini yitirmesi immune cevabin duzenlenmesi ve kendi kendine tolere edilebilirligin devamliliginda fas in onemli bir rol oynadigina isaret eder.

Conversely, inappropriate induction of apoptosis may also lead to
pathological conditions. Diger taraftan, apoptosisin uygunsuz bir sekilde baslatilmasi patolojik durumlarla karsilasilmasina neden olabilir.

Fas is critically involved in the progression of viral diseases such as HIV-1 or hepatitis B virus infection, in which massive apoptosis occurs. Hiv-1 veya hepatit gibi viruse bagli ve yogun miktarda apoptoz olusmasina enden olan durumlarda fas ciddi bir sekilde progrese dahildir.

It was shown that indirect mechanisms lead to sensitization of
noninfected T cells toward AICD after HIV-1 infection (82, 83). Indirekt mekanizmalar, hiv-1 enfeksiyonundan sonra AICD yonunde enfekte olmamis t hucrelerinin hassaslamalarina neden oldugu sonucuna neden oldugu belirtilmistir.

The two HIV- 1-derived proteins gp120 and Tat activate FasL expression in T cells, causing the death of uninfected T lymphocytes. This results in the continuous depletion of CD4+ T cells during AIDS disease. gp si 120 olan proteinlerden elde edilmis 2 hiv-1 ve t hucrelerinde tat aktif belirtili fasl, enfekte olmamis t lenfositlerinin olumune neden olurlar. Bu sonuc, aids sirasinda cd4 + t hucrelerinin devamli surette azalamlarina neden olur.

FasL is also responsible for the maintenance of immune privilege, which
characterizes the ability of certain organs to suppress graft rejection, even
when transplanted in nonmatched individuals (84). Fasl ayni zamanda, birbirleri ile uyum saglamayan bireylere nakil yapilmasi durumu da dahil olmak uzere, belli bazi organlarin nakli reddetmesi durumunu baskilama (engelleyen) yetenegi gibi karakterize edilmis bir immune system ayricaliginin devamliligindan sorumludur.

In this case, FasL acts by killing infiltrating lymphocytes of the host, preventing the resulting inflammation from destroying the tissue (85–87). Bu durumda fasl konaktaki suzucu lenfositlerin oldurecek sekilde davranarak, dokunun yok olmasi nedeniyle olusacak enflamasyonun engellenmesine neden olur.

FasL-mediated depletion of cytotoxic T lymphocytes may not only be beneficial, however, but may also have a role in aiding tumor cells to escape host immune surveillance. Fasl yonelimli sitotoksik t lenfositlerinin yok olmasi sadece yararli degildir, bu durum ayni zamanda tumor hucrelerinin konak immune gozetimine kacmalarina yardimci olur.

High constitutive FasL expression has been found in distinct tumor lineages, such as
colon, lung, renal carcinoma, melanoma, hepatocellular carcinoma, astrocytoma, and T cell- and B cell-derived neoplasms (88–94). Yuksek konsantrasyondaki fasl yapici belirtiler, belirgin tumor turleri, ornegin; kolon, akciger, bobrek urlari, melanom, karacigeri ilgilendiren karsinomlar, astrositom (beyinle ilgili bir tumor), t hucreleri ve b hucrelerinden kaynaklanan tumorlerde gozlenmistir.


This suggests that the same mechanisms responsible for protecting tissues from autoimmune destruction may be used by tumors to eliminate activated lymphocytes
which attempt to attack tumor cells. Benzer mekanizmanin otoimmun yikimdan dokulari korumakla gorevli oldugu anlamina gelmesi, bunun Tumorlu hucrelere saldiri girisiminde bulunan aktive edilmis lenfositlerin elimine edilmesinde kullanilabilecgi anlamina da gelir.


Maintenance of immune system homeostasis thus depends on the strict
control of cell proliferation and cell death through apoptosis, and many
disease states result from errors in the regulation of apoptosis. Immune sistem homeostasisinin devamliligi apoptosis yoluyla gerceklesen hucre olumlerindeki hucre cogalmasi durumunun siki bir sekilde kontrolune baglidir ve bircok hastalik apoptosisn duzenlenmesindeki hatalardan kaynaklanmaktadir.