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
Give an example of hoe a failure of regulatory cell activity can break tolerance.
Defects in TGFβ production.
What is anterior chamber associated immune deviation ACAID induced and regulated by?
Induced by pigmented epithelial cells interacting with antigen-loaded APCs in the AC. It is regulated by TGFβ.
What 3 T cells does aqueous humour inhibit the proliferation and function of?
Th1 cells and antigen-specific CD4 and CD8 T cells.
What is anterior chamber associated immune deviation ACAID induce the differentiation of?
Regulatory T cells
When tissue damage, inflammation or infection occurs, what happens to venule endothelial cells? What two types of molecules are upregulated and where?
Venule endothelial cells transform into high endothelial venules.
Adhesion molecules are upregulated early on retinal vascular endothelium.
Co-stimulatory molecules are upregulated on antigen presenting cells.
Name three common indications for corneal transplantation.
Keratoconus
Stromal dystrophies
Keratitis
What is the major cause of corneal graft failure?
Irreversible immunologic rejection
When rejection occurs, what is it due to?
Recognition of foreign MHC molecules
Describe HLA polymorphism: is it generated by gene rearrangement during development or is it inherited?
Inherited
In what fashion are HLA genes expressed?
Co-dominant fashion
Why will tissue from most donors be seen by the recipient immune system as foreign, with resect to HLA genes?
In a population, there are many combinations of HLA alleles.
Do most grafts need immunosuppressives, or is this only for severe cases?
Most grafts.
Can corneal transplants be done without HLA matching? What about bone marrow? Do they require immunosuppressives for life?
Cornea - no HLA matching needed, with topical not systemic immunosuppressives.
Bone marrow - requires HLA matching and at least short term immunosuppression.
Does rejection usually occur in the eye? Explain why this is the case (3).
No, due to ACAID, the presence of TGFβ, and the presence of the spleen.
What two symptoms occur when corneal graft rejection occurs.
Inflammation and oedema
What class MHC are upregulated with a corneal graft rejection (2), and where does this occur (6).
Class I - expressed on corneal epithelium, keratinocytes, and endothelial cells.
Class II - upregualted on dendritic cells in basal epithelia and on endothelial cells.
What type of molecule is upregulated with a corneal graft rejection?
Adhesion molecules.
What cell is upregulated with a corneal graft rejection?
Dendritic cells
What does a corneal graft rejection induce?
Corneal lymphangiogenesis.
What happens to the anterior chamber during a corneal graft rejection?
Inflammation
The number of which donor cells may influence the acceptance of a corneal transplant?
The number of donor dendritic cells.
What do host dendritic cells do to a corneal graft? What does this imply?
They colonise the graft implying it may be the site of antigen presentation.
Rapid wound healing is directly related to what?
Rejection.
Name 6 determinants of poor graft survival.
Prior vascularisation Previous grafts Recurrence of herpetic infection Youth Increased IOP Keratitis
The depletion of what on a donor corneal graft increases graft survival?
MHC II
Name two high risk immunosuppressives.
Cyclosporin A and topical corticosteroids
What two drugs are used to treat rejection episodes.
Prednisolone, with possible topical corticosteroids.
Can antibodies against costimulatory and adhesion molecules be used to prevent rejection?
Yes, success in animal models, but these are difficult to deliver locally.
