Immunology Case studies Flashcards
What is atopy?
the tendency to develop IgE antibodies against innocuous antigens (allergens)
steps of allergy
- atopy
- sensitisation
- typical reaction hx and/or positive provocation
Tests for sensitisation
skin prick test
measure serum specific IgE
contents of granules in masst cells
histamine (h1-4R)
proteases e.g. tryptaase
proteoglycans
cytokines
sensitisation vs allergy
In allergy you have the sx, not just the presence of the IgE
Sx of allergic reactions
skin/mucosa:
- urticarial rash
- swelling
- angioedema
- erythema
respiratory:
- wheeze
- bronchoconstriction
- chest tightness
- cough
- haufever sx: runny nose, eye itching
CVS
- shock due to systemic vasodilatation
- compensatory tachycardia
- LOC
- empty ventricle syndrome
- palpitations
GI
- vomiting
- diarrhoea
- cramps
What causes swelling in allergy?
mast cell degranulation causes vasodilation -> leaky
Why does BP drop in allergic reactions?
systemic dilatation due to mast cell degranulation
you also get a compensatory tachycardia
What is anaphylaxis
severe allergic reaction that has an A, B or C problem + skin changes/angioedema.
Do you need a BP drop to diagnose anaphylaxis?
no
you just need an A, B or C problem.
What medications do we use to treat anaphylaxis?
adrenaline
fluids
How does adrenaline treat anaphylaxis?
vasoconstriction
bronchodilates
acts on beta1 receptors of immune cells and stop them from releasing
Why are antihistamines no longer used in anaphylaxis?
do not reverse the CV effects or bronchocontriciton
only helps with the rash
act still continues to progress
masks skin and resp manifestations even thought the reaction is still regressing
Why are steroids no longer used in anaphylaxis?
take a long time to work
biphasic reaction in anaphylaxis
de novo synthesis process
release immune mediators e.g. leukotrienes, prosstaglandins, prostacyclin, thromboxane
takes minutes to hours
therefore wait 6h before sending someone with/post anaphylaxis home
bispaahsic reaction
in anaphylaxis
in hayfever
how long do you keep someone in A&E post anaphylaxis
6h
Hospital discharge plan post anaphylaxislaxis
- avoidance advice
- educate on allergy
- action plan
- allergy referral
may give epipen depending on the allergen they react to e.g. yes in nuts, no in penicillin
what blood test level is useful in anaphylaxis?
tryptase
during reaction and baseline
What protein is associated with allergy to peanuts?
Ara h2
PR10
pollen protein
can be found in peanuts, hazelnuts and
this protein is denatured by heat so
Pollen food syndrome
allergy to PR10
avoid these nuts in and foods in raw forms but can have them in cooked forms
have haufever usually ?
Why do people need to have 2 EpiPens ?
They might need one an hour later (delayed reaction?)
Why do people need to have 2 EpiPens ?
They might need one an hour later (delayed reaction?)
What is the most appropriate first line treatment for anaphylaxis?
adrenaline
Which disorders are associated with recurrent meningococcal speticaemia/meningitis?
What immune deficiency is associated with meningococcal sepsis/meningitis?
complement deficiency
(recurrent infection with encapsulated organisms)
SPUR
serious
persistent
unusual
recurrent
What should you ask yourself if you think someone might have amn immune deficiency?
SPUR
serious
persistent
unusual
recurrent
Which immunological tests would you request in recurrent infection with encapsulated organisms?
complement - C3 and C4
CH50 (FUNCTIONAL TESTS)
AP50
serum Ig
protein phoresis ?
What are CH50 and AP50 tests?
functional tests of complement
downstream of C3 and C4
How do you manage someone with complement deficiency?
- vaccination (MenACWY, MenB, pneumococcal vaccination, HiB vaccination)
- daily prophylactic penicillin
- tests family
-…
what infections are people with complement deficiency at risk of?
encapsulated organisms (meningococcus, pneumococcus, haemophilus)
particularly the final pathwaty and the common pathway
Anti_CCP
seen in RA
What disease should you screen people with SLE for?
APS
Clinical criteria for APS
- intravascular thrombosis (arterial or venous)
- recurrent miscarriage
tests for APS
anti-cardiolipin ab
beta2glycoprotein1 antibody
lupus anticoagulant test
clotting asset - prolonged AAPTT or dRVVT that doesn’t correct with normal pooled plasma but corrects with phospholipids
What test should you do for monitoring patients with SLE?
urine dip every time in clinic
U&E
red cell casts
feature of active, proliferative nephritis
What drugs can be useful in SLE?
prednisolone
anifrolumab (in some)
azathioprine
hydroxychloroquine (pretty much everyone with lupus)
rituximab (deplete B cells, particularly good in renal disease)
belimumab
mycophenolate mofetil (steroid sparing)
adalimumab
you might use cyclophosphamide if they are very unwell, quite quick and effective
NOT
allopurinol
adalimumab)
colchicine (inhibits neutrophils)
what disease is anti-dsDNA associated with?
SLE
most specific antibody
What is RA?
peripheral symmetrical poly arthritis and stiffness persisting for more than 6 weeks
What is rheumatoid factor?
antibody against Fc portion of IgG
you can also have IgM and IgA RF
60-70% sensitive and 60-70% specific
what is anti-ccp?
ab against cyclic citullinated peptides
highly specific for RA (95%)
polymorphisms within OADU enzymes nay increase generation citrullinated residues in patients wh develop RAA
Why is smoking associated with RA?
increases the amount of citrullinated proteins in the lung - this may play a role
twin concordance for RA
30% identical
5% non identical
what HLA are associated with RA
HLA DR4 subtypes Dw4, Dw14, Dw15
HLA DR1 also predisposes
PADI type 2 and 4
- certain polymorphisms increase citrullination of proteins
- peptidularginine deiminase
PTTPN 22
protein tyrosine phosphatase……
….
Key cytokines in RA
TNF alpha
IL-6
T-cells
B-cells
Macrophages (tif alpha)
synovial cells and fibroblasts (il-6)
1st line management of RA
DMARDs
methotrexate
sulphasalazine, hydroxychloroquine, leflunomide
What if DMARDs don’t work in RA?
specific biologics
biologic DMARDs and Jakinibs
TNF-alpha antagonists (infliximab, entarcept)
tocilizumab
rituximab
abatacept
Why do you need to treat RA?
to prevent destructive joint disease.
what to do before starting biologics?
make sure they are vaccinated
ask about TB exposure + CXR
screen for HIV, Hep B, Hep C
check if they had SA in the past - risk of it becoming a problem again
/What cancers are people treated for RA at higher risk of?
non melanoma skin cancer
most specific antibody for RA?
anti-ccp
Ix in ?multiple myeloma
serum immmunoglobulins
serum protein electrophoresis (monoclonal band in gamma region)
urien electrophoresis (free light chains detected)
R-ISS
multiple myeloma
staging
Why are patient with myeloma more susceptible to infection
FUNCTIONAL ANTIBODY DEFICIENCY
even though their Ig is high, it is mainly monoclonal
only a small amount of polyclonal antibodies
Why would you get anaemia in multiple myeloma?
seen in most patients with MM
mechanism:
- space limitation due to white cell precursors in bone marrow
- ???
why is the ESR raised in multiple myeloma?
erythrocytes clump faster because there are more protein constituents in plasma which increases the attractant charge between the red cells
this makes them fall more quickly through the capillary/tube
therefore also Roleaux on blood film
Roleaux on blood film
stack of RBCs
can be seen in multiple myeloma
add if seen anywhere else
Why is calcium increased in multiple myeloma?
???
median survival for multiple myeloma now
120 months / 10 years
key question in mx of myeloma
are you eligible for a stem cell transplant
autologous done in multiple myeloma?
What would suggest that aa child has a
unusual organisms
recurrent
……
Reasons why children may have abnormally many infections?
CF
structural lung disease
asthma
ciliary disorders
foreign body
HIV
primary immune deficiency
ix for ?immune deficiency
FBC
U&E
LFT
CRP
sweat test
CXR
Ig
check immune response to vaccination
FISH for immune deficiency down the line
where is BTK important/
BTK is an important protein in development of B-cells
What is BTK?
BTK
over expression in BTK is associated with some haem malignancies e.g. CLL -> Ibrutinib can be used to specifically target it
also may be overactive in AID
BTK controls the NLRP3 inflammasome
involved in secretion and production of IL-1beta (and IL-18)
X-linked agammaglobulinaemia
failure of pre-B cells to mature in the BM
failure to produce IG
Mx of X-linked agammaglobulinaemia
Ig replacement therapy
given every 3w IV at hospital or weekly SC at home
indefinite treatment
murtaation in Bruton tyrossine kinase gene are a cause of which immunodeficiency?
XLA (x- linked agammaaglobinaemia)
What causes CVID?
adult onset antibody deficiency syndrome
more details here xxx
What causes selective IgA deficiency
dendritic cell neoplasm types
???
