L12 - Autoimmune diseases

Question 1

What is autoimmunity?

Answer 1

immune responses to self-antigens

Question 2

Autoimmune disease

Answer 2

an adaptive response to self antigens that contribute to tissue damage

Question 3

What is tolerance?

Answer 3

A state of immunological non-reactivity to an antigen

Question 4

Whats is negative selection?

Answer 4

A test for self tolerance
it tests the binding capability of CD4 and CD8 specifically.
. If a T cell binds, via CD4 or CD8, a self-MHC molecule that isn’t presenting an antigen, or a self-MHC molecule that presenting a self-antigen, it will fail negative selection and be eliminated by apoptosis.

Question 5

What is positive selection?

Answer 5

Ensures MHC restriction by testing ability of MHC1 and MHC2 to distinguish between self and non-self proteins. In order to pass the positive selection process, cells must be capable of binding only self-MHC molecules. If these cells bind nonself molecules instead of self-MHC molecules, they fail the positive selection process and are eliminated by apoptosis.

Question 6

Compare rigorous and permissive negative selection

Answer 6

Rigorous -
low risk of autoimmunity but a poor repertoire and increased suceptibility to infection
Permissive negative selection - produces a broad repertoire, lowers risk of infection but higher risk of autoimmunity

Question 7

What are peripheral tolerance mechanisms?

Immunological hierarchy

Answer 7

IMMUNOLOGICAL HIERARCHY - lots of different things are needed to get a response. B cells might recognise something but wont do anything unless there is help from CD4 T cell. CD4 T cell won’t be activated unless antigen is presented in an inflammatory context with TLR ligation

Question 8

Antigen segregation

Answer 8

Physical barriers to sequested antigen

Question 9

Peripheral anergy

Answer 9

Weak signalling between APC/ CD4 T cell without co-stimulation causes T cells to become non-responsive

Question 10

Regulatory T cells

Answer 10

CD25+FoxP3 positive T cells and other types of regulatory T cells actively suppress immune responses by cytokine and juxtacrine signalling

Question 11

cytokine deviation

Answer 11

Change in T cell phenotype eg Th1 to Th2 may reduce inflammation

Question 12

Clonal exhaustion

Answer 12

Apoptosis post-activation by activation-induced cell death

Question 13

How are AIDs classified?

Answer 13

Organ specific - T1DM, Graves disease, Hashimotos

Non-organ specific
Systemic lupus erythmatosis
Rheumatoid arthiritis

Question 14

Pathogenic mechanism of AID: autoantibodies

Answer 14

Type 2 hypersensitivity
Antibody clearly pathogenic
criteria: disease can be transferred between experimental animals by infusion of serum, or during gestation to cause problems in fetus
Removal of antibody by plasmapharesis is beneficial
A pathogenic antibody can be identified and characterised

Question 15

Mechanism of graves thyroiditis?

Answer 15

1 - pituitary gland secretes TSH which acts on thyroid to induce release of Thyroid hormones

2- Thyroid hormones act on the pituitary to shut down production of TSH, supressing further TH synthesis

3 - Autoimmune B cell makes antibodies against TSH receptor that can also stimulate TH production

4 - TH shut down TSH production but have no effect on autoantibody production, which continues to cause excessive thyroid hormone production

Question 16

Mechanism - myasthenia gravis?

Answer 16

Autoantibodies attack components of the postsynaptic membrane of the NMJ. leads to weakness and fatigue of skeletal muscle.
Ach receptors internalized and degraded. No sodium influx - no muscle contraction

Question 17

What is spontaneous urticaria?

Answer 17

A condition that presents with hives and swelling

caused by IgG FceR1 antibody cross linking mast cell receptors causing degranulation

Question 18

Describe the mechanism of AID by T cells

Answer 18

type 4
tissue damage caused by T cell dependent mechanisms
T cells activate macrophages and other innate immunity elements
CD8 T cells damage tissue directly