Immunology Flashcards
Signs to ?immunodeficiency
Severe, recurrent or invasive infections
Severe, recurrent or disproportionate inflammation
Unusual site/organism of infection
Unexplained lymphoproliferation
What is SCID
Severe combined immunodeficiency
Group of inherited genetic disorders characterised by a deficiency in lymphocytes
T cells are absent in most forms, B and NK vary
X linked is most common = boys = t neg, B +
Lymphocyte count of <2 in an infant <6 months is what until proven otherwise
SCID
? up to 1 yr really
SCID symptoms
Severe, recurrent infection Failure to thrive Chronic diarrhoea ?absent lymph ?erythematous rash
Which vaccines are CI in SCID kids
Live:
1) BCG
2) rotavirus
3) polio
4) VZV (chickenpox)
5) MMR
6) yellow fever
7) LAIV
How is SCID diagnosed
- Lymphocyte phenotyping, flow cytometry
- Lymphopenia
- May see eosinophelia
- Absent thymic shadow on CXR
How is SCID managed
- Gene therapy, BMT before infection
- prophylactic antifungal, abx, antiviral, igg
- No live vaccine
- No breast feeding (CMV)
Characteristic presentation of an antibody deficiency and give eg
Recurrent 1) otitis media/sinusitis 2) conjunctivitis 3) pneumonias tend to present when maternal igG wanes (6-9m) XLA (brutons)
What is hyper igM syndrome
Raised or normal igM, deficient igG,A,E because inability for B cells to class switch eg secondary to T C40L abnormality (X linked)
Tx of antibody deficiency
Prophylactic abx
replace igG
How is primary antibody deficiency diagnosed
- Serum igG,A,M + repeat
- FBC to look for wider lymphopenia (SCID), anaemia, thrombocytopenia and neutropenia
- Flow cytometry and genetic testing
How would an absolute neutrophil deficit present?
Mouth ulcers
Stomatitis
Recurrent fever
Neutropenic sepsis
Causes and tx of absolute neutrophil deficiency
SCN
Cyclical
Secondary eg to chemo
Treat: GCSF ?AML
Cause, presentation + tx of neutrophil chemotaxis defect
Leukocyte adhesion deficiency (Cd18) No pus at site of infection Skin infection, perianal fistula Delayed umbilical cord detachment Enlarged lymph node tx: stem cell transplant
How do chronic granulomatous diseases present
Early onset deep seated catalase + infections (staph, Aspergillus, Norcardia, Serratia)
IBD like disease, perianal abscess
Tx of CGDs
AlloBMT, gene therapy
Describe normal complement pathway
Add pic + MAC
Deficiency in which part of complement increases risk of nicerria meningitidis
C5b-9
What is CVID
Common variable immune deficiency is a hypogammoglobulinaemia of unknown genetic causes especially in adulthood
Can have recurrent infections, autoimmunity and other manifestations
Tx: IgG replace, rarely alloBMT
What infections do PPIs give rise to
C diff, enterobacter, norovirus
Which infections do anticholinergics give rise to
Dental, UTi
Which infections does chemo give rise to
Neutropenia -> fungal and extracell bac eg E coli, staph aureus
What is rituximab, indications
Anti Cd20 antibody acting on peripheral B cells for lymphoma, leukaemia and some AI
SE: immunodeficiency because hypogammaglobulinaemia
What is infliximab, indications
Anti TNFr igG a cytokine used in RA
TNF a = bone erosion, cartilidge destruction, inflammation, malaise etc
What is Entanercept
Binds to TNFa itself unlike infliximab
Link between infliximab, entarecept and TB
tnf a is produced by cells that maintain granulomas so anti tnfa therapy = worsen latent tb
What is tocilizumab, indication, se
Anti il6 cytokine for RA
stop inflammation but
- skin and soft tissue infection without redness
- diverticulitis
What is eculizumab and SE
C5 complement blocker for rare diseases where MAC haemolyses RBCs eg atypical haemolytic, uraemic syndrome, paroxysmal nocturnal haemoglobinuria
but less c5
- risk of meningococcal and gonococcal infection
Describe the natural process of preventing autoimmunity
Positive and negative t cell selection occurs in thymus
If a t cell receptor binds tightly to mhc on thymus cells = negative selection
If a t cell receptor binds lightly = induce t reg cell (can also occur in periphery)
rest go to periphery as naive cd4 and cd8 cells
Function of t reg cells
Immunosuppression Il10 and tgfB
Limit APC activity (AI) via ctla4
Disrupt other T cell expansion
Kills immune cells
Define autoimmunity
Inappropriate, self directed inflammation caused by autoreactive T and B cell responses when central/peripheral tolerance/reg mechanisms fail
Drugs causing SLE (AI)
- Procainamide (antiarrhythmia)
- Quinidine (antiarrhythmia)
- Hydralazine (antihypertensive)
Principles of AI management
- Steroids = modulate gene expn of inflamm cells
- Antimetabolites = target dna synthesis of rapidly dividing lymphocytes in inflammation
- Calcineurin inhibitors stop IL2 mediated cell proliferation but chronic renal toxicity eg cyclosporine, tacrolimus, and pimecrolimus
- Biologic
Describe how a type 1 hypersensitivity reaction works
- Exposure to allergen
- Sensitisation = APC takes antigen to naive t cell. T cell responds -> Th2 cell specific to the antigen is primed
Th2 releases il4 so that B cell switches from igM to igE
the igE is attached to mast cell/eosinophil/basophil - Re exposure to allergen = mast cell degranulation to release:
Histamines, prostaglandins, leukotrienes, PAF, tryptase - Long term exposure can -> chronic inflammation, tolerance
Describe how T2 hypersensitivity works
igG response to antigen on a cell eg transfusion reaction
Describe how T3 hypersensitivity reaction works
igG response to circulating antigens -> complexes that damage eg RA, vasculitis
Describe how T4 hypersensitivity reactions work
Antigen sensitised to allergen -> >th1 primed
T cells release cytokines, recruit macrophages etc on re-activation
NOT b cell mediated
EG contact dermatitis
Takes >4 hours usually 1-2 days post exposure, longer to resolve, not life threatening
How is allergy confirmed
- History
- ssIgE if history +
- total igE
- skin prick test = igE mediated local histamine reaction in 20 mins
Allergic rhinitis
Type 1 to aeorallergens
nasal and eye symptoms
Tx includes steroids, antihistamines, ipratroprium bromide, LTRA
Allergic asthma
type 1 igE mediated initially but the hypersensitive bronchus then responds to non allergic stimuli
TX: avoid, b2a, steroids, LTRA, sodium chromoglycate in kids to stabilise mast cells
What is atopic triad
- Allergic rhinitis
- Allergic asthma
- Atopic dermatitis
1 is an independent risk factor for 2
Atopic dermatitis
Complex response to multiple allergens likely due to genetic barrier defect (filaggrin keratinocyte layer)
so have allergic skin disease + immunodeficiency + chronic inflammation
IgE v high, strong link with food allergy as kid
TX: avoid, prevent scratching, moisturise, abx creams, steroids, tacrolimus (calcineurin inhibitor of t cell proliferation)
common drugs which have been linked to steven johnsons syndrome
allopurinol carbamezapine phenytoin lamotrigine sertraline sulfasalzine
Define anaphylaxis
Severe , life threatening, systemic type 1 hypersensitivity reaction usually occuring within 60 minutes of exposure to pre-sensitised allergen
the response may be biphasic (2nd attack in 8 hours)
Differentials for anaphylaxis
- CSU (hives but longer onset, recurrent, longer to resolve)
- Asthma attack
- Anxiety induced hyperventilation
- Vocal cord dysfunction (esp in asthmatics)
- Hereditary angiodema (c1 esterase inhibitor deficiency, no rash)
- Mastocytosis
- Scombroid poisoning from not cooling fish quickly
- Carcinoid syndrome (paraneo) - flush, diorrhoea
- Opiods
- Excercise induced
- Hypotension, syncope
Acute anaphylaxis management
- AtoE
- IM 1 in 1000 0.5ml (auto pen wait 5 mins)
- high flow ox
- Fluid challenge 500ml 4 times
- Bronchodilators
- 200mg IV hydrocortisone or 40mg oral
- 10mg IV chlorphenamine (antihistamine)
