Immuno - case studies Flashcards
What is atopy?
propensity to develop IgE antibodies against harmless allergens (antigens)
What is sensitisation?
Presence of IgE antibodies + binding to mast cells + basophils (ready to react on next exposure)
What is allergy?
Sensitization (skin prick or blood test) + exposure resulting in allergic reaction (take hx)
How does an allergic reaction affect different body systems?
Skin + mucosa: Urticaria + Angiodema (90%)
Resp: Wheeze, SOB, cough, chest tightness, runny nose, sneezing, stridor (85%)
CVS: hypotension, compensatory tachycardia, reduced consciousness
GI: D+V, cramps
What is the pathophysiology of skin reactions in anaphylaxis?
Vasodilation
Increased permeability
Increased peripheral perfusion
Acts on local nerve fibres causing itching
What causes the respiratory symptoms of anaphylaxis?
Smooth muscle contraction causing bronchoconstriction
What causes the cardiovascular symptoms of anaphylaxis?
Vasodilatation systemically
Can lose 1/3 of entire blood volume in 10 mins
What causes GI symptoms of anaphylaxis?
Intestinal oedema
What is anaphylaxis?
Severe allergic reaction with sudden onset A B or C problem
+ usually skin changes
Immediate management of anaphylaxis - 6 points
- Remove trigger + lie flat/ sit
- IM adrenaline 500mcg (0.5ml)
- Airway Mx
- High flow O2
- Repeat Adrenaline after 5 mins
- IV fluid bolus 500-1000ml
What does adrenaline do to help in anaphylaxis?
Vasoconstriction: reverses problems in skin, gut + CVS
Bronchodilator: reverse resp problem
Acts on B2 receptor on immune cells: stops release of inflammatory mediators
Why are fluids needed in anaphylaxis?
To restore intravascular volume to allow for restoration of cardiac output
If no access to fluids i.e. outside hospital: give adrenaline + raise legs
Why are antihistamines, bronchodilators and steroids no longer advised in anaphylaxis?
Antihistamines: make rash better but distract from life-threatening cardio/ resp manifestations
Bronchodilators: distract from cardio manifestations
Steroids: take hours to have effect
Why should an anaphylactic patient be kept in for 6h?
Anaphylaxis late phase reaction is a repeat of anaphylaxis, but tends to be milder.
Tends to occur in first 6h after initial reaction (though can be up to 72h)
What serum measurement can be used to determine whether a reaction was anaphylactic?
Serum tryptase
Baseline + 20% of baseline + 2
Disorders associated with recurrent meningococcal meningitis
Complement deficiency
Antibody deficiency
Any disruption to BBB: skull fracture, hydrocephalus
Which infections if recurrent may indicate a complement deficiency?
Encapsulated organisms:
Neisseria meningitis
Gonococcus
H influenzae B
Pneumococcus
What kinda infections make you suspicious of an immunodeficiency?
SPUR Serious Persistent Unusual Recurrent
Suspected complement deficiency - what Ix are ordered?
C3
C4
CH50
AP50
Complement components in classical pathway
C1
C2
C4
Complement components of the alternate pathway
Factor B H I (from bacterial cells wall)
Complement components of the final common pathway
C5-9
What is CH50?
Functional test of integrity of CLASSICAL complement cascade
All components of the cascade need to be in place for the test to give a +ve (normal) result
What is AP50?
Functional test of integrity of ALTERNATIVE complement cascade
All components of the cascade need to be in place for the test to give a +ve (normal) result
Normal C3
Normal C4
Absent CH50
Absent AP50
What does this indicate?
Deficiency in final common pathway
How would you manage a patient with deficiency in the final common complement pathway?
Meningococcal vaccine
Pneumococcal vaccine
HiB vaccine
Daily prophylactic penicillin
Monitor closely
(v susceptible to encapsulated bacteria)
What is the most specific antibody for SLE?
dsDNA antibodies
Tests to investigate lupus nephritis?
Urinalysis (proteinuria + haematuria)
urine microscopy - red cells + casts
Renal biopsy: diffuse proliferative nephritis
Immune complex + complement deposition
What syndrome should SLE patients be screened for? What is the criteria for diagnosis?
Anti-phospholipid syndrome
Dx: 1 clinical + 1 lab criteria
What are the 2 clinical criteria for anti-phospholipid syndrome?
Intravascular thrombosis (arterial + venous)
Recurrent miscarriage (>3)
Give 3 signs of anti-phospholipid syndrome on examination/ testing
Prominent Lived reticular (mottled skin)
Mild thrombocytopenia
Libmann Sachs endocarditis (sterile)
What are the lab criteria for antibphospholipid syndrome?
Antibodies to anionic phospholipids: anti-cardiolipid antibodies
Antibodies to beta-2-glycoprotein 1
Lupus anticoagulant test
When investigating for anti phospholipid syndrome, what should be remembered?
APS is pro-thrombotic in vivo even though it is a/w an anti-coagulant effect in in vitro tests
What immunological tests can monitor SLE activity?
Immune complexes activate classic complement pathway
Consume complement
The more active the disease, the more complement is consumed
C4 tends to go down first, then C3
SLE - what kinda hypersensitivity disorder is it?
Type III: immune complex mediated
antinuclear antibodies bind to bare cells. these complexes activate complement + attract WBCs
Rituximab - which cells does it deplete?
Antibody to CD20
mature B cells (but not plasma cells)
Mycophenolate Mofetil - which cells does it affect?
T cells > B cells
Azathioprine - which cells does it affect
T cells
Penicillin for CAP –> 3 days later:
Fever, arthralgia, vasculitic skin rash, proteinuria, haematuria, raised transaminases, disorientation
Serum sickness
WTF is the pathophysiology behind serum sickness
Penicillin is recognised as a neo-antigen: SENSITISATION. stimulates a strong IgG response
On next exposure –> IMMUNE COMPLEX FORMATION w circulating penicillin + mass IgG production –> complex deposits in glomeruli + skin + joints
Clinical features of serum sickness
Arthralgia
Renal dysfunction
Purpuric rash
(immune complex deposition in small vessels)
Ix to confirm Dx of serum sickness
- complement levels - LOW due to immune complex activation
- specific IgG to penicillin
- Skin and kidney biopsies
Serum sickness: Type of hypersensitivity disorder
Type III
FTT +recurrent infections (tonsillitis, pneumonia, ROM, cellulitis):
Ddx?
CF DM Bruton's SCID Hyper IgM Cytokine deficiency
having ATOPIC DISEASE
Evaluation of lymphocyte immunodeficiency - which Ix?
T-cells (CD4 + 8)
B-cells
IgM, IgA, IgG
Ix for suspected phagocyte deficiency
NBT
Neutrophil count
Leukocyte adhesion markers
Treatment of Bruton’s
Immunoglobulin replacement every 3 weeks
Why are multiple myeloma patients susceptible to infections
The mass clonal proliferation of one plasma cell –> suppresses production of normal Ig
Why are multiple myeloma patients often anemics?
Crowding out of normal RBCs in BM by plasma cells
Tumour releases cytokines which inhibits normal BM function
Why is ESR elevated in Multiple Myeloma
High protein content in plasma –> increases attractant charge
RBCs tend to clump together so they fall more quickly through plasma.
X-ray lesions in multiple myeloma
lytic lesions “punched out”
What is Rheumatoid arthritis? (3)
Peripheral, symmetrical, polyarthritis with stiffness
Persists for > 6w
May be a/w RF +/- anti-CCP Ab
What is the most specific antibody to test for RA?
Anti-citrullinated protein antibodies
(Anti-CCP are a subset of which)
How is recent childbirth significant in rheumatoid arthritis
Switch of T cell type responses post pregnancy- more likely to develop RA
Which class of Ig is rheumatoid factor? what does rheumatoid factor target
IgM which targets Fc portion of human IgG
what does anti-CCP stand for
anti-cyclic citrullinated protein
How are CCPs formed?
Arginine residues are converted to citrulline residues by PADI enzymes
What can affect the degree of CCP generation?
Polymorphisms in PADI enzymes
If lose tolerance to CCPs, highly likely to develop RA
What 2 situations predispose to RA?
Smoking: increases citriilunation of proteins in the lungs (increase in citrilunated protein load)
Gum infections promote citrullination. The causative bacteria is the only bacteria with PADI enzyme.
2 HLA associations with Rheumatoid arthritis?
DR4 (subtypes Dw4, 14, 15)
DR1
PADI stands for?
Peptidylarginine deiminase
Why are PADI enzymes are important?
PADI enzymes act to turn arginine residues into citrulline residues
Polymorphisms (type 2 + 4) of PADI –> more citrulline resiudes –> more likely to develop RA
PTPN22 is an enzyme important in rheumatoid arthritis. what is its function?
Lymphocyte specific tyrosine phosphatase which suppresses T cell activation
In RA, the 1858T allele increases RA susceptibility (+SLE + T1DM)
Genetic predisposition to Rheumatoid arthritis
- HLA DR1 + 4
- PTPN22 - 1858T allele
- PADI enzyme (PMs type 2 + 4)
1st line tx of rheumatoid arthritis
DMARDs inc methotrexate
If methotrexate is not tolerated - which DMARds are used for rheumatoid arthritis
Sulphasalazine
Hydroxychloroquine
name 2 anti-TNFalpha agents
infliximab
Adalimumab
Tocilizumab - MOA? use?
Anti-IL6 receptor
Rheumatoid arthritis
Beyond DMARDs - state 4 diff drugs used to treat Rheumatoid arthritis
Infliximab (anti-TNFa)
Abatacept (anti-CTLA4)
Tocilizumab (anti-IL6)
Rituximab (depletes B cells, anti-CD20)
Natalizumab - MOA? use?
MOA: anti-alpha4 intern
Use: relapsing remitting MS
Use for basiliximab
prevention of transplant rejection
