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Immunology > 6 - autoimmunity > Flashcards

6 - autoimmunity Flashcards

1
Q

define immunological tolerance?

A

unresponsiveness to an antigen that is induced by previous exposure to that antigen

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2
Q

define tolerogens?

A

antigens which induce tolerance

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3
Q

what is self-tolerance?

A

tolerance to self antigens

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4
Q

what is the result of failure of self tolerance?

A

immune reactions against autologous (self) antigens

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5
Q

what is autoimmunity?

A

immune reactions against autologous (self) antigens

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6
Q

what does autoimmunity cause?

A

autoimmune diseases

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7
Q

what do T and B cells do to avoid autoimmune disease?

A

they must eliminate/ downregulate their self-reactive molecules

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8
Q

2 types of tolerance involved in immunological tolerance?

A

central, peripheral

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9
Q

describe tole of thymus in central tolerance?

A

thymus plays important role in eliminating T cells with high affinity to self-antigens

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10
Q

what is important in B cell tolerance?

A

bone marrow

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11
Q

describe peripheral tolerance?

A

Mature lymphocytes that recognise self antigens in peripheral tissues become incapable of activation or die by apoptosis

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12
Q

what happens to T cells that bind to antigens with high affinity in the thymus?

A

deleted through -ve selection

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13
Q

how are autoreactive T cells managed in peripheral tolerance?

A

they are inhibited by regulatory T cells

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14
Q

what leads to activation-induced death of T cells in peripheral tolerance?

A

repeated antigenic stimulation

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15
Q

5 mechanisms of peripheral tolerance?

A

anergy,
Deletion (cell death), Antigen recognition without co-stimulation,
Treg suppression,
anatomical barriers

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16
Q

define anergy?

A

functional unresponsievness

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17
Q

describe mechanism of anatomical barriers for peripheral tolerance?

A

Some self antigens are sequestered from the immune system by anatomic
barriers

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18
Q

name 3 scenarios where peripheral tolerance can be overcome?

A

Inappropriate access of self-antigens,
Inappropriate or increased local expression of co-stimulatory molecules,
Alterations in self-molecules presentation to immune system

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19
Q

when is peripheral tolerance more likely to happen and what is the reason for this?

A

when inflammation/ tissue damage is present - due to the increased activity of proteolytic enzymes

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20
Q

activity of proteolytic enzymes?

A

cause intra/extra-cellular protein breakdown, therefore increasing concentration of peptides presented to responsive T cells

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21
Q

name 3 factors which may alter the structure of self-peptides?

A

viruses, free radicals, ionising radiation

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22
Q

name 3 factors which aid normal autoimmunity in becoming an autoimmune disease?

A

environmental factors, genetics, infections

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23
Q

define autoimmunity?

A

Adaptive immune responses to self antigens

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24
Q

define autoantibodies?

A

antibodies directed at normal cellular components, referred to as autoantigens

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25
Q

when do autoimmune diseases occur and what are they mediated by?

A

occurs when autoreactive T cells or autoantibodies

cause tissue damage through hypersensitivity reaction types II, III and IV

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26
Q

do healthy individuals produce autoantibodies?

A

yes but at very low level and low affinity

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27
Q

what do B1 cells secrete?

A

natural antibodies, which are a major source of autoantibodies

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28
Q

what activates complement to help clear invading bacteria?

A

natural antibodies binding to antigens with low affinity on bacteria

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29
Q

what does an individual with no inherited A or B antigens produce?

A

IgM anti-A and anti-B antibodies, even if they have never been exposed to red cells from another person

30
Q

what can natural antibodies bind to?

A

normal cellular constituents - e.g. DNA

31
Q

name 2 types of factors which lead to the breakdown of T cell tolerance?

A

genetic predisposition, environmental factors

32
Q

name 3 possible points in the pathway of tolerance which can break down, leading to autoimmune disease?

A

complement is defective, no regulatory T cells to inhibit T cells, self antigen is missing from thymus

33
Q

which gene mutation leads to central tolerance not taking place?

A

AIRE

34
Q

what can B27 HLA association lead to?

A

ankylosing spondylitis, reiter disease

35
Q

what can DR2 HLA association lead to?

A

goodpasture syndrome

36
Q

what can DR3 HLA association lead to?

A

addison disease, Sicca syndrome, Hashimoto thyroiditis, Myasthenia gravis

37
Q

what can DR4 HLA association lead to?

A

insulin-dependent DM

38
Q

what type of mutations are implicated in the breakdown of immune tolerance?

A

common polymorphisms, rather than rare mutations

39
Q

name 3 environmental factors which can breakdown tolerance?

A

infection, drugs, UV radiation

40
Q

3 ways in which infection can breakdown tolerance?

A

Molecular mimicry, Upregulation of co-stimulation, Antigen breakdown and presentation changes

41
Q

2 ways in which drugs can breakdown tolerance?

A

molecular mimicry, genetic variation in drug metabolism

42
Q

2 ways in which UV radiation can breakdown tolerance?

A

Trigger for skin inflammation, Modification of self-antigen

43
Q

describe molecular mimicry?

A

Structural similarity between self-proteins and microbial antigens may trigger an autoimmune response

44
Q

name 3 diseases which are a consequence of molecular mimicry?

A

rheumatic fever, insulin-dependent DM, guillain-Barre syndrome

45
Q

associated disease - AIRE mutations?

A

multiple autoimmune diseases

46
Q

associated disease - polymorphisms in insulin gene?

A

T1 DM

47
Q

associated disease - MHC polymorphisms?

A

T1 DM, coeliac disease, SLE, etc.

48
Q

associated disease - MBL, complement C1 polymorphisms?

A

SLE

49
Q

associated disease - infections?

A

T1 DM, MS,

50
Q

associated disease - medications?

A

SLE

51
Q

associated disease - UV light?

A

SLE

52
Q

associated disease - gluten?

A

coeliac disease

53
Q

how do autoimmune diseases present in families?

A

show clustering within families

54
Q

M:F - autoimmune diseases?

A

almost all are more common in women - exception = ankylosing spondylitis

55
Q

what are non-organ specific autoimmune diseases associated with?

A

autoimmune responses against self-molecules which are widely distributed throughout the body

56
Q

what determines where the autoimmune disease lies in the spectrum?

A

the location of the antigen

57
Q

how is autoimmunity triggered in SLE?

A

fragments of DNA persist (not removed by innate immune system) - IgG and DNA form immune complex

58
Q

4 mechanisms for treating the self-reactive lymphocyte in autoimmune diseases?

A

inhibition of lymphocyte function, re-induction of anergy, removal of co-stimulation, induction of inhibitory T cells

59
Q

how to treat tissue damage caused by autoimmune diseases?

A

anti-inflammatory drugs

60
Q

how to treat organ dysfunction caused by autoimmune diseases?

A

replacement therapy

61
Q

disease related to TSH receptor?

A

hyper/hypo- thyroidism

62
Q

disease related to insulin receptor?

A

hyper/hypo- glycaemia

63
Q

disease related to acetylcholine receptor?

A

myasthenia gravis

64
Q

disease related to epidermal cell adhesion molecules?

A

blistering skin diseases

65
Q

disease related to factor VIII (plasma protein)?

A

acquired haemophilia

66
Q

disease related to beta-2 glycoprotein I (plasma protein)?

A

antiphospholipid syndrome

67
Q

disease related to RBCs?

A

haemolytic anaemia

68
Q

disease related to platelets?

A

thrombocytopenic purpura

69
Q

name 6 diseases associated with intracellular enzyme self-antigens?

A

thyroiditis, hypothyroidism, addison disease, autoimmune diabetes, systemic vasculitis, 1y biliary cirrhosis

70
Q

name 4 diseases associated with intracellular molecules involved in transcription and translation as self-antigens?

A

SLE, diffuse scleroderma, polymyositis, limited scleroderma

Immunology (9 decks)

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