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89 Cards in this Set
- Front
- Back
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On a B- cell what can you tell by these markers? CD19 CD20 CD34 CD10 CD3 |
CD19 and 20 are on all b cells CD 34 is a stem cell marker CD10 is found on immature B cells CD3 is on T-cells (all t cells) not b cells |
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What cells would have light and heavy chains? aB and yg? |
light and heavy chains on Bcells T-cells have the others |
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What the? |
pituitary (anterior) parathyroid glands Entero-pancreatic cells (the 3 ps)
More recently duodenal gastrinomas, carcinoid tumours, adrenal carcinomas and lipomas have been found to be more common than the normal population
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Autoimmune polyendocrine syndrome type 1: what is it? how does it manifest? |
Autosomal recessive disorder due to mutated autoimmune regulator (AIRE) gene leads to -failure to express tissue specific antigens and therefore failure to delete tissue specific t -cells and auto reactive t cells are released and lymphocytes infiltrate multiple tissues and there's a wide range of autoantibodies
3 main manifestations -chronic mucocutaneous candidiasis due to antibodies against IL17 and IL22 cytokines -autoimmune hypoparathyroidism -autoimmune addisons Multiple other autoimmune phenomena |
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How are regulatory T-cells differentiated? How do they work? In what circumstances may someone lack FoxP3?
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Usually express CD25 and express transcription factor foxp3
10-15%
CD25 mops up IL2, CTLA4 is an inhibitory signalling molecule on activated Tcells, they induce inhibitory cytokines IL10 and TGFB, they secrete inhibitory cytokines IL10, TGFB, IL35, and IL9 and they cause cytolysis of other cells
If you lack Foxp3 you lack regulatory t cells |
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What is IPEX? What causes it? How does it manifest? |
immune dysfunction, polyendocrinopathy, enteropathy, x-linked
FoxP3 defect
It's a frequently fatal syndrome found in the first few months. it causes autoimmune diabetes/thyroiditis, diarrhoea, haemolytic anaemia, ITP and neutropenia. The atopy component includes eczema, food allergy and eosinophilia and patients also have lymphadenopathy and splenomegaly |
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Which toll like receptor is responsible for shock in gram negative sepsis? What does is bind? What does it induce? |
TLR4 It binds bacterial lipopolysaccharide in concert with CD14 and MD-2 It induces cytokines and co-stimulatory molecules |
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Do B or T cells recognize intact antigens? |
B cells, t cells need in processed and packaged with MHC (class II on CD4 and class I on CD8) |
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What is ABATACEPT? What condition is it licensed for? How does it work? |
CTLA4-Ig Rheumatoid arthritis it out-competes CD28 for B7 on APC which leads to decreased activation of t -cells |
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What is IL2? |
A t cell growth factor which drives resting t cell division |
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Name 4 drugs that raise plasma urate? |
Thiazides loop diuretics cyclosporin tacrolimus ethambutol pyrazinimide low dose salicylates levodopa ribavirin interferon teriparatide nicotinic acid cytotoxoc chemo |
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Why worry if a dialysis patient has gout? What x-ray changes are seen in gout? |
it increases the risk of death
preservation of joint space with erosions esp if there's an overhanging edge |
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what is the urate target in a patient with gout? What SEs need to be watched for in; benzbromarone use? Allopurinol? |
<0.36 except if tophi, erosions, persistent symptoms or multiple joints involved then it's <.3
Liver failure
hypersensitivity syndrome - 18% mortality, occurs in the first 6 weeks of treatment |
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What complement components are associated with SLE? |
C1q and C4 |
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What are the manifestations of ANA negative lupus? |
Subacute cutaneous lupus, musculoskeletal complainta, SSA+ |
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Describe the classification of lupus nephritis
How are they treated? |
Class I - minimal mesangial (normal light microscopy) Class II - mesangial proliferative Class III - focal proliferative (<50%glom) Class IV - diffuse proliferative (>50%) CLass V - membranous GN Class VI - advanced sclerosing (>90%)
I, II, and VI - acei, ARB, no immunosuppression III and IV - induction mycophenylate or cyclophosphamide and pulsed steroids and then maintenance on steroid sparing agent (MMF or AZA) |
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Name three risk factors for progressive SLE NEPHROPATHT
In which of these risk factors may rituximab help? |
increased creatinine at the time of biopsy HTN Nephrotic range protenuria Anaemia with HCT <26% Black race severity of tubulointerstitial disease Crescent formation
Rituximab only works in african americans and hispanics |
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Which lupus drugs are contraindicated in pregnancy?
What can be used? |
Methotrexate, Mycophenylate, Leflunomide and cyclophosphamide are contraindicated
Hydroxychloroquine is appropriate in mild disease and pred and azathioprine can be used if neccessary |
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If a pregnant woman reports her niece was born with Congenital heart block which antibody should you consider testing for? |
ENA (particularly SSA/SSB) looking for neonatal lupus |
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Neonatal cardiac lupus
When does congenital heart block occur? How is it treated? What is the recurrence rate? |
most often in weeks 18-24/40
Monitor with fetal echo, dexamethasone if 2nd degree or new onset. IVIG DOESN'T work 60%need a pacemaker 20% die
Recurrence rate 18%
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What drugs are associated with drug induced SLE? |
methyldopa hydralazine procainamide isoniazid TNF inhibitors |
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What are the diagnostic criteria for antiphospholipid syndrome? |
Repeatedly elevated aCL, Beta2GP1, or LAC (12 weeks apart) Prior pregnancy lost either >1st trimester, or three consecutive first trimester or preterm birth for preeclampsia or placental insufficiency Prior thrombosis |
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Describe limited sclerosis
What is the prognosis |
-skin thickening distal to elbows and knees but may include face and neck -long history of raynaud's -lung disease in 30% -Pulm HTN in 10% -CREST is a specific subtype
Okay prognosis, 91% 10yr survival (was 78% in 1993) |
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Describe diffuse sclerosis what antibody is associated with pulmonary involvement? What is the prognosis? |
-distal and proximal (trunk too) skin thickening -visceral disease 10% renal crisis in the first 4 yrs -50% lung (scl-70 increased risk, anticentromere is protective) -10% cardiac
74% 10 yr survival (was 43% in 1993)
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What is primary raynauds? What clinical and lab findings are present in primary raynauds? |
primary raynauds affects 4-15% of the population. Clinically it begins in adolescence and results in no tissue injury. It's symetrical, reversible in 15 minutes and spares the thumb. On lab testing they should have a negative ANA and normal nail fold capillaries |
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What antibody is associated with raynaud's |
90-99% SSc |
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When should you suspect pulm HTN in sclerosis?
What is the prognosis?
Ho would you screen for it? |
in diffuse or limited disease. Suspect if DLCO<50% and HRCT and long volumes relatively normal
Untreated 2 yr survival <50%, treated it's 80%
Lung function tests, TTE, HRCT to assess ILD, V/Q scan and yearly screening, 6 monthly in early diffuse disease |
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In regards to the alphabet soup of systemic sclerosis: what does anti-centromere Ab suggest |
Anti-centromere Ab - seen in 60 |
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What percentage of patients get allopurinol hypersensitivity syndrome? What is it? |
0.4%
DRESS - drug rash, eosinophilia and systemis symptoms |
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ALphabet soup for scleroderma:
What is known about- Centromere lcSsc Scl-70 RNApol Th/To |
lcSsc - 60% - decreased risk of severe lung disease Scl-70 - 45% diffuse, 15 % limited predictive of ILD RNApol - 20%- severe skin involvement renal disease assoc (1 and 111) Th/To - poor outcome in limited disease |
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What genes confer risk for ank spond? |
HLA B27 ERAP-1 Interleukin 23 receptor genes TNF associated genes |
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reactive arthritis is associated with which HLA antigen? HLA- B27 HLA- a3 HLA - DR4 HLA-B5 HLA-DR3 |
hla- B27 |
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Describe the pathogenesis of TTP. |
Abnormally large and sticky multimers of von Willebrand's factor cause platelets to clump within vessels. There is a deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns large multimers of von Willebrand's factor. TTP overlaps with haemolytic uraemic syndrome (HUS) but TTP more likely to have neuro signs or purpure. |
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What can trigger TTP? |
infection (uti or gastro) pregnancy drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir tumours SLE HIV |
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What disease is associated with HLA DR4? |
70% of rheumatoid arthritis patients are HLA DR4. 90% of patients with Felty's syndrome are HLA DR4 (splenomegaly, RA and neutropenia) |
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What mechanisms predispose to clots in nephrotic sx? |
Loss of antithrombin-III, proteins C and S and an associated rise in fibrinogen levels predispose to thrombosis. Loss of thyroxine-binding globulin lowers the total, but not free, thyroxine levels. ( you pee 'em out, you still keep making them though) |
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What are the modified new York criteria for ank spond? WHat constitutes definite ank. spond? |
Clinical criteria: -low back pain and stiffness for >3months not relieved by rest but better with exercise -lumbar spine mobility limited in sagittal and frontal planes -Limited chest expansion Radiological -sacroliiitis grade to or worse bilaterally or unilateral grade 3 or 4
It's definite ank spond if there's radiological criterion and at least 1 clinical |
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WHat is diffuse, idiopathic, skeletal hyperostosis? What are risk factors? |
ossification of the anterior longitudinal ligament. Risk factors: male>50 diabetes in 20% NOT HLA B27 |
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WHat is the most common HLA linked to ankylosing spondylitis? |
HLA - B2705 |
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Yada Yada ... HLA B27... but what 3 other genes are associated with ank spond? |
ERAP1 - involved in trimming peptides for MHC class1 and cleaves recptors (ie downregulates) IL-1, IL-6 and TNF |
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What extra articular manifestations are seen in ank spond? |
anterior uveitis psoriasis 20% IBD upper lobe fibrosis Aortic regurg Conduction abnormalities |
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WHat is the worst prognostic marker in Ank spond? What is the RR for vertebral fractures in the 50% of AS patients with T-score<-1? |
early hip arthritis
6-8 fold vertebral fracture risk, limbs not at increased risk of fracture |
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What is infliximab? |
It's a TNF inhibitor. A chimeric mouse-human monoclonal antibody directed against soluble and membrane bound TNF |
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what is adalimumab? what is golimumab? |
Humira. a humanised monoclonal antibody against TNF. Golimumab is the same but given monthly not fortnightly |
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what is etanercept? |
a decoy antibody. p75 receptor fused to human IgG which competitively inhibits TNF |
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How do TNF inhibitors impact ankylosing spondylitis? Does disease recur when TNF inhibitors are ceased? |
long term effectiveness has been demonstrated. they improve functional ability, spinal mobility, and extraarticular features. Disease recurs within 3-12 months of cessation
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How does somebody with ankylosing spondylitis qualify for a TNF alpha inhibitor? WHat qualifies them to continue? |
Definite ank spond on the new York modified criteria and they have tried two or more NSAIDs over three or more months and failed to improve. To continue they need to improve on the basdai score (sx based) and crp and esr need to be low or improve |
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Where can a hidden plaque be in psoriasis? ANd what can trigger a flare in sx? what features are highlighted in the moll and wright classification? |
Check the belly button and trauma often precedes symptoms Moll and wright: arthritis with dip joint involvement arthritis mutilans symmetric polyarthritis asymmetric oligoarthritis predominant spondylitis |
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what are the key radiographic findings in psoriatic arthritis? |
Destruction: large eccentric erosions osteolysis and widening of the joint space tuft resorption Proliferation: periostitis of shaft of metacarpal/tarsal proliferation of adjacent joints ankylosis PENCIL IN CUP |
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What proportion of patients with psoriatic arthritis have sponyloarthritis.How can you tell psoriatic and ank spond apart?
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25% Syndesmophytes are less common, they're less symettrical and they're bulkier. the cervica lspine is involved in 70-75% |
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WHat treatments are used for symptomatic relief in psoriatic arthritis? For disease control in peripheral arthritis? FOr disease control in psoriatic spondyloarthropathy? |
NSAIDs for symptom control Methotrexate, sulfasalazine and leflunomide for arthritis. Gold and cyclosporine are also used. TNF inhibitors slow radiographic changes in peripheral arthritis and psoriatic spA |
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WhAT IS APREMILAST? When is it used? What side effects are seen? |
Inhibits PDE4 (proinflammatory) It is used in psoriatic arthritis. Side effects: nausea, diarrhoea, headache and weight loss. |
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What bacterias cause reactive arthritis? |
chlamydia - 4% develop reactive arthritis salmonell Yersinia, shigella Campylobacter Clostridium |
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in inflammatory bowel disease patients with enteropathic arthritis when should proctocolectomy be considered? |
It results in arthritis remission in UC only |
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in IBD assoc arthritis what agents can be considered? |
NSAIDs increase risk of IBD flare Infliximab and adalimumab work for peripheral and axial disease |
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What are the three cardinal signs of APECED? autoimmune polyenocrine syndrome type 1 due to AIRE gene defect |
-chronic mucocutaneous candidiasis due to antibodies to TH17 cytokines -autoimmune hypoparathyroidism -autoimmune addisons |
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Name the CTLA4 Ig that's taking the world by storm and causing autoimmunity the world over? |
Abatacept |
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What do calcineurin inhibitors do? |
they inhibit Il-2 induction which causes immunosupression |
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what cytokines are linked to atopy (Th2) |
IL4 (stimulates naive t cells to make more Th2 cells) IL13(promote igEswitching in b cells) IL5 (attracts eosinophils) |
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WHich three cardinal cytokines drive the acute phase response? |
IL-1 IL-6 TNF |
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Where are NK cells derived from? When are they particularly useful to us? |
Bonemarrow they step in when a viral infected cell or tumour cell downregulates MHC expression |
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What infections may be seen in impaired/absent antibody response? What bugs predominate? |
sinusitis bronchitis otitis media pneumonia bronchiectasis skin infections infectious diarrhoea Polysaccharide encapsulated: strep pneumoniae HIB Strep pyogenes Branhamella |
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What infections does a lack of neutrophils/monocytes predispose to? |
high grade bacterial infections with staph aureus E.COli Mirabili Serratia Pseudomonas and invasive fungal infections |
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How would you investigate for suspected common variable immune deficiency? |
IgG is low. IgA and IgM can also be low ELectrphoresis shows hypogamma and there is an impaired response to vaccines |
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What drugs can cause low IgA? |
Carbamazepine, sulfasalazine, captopril, gold, valproate, penicillamine and NSAIDs |
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Which fractures can raloxifene prevent? hip vertebral radial Penile |
vertebral |
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What agents prevent hip and vertebral fractures? raloxifene alendronate zoledronate denosumab |
alendronate zoledronate denosumab |
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How long is pulsed parathyroid anabolic for? 12 months 18 months 24months 36months |
18 months |
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What condition is seen with LRP5 mutation? Hodgkins lymphoma Pancreatitis Sclerosteosis Osteoporosis |
Sclerosteosis - that thick jawwed, sinking american family! |
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How can you treat paget's disease? |
bisphosphonate calcitonin analgesia surgery if joint replacement or spinal decompression is neccessary |
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What medication commonly causes hypercalcaemia? -bisphosphonates -loop diuretics -lithium |
Lithium, thiazides, calcitriol and calcium carbonate can all do it |
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What gene is not associated with a risk of developing RA? DRB1 STAT4 PADI PTPN22 STAT3 |
STAT3 |
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What of the following is not a risk factor for RA? Smoking Periodontitis herpes labialis gut dysbiosis Anti-ccp (enolase)
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herpes labialis |
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Of the following which are protective in RA? TNF IL-1 IL-6 IL-17 Treg IL-12/23 JAK OPG Citrullination |
OPG and Treg |
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Which of the following cells are predominantly found in RA synovial tissue? M'phages PMN CD4 T cells Synovial fibroblasts Th17 cells |
PMN more in fluid |
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what is rheumatoid factor usually? AN IgG against osteoblasts AN IgM against the Fc portion of IgG An IgG against the OPG receptor
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It is usually an IgM against the Fc portion of IgG |
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which are predictive of the erosive damage of RA? high Rheumaoid factor titre TNF levels in serum Anti-CCP antibody Erosions |
1 erosions 2anti-CCP Rheumatoid factor probably tissue tnf is predictive but serum isn't |
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How is methotrexate excreted? How many patient swith RA does MTX help? |
renal excretion effective in 75% of patients |
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How does leflunomide work? How is toxicity treated? |
inhibits pyrimidine synthesis cholestyramine sequesters the drug |
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What are infliximab, etanercept and adalimumab? |
TNF inhibitors |
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what common cancer do the TNF inhibitors etanercept, infliximab and adulimumab predispose to? |
skin cancer, melanoma and others |
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How long do you need to treat latent tb before starting a tnf inhibitor? active TB? |
latent isoniazid- 4 to 6 weeks active 2 months |
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which is an absolute contraindication to TNF inhibitors? -past hx TB -coeliac -prior cellulitis -optic neuritis |
optic neuritis |
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What is abatacept? |
a CTLA4 Ig mimic |
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In RA tocilizumab blocks IL6. It increases total and HDL cholesterol and decreases CRP. WHat effect does it have on cardiovascular risk? |
decreased CVS risk |
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WHich is B-cell depleting? -Anti CD20 -Anti CD22 -Anti CD 40 -CTLA4Ig which block costimulation? |
Anti CD20 is depleting anti CD40 and CTLA4Ig block co stimulation |
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After an infusion of rituximab when do B-cells return to normal levels? |
6 to 18 months later |
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DOes denosumab (ab to RANKL) change clinical disease in RA? |
No change to clinical course |
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CAn methotrexate and leflunomide be used in pregnancy or breastfeeding? WHat can be used in RA in pregnancy |
Cease methotrexate 3-9 months before conception. No leflunomide or methotrexate until after breast feeding. Sulphasalazine and hydrozychloroquine with low dose steroids can be used |
