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Im+Haem yien > Autoimmunity > Flashcards

Autoimmunity Flashcards

1
Q

What is immunological tolerance?

A

Immunological tolerance = unresponsiveness to an antigen that is induced by previous exposure to that antigen

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2
Q

The same antigen may induce tolerance or immune response depending on..?

A
  • Conditions of exposure
  • Absence of other stimuli
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3
Q

What are tolerogens?

A

Tolerogens = antigens that induce tolerance

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4
Q

What is self-tolerance?

A

Self-tolerance = tolerance to self-antigens:

  • Failure of this is called autoimmunity, and diseases they cause are autoimmune diseases
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5
Q

What is done by the body to avoid autoimmune disease?

A
  • T and B cells bearing self-reactive molecules must be eliminated
  • Achieved by central and peripheral tolerance
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6
Q

What are important organs for central tolerance?

A
  • Thymus
    • Eliminates T cells with high affinity to self-antigens
  • Bone marrow
    • B cell tolerance
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7
Q

Describe the mechanism of central tolerance?

A
  1. Within cortex of thymus, T cell progenitors are tested against antigens
    1. If they do not react at all they die – death by neglect
    2. If they have strong recognition for self-antigens they die – negative selection
    3. If this does not happen they develop further – positive selection
    4. If low affinity to self-antigens they can develop into Treg cells still
  2. Cells go into periphery
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8
Q

Where does central tolerance occur for T cells?

A

Cortex of thymus

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9
Q

Where does central tolerance for B cells occur?

A

Bone marrow

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10
Q

What is peripheral tolerance?

A

Safety mechanism encase some reaction cells escape primary tolerance:

  • Mature lymphocytes that recognise self-antigens in peripheral tissues become incapable of activation or die by apoptosis
  • Can happen due to absence of certain antigens within thymus/bone marrow
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11
Q

What are some of the different mechanisms of peripheral tolerance?

A
  • Anergy (functional unresponsiveness)
    • Stimulation without co-stimulation, which is required
  • Antigen recognition without co-stimulation
  • Treg suppression
    • Autoreactive T cells inhibited by Treg cells
  • Deletion (cell death)
  • Self-antigens hidden from immune system by anatomical barriers
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12
Q

Overcoming peripheral tolerance can result from?

A
  • Inappropriate access of self-antigens
  • Inappropriate or increased local expression of co-stimulatory molecules
  • Alterations in the ways in which self-molecules are presented to immune system
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13
Q

What increases the risk of overcoming peripheral tolerance?

A
  • Inflammatory or tissue damage
    • Due to increased activity of proteolytic enzymes, leading to high concentrations of peptides being presented to responsive T cells
  • Infection
    • Structure of self-peptides altered by viruses, free radicals or ionising radiation thus bypassing previously established tolerance
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14
Q

How can inflammation or tissue damage allow peripheral tolerance to fail?

A
  • Due to increased activity of proteolytic enzymes, leading to high concentrations of peptides being presented to responsive T cells
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15
Q

How can infection cause peripheral tolerance to fail?

A
  • Structure of self-peptides altered by viruses, free radicals or ionising radiation thus bypassing previously established tolerance
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16
Q

What does autoimmunity occur due to?

A

Occurs due to breakdown of tolerance, where autoreactive T cells or autoantibodies cause tissue damage through hypersensitivity reactions types II, III and IV, could be due to:

  • Genes
  • Infections
  • Environmental factors
17
Q

What is autoimmunity?

A

Autoimmunity = adaptive immune responses to self-antigens

18
Q

What are autoantibodies?

A

Autoantibodies = antibodies directed at normal cellular components, referred to as autoantigens

19
Q

Does the presence of autoantibodies always indicate disease?

A

Most healthy people produce low amounts of autoantibodies, with low affinity

20
Q

What do natural antibodies do?

A

B1 cells secrete natural antibodies that are major source of autoantibodies (part of innate immune system):

  • Bind with low affinity to antigens on a variety of bacteria, activating complement to help clear bacteria rapidly
  • Cross-react with inherited A and B antigens of red cells
    • Unless inherited either A or B antigens, people make IgM anti-A and anti-B antibodies even if they have never been exposed to red cells from another person
  • Can bind to normal cellular constituents such as nuclear proteins and DNA
21
Q

What can breakdown of T cell tolerance occur due to?

A
  • Genetic predisposition
    • Poor expression of self-antigen in thymus
    • HLA with poor binding for self-antigen
      • Alleles of MHC – common polymorphisms rather than rare mutations implicated in breakdown of immune tolerance leading to disease
  • Environmental factors
    • Infections
      • Molecular mimicry – mimic self-molecules, so immune system reacts to autoantigens as well as infection/drugs
      • Upregulation of co-stimulation
      • Antigen breakdown and presentation changes
    • Drugs
      • Molecular mimicry
      • Genetic variation in drug metabolism
    • UV radiation
      • Trigger for skin inflammation
      • Modification of self-antigen
22
Q

What is molecular mimicry?

A
  • Molecular mimicry – mimic self-molecules, so immune system reacts to autoantigens as well as infection/drugs
23
Q

What are some genetic predispositions to breakdown of T cell tolerance?

A
  • Poor expression of self-antigen in thymus
  • HLA with poor binding for self-antigen
    • Alleles of MHC – common polymorphisms rather than rare mutations implicated in breakdown of immune tolerance leading to disease
24
Q

What are some diseases that HLA gene alleles are associated to?

A
25
Q

What does HLA stand for?

A

Human leukocyte antigen

26
Q

What are some microbial antigens that are similar to self-antigens and so can cause molecular mimicry?

A
27
Q

What are some risk factors for autoimmune disease?

A
28
Q
A
29
Q

Describe the epidemiology of autoimmune disease?

(prevalence, age, sex)

A
  • Prevalence 3%
  • Clustering within families
  • Peak onset 15-65 years (exception T1 diabetes)
  • Almost all more common in woman (exception ankylosing spondylitis)
30
Q

How can autoimmune disease be classified?

A
  • Non-organ specific
    • Affect multiple organs
    • Associated with autoimmune responses against self-molecules that are widely distributed
    • Intracellular molecules involved in transcription and translation
  • Organ specific
    • Restricted to one organ
    • Endocrine glands
31
Q

What are examples of autoimmune diseases?

A
32
Q

What is the self-antigen involved in the following diseases:

  • hyper/hypothyroidism
  • hyper/hypoglycaemia
  • myasthenia graves
  • acquired haemophilia
  • haemolytic anaemia
  • SLE
A

and SLE is double stranded DNA and histones

33
Q

Describe the mechanism behind type 1 diabetes?

A
34
Q

What does SLE stand for?

A

Systemic lupis erythematosus

35
Q

What is the antigen involved in SLE?

A

DNA

36
Q

Describe the mechanism behind SLE?

A
37
Q

Describe the treatment goals for autoimmune disease?

A
  • Suppression of damaging immune response
    • Before irreversible tissue damage
    • Problems with specificity of treatments and toxicity
  • Replacement of the function of the damaged organ
    • Such as hypothyroidism and insulin dependent diabetes mellitus

Im+Haem yien (23 decks)

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