Tolerance, autoimmunity, transplantation Flashcards
What is immunological tolerance?
Immunological tolerance is a complex series of mechanisms that impair the immune system to mount responses against self antigens. Central tolerance occurs when immature lymphocytes encounter self antigens in the primary lymphoid organs, and consequently they die or become unreactive.
How can immunological tolerance be breached?
Tolerance can be broken naturally (as in autoimmune diseases) or artificially (as shown in experimental animals, by x-irradiation, certain drug treatments and by exposure to cross reactive antigens).
What immunological responses and which components of the immune system are
involved in autoimmunity?
Major risk factors for autoimmunity
How are alloantigens from transplanted organs presented to the hosts T-cells?
Why do we say that allograft rejection follows the rules of immune specificity and
memory?
What are the causes/mechanisms of transplant rejection in MHC identical
transplantations?
What is graft versus host disease?
Tolerance
prevention of an immune response against self structures
Central Tolerance
deletion or inactivation of self-reactive lymphocytes before they mature
PLO
Primary lymphoid organs
Peripheral Tolerance
It takes place in the immune periphery (after T and B cells egress from primary lymphoid organs). Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease. Peripheral tolerance prevents immune response to harmless food antigens and allergens, too.
Promotes peripheral tolerance:
Route or timing of exposure (Oral exposure/ Early in life)
* High dose antigen/ long term antigen exposure
* Low levels of costimulation
* Immature antigen presenting cells (APC)
Regulatory T cells (Treg )
are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. It has been shown that Tregs are able to inhibit T cell proliferation and cytokine production and play a critical role in preventing autoimmunity.
Natural Treg, (tTreg )
– Peripheral (Induced) Treg
Immunophenotype:
– CD4+, CD25++, FoxP3+,CTLA-4
Autoimmunity
an aberration in the body’s normal development such that the immune system mounts an attack against its own cells. The etiology behind autoimmune diseases is multifactorial, with genetic, hormonal, and environmental factors all playing a role.
Autoantibodies
Againstreceptors:Inhibitoryorstimulating
– Otherantigens:inflammation
– Fcmediatedphagocytosis
– Fc activation of neutrophils ,eosinophils,basophils,mastcells
– Immuncomplex
- circulation og deposition
– Complement
Membran Attac complex