(11,12) This result suggested that immune responses to RNA but not DNA are crucial in the development of lupus though it is not yet clear why RNA-related self-antigens
but not DNA ones are pathogenic.
targeted in linear IgA disease are proteins in the lamina lucida and lamina densa of the basement membrane zone, and the tissue damage is caused by T lymphocytes and neutrophils and by cytokines and inflammatory mediators released into the microenvironment.
Immune response to microbial antigens could result in activation of T cells that are cross-reactive with self-antigens
. This is due to the fact that a single T cell can respond to various peptides with similar charge distribution and overall shape [20, 69].
During mechanical injury, self-antigens
and cytokines are released without consistently stimulating pathogen-specific responses.
Tomofuji et al., "Fezf2 orchestrates a thymic program of self-antigen
expression for immune tolerance," Cell, vol.
Glossary Abs: Antibodies AMR: Antibody-mediated rejection AT1: Angiotensin II type 1 CAV: Chronic allograft vasculopathy Col V: Collagen type V HLA: Human leukocyte antigens K[alpha]1T: k-alpha 1 tubulin LRA: Lung-restricted autoimmunity LTx: Lung transplantation MHC: Major histocompatibility complex MICA: MHC class I-related chain A NOD: Nucleotide-binding oligomerization domain OLT: Orthotopic liver transplantation PGD: Primary graft dysfunction PRR: Pathogen-recognition receptors RIG: Retinoic acid-inducible gene SAgs: Self-antigens
TG: Transplant glomerulopathy Tregs: CD[4.sup.+]CD[25.sup.+]Foxp[3.sup.+] regulatory T-cells.
In the nondiseased state, DCs are responsible for the induction and maintenance of tolerance towards self-antigens
. The induction of T cell tolerance is dependent on whether a DC is tolerogenic or immunogenic during autoantigen presentation, and also on the contribution of autoreactive T cells that may escape from the thymus.
The state of unresponsiveness of the immune system to antigens is known as immune tolerance, and this involves tolerance to self-antigens
, which is established and maintained to avoid host damage.
Mariuzza, "Structure of a TCR with high affinity for self-antigen
reveals basis for escape from negative selection," EMBO Journal, vol.
While the innate immune system relies on the recognition of particular types of molecules that are common to many pathogens but absent in the host, other safety mechanisms exist in the adaptive immune system to provide 'tolerance, 'enabling the body to control the extent and duration of an immune response, as well as preventing unwanted responses mediated against self-antigens
Immunological tolerance is defined by the unresponsiveness of the host immune system to self-antigens
and environmental innocuous antigens, while retaining the capacity to react specifically to countless foreign antigens.
But if they spot foreign antigens, like those from bacteria or viruses, or mutated self-antigens
, they kill the cell before the damage spreads.