Tolerance And Autoimmunity Flashcards
3 key properties of human immune system
Highly diverse antigen receptor that enables recognition of infinite number of pathogens
Immune memory
Immunologic tolerance( avoid attack to normal cells)
Define Tolerance
Tolerance refers to specific immunologic non reactivity to an antigen resulting from a previous exposure to the same antigen
Most important form is to self antigens but its possible to induce tolerance to non self antigens
An antigen that induces tolerance( Tolerogen )
Theories on induction of tolerance
R.D Owen observation
This observation demonstrated that tolerance could be induced by exposure to antigens in utero irrespective of whether they’re self or foreign.
F.M Burnet theory(Clonal Selection Theory)
Each lymphocyte is specific for only one antigen and if a lymphocyte met this antigen during early development , it will be deleted from the repertoire
Modified by J.Lederberg
Suggested correctly that it was the stage in the development of the lymphocyte that was critical rather than the animal
Medewar (transfer of hemopoietic cells from histoincompatible mice at different times after birth)
Found that if cells were transferred in the first few days of life and not later, the mice developed life long tolerance to the antigen of the donor.
Factors determining induction of tolerance or immune response after antigen challenge
Physical form of antigen Route of administration Dose of antigen Age of responding animal Differentiation state of cells
Division of tolerance
Central & Peripheral Central: Site for t cells is the thymus Site for b cells is the bone marrow The mechanism is clonal deletion
Peripheral:
Site- everywhere in the body
Cells- both t and b
Mechanism- anergy, cell death, immune deviation
Mechanism of Central tolerance
CD4+ T cell self tolerance is the most important and occur at a lower antigen threshold than that for B and CD8+ cells
Mechanism of central tolerance include thymus and bone marrow and mostly due to elimination or inactivation of those t and b cells that recognize self antigens (clonal deletion or abortion)
T cells with low affinity for Mhc complex die in thymus( do no receive signals that’ll prevent spontaneous apoptosis)
T cells with high affinity for Mhc complexes undergo apoptosis and die( Negative selection)
T cells with intermediate affinity for this complex mature in thymus and migrate to periphery (Positive selection)
Mechanism of peripheral tolerance
Mechanisms acting on B and T lymphocytes after they’ve left the primary lymphoid organs
1Clonal Deletion 2Clonal Anergy 3Regulatory T cells 4Clonal Ignorance 5Anti idiotype antibodies 6Termination of tolerance
