Autoimmune Disease

Question 1

What is immune tolerance?

Answer 1

State of unresponsiveness of the immune system to substances or tissues which have potential to induce an immune response

Question 2

What 3 mechanisms achieve self tolerance?

Answer 2

1. Central tolerance
2. Peripheral tolerance
3. Acquired tolerance

Question 3

Why is immune tolerance important?

Answer 3

Give the immune system the capacity to deal with many diverse pathogens but avoid self-reactivity

Question 4

In which 2 ways can self-reactive receptors be eliminated?

Answer 4

1. Physically

2. Functionally

Question 5

What mechanism controls the induction and maintenance of lymphocyte tolerance?

Answer 5

Central importance

Question 6

Why is the induction and maintenance of lymphocyte tolerance of central importance?

Answer 6

1. It determines how the immune system discriminates between self and non-self
2. It determines how the system responds to different forms of foreign antigens

Question 7

How is central tolerance achieved with respect to T cells?

Answer 7

Immature T cells are which react with self-antigens are deleted in the thymus by apoptosis

Question 8

How is central tolerance achieved with respect to B cells?

Answer 8

Undergo apoptosis or receptor-editing to produce a non-self receptor in the bone marrow

Question 9

What are the 2 stages of positive and negative selection of thymocytes in the bone marrow?

Answer 9

1. Positive selection of cells whose receptors bind to MHC molecules
2. Positive selection of cells with low-affinity receptors for self-MHC

Question 10

Name 2 reasons self-reactive B and T cells escape central tolerance?

Answer 10

1. Recognize self-antigens not expressed or present in the bone marrow or thymus
2. Remain in a state of clonal ignorance

Question 11

What occurs to self-reactive B and T cells which escape central tolerance?

Answer 11

Enter the peripheral circulation

Question 12

What does anergic mean?

Answer 12

The cell cannot divide or clone

Question 13

What 2 things can occur when a B cell encounters a self-antigen in the peripheral system?

Answer 13

1. Clonal deletion

2. Cell becomes anergic

Question 14

What suppresses the reaction of T cells to self antigens?

Answer 14

Regulatory T cells

Question 15

Name 3 ways which regulatory T cells suppress the action of T cells to self-antigens?

Answer 15

1. Direct contact with the target cell
2. Production of inhibitory cytokines IL-10 and TGF-b
3. Scavenging of IL-2, a key T cell growth factor

Question 16

How are self-reactive B and T cells activated if they persist in normal subjects?

Answer 16

Environmental triggers

Question 17

What are the 2 classifications of autoimmune diseases?

Answer 17

1. Organ specific

2. Systemic (non-organ specific)

Question 18

What does the classification of an autoimmune disease depend on?

Answer 18

Whether the response is primarily against antigens localized to particular organs or against widespread antigens

Question 19

Name 5 examples of organ specific autoimmune diseases

Answer 19

1. Type I diabetes
2. Goodpasture’s syndrome
3. Multiple sclerosis
4. Grave’s disease
5. Myasthenia gravis

Question 20

Name 4 examples of systemic autoimmune diseases

Answer 20

1. Rheumatoid arthritis
2. Systemic Lupus Erythematosus (SLE)
3. Discoid Systemic Lupus Erythematosus
4. Primary Sjogren’s syndrome

Question 21

What is Grave’s disease a common cause of?

Answer 21

Hyperthyroidism

Question 22

What is hyperthyroidism?

Answer 22

Over-production of thyroid hormone which causes enlargement of the thyroid

Question 23

What are 3 symptoms of hyperthyroidism, excluding enlarged thyroid?

Answer 23

1. Exophthalmos
2. Heat intolerance
3. Anxiety

Question 24

What is exophthalmos?

Answer 24

Bulging eyes

Question 25

How does negative feedback of the thyroid cells usually work?

Answer 25

- Pituitary gland produces TSH which binds to thyroid cell receptor - Stimulates hormone synthesis - Negative feedback regulates pituitary gland

Question 26

How does Grave's disease differ to regular negative feedback of thyroid cells?

Answer 26

Auto-antibody binds to receptor and there is no negative feedback loop (there is no organ which can be signalled to stop producing antibodies as with TSH)

Question 27

How does myasthenia gravis occur?

Answer 27

Autoantibodies to the acetylcholine receptor block nerve signals to the muscles which become non-functional

Question 28

How does type I diabetes occur?

Answer 28

Autoantibodies attach beta-cells of the pancreas which produce insulin so plasma glucose rises

Question 29

Name 2 organ-specific autoimmune disease with manifestations in the mouth

Answer 29

1. Pemphigus | 2. Pemphigoid

Question 30

What physical symptoms can pemphigus vulgaris cause?

Answer 30

Blisters develop on skin and lining of the mouth, nose, throat and genitals

Question 31

What is desmoglein?

Answer 31

A protein which holds cells of skin and mucous membrane together

Question 32

Why do blisters develop as a cause of pemphigus vulgaris?

Answer 32

Autoantibodies combine with desmogleins so the cells in the skin no longer stick properly and fall apart

Question 33

What is the major difference between pemphigus and pemphigoid?

Answer 33

Blisters are sub-epidermal rather than intra-epidermal in pemphigoid

Question 34

What is the difference between SLE and discoid SLE?

Answer 34

Two ends of a spectrum where SLE has severe involvement of kidney, joints, brain and skin and discoid SLE is benign, chronic and purely cutaneous

Question 35

How can SLE manifest in the oral cavity?

Answer 35

Lesions can affect the oral mucosa and salivary gland including erythematous areas and ulcers on the lips and oral mucosa

Question 36

What causes SLE?

Answer 36

RBCs and platelet autoantibodies lead to complement-mediated lysis of cells (type II hypersensitivity)

Question 37

Name 5 physical manifestations of SLE

Answer 37

1. Fever 2. Arthritis 3. Skin rashes 4. Pleurisy 5. Kidney dysfunction

Question 38

Who is affected by SLE?

Answer 38

Women between 20-40 years old affecting females at a 10:1 ratio compared to males

Question 39

What is Sjogren's syndrome?

Answer 39

An autoimmune disease involving the inflammation salivary and tear glands and some other tissues of the body

Question 40

Who is affected by Sjogren's syndrome?

Answer 40

Mostly female patients

Question 41

What can complicate Sjogren's syndrome?

Answer 41

Infections of the eyes, breathing passages and mouth

Question 42

What is molecular mimicry?

Answer 42

Sequence similarities between foreign and self-peptide chains

Question 43

What is a potential complication of molecular mimicry?

Answer 43

An antibody produced in response to a virus can recognise and attack self-antigens due to similar peptide chains