Autoimmunity

Question 1

What are the 4 gene regions that are expressed to form the heavy chains variable region of an antibody?

Answer 1

V segments (40 segments)
D segments (24 segments)
J segments (6 segments)
Contant region (Mu, delta, gamma, alpha and epsilon segments)

Question 2

What are the 3 gene regions that are expressed to form the light chains variable region of an antibody?

Answer 2

V segments (45 segments)
J segments (5 segments)
Contant region (Kappa or lambda segments)

Question 3

How are antibody variable regions expressed?

Answer 3

Segments are chosen at random, 1 from each of the segment types, VJD and constant

Question 4

What are the 3 outcomes of antigen receptors for a progenitor T or B cell?

Answer 4

Unsuccessful antigen receptor
Successful antigen receptor
Self-reactive antigen receptor

Question 5

How are autoreactive immune cells destroyed or inactivated?

Answer 5

using tolerance mechanisms
Central tolerance - Deletion of lymphocytes in the primary lymphoid tissue
Peripheral tolerance - Deletion of lymphocytes that escape the primary lymphoid tissue, by T regulatory cells

Question 6

What is the function of a regulatory T cell?

Answer 6

They are crucial for suppression of hyper-reactive and auto-reactive T cells via the production of anti-inflammatory cytokines

Question 7

What does IPEX stand for?

Answer 7

Immune dysregulation, Polyendocrinopathy, Enteropathy and X-linked inheritance Syndrome

Question 8

What are the symptoms of IPEX syndrome?

Answer 8

Severe infection
Intractable diarrhoea
Eczema
Onset Type I diabetes
Autoimmune manifestation

Question 9

What causes IPEX syndrome?

Answer 9

Mutation of the FOXP3 gene
Prevents the production of regulatory T cells

Question 10

What are the 2 types of genetic factors that can cause auto immunity

Answer 10

Single gene mutations - e.g. IPEX syndrome
Complex gene mutations - e.g. MHC genes

Question 11

How many MHC-I molecules does each cell have?

Answer 11

6:
2x HLA-A
2x HLA-B
2x HLA-C

Question 12

How many MHC-II molecules do APCs express?

Answer 12

6:
2x HLA-DR
2x HLA-DQ
2x HLA-DP

Question 13

What are some examples of environmental factors that can increase risk of autoimmunity?

Answer 13

Infection
Smoking
Hormone levels
Tissue damage

Question 14

What are some examples of autoimmune mechanisms?

Answer 14

Molecular mimicry
Alterations to self-antigens
Antigen sequestration
Bacterial superantigens

Question 15

How does acute rheumatic fever occur?

Answer 15

It occurs after a Group A Streptococcal infection
Strep. M5 proteins are similar in structure to cardiac tissue proteins, so when an immune response is triggered against the pathogen, the cardiac tissue is also attacked and damaged

Question 16

How does Drug-induced haemolytic anaemia occur?

Answer 16

Antibodies become directed against RBCs as a result of a drug

Question 17

What is antigen sequestration?

Answer 17

The hiding of antigens behind anatomical structures

Question 18

How can antigen sequestration lead to an autoimmune response?

Answer 18

Sequestered self antigens can be released during infection, leading to an autoimmune response

Question 19

What is an example of an autoimmune disease caused by antigen sequestration?

Answer 19

Post-traumatic autoimmune uveitis

Question 20

How do bacterial super antigens cause autoimmunity?

Answer 20

Super antigens can activate all lymphocytes when they interact with an antigen presenting cell, even if there is no peptide antigen present

Question 21

What is Goodpasture’s syndrome?

Answer 21

An autoimmune disease that affects the lungs and kidneys, causing pulmonary alveolar haemorrhage and glomerulonephritis

Question 22

What causes Goodpasture’s syndrome?

Answer 22

the presence of auto reactive antibodies to the alpha 3 chain of type IV collagen, found in the basement membrane of the alveoli and glomeruli

Question 23

What are the treatment options for Goodpasture’s syndrome?

Answer 23

Immunosuppressive drugs
Anti-inflammatory drugs
Plasmapheresis
Smoking cessation

Question 24

What are some examples of autoimmune diseases caused by type III hypersensitivity reactions?

Answer 24

Systemic Lupus erythematosus
Rheumatoid arthritis
Glomerulonephritis

Question 25

What occurs in SLE?

Answer 25

Increase apoptosis of cells combined with defective clearance of apoptotic clearance, as well and dysregulation of neutrophil NETs

Question 26

What are examples of autoimmune diseases driven by type IV hypersensitivity reactions?

Answer 26

Heart - Autoimmune myocarditis
Pancreas - Diabetes mellitus type I
Thyroid - Hashimoto’ thyroiditis
Nervous system - Multiple Sclerosis
Musculoskeletal system - Rheumatoid arthritis