Lecture 5 - Autoimmunity Vs Autoimmune Disease

Question 1

What are some autoimmune diseases of the Thyroid?

Answer 1

Graves’ disease
Hashimoto’s disease
Thyroiditis

Question 2

What are some common autoimmune disease?

Answer 2

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

Question 3

What is autoimmunity?

Answer 3

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

Question 4

What is an autoimmune disease?

Answer 4

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

Question 5

What is immunological tolerance?

Answer 5

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

Question 6

What are the 3 general ways that autoimmunity occurs?

Answer 6

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

Question 7

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

Answer 7

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

Question 8

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

Answer 8

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

Question 9

What are the 2 categories of autoimmune disease?

Answer 9

Organ specific

Non-organ specific

Question 10

What are organ specific immune diseases?

Answer 10

One or multiple self antigens within ONE single organ or tissue

Question 11

What are non-organ specific autoimmune diseases?

Answer 11

Wide distribution of self antigens throughout the body

Question 12

What are some organ specific autoimmune diseases?

Answer 12

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

Question 13

What are the self antigens targeted in Hashimotos thyroiditis?

Answer 13

Thyroid peroxidase and thyroglobulin

Question 14

What are the self antigens targeted in T1DM?

Answer 14

Multiple proteins in pancreatic islet cells

Question 15

What are the self antigens targeted in Multiple sclerosis?

Answer 15

Myelin sheath

Question 16

What are the self antigens targeted in Goodpastures disease?

Answer 16

Glomerular/alveolar basement membrane in kidney

Question 17

What are the self antigens targeted in Addisons disease?

Answer 17

Steroid-21 hydroxylase in adrenal cortex

Question 18

What are the self antigens targeted in Graves disease?

Answer 18

Thyroid stimulating hormone receptor

Question 19

What are the self antigens targeted in Myasthenia gravis?

Answer 19

Acetylcholine receptors at neuromuscular junctions

Question 20

What are the self antigens targeted in pernicious anemia?

Answer 20

Intrinsic factor in the terminal ileum
Parietal cells

Question 21

What are some non-organ specific autoimmune diseases?

Answer 21

Autoimmune haemolytic anaemia
Rheumatoid arthritis
Systemic Lupus Erythematosus

Sjogrens syndrome

Question 22

What are the self antigens targeted in Autoimmune haemolytic anaemia?

Answer 22

Red blood cell antigens

Question 23

What are the self antigens targeted in Rheumatoid arthritis?

Answer 23

Rheumatoid factor (Fc portion of IgG)

Question 24

What are the self antigens targeted in Systemic Lupus Eythematosus?

Answer 24

Double stranded DNA + other nuclear proteins (histones)

Question 25

What are the mechanisms by which autoimmune disease causes damage?

Answer 25

Complement activation Neutrophil activation Antibody-mediated cell cytotoxicity Cytotoxic T cell Macrophages

Question 26

What are some autoimmune diseases that are Type IV hypersensitivity reactions? What’re are the clinical outcomes of each disease?

Answer 26

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

Question 27

What are some autoimmune diseases that are Type II hypersensitivity reactions? What’re are the clinical outcomes of each disease?

Answer 27

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

Question 28

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

Answer 28

Plasmapheresis

Question 29

What are primary autoantibodies?

Answer 29

When the antibodies are what is driving the disease

Question 30

What are secondary autoantibodies?

Answer 30

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

Question 31

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

Answer 31

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

Question 32

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

Answer 32

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

Question 33

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

Answer 33

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

Question 34

What is specificity?

Answer 34

% of individuals who dont have condition that the test excludes

Question 35

What is sensitivity?

Answer 35

% of individuals with a condition that the test identifies

Question 36

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

Answer 36

Immunofluroescence Radioimmunoassay Coombs test (autoimmune haemolytic anaemia)

Question 37

How do you diagnose an autoimmune disease?

Answer 37

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

Question 38

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

Answer 38

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

Question 39

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

Answer 39

IgG

Question 40

How may myasthenia gravis present in a mother and infant?

Answer 40

Mother = double vision, Ptosis, muscle weakness Infant = hypotonic, resp problems, poor sucking

Question 41

What is the treatment for myasthenia gravis?

Answer 41

Acetylcholinesterase antagonists: Pyridostigmine Neostigmin

Question 42

What is the test used to diagnose myasthenia gravis?

Answer 42

Edrophonium test

Question 43

How does the edrophonium test work?

Answer 43

Edrophonium is a drug that increases the levels of ACh at the neuromuscular junction If the symptoms are alleviated this diagnoses myasthenia gravis

Question 44

What are the risk factors for autoimmune diseases?

Answer 44

FHx: -sibling -identical twin Other genetic factors = AIRE mutations, MHC variants Environmental: -hormones -infections -drugs

Question 45

How are AIRE mutations linked to autoimmunity?

Answer 45

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

Question 46

What are some autoimmune diseases much more common in women?

Answer 46

Hashimotos Systemic Lupus Erythematosus Priamry biliary cirrhosis Autoimmmune hepatitis Graves

Question 47

What causes Rheumatic fever?

Answer 47

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

Question 48

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

Answer 48

Campylobacter jejunis glycoproteins affecting myelin associated gangliosides

Question 49

What is the microbial infection that can cause T1DM?

Answer 49

Coxsakieviruse B4 nuclear protein attacking pancreatic islet cells

Question 50

What microbe can cause haemolytic anaemia?

Answer 50

Chlamydia trachomatis attacking RBC antigens

Question 51

Go to slide 23 and diagnose:

Answer 51

GBS (guillian barre syndrome)

Question 52

What are some therapeutic drugs for autoimmune conditions like SLE?

Answer 52

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

Question 53

What are some autoimmune diseases plasmapheresis is good for?

Answer 53

Myasthenia gravis Goodpastures syndrome Graves’ disease

Question 54

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

Answer 54

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

Question 55

What is the mechanism of action of azathioprine?

Answer 55

Broken down to 6MP Then into TIMP by TPMT

Question 56

How do you treat hypothyroidism?

Answer 56

Oral thyroid hormones like Levothyroxine Then monitor bloods

Question 57

How is Graves’ disease treated?

Answer 57

Anti thyroid hormones (Carbimazole) Thyroidectomy

Question 58

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

Answer 58

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

Question 59

Why do you get exophthalmos in graves?

Answer 59

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