MIIM - Immunopathology II - Week 5 Flashcards
What three types of hypersensitivity mediate autoimmunity?
Type II, III, and IV
What is autoimmunity due to the activation of?
The activation of self-reactive B and T cells.
Name three factors that affect the development and severity of autoimmune diseases.
Genetic background
Age
Presence of a trigger
Distinguish between organ-specific and non-organ specific autoimmunity.
Organ specific - antibody directed against a tissue specific antigen
Non-organ specific - systemic deposition of antibody-antigen complexes
What is the main tolerance mechanism for T cells? How may it fail?
Deletion of T cells which recognise self-peptide-MHC complexes
It may fail if antigens are not expressed in the thymus.
Name four retinal antigens against which circulating T and B cells have been detected.
Arrestin
IRBP
Rhodopsin
Recoverin
Name an iris/choroid antigen against which circulating T and B cells have been detected.
Melanin associated protein
Describe ignorance in terms of peripheral tolerance mechanisms.
Mature T cells do not enter healthy tissues, so do not meet their antigen.
Activated, but not naïve T cells leave circulation and enter peripheral tissue. So naïve self reactive T cells may never encounter their antigen.
Describe how deletion occurs in terms of peripheral tolerance mechanisms (corneal epithelium).
Corneal endothelium and pigmented epithelial cells express Fas-L which binds Fas-expressing-activated lymphocytes, resulting in apoptosis.
Describe how anergy occurs in terms of peripheral tolerance mechanisms.
T cell recognition of peptides in the absence of co-stimulation results in anergy of the T cell.
Describe how suppression occurs in terms of peripheral tolerance mechanisms.
Suppression due to the expansion of specific regulatory T cells.
Describe briefly the anergy of a self-reactive T cell that has gained access to its antigen in tissues.
Without co-stimulation, a self-reactive T cell cannot respond to its antigen.
What must antigen presenting cells do in order to activate CD4 T cells effectively?
Differentiate and express co-stimulatory molecules and peptides with MHC
What kind of T cells have a higher affinity for self-peptides?
T regulatory cells
What kind of T cell can secrete TGFβ, and what does it do?
Regulatory T cells. Its a cytokine that suppresses many responses.
Describe molecular mimicry breaking tolerance.
Some retinal antigens having aa sequences similar to bacterial and viral antigens.
Describe bystander activation due to infection breaking tolerance.
Upregulation of co-stimulatory molecules during infection allows activation of self-reactive T cells
Describe how polyclonal B cell activation can break tolerance.
Induction of self-reactive B cells
