Autoimmunity - 4 Flashcards
define autoimmunity
Autoimmunity: Immune response against the host
due to the loss of immunological tolerance of selfantigen(s)
define an autoimmune disease
disease caused by tissue damage or disturbed physiological responses due to an auto immune response
8 organ specific diseases - H, DM, P, MS,GDp, A,G, MyG, PA
4 non organ specific diseases
name them and give their self antigen AHA,RHa,SLE,SJ
then give the clinical outcome and what type of hypersensitivity reaction they are
Hashimoto’s thyroiditis - thyroid peroxidase and thyroglobulin - hypothyroidism - Type IV
Type1 diabetes mellitus* - pancreattic islet cells - hyperglycemia - type IV
Multiple sclerosis - mylein sheath - demylenating disease - type IV
Goodpasture’s disease - glomeluar/alveolar BM - glomerulonephritis - type II
Addison’s disease - steroid 21 hydroxylase - adrenal insufficency - Type II-IV ?
Graves’ disease - thyroid stimulating hormone receptor - hyperthyroidism - Type II
Myasthenia gravis - ach receptor at the NMJ - skeletal muscle weakness - Type II
Pernicious anaemia* - IF at terminal ileum - vit B12 def. - type II
Non-organ specific
Autoimmune haemolytic anaemia - RBC antigens - anaemia - type II
Rheumatoid arthritis - Rheumatoid factor - Fc portion of IgG - inflammatory arthritis + systemic - type II-IV
Systemic lupus erythematosus (SLE)* - DsDNA - Multisystem disease - everything - type III
Sjogren’s syndrome* - neuclear antigens - Ro and La - dry eyes,dry mouth, arthritis - Type IV
8 organ specific diseases - H, DM, P, MS,GDp, A,G, MyG, PA
4 non organ specific diseases
name them and give their self antigen AHA,RHa,SLE,SJ
then give the clinical outcome and what type of hypersensitivity reaction they are
give the treatment option
Hashimoto’s thyroiditis - thyroid peroxidase and thyroglobulin - hypothyroidism - Type IV - Replacement therapy
Type1 diabetes mellitus* - pancreattic islet cells - hyperglycemia - type IV - Replacement therapy
Multiple sclerosis - mylein sheath - demylenating disease - type IV - anti inflam and MCA’s
Goodpasture’s disease - glomeluar/alveolar BM - glomerulonephritis - type II - plasmaphersis
Addison’s disease - steroid 21 hydroxylase - adrenal insufficency - Type II-IV ? - replacment therapy
Graves’ disease - thyroid stimulating hormone receptor - hyperthyroidism - Type II - anti thyroid drugs/immunosupress
Myasthenia gravis - ach receptor at the NMJ - skeletal muscle weakness - Type II -anticholinesterase drugs/immunosupress
Pernicious anaemia* - IF at terminal ileum - vit B12 def. - type II - replacment theraphy
Non-organ specific
Autoimmune haemolytic anaemia - RBC antigens - anaemia - type II - anti - inflam and splenectomy
Rheumatoid arthritis - Rheumatoid factor - Fc portion of IgG - inflammatory arthritis + systemic - type II-IV -immunosupress/MCA’s
Systemic lupus erythematosus (SLE)* - DsDNA - Multisystem disease - everything - type III - immunosupress/MCA’s
Sjogren’s syndrome* - neuclear antigens - Ro and La - dry eyes,dry mouth, arthritis - Type IV
what is the general pathophsy of autoimmune disease ?
Hypersensitivity reactions • Autoantibody driven o Complement activation o Antibody-mediated cell cytotoxicity o Neutrophil activation
• Autoreactive T cell driven
o Cytotoxic T cells
o Macrophages
this all will lead to tissue fibrosis - and hence loss of function of tissue
3 criteria to diagnose a disease as autoimmune
- Presence of autoantibodies/autoreactive T cells
- Levels of autoantibodies correlate with disease severity
- Autoantibodies/autoreactive T cells found at the site of tissue damage
- Transfer of autoantibody or autoreactive T cells to a healthy host induces the autoimmune disease
- Clinical benefit provided by immunomodulatory therapy
- Family history
outline which disease have 1o autoantibodies and which have 2o autoantiboides
Primary autoantibodies(rare): (known as pathogenic) • Anti-TSHR antibodies in Graves’ disease
- Anti-acetylcholine receptorn antibodies in Myasthenia gravis
- Anti-voltage-gated Ca2+ channel antibodies in Lambert-Eaton myasthenia syndrome
- Anti-Glomerular basement membrane antibodies in Goodpasture’s syndrome
Secondary autoantibodies
- Anti-nuclear antibodies in SLE
- Anti-gastric parietalcell antibodies in pernicious anaemia
- Anti-thyroid peroxydase antibodies in Hashimoto thyroiditis
- Anti-Rheumatoid Factor antibodies in Rheumatoid arthritis
while not all patients will show serum autoantibodies (ranges btwn 30 - 90% depending on condition)
we test for them and can provide a diagnosis
bouns
how do we detect autoantibodies/ autoreactive T cells at site of tissue damage
biposy !!
look for T cells
do immunoflurescence
radio immunoassays ect
look at slides on lecture
what antibody do babies get from their mother
how does this relate to autoimmune diseases
they get IgG only
the baby will also get any IgG autoantibodies and so for the 1st 6 months have neonatal autoimmune disease
such as
platlets autoantibody - cause thrombocytopenia and cell lysis
RBC’s - heamolytic aneamia - cell lysis
TSH receptor - neonatal graves ect
list some genetic and environmental factors that can trigger auto immunity ?
§ Genetic factors
o Increased risk with an affected sibling (8X)
o Increased risk with an affected identical twin (30X)
o AIRE mutations (APECED syndrome) that affect central tolerance
o Autoimmune disease associated with MHC variants (HLADR3/DR4)
§ Environmental factors
o Hormones - women more prone to most autoimmune conditions due to hormones
o Infections
o Drugs
outline some infectious factors with autoimmunity
infections can do molecular mimicary of self
this can lead to the body producing antibodies that are against disease and self
so can cause a development of autoimmunity
ie strep P - antigen in cardiac muscle - causes rheumatic fever (lifelong)
camylobacter jejuni - myelin gangliosides - gullian barre syndrome (neuronal attack that can lead to paralysis)
theraputic stratagies for autoimmune disease
palsma exhange - goodpastures
immunosupressants - Anti T cell, Anti proliferative ect
anti inflammation
repalcement surgery
also monocolonal antibodies (drug name - MAB)
