tolerane
ability to recognise self tissue and antigens
autoimmunity
breakdown of self tolerance
production of auto antibodies causing autoimmunity
aetiology of autoimmunity
- genetic predisopsition
- triggering event such as envionment or hormones
- immune regulation break in tolerance
what are the types of break down in tolerance leading to autimmunity?
- molecular mimicry
2. defensive apoptosis B cells kill cells
organ specific autoimmunty
mysasthenia gravis
haemolytic anaemia
no organ specific autoimmunity
rheumatic arthiritis
SLE
ANA
antinuclear antibodies
type of AB binding to the nucleus
how are ANAs detected
patient serum added to slide and incubated
any ANAs in sample with bind to substrate on slide
additon o a labelled IgG will be viewed under flourscence
what substrates are used for ANA testing
Hep 2/2000 or rodent tissue
ANA substrate slides
slides coated with substrates for ANAs
- rodent tissue
- Hep-2 cells
- Hep 2000 ells
outline the cell cycle
G0 - cell cycle arrest G1 - cellular building blocks made and chromosomes duplicated S - synthesis of building blocks G2 - cell double checks everyhing making repairs before divisoion Mitosis
negative ANA
no discernable pattern
DO NOT confuse intesitity with positive result
Homogenous ANA result
- interphase cells seen
smooth staining, nucleoi seen - metphase
clinical relevance of homoegeous ANA
SLE
speckled ANA
interphase, speckled nucleus
metaphase mitotic cells
clinical significance of speckled ANA
SLE and Sjogrens syndrome
nucleolar ANA
interhase cells stain only nucloli
clinical significance of nucleolar ANA
systemic sclerosis and polymyositsis
centromere ANA
interphase cells with 4 discrene speckles evenly around nucleus
speckles can align in metaphase
clinical relevance of centreomere ANA
seen in CREST
Hep-2000 antigens
SS-A/RO
some interphase cells hyperexpress this antigen leading to tronger nucleolr and speckled staining
cytoplasmic antigens
ANA can also be used to report cytoplasmic patterns
- cytoskeleton
- mitochinidra proteins
- ribosomal antigens
- organelles
cytoskeltal antibodies
mitotic spindle stained
mitochndrial Antibodies
cytoplasmic pattern
ribosomal antibodies
cloudy fine speckling in cytoplam
what is titering?
deterimes amount of AB present to give indication of disease
used when mixed patterns of ANA is seen and helps separate the patterns for identifcation
what is ENA
extracable nuclear antigen
what kinds of DNA testing can be done as a follow up from ANA testing
ELISA test
- dsDNA antigen added to patient serum
- series of inbuaton and washing stages
- plate read at wavelengh to determine IgG DNA
ENA testing
ENA antigens added to patient sereum
can determine IgG ENA
can quanitfy antibody amount
what are systemic rheumatic disases
sytemic rheumatic diseases
non-organ specific and cause varied symptoms
what is SLE
systemic lupus erythmeatous
what does SLE affect
lungs heart kidneys arthuritis joints circulation< rayaulds
aetiology of SLE
underlying cause not fully known
what is drug induced SLE
can be cause by a hypersensitivity reaction to a medication triggering the autoimmunity
ANA pattern for SLE
homogenous or speckled
SLE symptoms
arthralgai fever arthritis skin rash anaemia renal invovlement pleuisy butterfly rash photosensitivity hari loss raynaulds seizures ulcers
treatment of SLE
no cure nly management
- protection against phosensitivtyi with cloting and creams
- NSAIDS, nonsteriodial anti inflamatory meds for arthiritis and pleurisy
- cortiocosteriods for rashes
what about the more serious symptoms of SLE like aeneamie, heart invovlement and lung and liver too
requires high dose corticosteriods
cyttoxic drugs to block cell growth
specialise doctors
SLE prognosis
improved over past few eyars
early treatment is key for long term progress
SLE in adults less serious than in children
examples of other autoimmune disaeses
SLE sjogrens syndrome scleroderma raynaunds dermatomyosis