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2.1 Molecular Immunology > Greg - Clinical Immunology (autoimmunity) > Flashcards

Greg - Clinical Immunology (autoimmunity) Flashcards

1
Q

What is an autoimmune reaction?

A

A reaction against self

The immune system targeting an autoantigen - self antigen

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2
Q

How many known autoimmune diseases are there?

A

There are 100+ diseases

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3
Q

Classify auto immune diseases

A

Organ-specific

Systemic

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4
Q

Give an example of an organ-specific autoimmune disease

A

Type 1 diabetes

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5
Q

Give an example of a systemic autoimmune disease

A

Systemic lupus erythematosus

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6
Q

Why are auto-immune conditions usually life long?

A

Because the antigen cannot be eradicated, stimulus is constant therefore disease is usually life-long

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7
Q

Give two occasions where the immune system must be suppressed?

A

Pregnancy

Transplant

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8
Q

In what case can an autoimmune condition be reversed?
(2)

A

If the autoimmune condition is diagnosed in childhood

The condition can burn out in puberty

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9
Q

What is an autoantigen?
(3)

A

An antigen of human

If an antigen is in organ e.g. pancreas it will only manifest locally

If antigen is in areas such as the joint it can be widespread

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10
Q

What is systemic disease?

A

A disease that can manifest anywhere in the body

e.g. systemic lupus erythematosus

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11
Q

Give two diseases that affect the nervous system

A

Multiple sclerosis

Myasthenia gravis

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12
Q

Give two diseases that affect the endocrine system

A

Type 1 diabetes mellitus

Grave’s disease

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13
Q

Give two diseases that affect the skin

A

Psoriasis

Dermatomyositis

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14
Q

Give two diseases that affect the GIT

A

Ulcerative colitis

Crohn’s Disease

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15
Q

Give two diseases that affect the bones

A

Reumatoid arthritis

Sjogren’s syndrome

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16
Q

Who do autoimmune disease affect most, males or females

A

Females

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17
Q

How does autoimmunity come about?
(3)

A

Initiated by a loss of tolerance

Autoreactive T cells should be deleted in the thymus -> in disease they are not -> out of the thymus they cause disease

Patients have some predisposing genetic background

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18
Q

Give an example of a mild disease

A

Psoriasis

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19
Q

Give an example of a fatal disease

A

Primary progressive MS

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20
Q

How can you have a predisposition to autoimmune conditions?

A

Mutations are found on the HLA region -> risk is transferred here

Having the gene does not mean you will have the disease but you will be at a very high risk

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21
Q

Give some things that can increase your risk of autoimmunity

A

Infections can increase the risk of autoimmunity

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22
Q

What is diabetes?

A

Loss of blood sugar control

23
Q

How does insulin work in normal patients

A
  • consumption of food is followed by insulin production
  • insulin binds to insulin receptors on cells
  • glucose transporters are moved to the cell surface
  • available glucose is then taken into the cell
24
Q

What happens in type 1 diabetes?

A

Insulin production is stopped

Autoimmune

25
Q

What happens in type 2 diabetes?

A

Insulin resistance develops

Usually lifestyle-related

26
Q

What is the main culprit in type 1 diabetes

A

The autoreactive T cell

27
Q

What roll do autoreactive T cells have in type 1 diabetes

A

They lead the selective destruction of insulin-producing beta-cells

T cells made against antigens in the pancreas- against insulin - against GAD65 - against islet-cell antibodies

28
Q

What roll do B cells have in type 1 diabetes
(3)

A

They produce anti-insulin antibodies

They produce anti-glutamic acid decarboxylase 65 (GAD65) antibodies

Anti-islet cell antibodies

29
Q

What is GAD65

A

Glutamic acid decarboxylase 65

30
Q

Why does the T cell attack the beta cells?

A

T cell acts like the B cell is infected with a virus

They only attack the Beta cells

31
Q

Why can we not reverse diabetes at the moment
(2)

A

There is no stem cell for Beta cells

However Harvard has been able to make a stem cell into a beta cell -> which hopefully in the future can be put back into the body

32
Q

What three methods are there to diagnosing autoimmune conditions?

A

The detection of antibodies

The detection of generic markers of inflammation - ESR and CRP

Measuring other generic marks of health - platelet levels and anaemia

33
Q

What are two generic markers of inflammation?

A

ESR

CRP

34
Q

What are two generic markers of health

A

Platelet levels

Anaemia (rbc count)

35
Q

How do we detect autoantibodies by fluorescence?

A

Uses commercially available, labelled antibodies to detect patient autoantibodies in serum, or tissue

36
Q

Give some examples of commercially available antibodies
(5)

A

Anti-nuclear antibodies

Anti-neutrophil cytoplasmic antibodies

Endomysial antibodies

Anti-glomerular basement membrane antibodies

Lupus skin

37
Q

What is direct immunofluorescence

A

Detecting antibodies in human tissue samples

38
Q

How do we carry out direct immunofluorescence?
(2)

A

We take a biopsy from a patient

Antibodies here are bound to antigen

39
Q

Give an example of how we use direct immunofluorescence

A

Autoantibodies in the skin of lupus patients

40
Q

What is indirect immunofluorescence?

A

Detecting antibodies from patient serum

41
Q

How do we carry out indirect immunofluorescence

A

Antibodies are in serum

These react with antigen

There is a fluorescent reaction

42
Q

Give an example of how we use indirect immunofluorescence

A

Used to detect antinuclear antibodies

43
Q

How do we use direct immunofluorescence to detect systemic lupus erythematosus?
(4)

A

Patients with lupus may have antibodies deposited in their skin (butterfly rash) at the dermoepidermal junction

A skin biopsy is taken from the patient

Biopsy is sectioned and stained with anti-human IgM-FITC antibodies

Gives green fluorescence band -> ‘lupus band’

44
Q

Where does lupus deposit autoantibodies?

A

At the dermoepidermal junction

45
Q

What is used to stain for antibodies in lupus?

A

Anti human IgM FITC antibodies

46
Q

What does a positive test for lupus look like|?

A

A positive test results in apple green fluorescence at the dermoepidermal junction

47
Q

Explain how we use indirect immunofluorescence to detect anti-nuclear antibodies

A

Anti-nuclear antibodies are used to diagnose autoimmune connective tissue diseases such as rheumatoid arthritis and lupus

48
Q

How are anti-nuclear antibodies produced
(3)

A

Company grows cells on slide

Hep2 cell line

These cells have a nice big nucleus so any reaction is easy to see

49
Q

How are autoantibodies detected?

A

Via immunoassay e.g. ELISA

Immunocap

50
Q

Why would ELISA be better than fluorescence detection of antibodies

A

ELISA is faster, automated and quantitative

51
Q

How does immunocap work?

A

Each cap is coated with different antigens

Add diluted patient sample

Wash

Add conjugated antibody

52
Q

What type of autoantibodies are used in ELISA?

A

They tend to be IgG/IgM/IgA in nature

53
Q

How does immunocap assay work?
(7)

A

Autoantigen is pre-coated on a cap

Diluted patient serum is added and specific IgG if present will bind

Unbound serum proteins are washed away

A fluorescently-labelled secondary anti-IgG is added

Unbound secondary antibody is washed away

Fluorescence signal is measured

Fluorescence is proportional to anti-peanut antibody concentration

2.1 Molecular Immunology (19 decks)

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