Inflammatory diseases Flashcards
What is atopy?
genetic predisposition to developing these allergies
how do allergies happen?
The body produces IgE against innocuous substances e.g. peanuts
What is anaphylaxis?
is the airways being constricted until suffocation occurs.
Is an allergy the breakdown or delay of tolerance?
yes
the antibody IgE binds to what cell?
mast cells
How does the mast cell release granules when IgE binds?
the allergen crosslinks the IgE
What do mast cell granulomas release?
histamine
What does histamine do if the allergy is in the blood stream?
will cause fluids to go into the skin and you will get hives or anaphylaxis.
If allergens enter through the skin what does histamine do?
will cause a wheel (swelling) and flair (redness) response.
What does histamine do when you inhale allergens?
sneezing, nasal irritation and increased production of mucus. You might get asthma
what does histamine do if you ingest an allergen?
– diarrhea and vomiting or can diffuse into the bloodstream.
Is childhood exposure to possible allergens good?
yes
How do you treat a peanut allergy?
Avoidance, epi-pen, hospital treatment or oral immunotherapy.
What does an epi-pen do?
inject and the adrenaline can reverse the effects of histamine, increases blood pressure, increased heartrate, relaxes smooth muscle.
What do antihistimines do?
prevent the action of histamine of various histamine receptors
What can antihistimines be used for apart from stopping histamine?
Antiemetic (car and sea sickness – relax smooth muscle of the gut which reduces the chances of vomiting), sedation
what causes rheumatoid arthritis?
unsure, could be genetic, could be smoking, could be stress
What membrane in the small joints is inflammed in rheumatoid arthritis?
synobial membrane
What enters the synobial membrane tissue when inflammed during arthritis?
T-cells
After entering the cell in arthritis the T-cell responds to what dispalyed by the macrophages?
autoantigens
What does the T-cell release when responding to autoantigens?
interferon-gamma
what does interferon-gamma make macrophages do?
release pro-inflammatory cytokines
What do pro-inflammatory cytokines target in rheumatoid arthiritis?
fibroblasts
what do fibroblasts release?
MMP (proteases) and RANK ligand
What do MMPs do?
break down proteins such as soft tissues
what does RANK ligand do?
triggers osteoclasts which break down bone
How do you treat rheumatoid arthritis?
steroids and aTNF antagonists
Examples of TNF antagonists: How does the antagonist Etanercept work?
TNFR receptor fuses to the IgG antibody which competes with TNF receptor in the tissue and mops up TNFalpha meaning the cytokine will be less so less inflammation.
How does the antagonist infliximab work?
monoclonal antibody which can bind to TNFalpha
What happens when you get infected with TB?
Macrophages will ingest and phagocytose the mycobacteria, some of which is destroyed but others will remain within cytoplasm of the macrophage.
what happens to the TB in the cytoplasm of macrophages?
CD4 T cells release interferon gamma which activates infected macrophages to release TNF alpha
what does the macrophage releasing TNF-alpha do to itself
Activates macrophages further and develop protective structures called granulomas
what are granulomas surrounded by and what does this do?
T-cells which secrete interferon gamma to make macrophages more activated so it can keep the mycobacteria within.
what happens to granulomas if you take infliximab?
break down releasing microbacteria making TB active once more and form new granulomas outside of the lungs
ulcerative colitis: what do dendritic cells do?
sample the contents of the gut lumen.
What recognises bacteria?
Pattern recognition receptors (PRR)
In normal circumstances what does PRR signalling trigger?
anti-inflammatory responses.
Why would bacteria be able to breakdown the gut barrier?
some bacteria can use mucus as a form of energy or something from the gut will go into the gut lumen and cause inflammation.
What happens if the gut barrier is broken down?
bacteria can flood into another area of the body
What do T-cells do in the inflammatory response to commensals being in the wrong place?
increasing pro-inflammatory cytokines.
What happens if people have genetic mutations in PRR?
anti-inflammatory response to make a pro-inflammatory respons
How do lymphocytes enter microbial tissue?
MAdCAM1 adhesion.
What are some targets for ulcerative colitis?
target TNF-alpha, IL-6 receptor inhibition etc.
What are signs of SIRS and Sepsis?
Temp more than 38 and lower than 36
Tachycardia
Hypo or hyperventilation
Low or high White blood count
What is SIRS?
Systemic Inflammatory response syndrome (SIRS)
What is sepsis?
SIRS due to infection
What occurs during sepsis? (what gets into the blood stream and what happens from there?)
bacteria get into blood and disseminate through the body. lots of macrophages in the spleen releases TNF-alpha which acts on small blood vessels in the body
What does TNF-alpha do to small blood vessels?
vasodilaton,
increased premeability - leak of all fluids,
diseminated intravascular coagulation –clots,
vascular collapse,
reduced prefusion of organs leading to organ failure and death
How do you treat sepsis list?
Early recognition
Supportive therapies – ventilation, perfusion, fluids
Regular blood monitoring
Broad spectrum antibiotic – early stages of sepsis – but you want to identify the infection quickly.
Remove source of infection e.g. infected joint, peritoneal abscess, appendix.
Examples of steroidal anti-inflammatory drugs?
Hydrocortisone, prednisolone, dexamethasone
Do steroidal anti-inflammatory drugs decrease diapedesis and inflammatory cell activation?
yes
Do steroidal anti-inflammatory drugs increase T-cell activation?
No they decrease it
Do steroidal anti-inflammatory drugs decrease fibroblast function?
yes
Do steroidal anti-inflammatory drugs decrease expression of COX-2 (prostaglandins)?
yes
Do steroidal anti-inflammatory drugs decrease release of anti-inflammatory mediaters?
yes
Do steroidal anti-inflammatory drugs increase release of anti-inflammatory cytokines?
yes
Whats the best NSAID for inflammation?
ibroprofen
