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Immunity > Lecture 5 - Autoimmunity Vs Autoimmune Disease > Flashcards

Lecture 5 - Autoimmunity Vs Autoimmune Disease Flashcards

1
Q

What are some autoimmune diseases of the Thyroid?

A

Graves’ disease
Hashimoto’s disease
Thyroiditis

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2
Q

What are some common autoimmune disease?

A

Systemic Lupus Erythematosus
Type 1 diabetes
Graves’ disease
Hashimoto’s disease
Rheumatoid arthritis
Multiple Sclerosis
Guillain Barre Syndrome

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3
Q

What is autoimmunity?

A

The immune response against the. Host due to loss of immunological tolerance of self-antigens

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4
Q

What is an autoimmune disease?

A

Conditions caused by tissue damage or disturbed physiological responses due to an immune response against self-antigens (Symptomatic)

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5
Q

What is immunological tolerance?

A

The diverse range of host processes that prevent potentially harmful immune responses against host antigens (self antigens)

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6
Q

What are the 3 general ways that autoimmunity occurs?

A

Breakdown of central tolerance
Breakdown of peripheral tolerance
Activation of auto reactive B cells

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7
Q

What is central tolerance and how can it break down leading to autoimmunity?

A

Lymphocytes in lymphoid tissue delete/destroy auto reactive T and B cells

Failure to delete the auto reactive T or B cells lead to damage to host cells through the auto reactive T and B cells

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8
Q

What is peripheral tolerance and how can it break down leading to autoimmunity?

A

Regulatory T cells outside of lymphoid tissue normally destroy autoreactive T or B cells

Loss of regulatory T cells leads to autoreactive cells remaining unchecked

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9
Q

What are the 2 categories of autoimmune disease?

A

Organ specific

Non-organ specific

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10
Q

What are organ specific immune diseases?

A

One or multiple self antigens within ONE single organ or tissue

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11
Q

What are non-organ specific autoimmune diseases?

A

Wide distribution of self antigens throughout the body

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12
Q

What are some organ specific autoimmune diseases?

A

Hashimotos Thyroiditis
T1DM
MS
Goodpastures disease
Addisons disease
Graves’ disease
Myasthenia gravis
Pernicious anaemia

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13
Q

What are the self antigens targeted in Hashimotos thyroiditis?

A

Thyroid peroxidase and thyroglobulin

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14
Q

What are the self antigens targeted in T1DM?

A

Multiple proteins in pancreatic islet cells

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15
Q

What are the self antigens targeted in Multiple sclerosis?

A

Myelin sheath

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16
Q

What are the self antigens targeted in Goodpastures disease?

A

Glomerular/alveolar basement membrane in kidney

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17
Q

What are the self antigens targeted in Addisons disease?

A

Steroid-21 hydroxylase in adrenal cortex

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18
Q

What are the self antigens targeted in Graves disease?

A

Thyroid stimulating hormone receptor

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19
Q

What are the self antigens targeted in Myasthenia gravis?

A

Acetylcholine receptors at neuromuscular junctions

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20
Q

What are the self antigens targeted in pernicious anemia?

A

Intrinsic factor in the terminal ileum
Parietal cells

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21
Q

What are some non-organ specific autoimmune diseases?

A

Autoimmune haemolytic anaemia
Rheumatoid arthritis
Systemic Lupus Erythematosus

Sjogrens syndrome

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22
Q

What are the self antigens targeted in Autoimmune haemolytic anaemia?

A

Red blood cell antigens

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23
Q

What are the self antigens targeted in Rheumatoid arthritis?

A

Rheumatoid factor (Fc portion of IgG)

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24
Q

What are the self antigens targeted in Systemic Lupus Eythematosus?

A

Double stranded DNA + other nuclear proteins (histones)

25
Q

What are the mechanisms by which autoimmune disease causes damage?

A

Complement activation
Neutrophil activation
Antibody-mediated cell cytotoxicity

Cytotoxic T cell
Macrophages

26
Q

What are some autoimmune diseases that are Type IV hypersensitivity reactions?

What’re are the clinical outcomes of each disease?

A

Hashimoto’s thyroiditis (Hypothyroidism)
T1DM (Hyperglycaemia)
Multiple Sclerosis (Demyelinating disease)

27
Q

What are some autoimmune diseases that are Type II hypersensitivity reactions?

What’re are the clinical outcomes of each disease?

A

Goodpastures disease (glomerulonephritis)
Graves’ disease (Hyperthyroidism)
Myasthenia gravis (skeletal muscle weakness)
Pernicious anemia (Vit B12 deficiency)

Autoimmune haemolytic anaemia (anaemia)

28
Q

What process gives temporary relief when an autoimmune condition is caused by primary autoantibodies?

A

Plasmapheresis

29
Q

What are primary autoantibodies?

A

When the antibodies are what is driving the disease

30
Q

What are secondary autoantibodies?

A

They are antibodies that done drive the disease but are present later in the disease

31
Q

What are some primary autoantibodies and what conditions are they found in?

A

Anti-TSHR antibodies in Graves
Anti-ACh receptor antibodies in Myasthenia Gravis
Anti Ca2+ Voltage-Gated antibodies in Lambert Eaton Myasthenia syndrome
Anti-glomerular basement membrane antibodies in Goodpastures syndrome

32
Q

How does lambert-Eaton myasthenia syndrome differ from myasthenia Gravis?

A

MG caused by anti acetyl choline receptor antibodies
Whereas Lamber Eaton syndrome has the same symptoms but is caused by anti Ca2+ voltage gated ion channel antibodies

33
Q

What are the secondary autoantibodies seen in:
-SLE
-Pernicious anaemia
-Hashimoto’s thyroiditis
-Rheumatoid arthritis

A

SLE - Anti-nuclear antibodies (double stranded DNA)
Pernicious anaemia - anti-gastric parietal cell
Hashimotos - anti-thyroid peroxidase antibodies
Rheumatoid - anti-rheumatoid factor

34
Q

What is specificity?

A

% of individuals who dont have condition that the test excludes

35
Q

What is sensitivity?

A

% of individuals with a condition that the test identifies

36
Q

What are some ways of identifying autoantibodies and autoreactive T cells?

A

Immunofluroescence
Radioimmunoassay

Coombs test (autoimmune haemolytic anaemia)

37
Q

How do you diagnose an autoimmune disease?

A

Presence of autoantibodies/autoreactive T cells
Levels of autoantibodies correlate with disease severity
The auto cells at site of damage
Symptomatic

38
Q

What are some examples of autoimmune disease that can be transferred from mother to neonate?

A

Thrombocytopenia
Haemolytic anaemia
Neonatal Graves’ disease
Neonatal myasthenia gravis
Neonatal SLE

39
Q

What type of immunoglobulins are able to be transferred from pregnant mother to fetus in autoimmune disease?

A

IgG

40
Q

How may myasthenia gravis present in a mother and infant?

A

Mother = double vision, Ptosis, muscle weakness

Infant = hypotonic, resp problems, poor sucking

41
Q

What is the treatment for myasthenia gravis?

A

Acetylcholinesterase antagonists:
Pyridostigmine
Neostigmin

42
Q

What is the test used to diagnose myasthenia gravis?

A

Edrophonium test

43
Q

How does the edrophonium test work?

A

Edrophonium is a drug that increases the levels of ACh at the neuromuscular junction

If the symptoms are alleviated this diagnoses myasthenia gravis

44
Q

What are the risk factors for autoimmune diseases?

A

FHx:
-sibling
-identical twin

Other genetic factors = AIRE mutations, MHC variants

Environmental:
-hormones
-infections
-drugs

45
Q

How are AIRE mutations linked to autoimmunity?

A

AIRE genes are what code for transcription for gene telling T cells to not react to self antigens (important in central tolerance)

46
Q

What are some autoimmune diseases much more common in women?

A

Hashimotos
Systemic Lupus Erythematosus
Priamry biliary cirrhosis
Autoimmmune hepatitis
Graves

47
Q

What causes Rheumatic fever?

A

Post streptococcal infection due to streptococcus pyogenes M PROTEIN binding to antigen in cardiac tissue

48
Q

What is the microbe that can cause Guillain-Barré syndrome?

A

Campylobacter jejunis glycoproteins affecting myelin associated gangliosides

49
Q

What is the microbial infection that can cause T1DM?

A

Coxsakieviruse B4 nuclear protein attacking pancreatic islet cells

50
Q

What microbe can cause haemolytic anaemia?

A

Chlamydia trachomatis attacking RBC antigens

51
Q

Go to slide 23 and diagnose:

A

GBS (guillian barre syndrome)

52
Q

What are some therapeutic drugs for autoimmune conditions like SLE?

A

Hydralazine (antihypertensive)
Isoniazid (anti-TB)
Minocycline (Antibiiotc often used in acne)

53
Q

What are some autoimmune diseases plasmapheresis is good for?

A

Myasthenia gravis
Goodpastures syndrome
Graves’ disease

54
Q

What are some immunosuppressive drugs that can work to treat autoimmune conditions by targeting autoreactive T cells?

A

Methotrexate (anti-metabolite)
Azathioprine (anti-proliferative)
Cyclophosphamide (cytotoxic)
Cyclosporin (anti-T cell therapy)

55
Q

What is the mechanism of action of azathioprine?

A

Broken down to 6MP
Then into TIMP by TPMT

56
Q

How do you treat hypothyroidism?

A

Oral thyroid hormones like Levothyroxine
Then monitor bloods

57
Q

How is Graves’ disease treated?

A

Anti thyroid hormones (Carbimazole)
Thyroidectomy

58
Q

What is the mechanism of action of Carbimazole in treating Graves’ disease?

A

Inhibits thyroid peroxidase so can oxidise iodide so cant add it to tyrosine to make thyroglobulin so less T3 and T4. Can be made

59
Q

Why do you get exophthalmos in graves?

A

Local inflammation in orbital tissue
Inflammatory cytokines driven by T cells leads to increased expression of orbital antigens that cross react with thyroid antigens

Immunity (9 decks)

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