Lecture 5 - Autoimmunity Vs Autoimmune Disease Flashcards
What are some autoimmune diseases of the Thyroid?
Graves’ disease
Hashimoto’s disease
Thyroiditis
What are some common autoimmune disease?
Systemic Lupus Erythematosus
Type 1 diabetes
Graves’ disease
Hashimoto’s disease
Rheumatoid arthritis
Multiple Sclerosis
Guillain Barre Syndrome
What is autoimmunity?
The immune response against the. Host due to loss of immunological tolerance of self-antigens
What is an autoimmune disease?
Conditions caused by tissue damage or disturbed physiological responses due to an immune response against self-antigens (Symptomatic)
What is immunological tolerance?
The diverse range of host processes that prevent potentially harmful immune responses against host antigens (self antigens)
What are the 3 general ways that autoimmunity occurs?
Breakdown of central tolerance
Breakdown of peripheral tolerance
Activation of auto reactive B cells
What is central tolerance and how can it break down leading to autoimmunity?
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
What is peripheral tolerance and how can it break down leading to autoimmunity?
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
What are the 2 categories of autoimmune disease?
Organ specific
Non-organ specific
What are organ specific immune diseases?
One or multiple self antigens within ONE single organ or tissue
What are non-organ specific autoimmune diseases?
Wide distribution of self antigens throughout the body
What are some organ specific autoimmune diseases?
Hashimotos Thyroiditis
T1DM
MS
Goodpastures disease
Addisons disease
Graves’ disease
Myasthenia gravis
Pernicious anaemia
What are the self antigens targeted in Hashimotos thyroiditis?
Thyroid peroxidase and thyroglobulin
What are the self antigens targeted in T1DM?
Multiple proteins in pancreatic islet cells
What are the self antigens targeted in Multiple sclerosis?
Myelin sheath
What are the self antigens targeted in Goodpastures disease?
Glomerular/alveolar basement membrane in kidney
What are the self antigens targeted in Addisons disease?
Steroid-21 hydroxylase in adrenal cortex
What are the self antigens targeted in Graves disease?
Thyroid stimulating hormone receptor
What are the self antigens targeted in Myasthenia gravis?
Acetylcholine receptors at neuromuscular junctions
What are the self antigens targeted in pernicious anemia?
Intrinsic factor in the terminal ileum
Parietal cells
What are some non-organ specific autoimmune diseases?
Autoimmune haemolytic anaemia
Rheumatoid arthritis
Systemic Lupus Erythematosus
Sjogrens syndrome
What are the self antigens targeted in Autoimmune haemolytic anaemia?
Red blood cell antigens
What are the self antigens targeted in Rheumatoid arthritis?
Rheumatoid factor (Fc portion of IgG)
What are the self antigens targeted in Systemic Lupus Eythematosus?
Double stranded DNA + other nuclear proteins (histones)
What are the mechanisms by which autoimmune disease causes damage?
Complement activation
Neutrophil activation
Antibody-mediated cell cytotoxicity
Cytotoxic T cell
Macrophages
What are some autoimmune diseases that are Type IV hypersensitivity reactions?
What’re are the clinical outcomes of each disease?
Hashimoto’s thyroiditis (Hypothyroidism)
T1DM (Hyperglycaemia)
Multiple Sclerosis (Demyelinating disease)
What are some autoimmune diseases that are Type II hypersensitivity reactions?
What’re are the clinical outcomes of each disease?
Goodpastures disease (glomerulonephritis)
Graves’ disease (Hyperthyroidism)
Myasthenia gravis (skeletal muscle weakness)
Pernicious anemia (Vit B12 deficiency)
Autoimmune haemolytic anaemia (anaemia)
What process gives temporary relief when an autoimmune condition is caused by primary autoantibodies?
Plasmapheresis
What are primary autoantibodies?
When the antibodies are what is driving the disease
What are secondary autoantibodies?
They are antibodies that done drive the disease but are present later in the disease
What are some primary autoantibodies and what conditions are they found in?
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
How does lambert-Eaton myasthenia syndrome differ from myasthenia Gravis?
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
What are the secondary autoantibodies seen in:
-SLE
-Pernicious anaemia
-Hashimoto’s thyroiditis
-Rheumatoid arthritis
SLE - Anti-nuclear antibodies (double stranded DNA)
Pernicious anaemia - anti-gastric parietal cell
Hashimotos - anti-thyroid peroxidase antibodies
Rheumatoid - anti-rheumatoid factor
What is specificity?
% of individuals who dont have condition that the test excludes
What is sensitivity?
% of individuals with a condition that the test identifies
What are some ways of identifying autoantibodies and autoreactive T cells?
Immunofluroescence
Radioimmunoassay
Coombs test (autoimmune haemolytic anaemia)
How do you diagnose an autoimmune disease?
Presence of autoantibodies/autoreactive T cells
Levels of autoantibodies correlate with disease severity
The auto cells at site of damage
Symptomatic
What are some examples of autoimmune disease that can be transferred from mother to neonate?
Thrombocytopenia
Haemolytic anaemia
Neonatal Graves’ disease
Neonatal myasthenia gravis
Neonatal SLE
What type of immunoglobulins are able to be transferred from pregnant mother to fetus in autoimmune disease?
IgG
How may myasthenia gravis present in a mother and infant?
Mother = double vision, Ptosis, muscle weakness
Infant = hypotonic, resp problems, poor sucking
What is the treatment for myasthenia gravis?
Acetylcholinesterase antagonists:
Pyridostigmine
Neostigmin
What is the test used to diagnose myasthenia gravis?
Edrophonium test
How does the edrophonium test work?
Edrophonium is a drug that increases the levels of ACh at the neuromuscular junction
If the symptoms are alleviated this diagnoses myasthenia gravis
What are the risk factors for autoimmune diseases?
FHx:
-sibling
-identical twin
Other genetic factors = AIRE mutations, MHC variants
Environmental:
-hormones
-infections
-drugs
How are AIRE mutations linked to autoimmunity?
AIRE genes are what code for transcription for gene telling T cells to not react to self antigens (important in central tolerance)
What are some autoimmune diseases much more common in women?
Hashimotos
Systemic Lupus Erythematosus
Priamry biliary cirrhosis
Autoimmmune hepatitis
Graves
What causes Rheumatic fever?
Post streptococcal infection due to streptococcus pyogenes M PROTEIN binding to antigen in cardiac tissue
What is the microbe that can cause Guillain-Barré syndrome?
Campylobacter jejunis glycoproteins affecting myelin associated gangliosides
What is the microbial infection that can cause T1DM?
Coxsakieviruse B4 nuclear protein attacking pancreatic islet cells
What microbe can cause haemolytic anaemia?
Chlamydia trachomatis attacking RBC antigens
Go to slide 23 and diagnose:
GBS (guillian barre syndrome)
What are some therapeutic drugs for autoimmune conditions like SLE?
Hydralazine (antihypertensive)
Isoniazid (anti-TB)
Minocycline (Antibiiotc often used in acne)
What are some autoimmune diseases plasmapheresis is good for?
Myasthenia gravis
Goodpastures syndrome
Graves’ disease
What are some immunosuppressive drugs that can work to treat autoimmune conditions by targeting autoreactive T cells?
Methotrexate (anti-metabolite)
Azathioprine (anti-proliferative)
Cyclophosphamide (cytotoxic)
Cyclosporin (anti-T cell therapy)
What is the mechanism of action of azathioprine?
Broken down to 6MP
Then into TIMP by TPMT
How do you treat hypothyroidism?
Oral thyroid hormones like Levothyroxine
Then monitor bloods
How is Graves’ disease treated?
Anti thyroid hormones (Carbimazole)
Thyroidectomy
What is the mechanism of action of Carbimazole in treating Graves’ disease?
Inhibits thyroid peroxidase so can oxidise iodide so cant add it to tyrosine to make thyroglobulin so less T3 and T4. Can be made
Why do you get exophthalmos in graves?
Local inflammation in orbital tissue
Inflammatory cytokines driven by T cells leads to increased expression of orbital antigens that cross react with thyroid antigens
