MIIM - Immunopathology II - Week 5

Question 1

What three types of hypersensitivity mediate autoimmunity?

Answer 1

Type II, III, and IV

Question 2

What is autoimmunity due to the activation of?

Answer 2

The activation of self-reactive B and T cells.

Question 3

Name three factors that affect the development and severity of autoimmune diseases.

Answer 3

Genetic background
Age
Presence of a trigger

Question 4

Distinguish between organ-specific and non-organ specific autoimmunity.

Answer 4

Organ specific - antibody directed against a tissue specific antigen
Non-organ specific - systemic deposition of antibody-antigen complexes

Question 5

What is the main tolerance mechanism for T cells? How may it fail?

Answer 5

Deletion of T cells which recognise self-peptide-MHC complexes
It may fail if antigens are not expressed in the thymus.

Question 6

Name four retinal antigens against which circulating T and B cells have been detected.

Answer 6

Arrestin
IRBP
Rhodopsin
Recoverin

Question 7

Name an iris/choroid antigen against which circulating T and B cells have been detected.

Answer 7

Melanin associated protein

Question 8

Describe ignorance in terms of peripheral tolerance mechanisms.

Answer 8

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.

Question 9

Describe how deletion occurs in terms of peripheral tolerance mechanisms (corneal epithelium).

Answer 9

Corneal endothelium and pigmented epithelial cells express Fas-L which binds Fas-expressing-activated lymphocytes, resulting in apoptosis.

Question 10

Describe how anergy occurs in terms of peripheral tolerance mechanisms.

Answer 10

T cell recognition of peptides in the absence of co-stimulation results in anergy of the T cell.

Question 11

Describe how suppression occurs in terms of peripheral tolerance mechanisms.

Answer 11

Suppression due to the expansion of specific regulatory T cells.

Question 12

Describe briefly the anergy of a self-reactive T cell that has gained access to its antigen in tissues.

Answer 12

Without co-stimulation, a self-reactive T cell cannot respond to its antigen.

Question 13

What must antigen presenting cells do in order to activate CD4 T cells effectively?

Answer 13

Differentiate and express co-stimulatory molecules and peptides with MHC

Question 14

What kind of T cells have a higher affinity for self-peptides?

Answer 14

T regulatory cells

Question 15

What kind of T cell can secrete TGFβ, and what does it do?

Answer 15

Regulatory T cells. Its a cytokine that suppresses many responses.

Question 16

Describe molecular mimicry breaking tolerance.

Answer 16

Some retinal antigens having aa sequences similar to bacterial and viral antigens.

Question 17

Describe bystander activation due to infection breaking tolerance.

Answer 17

Upregulation of co-stimulatory molecules during infection allows activation of self-reactive T cells

Question 18

Describe how polyclonal B cell activation can break tolerance.

Answer 18

Induction of self-reactive B cells

Question 19

Give an example of hoe a failure of regulatory cell activity can break tolerance.

Answer 19

Defects in TGFβ production.

Question 20

What is anterior chamber associated immune deviation ACAID induced and regulated by?

Answer 20

Induced by pigmented epithelial cells interacting with antigen-loaded APCs in the AC. It is regulated by TGFβ.

Question 21

What 3 T cells does aqueous humour inhibit the proliferation and function of?

Answer 21

Th1 cells and antigen-specific CD4 and CD8 T cells.

Question 22

What is anterior chamber associated immune deviation ACAID induce the differentiation of?

Answer 22

Regulatory T cells

Question 23

When tissue damage, inflammation or infection occurs, what happens to venule endothelial cells? What two types of molecules are upregulated and where?

Answer 23

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.

Question 24

Name three common indications for corneal transplantation.

Answer 24

Keratoconus
Stromal dystrophies
Keratitis

Question 25

What is the major cause of corneal graft failure?

Answer 25

Irreversible immunologic rejection

Question 26

When rejection occurs, what is it due to?

Answer 26

Recognition of foreign MHC molecules

Question 27

Describe HLA polymorphism: is it generated by gene rearrangement during development or is it inherited?

Answer 27

Inherited

Question 28

In what fashion are HLA genes expressed?

Answer 28

Co-dominant fashion

Question 29

Why will tissue from most donors be seen by the recipient immune system as foreign, with resect to HLA genes?

Answer 29

In a population, there are many combinations of HLA alleles.

Question 30

Do most grafts need immunosuppressives, or is this only for severe cases?

Answer 30

Most grafts.

Question 31

Can corneal transplants be done without HLA matching? What about bone marrow? Do they require immunosuppressives for life?

Answer 31

Cornea - no HLA matching needed, with topical not systemic immunosuppressives.
Bone marrow - requires HLA matching and at least short term immunosuppression.

Question 32

Does rejection usually occur in the eye? Explain why this is the case (3).

Answer 32

No, due to ACAID, the presence of TGFβ, and the presence of the spleen.

Question 33

What two symptoms occur when corneal graft rejection occurs.

Answer 33

Inflammation and oedema

Question 34

What class MHC are upregulated with a corneal graft rejection (2), and where does this occur (6).

Answer 34

Class I - expressed on corneal epithelium, keratinocytes, and endothelial cells.
Class II - upregualted on dendritic cells in basal epithelia and on endothelial cells.

Question 35

What type of molecule is upregulated with a corneal graft rejection?

Answer 35

Adhesion molecules.

Question 36

What cell is upregulated with a corneal graft rejection?

Answer 36

Dendritic cells

Question 37

What does a corneal graft rejection induce?

Answer 37

Corneal lymphangiogenesis.

Question 38

What happens to the anterior chamber during a corneal graft rejection?

Answer 38

Inflammation

Question 39

The number of which donor cells may influence the acceptance of a corneal transplant?

Answer 39

The number of donor dendritic cells.

Question 40

What do host dendritic cells do to a corneal graft? What does this imply?

Answer 40

They colonise the graft implying it may be the site of antigen presentation.

Question 41

Rapid wound healing is directly related to what?

Answer 41

Rejection.

Question 42

Name 6 determinants of poor graft survival.

Answer 42

Prior vascularisation
Previous grafts
Recurrence of herpetic infection
Youth
Increased IOP
Keratitis

Question 43

The depletion of what on a donor corneal graft increases graft survival?

Answer 43

MHC II

Question 44

Name two high risk immunosuppressives.

Answer 44

Cyclosporin A and topical corticosteroids

Question 45

What two drugs are used to treat rejection episodes.

Answer 45

Prednisolone, with possible topical corticosteroids.

Question 46

Can antibodies against costimulatory and adhesion molecules be used to prevent rejection?

Answer 46

Yes, success in animal models, but these are difficult to deliver locally.