3. Autoimmunity Flashcards
what are autoimmune diseases driven by?
the presence of auto antibodies or auto reactive T cells resulting in organ fibrosis
also by genetic and environmental factors
what are the risk factors for developing an autoimmune disease?
female
usually post puberty
possible recent infection
define autoimmunity
the immune response against host due to the break in immunological tolerance for self antigens
define autoimmune disease
disease caused by tissue damage or disturbed physiological responses due to an auto immune response
how can an immune disease be subdivided?
organ specific - when the auto antigen is only present on one organic resulting in specific tissue damage
non organ specific - when the auto antigen is found in multiple sites resulting in damage throughout the body - usually type 3 hypersensitivity
how can the disease severity and activity be measured?
correlated to the level of auto reactive T cells/auto antibodies in serology or biopsy (coombs test)
(also depends on organ affected and type of hypersensitivity reaction)
what are the 2 most common auto immune diseases within the UK?
systemic lupus erythematosus
sjogren’s syndrome
what are some types of primary autoantibodies driving disease?
anti TSHR antibodies in Graves’ disease
anti acetylcholine receptor antibodies in myasthenia gravis
anti voltage gated calcium channel antibodies in Lambert-Eaton myasthenia syndrome
anti- anti glomerular basement membrane antibodies in Goodpasture’s syndrome
what are some types of secondary autoantibodies involved in disease (do not drive it, occur later)?
anti nuclear antibodies in SLE
anti gastric parietal cell antibodies in pernicious anaemia
anti thyroid peroxydase antibodies in hashimoto thyroiditis
anti rheumatoid factor antibodies in RA
why do neonates not fully inherit their mother’s autoimmune condition?
so although autoimmune diseases can be transferred, the effect on the neonate diminishes by 6 months when maternal IgE/IgG fades
what treatments are available for autoimmune diseases?
- plasma exchange to remove autoantibodies
- immunosupressive drugs to suppress autoreactive T cells
- anti inflammatory drugs (corticosteroids) to treat tissue damage
- replacement surgery to treat organ dysfunction
- targeted monoclonal antibodies
what is autoimmune rheumatic disease?
results from a break in immune tolerance by producing pathogenic antibodies which result in a group of diseases which affect multiple systems
how can the severity of ARD’s be defined?
presence of autoantibodies
clinical features
what approach should be used in taking a history for ARD’S (lupus)
constitutional symptoms - fever, fatigue, weight loss, night sweats, poor appetite 'Glove and sweater' glove - Raynauds Joint pains and swelling Hand rash sweater - Proximal muscle weakness > Myalgia Hair loss Eye and mouth dryness Nose bleeds Mouth ulcers Pleuritic chest pain Pericardial pain Truncal Rash/Photosensitivity Limb weakness
what might be found on a clinical examination in someone with ARD’s?
ulcers, muscle weakness, alopecia, rash
what blood analysis would be used to investigate ARD’S?
FBC, urea, electrolytes, creatinine, liver enzymes, CRP, plasma viscosity, ERS plus autoantibodies
what are some risk factors for SLE?
female (9:1)
afro caribbean > south asian> caucasian
genetics
what is used to diagnose lupus?
A RASH POINts Medical Diagnosis must equal 4/11 to be certain ANA positive Renal abnormalities Arthralgia/arthritis Serositis Haematologic abnormalities Photosensitivity Oral ulcers Immunological abnormalities Neurologic abnormalities Malar rash / Discoid Rash
how is lupus treated?
patient education- lifestyle modification and sunscreen
DAMARDs
steroids
IV cyclophosphamide (if severe)
what are some risk factors for rheumatoid arthritis?
female (3:1)
genetics
CVS disease?
how is RA diagnosed?
S factor diagnosis - stiffness, swelling, squeezing
how is RA treated?
DAMARDs and steroids
biologics for severe cases
define immunological tolerance
diverse range of host processes that prevent potentially harmful immune responses against host antigens (or self antigens)
what is the basis for autoimmune diseases?
failure to delete autoreactive B or T cells regulatory T cell defect impaired immunomodulation altered self antigens activation of autoreactive B cells
give some examples of organ specific and non organ specific diseases
Organ specific
1.Hashimoto’s thyroiditis
2.Type 1 diabetes mellitus
3.Multiple sclerosis
4.Goodpasture’s disease
5.Addison’s disease
6.Graves’ disease
7.Myasthenia gravis
8.Pernicious anaemia
1.Thyroid peroxidase and thyroglobulin
2.Multiple proteins in pancreatic islet cells
3.Myelin sheath (nerve fibers)
4.Glomerular/alveolar basement membrane (kidney)
5.Steroid-21 hydroxylase (adrenal cortex)
6.Thyroid-stimulating hormone receptor
7.Acetylcholine receptor (neuromuscular junction)
8.Intrinsic factor (terminal ileum) + parietal cells
Non-organ specific
1.Autoimmune haemolytic anaemia
2.Rheumatoid arthritis
3.Systemic lupus erythematosus (SLE)
4. Sjogren’s syndrome
1.Red blood cells antigens
2.Rheumatoid Factor (Fc portion of the IgG)
3.Double stranded DNA (dsDNA) + other nuclear proteins
(histones)
4.Nuclear antigens (Ro and La)
give some examples of autoimmune diseases, their type of hypersensitivity reaction and clinical outcome
Organ specific Hashimoto’s thyroiditis Type 1 diabetes mellitus Multiple sclerosis Goodpasture’s disease Addison’s disease Graves’ disease Myasthenia gravis Pernicious anaemia
Hypothyroidism Hyperglycaemia Demyelinating disease Glomerulonephritis Adrenal insufficiency Hyperthyroidism Skeletal muscle weakness Vitamin B12 deficiency
Type IV Type IV Type IV Type II Type II-IV (?) Type II Type II Type II Non-organ specific Autoimmune haemolytic anaemia Rheumatoid arthritis Systemic lupus erythematosus (SLE) Sjogren’s syndrome
Anaemia
Inflammatory arthritis + systemic features
Multisystem disease
Dry eyes, dry mouth and arthritis
Type II
Type III-IV
Type III
Type IV
how are certain autoantibodies/autoreactive T cells detected at the site of damage?
Organ specific Hashimoto’s thyroiditis Type 1 diabetes mellitus Multiple sclerosis Goodpasture’s disease Addison’s disease Graves’ disease Myasthenia gravis Pernicious anaemia Thyroid gland biopsy Human healthy pancreas - Human renal biopsy Human adrenal tissues - N/A Skeletal muscle biopsy Rat stomach Infiltration of T cells Indirect immunofluorescence - Immunofluorescence Indirect immunofluorescence - Radioimmunoassay Indirect immunofluorescence Non-organ specific Autoimmune Haemolytic anaemia Rheumatoid arthritis Systemic lupus erythematosus RBC Serum Serum Coombs test Agglutination Radioimmunoassay Immunofluorescence
give some examples of the maternal autoantibody transferred to neonate and therefore the disease that may be induced
platelets - thrombocytopenia red blood cell - haemolytic anaemia TSH receptor - Neonatal Graves' disease Ach receptor - neonatal myasthenia gravis nuclear antigen SSA/Ro - neonatal SLE
what are the genetic factors responsible for autoimmunity?
increaed risk with an affected sibling and identical twin
AIRE mutation
MHC variants - HLA mutations
which environmental factors are response for triggering autoimmunity?
hormones - perhaps oestrogen as females more affected
infection
drugs
give some examples of infectious factors causing autoimmunity
Microbial antigen Disease Streptococcus pyogenes M protein Antigen in cardiac muscle Rheumatic fever Campylobacter jejuniglycoproteins Myelin-associatedgangliosides Guillain-Barré syndrome Coxsakieviruse B4nuclear protein Pancreatic islet cells Diabetes (type 1) Chlamydia trachomatis Red blood cells Haemolytic anaemia
give some examples of drugs which induce autoimmunity
Drug Syndrome
D-penicillamine (Rheumatoid arthritis) = Myasthenia gravis, Pemphigus, Systemic lupus erythematosus, Glomerulonephritis
Methyl-dopa (antihypertensive)= Haemolytic anaemia
Hydralazine (antihypertensive)
Procainamide (antiarrhythmic)
Isoniazid (antituberculosis)
Minocycline (Antibiotic) = all equal Systemic lupus erythematosu
