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4) Metabolic Endocrinology > 11) Autoimmunity > Flashcards

11) Autoimmunity Flashcards

1
Q

What is the underlying cause of autoimmune diseases?

A

Production of antibodies and cytotoxic T-cells that target normal body cells

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2
Q

Does genetic predisposition affect the onset of autoimmune diseases?

A
  • They appear to develop spontaneously and at random

- The genetic component is not particularly strong

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3
Q

Which age group tends to develop autoimmune diseases?

A

Older individuals

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4
Q

Which gender group tends to develop autoimmune diseases?

A

Women

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5
Q

What are the two most common autoimmune diseases?

A
  • Thyroid diseases (autoimmune)

- Type I diabetes

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6
Q

What is the primary characteristic of vitiligo?

A

Depigmentation of the skin

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7
Q

What are the primary antibodies of vitiligo associated with? What is it implicated in?

A
  • Tyrosinase

- Melanin synthesis

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8
Q

What are the two autoimmune diseases that have a higher propensity in men than women?

A
  • Diabetes mellitus

- Ulcerative collitus

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9
Q

What are the six most common autoimmune diseases? (6)

A
  • Grave’s disease
  • Type 1 diabetes
  • Pernicious anemia
  • Rheumatoid arthritis
  • Hashimoto’s disease
  • Vitiligo
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10
Q

1 in __ individuals develop Graves’ disease, type 1 diabetes, pernicious anemia, rheumatoid arthrititis, Hashimoto’s disease and vitiligo, forming __% of affected individuals.

A

30

93

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11
Q

What is Sjogren’s syndrome?

A

Autoimmune disease in which there is an inability to produce tears

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12
Q

Why do females have a greater risk to develop autoimmune diseases?

A
  • Due to their hormones (estrogens)

- Immune system has to be depressed to allow implantation to occur during pregnancy

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13
Q

How do estrogens affect B-cell autoimmunity?

A
  • Estrogens stimulate B-cell autoimmunity

- Associated with reproductive years

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14
Q

How do estrogens affect T-cell autoimmunity?

A
  • Falling estrogens support T-cell autoimmunity

- Associated with post-menopausal years

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15
Q

Why do sex and specific stages of life influence the development of autoimmune diseases?

A

May be due to differences in hormones

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16
Q

What are three common theories to explain the etiology of autoimmunity?

A

1) T-cells may encounter self-antigens that are normally “hidden” from them
2) Triggered from infections
3) Diminished suppressor T-cell function

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17
Q

How may the encounter of T-cells with self-antigens that are normally “hidden” affect the development of autoimmunity?

A
  • Physical damage or trauma may expose these tissues

- T-cells become reactive to self following exposure to these tissues

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18
Q

How may infections trigger autoimmunity?

A

An infectious agent has an antigenic determinant that is similar or identical to self-antigen

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19
Q

What are the three factors that are related to the etiology of autoimmune diseases?

A
  • Genes
  • Immune regulation
  • Environment
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20
Q

What are examples of organ-specific autoimmune diseases?

A
  • T1DM
  • MS
  • Grave’s disease
  • Hashimoto’s
  • Addison’s disease
  • Myasthenia gravis
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21
Q

What are examples of systemic autoimmune diseases?

A
  • Rheumatoid arthritis
  • Scleroderma
  • SLE
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22
Q

What gland does hypophysitis affect? What is the auto-antibody?

A
  • Pituitary

- Anti-pituitary

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23
Q

What gland does Grave’s disease affect? What is the auto-antibody?

A
  • Thyroid

- TSH-receptor or anti-TPO

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24
Q

What gland does Hashimoto’s disease affect? What is the auto-antibody?

A
  • Thyroid

- Anti-TPO, anti-TG

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25
Q

What gland does autoimmune hypoparathyroidism affect? What is the auto-antibody?

A
  • Parathyroid

- Anti-parathyroid

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26
Q

What gland does T1DM affect? What is the auto-antibody?

A
  • Pancreas (B-cells)

- Anti-GAD, anti-insulin

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27
Q

What glands does type B insulin resistance with acanthosis affect? What is the auto-antibody?

A
  • Adipocytes, muscle cells

- Insulin receptor blocking

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28
Q

What gland does Addison’s disease affect? What is the auto-antibody?

A
  • Adrenal

- Anti-21-hydroxylase, anti-17a-hydroxylase, anti-P450scc

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29
Q

What are immunologically privileged sites? Provide examples.

A
  • Parts of the body that EXCLUDE immune responses

- Brain, eye, testes, uterus

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30
Q

What is a possible consequence of an injury to an immunologically privileged site?

A

Injury leads to exposure of antigens, which may lead to autoimmunity

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31
Q

Which autoantibodies may cross the placenta to affect the fetus?

A

IgG

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32
Q

How may a pregnant women with Grave’s disease affect her fetus?

A
  • Transfer of antibodies across the placenta to the fetus

- Newborn suffers from Grave’s disease

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33
Q

What is the treatment of a newborn with congenital Grave’s disease?

A
  • Plasmapheresis

- Removes maternal anti-TSHR antibodies

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34
Q

What are the three factors that regulate the steady-state of osteoimmunology?

A

1) Cytokines
2) Receptors
3) Apoptosis

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35
Q

Where does the blood system originate from?

A

Hematopoietic stem cells in the bone marrow

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36
Q

Where does B-cells immunocompetency occur? Where does T-cells immunocompetency occur?

A
  • B-cells: bone marrow

- T-cells: thymus

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37
Q

What are the two types of stem cells in the bone marrow?

A
  • Hematopoietic stem cells

- Mesenchymal stem cell

38
Q

What are the two progenitor cells that may differentiate from hematopoietic stem cells?

A
  • Lymphoid progenitor

- Myeloid progenitor

39
Q

What progenitor cell may differentiate from mesenchymal stem cells?

A

Multipotent progenitor

40
Q

What stem cell do osteoclasts arise from?

A

Hematopoietic stem cells (myeloid progenitor)

41
Q

What stem cell do osteoblasts arise from?

A

Mesenchymal stem cells (multipotent progenitor)

42
Q

Dendritic cells, macrophages, osteoclasts, neutrophils, platelets and erythryocytes are formed from which progenitor cell?

A

Hematopoietic stem cells (myeloid progenitor)

43
Q

T-cell progenitors, B-cells, NK cells and dendritic cells are formed from which progenitor cell?

A

Hematopoietic stem cells (lymphoid progenitor)

44
Q

Adipocytes, chondrocytes, myocytes, stroma, and osteoblasts are formed from which progenitor cell?

A

Mesenchymal stem cells (multipotent progenitor)

45
Q

What controls the development of B-cells?

A

A hierarchy of transcription factors

46
Q

_-cells conduct humoral immunity.

A

B

47
Q

_-cells conduct cellular immunity.

A

T

48
Q

How do B-cells complete their maturation?

A

Upon binding to non-self antigens and destroying infected cells

49
Q

What occurs to macrophages following phagocytosis? How are helper T-cells and cytotoxic T-cells implicated?

A
  • Macrophages present non-self antigens on their membranes

- Helper T-cells recognize non-self antigens and recruit cytotoxic T-cells

50
Q

What are two mechanisms by which the immune system is capable of recognizing virtually any foreign molecule?

A

1) Somatic recombination of the antibody light-chain and heavy-chain, producing 10^12 different types of antibodies
2) Recombination of genes encoding T-cell and B-cell receptor

51
Q

What is a downside of random rearrangements of DNA to produce a large number of T-cell and B-cell receptors?

A

May produce receptors that recognize “self”

52
Q

Developing lymphocytes express a large number of antigen receptors, which are (biased/not biased) by specificity.

A

not biased

53
Q

Are individuals capable of producing lymphocytes with the ability to recognize self antigens?

A

Yes, because antigen receptors on lymphocytes are not biased by specificity

54
Q

What must occur to prevent lymphocytes from reacting to self?

A

Self-reactive lymphocytes must be selected against (eliminated or inactivated) to prevent autoimmunity

55
Q

Define immunological tolerance.

A

Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen

56
Q

How does immunological tolerance differ from non-specific immunosuppression?

A

Immunological tolerance implies antigen specificity

57
Q

Define self-tolerance.

A

All individuals are tolerant of their own antigens

58
Q

What results from the breakdown of self-tolerance?

A

Autoimmunity

59
Q

What are possible therapeutic potentials of inducing tolerance?

A
  • Prevent graft rejection
  • Treat autoimmune and allergic diseases
  • Prevent immune responses in gene therapy (e.g. stem cell transplantation)
60
Q

What does central tolerance refer to?

A
  • Generative lymphoid organs

- Thymus (T-cells) and bone marrow (B-cells)

61
Q

What are the two possibilities of B-cells following the recognition of self-antigen (central tolerance)?

A

1) Apoptosis (deletion)

2) Receptor editing (change in receptor specificity)

62
Q

What are the two possibilities of T-cells following the recognition of self-antigen (central tolerance)?

A

1) Apoptosis (deletion)

2) Differentiation into regulatory (suppressor) T-cells

63
Q

What does peripheral tolerance refer to? What is its function?

A
  • Peripheral tissues

- Serves as a backup system (if a lymphocyte escapes central tolerance)

64
Q

What are the three possibilities of mature T-cells in peripheral tissues?

A

1) Anergy
2) Apoptosis (deletion)
3) Suppression

65
Q

Define anergy.

A

Neutralization of the cell (non-reactive)

66
Q

What occurs to self-reactive lymphocytes during central tolerance?

A

Immature self-reactive lymphocytes that recognize self-antigens in central lymphoid organs die by apoptosis

67
Q

What occurs to self-reactive lymphocytes during peripheral tolerance?

A

Mature self-reactive lymphocytes that recognize self-antigens in peripheral tissues are inactivated (anergy), killed (deletion) or suppressed

68
Q

Which cells are positively selected for?

A

Cells with very weak (to none) self-recognition

69
Q

What occurs if a stromal cell is capable of binding to an immature B-cell?

A

The stromal cell sends out a death ligand, causing apoptosis in the B-cell

70
Q

What occurs if there is no cross-linking between a stromal cell and an immature B-cell?

A

The B-cell survives

71
Q

What are the two conditions that may cause tolerance to fail, generating autoimmune diseases?

A

1) Wrong environment (e.g. viral infection)

2) Wrong genes or mutations

72
Q

What may a weakly stimulating self-antigen lead to?

A
  • Lymphoproliferative disorder (T-cell)

- Antibody-mediated systemic autoimmunity

73
Q

What may a stimulating self-antigen lead to?

A

Organ-specific autoimmunity (multi-organ)

74
Q

What may cross-reactivity with self due to a foreign antigen lead to?

A

Organ-specific autoimmunity

75
Q

What are the factors that may lead to the failure of central or peripheral self-tolerance?

A
  • Genetics
  • Environment
  • Diet (controversial)
  • Aging
  • Stress
  • Pregnancy
  • Trauma
  • Disease
76
Q

How are genetics related to autoimmunity?

A
  • Complex and polygenic, but significant

- Increased incidence in monozygotic twins in contrast to dizygotic twins

77
Q

Provide an example of how environment may affect autoimmunity.

A

Up to 20% of children prenatally infected with rubella develop T1DM

78
Q

Why may pregnancy be associated with an increased risk of autoimmune diseases?

A

The harbouring of a foreign object for a substantial period of time

79
Q

Describe the pathogenesis of T1DM throughout childhood.

A
  • B-cell pathology: autoantibodies
  • Pre-diabetes: loss of first phase of insulin response
  • Diabetes: loss of glucose tolerance
80
Q

Which antibodies are found in 90% of individuals with T1DM?

A
  • Anti-glutamic acid decarboxylase (GAD)

- Anti-IA-2

81
Q

Which antibody is found in 50% of individuals with T1DM?

A

Anti-insulin

82
Q

Which antibodies are found in individuals with Grave’s disease?

A
  • Anti-TSHR

- Anti-TPO

83
Q

Which antibodies are found in individuals with Hashimoto’s disease?

A
  • Anti-TPO

- Anti-TG

84
Q

Which antibody is found in individuals with Addison’s disease?

A

Anti-21-hydroxylase

85
Q

Rheumatoid arthritis is more susceptible in (women/men).

A

women

86
Q

How is rheumatoid arthritis associated with bone erosion?

A

Rheumatoid arthritis may lead to bone erosion by activating osteoclasts

87
Q

What is the target tissue of T1DM?

A

Islet B-cells of the pancreas

88
Q

What is the target tissue of multiple sclerosis?

A

Myelin-producing cells in the central nervous system

89
Q

What is the target tissue of rheumatoid arthritis?

A

Collagen-producing cells of the joints

90
Q

How does vitamin D3 affect the development of autoimmune diseases?

A
  • Reduced incidence of autoimmune diseases

- In areas of increased sunshine and/or rich diet in vitamin D3

4) Metabolic Endocrinology (15 decks)

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