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Microbiology And Immunology > Autoimmunity > Flashcards

Autoimmunity Flashcards

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1
Q

What are two examples of organ- specific autoimmune diseases?

A

Graves’ disease - TSH receptors in thyroid

Type 1 diabetes - insulin producing cells of pancreas

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2
Q

What is systemic lupus erythrematosus (SLE)?

A

Multi system disease

Characterised by autoantibodies to nuclear antigens

Eg. Double stranded DNA

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3
Q

What is auto immunity?

A

Immune attack or host components

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4
Q

What is immune tolerance?

A

Immune system does not attack self proteins or cells - its tolerant to them

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5
Q

Define central tolerance

A

Destroy self reactive T cell or B cells before they enter the circulation

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6
Q

Define peripheral tolerance

A

Destroy or control any self reactive T or B cells which do enter the circulation

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7
Q

What is central tolerance in terms of B cells?

A

If immature B cells in bone marrow encounter antigen in a form which can cross link their igM apoptosis is triggered

Any immature B cell will undergo apoptosis

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8
Q

What is central tolerance in term of T cells?

A

T cells recognise antigens that are presented to them by MHC - use be able to recognise foreign peptides that are bound to self-MHC

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9
Q

What is the correlation between T cell receptor and MHC binding?

A

If self MHC binding is too weak, my not be enough to allow signalling when bound with foreign peptides

If self MHC binding is too strong, may allow signalling irrespective of whether self or foreign is bound

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10
Q

When is a T cell determined as bing useless and what happens?

A

When the T cell doesn’t bind to any self-MHC at all

Death by neglect (apoptosis)

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11
Q

When is a T cell determined to be dangerous (NEGATIVE SELECTION)?

A

Binds to self-MHC too strongly

Apoptosis triggered - negative selection of T cell in thymus

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12
Q

When is a T cell determined as useful (POSITIVE SELECTION)?

A

Binds self MHC weakly

Signal to survive - positive selection

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13
Q

How can a developing T cell in the thymus encounter MHC bearing peptides expressed in other parts of the body?

A

A. Specialised transcription factor allows thymidine expression of genes that are expressed in peripheral tissues

Autoimmune regulator (AIRE)

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14
Q

What is the autoimmune regulator (AIRE)?

A

A Transcription factor that Promotes self tolerance by allowing the thymidine expression of gees from other tissues

Mutations in AIRE result in multi-organ autoimmunity

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15
Q

What are the three areas of peripheral tolerance?

A

Ignorance

Anergy

Regulation

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16
Q

What is the IGNORANCE of peripheral tolerance?

A

Antigen may be present in to low a concentration to reach the threshold. For T cell receptor triggering

Immunologically privalidged sites eg. Eye, brain - no T cells can enter this compartment

17
Q

What is the ANERGY of peripheral tolerance?

A

Naive T cells need costimulatory signals in order to become activated

Most cells lack costimulatory proteins and MHC class 2 - if a naive T cell sees it MHC peptide without appropriate costimulatory protein it becomes anergic

18
Q

What is the REGULATION of peripheral tolerance?

A

A subset of helper T cells known as Treg inhibit other T cells

19
Q

What is expressed by Treg cells?

A

Transcription factor FOXP3

Mutation in this gene leads to severe and fatal autoimmune disorder - IPEX syndrome

Crucial in the CD4 T cell function

20
Q

REVISION ACTIVITY

A

DRAW TREE DIAGRAM FROM LECTURE TO MAKE MINDMAP

21
Q

What genetic factors can increase the chance of autoimmune disease?

A

Endocrine factors - some conditions are more common in one gender than another

MHC - highly polymorphic

22
Q

What enviormental factors increase the risk of autoimmune disease?

A

Hygiene hypothesis - the environment no exposure to different pathogens - migration

Smoking and rheumatoid arthritis - study showed link

23
Q

What might trigger a breakdown of self-tolerance?

A

Loss of/problem with regulatory cells

Release of sequestered antigen

Modification of self proteins

Molecular mimicry - autoimmune response to molecule

24
Q

Describe what occurs during modification of self in citrullination

A

Citrullin is a amino acid not coded for by DNA

Arginine can be converted to citruline as a post-translational modification by PAD enzymes

Cirullinaation may be increased by inflammation

Autoantibodies to citrullinated proteins seen in rheumatoid arthritis - used for clinical diagnosis

25
Q

Describe what occurs during modification of self in rheumatic fever

A

Disease is triggered by infection with streptococcus pyogenes

Antibodies to step cell wall antigens may cross react with cardiac muscle

26
Q

What occurs during Graves’ disease?

A

Auto-antibodies bind thyroid stimulating hormone (TSH) receptor and stimulate it, resulting in hyperthyroidism

Disease can be transferred with igG antibodies

27
Q

What occurs during myasthenia gravis?

A

Autoantibodies find to acetylcholine receptor and block ability of acetyl choline to bind

Lead to receptor internalisation and degradation

Results in muscle weakness

28
Q

What occurs in SLE and vasculitis?

A

Autoantibodies to soluble antigens form immune complexes

Deposited in tissue (eg. blood vessels, joints)

Can lead to activation of compliance and phagocytosis cells

Immune complexes depositing in kidney can lead to entail failure

29
Q

How can newborn infants be cured from Graves’ disease?

A

Mother with Graves’ disease has anti-TSHR antibodies

Transfer of antibodies that mediate autoimmune diseases travel across placenta into fetus

Newborn infant also suffers from Graves’ disease

Plasmapheresis removed me tar all antibodies and cures the disease

30
Q

How do T cells play a role in autoimmune pathology?

A

Direct killing of cells by CD8 + CTL

Self destruction induced by cytokines such as TNFalpha

Recruitment and activtion of macrophages leading to bystander tissue destruction

CD4 cells providing help for Ab and cytotoxicity

Multiple sclerosis

Insulin depends diabetes mellitus

31
Q

What are TH7 cells?

A

Helper T cells that produce the cytokine IL-17

Implicate in autoimmune diseases including spondyloarthropathy, MS and diabetes

Highly inflammatory

Produce cytokines which are involved in the recruitment, migration and activation of immune cells

32
Q

What are some therapeutic strategies to deal with autoimmune disease?

A

Anti inflammatories - NSAID, corticosteroids

T and B cell depletion

Therapeutic antibodies

Antigen specific therapies, in development - increases Tregs

Microbiology And Immunology (29 decks)

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