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DEN 2027 - Disease Mechanisms > Autoimmune Disease > Flashcards

Autoimmune Disease Flashcards

1
Q

What is immune tolerance?

A

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

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2
Q

What 3 mechanisms achieve self tolerance?

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

Why is immune tolerance important?

A

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

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4
Q

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

A
  1. Physically

2. Functionally

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5
Q

What mechanism controls the induction and maintenance of lymphocyte tolerance?

A

Central importance

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6
Q

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

A
  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
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7
Q

How is central tolerance achieved with respect to T cells?

A

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

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8
Q

How is central tolerance achieved with respect to B cells?

A

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

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9
Q

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

A
  1. Positive selection of cells whose receptors bind to MHC molecules
  2. Positive selection of cells with low-affinity receptors for self-MHC
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10
Q

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

A
  1. Recognize self-antigens not expressed or present in the bone marrow or thymus
  2. Remain in a state of clonal ignorance
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11
Q

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

A

Enter the peripheral circulation

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12
Q

What does anergic mean?

A

The cell cannot divide or clone

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13
Q

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

A
  1. Clonal deletion

2. Cell becomes anergic

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14
Q

What suppresses the reaction of T cells to self antigens?

A

Regulatory T cells

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15
Q

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

A
  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
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16
Q

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

A

Environmental triggers

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17
Q

What are the 2 classifications of autoimmune diseases?

A
  1. Organ specific

2. Systemic (non-organ specific)

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18
Q

What does the classification of an autoimmune disease depend on?

A

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

19
Q

Name 5 examples of organ specific autoimmune diseases

A
  1. Type I diabetes
  2. Goodpasture’s syndrome
  3. Multiple sclerosis
  4. Grave’s disease
  5. Myasthenia gravis
20
Q

Name 4 examples of systemic autoimmune diseases

A
  1. Rheumatoid arthritis
  2. Systemic Lupus Erythematosus (SLE)
  3. Discoid Systemic Lupus Erythematosus
  4. Primary Sjogren’s syndrome
21
Q

What is Grave’s disease a common cause of?

A

Hyperthyroidism

22
Q

What is hyperthyroidism?

A

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

23
Q

What are 3 symptoms of hyperthyroidism, excluding enlarged thyroid?

A
  1. Exophthalmos
  2. Heat intolerance
  3. Anxiety
24
Q

What is exophthalmos?

A

Bulging eyes

25
Q

How does negative feedback of the thyroid cells usually work?

A
  • Pituitary gland produces TSH which binds to thyroid cell receptor
  • Stimulates hormone synthesis
  • Negative feedback regulates pituitary gland
26
Q

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

A

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)

27
Q

How does myasthenia gravis occur?

A

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

28
Q

How does type I diabetes occur?

A

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

29
Q

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

A
  1. Pemphigus

2. Pemphigoid

30
Q

What physical symptoms can pemphigus vulgaris cause?

A

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

31
Q

What is desmoglein?

A

A protein which holds cells of skin and mucous membrane together

32
Q

Why do blisters develop as a cause of pemphigus vulgaris?

A

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

33
Q

What is the major difference between pemphigus and pemphigoid?

A

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

34
Q

What is the difference between SLE and discoid SLE?

A

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

35
Q

How can SLE manifest in the oral cavity?

A

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

36
Q

What causes SLE?

A

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

37
Q

Name 5 physical manifestations of SLE

A
  1. Fever
  2. Arthritis
  3. Skin rashes
  4. Pleurisy
  5. Kidney dysfunction
38
Q

Who is affected by SLE?

A

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

39
Q

What is Sjogren’s syndrome?

A

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

40
Q

Who is affected by Sjogren’s syndrome?

A

Mostly female patients

41
Q

What can complicate Sjogren’s syndrome?

A

Infections of the eyes, breathing passages and mouth

42
Q

What is molecular mimicry?

A

Sequence similarities between foreign and self-peptide chains

43
Q

What is a potential complication of molecular mimicry?

A

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

DEN 2027 - Disease Mechanisms (20 decks)

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