Brainscape's Knowledge GenomeTM

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


See full index

Cellular and Molecular pathology > 26. Autoimmune Diseases > Flashcards

26. Autoimmune Diseases Flashcards

1. Understand the steps that lead to autoimmune disease. 2. Describe factors that influence the development of autoimmune disease. 3. Classify autoimmune disease by type of target and type of immune response.

1
Q

What is the ideal state of immunity?

A
  1. Balanced
  2. Not enough immunity can be lethal.
  3. Too much immunity can also be lethal.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What determines a patient’s background susceptibility to autoimmunity?

A

Genetic and environmental factors

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

What is needed for an autoimmune disease to develop?

A
  1. A trigger
  2. These are usually environmental
  3. They can be stochastic (random) and unavoidable due to the immune system relying on randomness.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is an autoimmune disease?

A

An immune process characterised by activation of adaptive immune cells that respond to self-antigens and cause immunopathology.
This includes all type of hypersensitivity except type 1.

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

What are the clinical groupings of autoimmunity?

A
  1. Organ-specific: T cell mediated
  2. Organ specific: Antibody mediated
  3. Systemic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How common is autoimmune disease?

A
  1. At least 80 different human diseases.
  2. 5-8% prevalence
  3. Many different targets.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Are autoimmune diseases increasing in incidence?

A

Yes…could be called an epidemic of autoimmunity.
They are also difficult to diagnose and new diseases continue to be found.

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

How does the nature of immune genes lead to autoimmune disease?

A
  1. They are highly polymorphic so there is lots of variability.
  2. Individual proteins vary between people and are present above 2% of the population.
  3. lots of proteins in the immune system are polymorphic.
  4. This provides lots of potential targets
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does the random rearrangement of antigen receptors lead to autoimmune disease?

A
  1. The immune system relies on randomness to be effective.
  2. It has evolved to produce an effective immune response to novel antigens.
  3. All mechanisms to reduce self-reactive immune cells is done after gene rearrangement is done.
  4. This means self-reactive receptors are generated all the time and some escape selection.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does the environment lead to autoimmune disease?

A
  1. Via environmental triggers like infection.
  2. You will produce an immune response to infection and this varies from person to person.
  3. Some infections can trigger autoimmunity.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Common autoimmune diseases: Graves’ disease

A

Stimulating antibodies against TSH receptor causing hyperthyroidism

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

Common autoimmune diseases: Hashimoto’s thyroiditis

A

Blocking antibodies and destructive T cells against thyroid antigens causing hypothyroidism.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Common autoimmune diseases: Rheumatoid Arthritis

A

Autoreactive T cells against joint synovium causing joint inflammation and destruction. Autoantibodies also present.

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

Common autoimmune diseases: Type 1 diabetes

A

T cells against ß islet cells causing ß cells destruction and lack of insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Common autoimmune diseases: Multiple Sclerosis

A

T cells against brain antigens causing destruction of myeline sheath and loss of nerve axons.

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

Common autoimmune diseases: SLE (lupus)

A

Autoantibodies to DNA, chromatin proteins and ribonucleoprotein antigens causing many systemic symptoms like glomerulonephritis and vasculitis.

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

What are the typical clinical features of autoimmune diseases?

A
  1. Family history showing a common hyperactive immune system.
  2. female predisposition.
  3. T-helper cell dependant or autoantibodies.
  4. Common association with HLA class 1
  5. Chronic course, relapses and remits
  6. Responds to immunosuppressive therapy.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are some genetic causes of autoimmunity?

A

Lots of points where a single gene mutation can lead to autoimmune disease but they are not common:
1. Fas/FasL affecting the deletion of autoreactive T cells.
2. Foxp3 affecting the generation of Treg cells.
3. CTLA4 affecting the inhibition of immune cells

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

What is sporadic autoimmunity?

A

Autoimmunity that arises in someone with autoimmune disease in the family but with a non-obvious genetic cause.
This is modulated by polymorphisms in many genes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the link between autoimmunity and resistance to infection?

A
  1. The immune system is designed to produce the best response but it is not perfect.
  2. If you develop a more aggressive response to infection it leads to resistance to infection
  3. BUT it can also lead to autoimmunity if it is triggered in the wrong way.
21
Q

What shows the link between genetics, the environment and autoimmune disease?

A
  1. As genetic sharing increases the risk of autoimmune disease also increases.
  2. But even if you are identical twins the other twin will only have a ~1/3 chance of also developing autoimmunity.
  3. This shows there are strong environmental factors at play.
22
Q

What do a lot of autoimmune diseases have a strong link to?

A

With different MHC alleles

23
Q

What genes are commonly associated with autoimmune disease?

A
  1. MHC genes that regulate autoantigen presentation and T cell repertoire selection.
  2. Genes that influence immune system activation and regulation.
  3. Most of these associations have unknown mechanisms.
24
Q

Why are MHC genes heavily linked to autoimmunity?

A
  1. They regulate antigen presentation so if you have a self antigen that cannot be presented on MHC then you cannot get autoimmunity against it.
  2. You need to have a MHC that can present autoantigens for autoimmunity to be triggered.
  3. Different MHC alleles have different abilities to present antigens.
  4. MHC also present antigens in the thymus for T cell selection and elimination of self reactive T cells.
25
Q

Why are T cell responses so important in auto immune disease?

A

They also effect T cell dependant B cell responses.

26
Q

What do other genes associated with autoimmune disease control?

A
  1. How fast the immune response is
  2. How strong the immune response is
  3. How long the immune response lasts
27
Q

How are infections linked to autoimmune disease?

A
  1. Some autoimmune diseases are always preceded by a certain infection.
  2. It doesn’t mean you will develop the disease if you get infected.
  3. BUT it does mean the infection is necessary to develop the autoimmune disease.
28
Q

What are 2 examples of autoimmune disease associated with infections?

A
  1. Group A streptococci and Rheumatic Heart disease due to molecular mimicry.
  2. Epstein-Barr virus and Multiple Sclerosis
29
Q

What are infections also associated with?

A

Relapsing in autoimmune diseases

30
Q

What is the hygiene hypothesis?

A
  1. The hypothesis that infection might sometimes prevent autoimmune disease and allergy.
  2. People who had more infection as a child has less autoimmune response as adults
31
Q

What trends were seen as infectious diseases decreased?

A

As infectious diseases decreased in incidence autoimmune diseases increased.

32
Q

What can make autoimmune diseases hard to study?

A

Their inherent randomness.

33
Q

How has migration shown the impact of environment on autoimmunity?

A
  1. Migrants moving from Pakistan to the UK show the UK trends in autoimmunity if they move as children. (under 15)
  2. This shows that childhood exposure is important for developing resistance to autoimmunity.
34
Q

Why do infections help with immunity?

A
  1. Individual immune systems are unique and a product of their education.
  2. These help educate central and peripheral tolerance mechanisms.
  3. This education lasts for life.
35
Q

What are the triggering mechanisms that lead to autoimmunity?

A
  1. Molecular Mimicry
  2. Bystander activation
  3. Abnormal immune regulation
36
Q

How does molecular mimicry lead to autoimmune disease?

A

An epitope from an infection looks the same as a self protein

37
Q

How does bystander activation lead to autoimmune disease?

A
  1. An ongoing infection can trigger a lot of damage and damage signals.
  2. This triggers a more aggressive adaptive immune response in the organ.
  3. This causes upregulation of cells including some self-reactive cells.
  4. This can be triggered by trauma.
38
Q

How does abnormal immune regulation lead to autoimmune disease?

A

The immune system doesn’t shut down after infection leading to failures in regulation of self-reactive T cells.

39
Q

T cell-mediated autoimmunity in a specific organ/tissue

A
  1. A type 4 hypersensitivity reaction
  2. Autoantigen specific CD4 T cells.
  3. Usually Th1 and Th17 induced by IFNy and Th17.
  4. Tissue destruction and disruption/loss of function.
  5. Autoimmunity is limited to the organ expressing the antigen.
40
Q

Antibody-mediated autoimmunity in target organs

A
  1. Autoantibodies occur in the absence of disease or precede disease.
  2. Type 2 hypersensitivity
  3. T helper cell dependant antibody isotypes.
  4. Some of these disease associated with tumours.
41
Q

What is different about autoantibody mediated diseases?

A

The presence of autoantibodies does not always mean clinical disease will be present.

42
Q

How does Graves’ disease work?

A
  1. Normally thyroid hormones are stimulated by TSH binding the TSH receptor and is controlled by negative feedback limiting the amount of TSH.
  2. In Graves’ disease an Autoantibody binds the TSH receptor and stimulates hormone synthesis independent from any regulation.
  3. This causes overproduction of thyroid hormones.
43
Q

Where do immune complex mediated system autoantibodies develop?

A

In the blood and then are distributed to the organs

44
Q

What do immune complex mediated system autoantibodies develop against?

A

DNA nucleoproteins

45
Q

What is systemic lupus erythematosus?

A
  1. High female bias
  2. Fever, weakness, arthritis, rashes, kidney dysfunction
  3. more common in african-american and hispanics
  4. antibodies to DNA, histones, RBCC platelets, leukocytes and clotting factors
  5. immune complexes form
46
Q

Diagnosis of autoimmune disease

A
  1. Clinical diagnosis
  2. Confirm with diagnostic tests
  3. exclude infections
47
Q

Treatment of autoimmune disease

A
  1. Replacement like in diabetes
  2. Immunosuppression
48
Q

What is the goal of treating autoimmune disease?

A

To be able to shut down antigen specific response and treat without systemic side effects.

Cellular and Molecular pathology (25 decks)

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