Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

SEM 4: Immunology > Autoimmunity > Flashcards

Autoimmunity Flashcards

1
Q

What is the action of Graves’ disease?

A

It is an antibody response against the TSH receptor in the thyroid. It leads to inflammation in the eyes due to low levels of TSH receptors expressed by the fibroblast in the eye. Therefore, thought to be mediated by B cells due to the antibodies.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the action in Type 1 disease?

A

T cells attack the beta cells in the pancreas leading to no production of insulin. Therefore, thought of to be mediated by T cells due to the direct killing of the cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are spondyloarthropathies?

A

A family of long-term (chronic) diseases of joints. It is MHC specific autoimmunity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the major gene associated with spondyloarthropathies?

A

HLA-B27

HLA B27-associated spondylarthropathies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Give examples of HLA B27-associated spondylarthropathies diseases

A

Ankylosing spondylitis, undifferentiated spondyloarthropathy, reactive arthritis, psoriatic arthritis, urethritis, iritis.
All of these are associated with bowel inflammation as well.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is spondyloarthropathy in the knee?

A

Arthritis in the knee joints and spine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is psoriasis?

A

Disease of the skin cut can get arthritis inflammation of the joint associated with B27.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is systemic lupus erythematosus (SLE)?

A

A multi-system disease characteristed by autoantibodies to nuclear antigens such as dsDNA. It is a disease of relapse and remission.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is autoimmunity?

A

When the immune system has various regulatory controls to prevent it from attacking self-proteins and cells. The failure of these controls will result in immune attack of host components which is autoimmunity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the 2 pathways that allow the immune system to know what to attack?

A

Central tolerance: destroy self-reactive T or B cells before they enter the circulation.

Peripheral tolerance: destroy or control any self-reactive T or B cell which now enter the circulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the central tolerane of B cells

A

B cells mature in the bone marrow and go through a series of maturation and differentiation pathways. They gain specific surface bound immunoglobulins which will be complementary to antigen.
When they mature in the bone marrow, if they recognise a self-antigen (for example from a stromal cell) and they bind to it via their IgM, an apoptotic signal will be triggered, and they will get destroyed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the action of T cells

A
  • T cells recognise antigens that are presented to them by MHC proteins.
  • Therefore, the T cells need to be able to recognise foreign peptides that are bound to self-MHC on either APCs.
  • This happens so a certain threshold is reached for the T cell to get activated.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is important about the binding between TCR and MHC binding?

A

TCR need to bind to self MHC not too weakly or else there will not be enough signalling when binding to the foreign antigen peptide and not too strongly binding otherwise lead to signalling and activation of the T cell irrespective of whether there is a foreign antigen on the groove or not.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is the central tolerance in T cells checked?

A
  • Is it useless: if it doesn’t bind to any self-MHC than it is killed by apoptosis.
  • Is it dangerous: if it binds to MHC too strongly, it is killed by apoptosis via negative selection.
  • Is it useful: If it binds to MHC weakly (but too weakly), it will survive via positive selection.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

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

A

A specialised transcription factor allows thymic expression of genes that are expressed in peripheral tissues. This gene is called AIRE.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is AIRE (autoimmune regulator)?

A

This is a gene which promotes self-tolerance by allowing in the thymic expression of genes from other tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What happens if there is mutations in the AIRE gene?

A

Mutations in this gene leads to multi-organ autoimmunity. It causes other diseases such as hypoparathyroidism, candidasis etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the function of peripheral tolerance for auto-active B cells and T cells?

A

They are able to escape central tolerance, and enter the circulation, therefore there needs to be a second way of controlling them. This is peripheral tolerance which is broken down into 3 main areas.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the 3 main areas of peripheral tolerance?

A
  • Ignorance
  • Anergy
  • Regulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the ignorance of peripheral tolerance?

A
  • This is when the T or B cells is not aware of the antigen presence, due to it being present in low concentrations.
  • Therefore, the threshold to activate the cell is not reached.
  • This may be in immunological privileged sites such as the eye or the brain.
21
Q

What is anergy of T cells (peripheral tolerance)?

A
  • This is when co-stimulatory signals needed to activate the cell such as naive T cells are not present. Most cells lack costimulatory proteins and MHC II.
  • This means that even if a naive T cell sees a self MHC antigen peptide molecule, without the appropriate costimulatory signals it becomes anergic.
  • This means it is less likely to be stimulated in the future even if the presence of co-stimulation.
  • Also, for a T cell to work, they need to see the MHC antigen complex on a professional APC (dendritic cell) and therefore, if it presented by a different type of cell for example it won’t get activated.
  • Therefore, anergy is a state where the immune cell will not response even though it recognises the MHC molecule because the correct signals are not present.
22
Q

What is the regulation of T cells in peripheral tolerance?

A

A subset of T cells are known as Treg cells (T regulator). These are inhibitor other T cells and prevent the overactivation of the immune system. When Treg cells bind to antigens on the surface of APCs, they can send negative signals to other cells via IL20 and TGFbeta. Treg cells express transcription factor FOXP3 which allows them to do their function.

23
Q

What happens to Treg when there are mutations?

A
  • Defective Treg cells are associated with multiple sclerosis.
  • Certain cytokines such as IL10 dampen down the immune response.
  • In cancer, there are increased levels of Treg.
  • In autoimmune diseases, there are decreased levels of Treg.
  • Mutation in FOXP£ leads to severe and fatal autoimmune disorder called IPEX.
24
Q

What is IPEX?

A

A severe and fatal autoimmune disorder which stands for immune dysregulation, polyendocrinopathy, enteropathy X linked syndrome.

25
Q

Summarise anergy, ignorance and immune regulation in Peripheral T cell tolerance

A

Anergy: Exposure to antigen but without appropriate costimulatory signals so no activation.

Ignorance: Immune privilege and sequestered antigen

Immune regulation: regulatory cells, Treg

26
Q

What is the genetics of MHC?

A

Each copy of chromosome 6 carries 3 different MHC class I genes and 3 different MHC class II genes. There are high levels of genetic variation polymorphisms, this is so the MHC molecule is able to recognise wide variety of antigens and peptides. MHC is associated with more diseases than any other region of the genome.

27
Q

In which gender is systemic lupus erythematosus (SLE) more common in?

A

It is 10 times more common in females than males.

28
Q

In which gender is multiple sclerosis more common in?

A

10 times more common in females than males.

29
Q

In which gender is diabetes more common in?

A

Equally common in females and males

30
Q

In which gender is ankylosing spondylitis more common in?

A

Approximately 3 times more common in males than females.

31
Q

What are the environmental factors that can influence the development of autoimmune diseases?

A

Hygiene hypothesis: NOD mice and SPF conditions

Smoking and rheumatoid arthritis

32
Q

What might trigger a breakdown of self-tolerance?

A
  • Loss of function or problem with regulatory cells
  • Release of sequestrated (hidden) antigen
  • Modification of self
  • Molecular mimicry
33
Q

What is citrullin?

A

An amino acid, not coded for by DNA.

34
Q

How is arginine converted to citrulline?

A

It is converted to citrulline as a post-translational modification by peptidylarginine deiminase (PAD) enzyme which means the structure is not different.

35
Q

What can lead to an immune response in the change in Citrullin and Arginine?

A

The change in shape of peptides might lead to immune response. Citrullination may be increased by inflammation.

36
Q

What is a modification of self-citrullination that can lead to an autoimmune disease?

A
  • The change in shape of peptides might lead to immune response.
  • Citrullination may be increased by inflammation.
  • There are auto-antibodies against citrullinated proteins seen in rheumatoid arthritis.
  • These are now used in clinical diagnosis.
37
Q

What is rheumatic fever?

A
  • It is a disease triggered by infection with Streptococcus pyogenes.
  • Antibodies which attack the bacteria cell wall, can sometimes cross-react with cardiac muscles leading to rheumatic fever.
38
Q

Describe the pathology behind Graves’ disease

A
  1. Auto-antibodies bind to TSH receptors and stimulate them, resulting in hyperthyroidism.
  2. The disease can be transferred with IgG antibodies.
  3. In Hashimotos, the anitbody binds to the same receptor but causes inflammation instead of overactivity.
39
Q

Describe the pathology behind Myasthenia Gravis

A
  1. Autoantibodies bind to acetylcholine receptor and block the ability of acetylcholine to bind.
  2. It also leads to receptor internalisation and degradation.
  3. This results in muscle weakness.
40
Q

Describe the pathology behind SLE and Vasculitis

A
  1. Autoantibodies and soluble antigens form immune complexes.
  2. These get deposited in tissues such as blood vessels, joints and renal glomerulus.
  3. This leads to activation of complement and phagocytic cells
  4. The immune complexes depositing in the kidney can lead to renal failure.
41
Q

What is the difference between autoimmune diseases mediated by IgG and normal autoimmune disease?

A
  1. Autoimmune diseases mediated by IgG can be transferred across the placenta.
  2. The patient makes anti-TSHR antibodies.
  3. This means if a mother has Graves’ disease, her antibodies can cross the placenta to the baby and bind to the baby’s TSH receptors leading to the baby suffering with Graves as well.
42
Q

What can cure Graves’ disease in baby’s?

A

Plasmapheresis removed maternal antibodies and cures the disease

43
Q

How can T cells activate autoimmune pathology?

A
  1. T cells can lead to the direct killing by CD8+ cells.
  2. They can release cytokines such as TNFalpha which leads to self-destruction of the cells.
  3. This recruits and activates macrophages which lead to bystander tissue destruction.
  4. T helper CD4 cells provide help for antibodies and cytotoxicity.
  5. This can all lead to multiple sclerosis and insulin dependent diabetes mellitus.
44
Q

What are Th17 cells?

A

Th17 cells are helper T cells that produce the cytokine IL17.

45
Q

What is the cytokine IL17?

A

It is a highly inflammatory cytokine which leads to recruitment, migration and activation of immune cells to the site of inflammation.

46
Q

Where do Th17 cells reside?

A

These cells live in the mucosal surfaces and the skin.

47
Q

What are Th17 cells associated with?

A

They are associated with autoimmune diseases such as spondyloarthropathy, MS and diabetes.

48
Q

What are therapeutic strategies of autoimmune diseases?

A
  • Anti-inflammatories such as NSAIDs and corticosteroids.
  • T and B cell depletion via anti-CD4 and anti-CD8.
  • Anti-TNF only works for a short amount of time as there will be a production of antibodies against those antibodies.
  • Anti-VLA-4 interferes with adhesion to stop inflammation.
  • Glatiramer acetate increases Treg cells.

SEM 4: Immunology (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions