Autoimmunity

Question 1

What is the definition of autoimmunity?

Answer 1

Loss of tolerance to self-antigens

Question 2

What is autoimmunity mediated by?

Answer 2

Mediated either by autoantibodies or self-reactive T cells
* can be localised, organ-specific or generalised
* tends to improve with immunsuppresive therapy

Question 3

What are Witebsky’s postulates?

Answer 3

1. Ig or autoreactive T cell must be demonstratable
2. Antibody to which the autoreactive T cell binds must be identified
3. The symptoms must be inducible in an experimental animal study

Question 4

What are the three main mechanisms in place to help revent autoimmunity?

Answer 4

• Deletion
• Anergy
• Regulation

Question 5

When does apoptosis of self-reactive T cells occur?

Answer 5

During negative selection
some self-reactive T cells survive and go on to become regulatory CD4+ T cells

Question 6

What occurs if the B cell central tolerance is lov-avidity self antigen recognition?

Answer 6

Anergic B cell rather than Deletion

Question 7

What is clonal deletion?

Answer 7

cell death induced by activation via Fas-Ligand signalling
* There is an increase in Fas expression on activated lymphocytes that are persistently stimulated by the antigen

Question 8

When does inactivation of lymphocytes that encounter the antigen occur?

Answer 8

Occurs in the absence of co-stimulation signals (CD28-B7/CD80&86 in TCL, CD40-CD40L in BCL )
The inactivation is reversible but difficult

Question 9

How does supression during peripheral tolerance work?

Answer 9

Mediated by T regulatory cells
* * Produce IL-4*
, IL-10, TGF-β → anti-inflammatory
* Express cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
* inhibitory receptor that binds to B7/CD80&86 on APCs (prevents binding CD28)

Question 10

What are the mechanisms overview of autoimmunity?

Answer 10

1. Exposure of previously hidden antigens
   * Can occur due to trauma, inflammation
2. Exposure of cross-reacting antigen
   * Pathogen epitope cross-reactivity with self antigens (molecular mimicry)
3. Bystander activation
   * Inadvertent stimulation of self-reactive lymphocyte in periphery
4. Alteration of self-antigen
   * e.g. drug binding to erythrocytes creating a new epitope
5. Dysregulation of immune system
   * Defects in T regulatory cell populations
6. Genetic predispositions
   * Familial disease related to MHC alleles in dogs
   * Multiple genetic defects usually required for disease

Question 11

What is molecular mimicry?

Answer 11

When the effector cells or moleucles attack a self-antigen because it bears similiar determinants to the main antigen

Question 12

What is a hapten?

Answer 12

small molecule that elicits an antibody response only when attached to the carrier

Question 13

What is an example of an autoimmune disease in veterinary medicine?

Answer 13

• Systemic - lupus
• Organ Specific- Diabetes mellitus type 1, IMHA, IMTP

Question 14

What is the pathogenesis of SLE?

Answer 14

the predominant antibody is the ANA
It forms immune complexes (type III hypersensitivity)
then deposits in the glomeruli, blood vessels, skin, synovial joints

Question 15

Why is there fever in SLE?

Answer 15

• Neutrophils (Type III HS!) produce IL-1 and TNF-α
  (mediate fever)

there is also crusting, ulcerations, renal failure …

Question 16

What are LE bodies?

Answer 16

phagocytes that have ingested an opsonised nucleus