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81 Cards in this Set

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What is rheumatoid arthritis? what are the risk factors?

Systemic chronic inflammatory disorder, risks include infection and smoking

What are the anti-bodies in RA? and which is specific to the disease?

- Rheumatoid factor


- Anti Citrullinated paptide (s)

what organs doe RA affect?

- skin (nodules)


- lungs (fibrosis)


- kidneys (amyloidosis)


- heart (pericarditis)


- blood vessels (artherosclerosis)

Explain what RF's are?

- Antibodies of any class


- Bind to the Fc region of IgG molecules (including themselves)


- Binding of the Fab region of one antibody and the Fc region of another in enhanced by defective glycosylation of the Fc region

What is the overall effect of RF's formation of complexes?

stable and proimflamatory activating compliment


- directly proportional to severity

What is the normal process for the production of T-cells?

- In the thymus


- Initial development as both CD8 and CD4


- Positive selection for low affinity self interaction with MHC 1 and MHC2


- Unselected cells undergo cell death

What happens when the T-cell selection process goes wrong in RA ?

- lymphopenia


- followed by self replication to restore numbers


- autoreactive cells



What is the significance of Treg in RA?

- reduced numbers


- limited ability to supress antigen presentation


- limited TGFb and IL-10

what functional class is a synovial joint?

diarthroses

what are the layers of the synovial joint?

- articular cartilage


- AJ capsule


- outer fibrous membrane


- inner synovial membrane


- synovial fluid



What cytokine do T-cells and macrophages contirubute to RA?

- Il-1/2/6/8/10/17


- TNFa


- PDGF


- TGFb

In RA where are the T-cells activated?


what happens to them when activated

-locally by APC


- by IL-6/1/21/22


- where they differenciate into Th-17 CD4+ to produce IL-17

What is the end result of the inflammation of the joint in RA?

extensive angiogenisis


- Pannus development


- cartilage and bone destruction

What are the subsets of CD4+ T-cells

- Th1 (INFy and TNFa)


- Th2 (IL-4/5/6)


- Treg (TGFb and IL-10)


- Th17 (IL-17)

what is the relative change from healthy treg and th17 cells in RA?

- treg decreased


- Th17 increased

what are the functions of


- INFy and TNFa


- IL-4/5/6


- TGFb and IL-10


- IL-17

- activate innate


- activate B-cell antibody production


- supress t cell response


- control inflammatory autoimmune response

what is the only cell found in cartilage

- Chondrocyte

what causes the stimulating of PGE2 production by chondrocytes and osteoblasts?

IL-17

How does IL-17 cause bone destruction?

- Induces RANK ligand expression to promote osteoclast differentiation


- PGE2 production


- release of H+ ions


cathepsin K enzyme

How does PGE2 contribute to RA?

- reduced collagen synthesis


- increase chondrocyte death


- increased MMP


- increased osteoclast formation


- increased angiogenic factor


- increased enothelial proliferation and reduced death

What enzyme is responible for PGE2 production?

- COX-2

what is the use of selective COX inhibitors?

reduces pain, oedema, vasodilation


- but little effect on disease progression

Name some selective COX-2 inhibitors

celecoxib and rofecoxib

name a DMARD?

sulfasalazine


- broken down to produce 5-amino salicylic acid

Name some drugs to treat RA?

- gold compounds


- penicillamine


- hydroxychloroquine


- immunosupressants


- Azathioprine

what diseases are good to corticosteriod treatment and which are bad?

G - RA, asthma


B- cystic fibrosis and COPD


better for eosinophil inflammation not neutrophil

What is the mechanism of glucocorticoids?

Cause the activation of


- anti-inflammatory genes


- and beta 2 receptor


- IL-10



what was the breakthrough with treatment for RA?

TNFa inhibitors in the form of anti-bodies


- IL-1 antagonist

what are the layers of the skin ?

- epidermis


- dermis (papillary and reticular)


- subcutaneous

What are the major cells of the epidermis?

- keratinocytes


- melenocytes


- langerhans cells


- mekel cells

What are the layers of the epidermis?

corneum


- lucidum


- granulosum


- spinosum


- basale

What are the innate denfence of the skin?

- impermeable barrier


- physical barrier


- Anti microbial - oil and defensins


- Acidic sweat





what are the barrier defects in AD?

-Reduced filaggrin expression


- decreased cerimide and sphingosine


- decreased antimicrobial production

how does stress effect the disease?

- increased corticotropin releaseing hoermone

- increase adrenocorticotropic hormone


- increased cortisol


causes


- decreased IL-18/1 and ceramide

what is the effect of Th2 cell cytokine in AD?

- decreased AMP's, filaggrin


- increased IgE

what is the role of staphlococcus areus in AD?

- Promote the itch- scratch cycle


- do not need co-stimulation

what are the treatments for AD?

- emollients


- antiseptics


- antibiotics


- topical corticosteroids



what are the immunosupressants for AD?

- antihistamines


- methotrexate


- cyclosporine

what is the defect in CF?

Structure and function of CFTR (cystic fibrosis transmmbrane conductance regulator) epressed by all endothelial cells

what chromosome is affected in CF?


and what is the most common defect?

-7


- delta-F508

What is the structure of the CFTR membrane?

- 2 transmembrane spanning regions


- 2 nucleotide binding domains


- regulatory domain



How does CFTR open?

- protein kinase A


- phosphorylates the Regulatory domain


- conformational change


- chloride ions leave the cell



What membrane proteins regulate CFTR?

- B2 (positivly)


- Syntaxin 1A (negativly)

What ion channel does CFTR regulate

ENaC

What are the classes of severity of CFTR?

- 1, no protein production


- 2, processing defects


- 3, regulation defects


- 4, conductance defects

What organs are affected?

- airways


- liver


- pancreas


- small intestine


- reproductive tract


- skin (sweat glands)

How is cystic fibrosis diagnosed?

- excessivly salty sweat 70mM


- failure to thrive + gain weight


- persistant chest infection

What are the transport systems in a bronchial cell?

-ENaC


- CFTR


-Na/K/Cl contransporter


- Na/K ATPase (Na leaves the cell through basel membrane)

How much greater is sodium re absorption in CF than in healthy cells?

10X greater

Name some bacteria that cause infection on CF?

- Staphylococcus aureus


- Pseudomonas aeruginosa

Where is pseudomonas aquired from?

-water sources

What are the events leading to chronic infection?

- decreased periciliary fluid results in reduced mucocilary transport


- mucus hyper secretion creates hypoxic zone


- formation of macrocolonies


- resistance of secondary defences


- increase hypoxic

What are the bacteria products of Pseudomonas?

- alginate (barrier)


- P. elastase (cleves antibodies and complement receptors)


- Pyocyanin (inhibits lymph proliferation)


-Exotoxin A (cytotoxic to macrophages)


- Leukocidin (cytotoxic to neutrophils and lymph)

What toll like receptor regonises LPS?

TLR4

what is the function of TNFa and IL-1 in the airways?

stimulate bronchial epithelium and fibroblasts to produce IL-8

what regulates the production of IL-8?

IL-10 from macrophages and epithelial cells

What are the difference in CF of the response to infection?

- absence of IL-10


- huge levels of IL-8


- Necrophilia recruitment causes more IL-8 (self amplifying)


- CFTR trafficking becomes stuck in the rough ER stimulating inflammation

What are the important anti-bacterial molecules of neutrophils?

- Proteases


- Defensins


- Bacterial permeability increasing enzyme

what generates the super oxide in neutrophils?

-NADPH oxidase

name an inhibitor of neutrophil elastase?

- alpha1-AT

what products protect from oxidant species? and what is its significance

Vitamin E/A/C


- pancreatic problem, no lipase, no fat soluble vitamins taken up


-reactive oxygen damages inhibitors of elastase leading to protease imbalance

main functions of neutrophil elastase?

- increases IL-8


- increases mucus secretion


- bronchiectasis


- c3b and igG clevage


- enhance EnaC

what is the sequence of event in CF leading to death?

- defective CF gene


- defective/ deficient CFTR


- increased Na absorption


- dessicated mucus


- bronchial obstruction


- infection


- inflammatin


- bronchiectasis, failure, death

what is bronchiectasis?

Perminent enlargement of parts of the lungs (also in COPD)

what drugs are used in the treatment of CF?

- antibiotics (colomycin)


- NSAIDS (Ibuprofen)


- Corticosteroids (not the best)


- bronchodilators


- mucolytics (DNase)


- anti-proteases



What are the bonds in the sputum of inflamed airways?

- hydrogen bonds


- ionic


- van der waals


- convalent disulfide


-physical entanglement


- extracellular actin and DNA

What are the aims of CF treatment?

- control infection


- reduce obstruction


- reduce inflammation


- fix basic defect


- transplant



name a prostaglandin, thromboxane and leukotriene?

-PGD2, PGE2, PGI2


- TXA2


- LTA4

WHAT IS THE SEQUENCE OF EVENTS THAT LEADS TO PROSTAGLANDIN SYNTHESIS?

- Phospholipid converted into aa


- AA converted to PGG2


- PGG2 converted into PGE2 ect


WHAT ACTION DO GLUCOCORTICOIDS INHIBIT?

PLA2 (phospholipase A2)


- breaks down phospholipids through ester linkage hydrolysis

what are the other sources of eicosanoids?

- ETE > PGE1

what enzyme makes Leukotriene ?


what drugs block LTR and this enzyme?

- 5-LOX


- zafirlukast (R)


- Zileuton (E)

what is the intracellular mechanism of prostaglandins?


name protaglandin receptor?

- G protein


- cAMP


- or phosphatidylinositol signal pathway causing increase ca2+


PPARy



What are the actions of eicosanoids?

- pyresis


- inflammation


- algesia


- pro-thrombosis



name 5 eicosanoids and give a function?

-PGE1(vasodilation)


-PGE2 (Fever)


-PGI2 (algesia)


- TXA2 (platelet aggregation)


- LTC4 (bronchoconstriction)

what are the roles of COX1 and COX2?

- gastric cytoprotection, haemostasis, regulation of platelet aggregation, renal function




- inflammation, allergy states

what are the uses of prostanoid mimetics?

- releif of GI irratation


- labour induction


- inhibition of platelet aggregation

name a selective COX-2 inhibitor?

- celecoxib

Theraputic use of NSAID's>?

anti inflammatory


- analgesic


- antipyretic


- antiplatlet

side effects of aspirin?

bronchospasm


- skin reactions


- compensated alkalosis


- asthma


- hyperthermia


increase bleed time



what are some of the indications of aspirin?

fever


injury


acute gout


rheumatoid arthritis


myalgia