Immu 11: Case studies in Immunology

Question 1

what happens in anaphylaxis

Answer 1

• type I hypersensitivity reaction
• cross-linking of IgE on mast cells
• leads to mast cell degranulation
• results in:
  
  • increased vascular permeability
  • smooth muscle contraction
  • inflammation and increased mucus production

Question 2

What type of reaction is anaphylaxis?

Answer 2

Type 1 hypersensitivity - cross-linking of IgE on the surface of mast cells, causing mast cells to degranulate and release histamines and leukotrienes

Question 3

what is the most common presentation of anaphylaxis

Answer 3

• urticaria/ angioedema
• followed by upper airway oedema

Question 4

what are the types of latex allergy (2)

Answer 4

• type 1 hypersensitivity to latex can gross react with foods eg avocado/banana (latex fruit syndrome)
• type 4 hypersensitivity - contact dermatitis, 24-48hrs after exposure

Question 5

3 methods of investigating latex allergy

Answer 5

• in vitro tests for specific IgE to latex
• in vivo skin prick testing
• in vivo patch testing

Question 6

what disorders are associated with recurring meningococcal meningitis infections (3)

Answer 6

• complement deficiency - increased risk of infection by encapsulated organisms
• antibody deficiency - recurrent bacterial infections - URTI/LRTI
• neurological - disturbance of BBB

Question 7

what history of infections suggests immune disorders (mnemonic)

Answer 7

SPUR

• Serious
• Persistant
• Unusual
• Recurrent

Question 8

Def in complement can result in what serious infectious condition?

What test would you do?

What results would you expect?

Answer 8

Meningicoccal sepsis

Test: AP50 (alterantive pathway) and CP50 (classical pathway)

Both AP50 and CP50 abnormal, suggesting that there must be something wrong with the final common pathway (as this is the only thing both tests share) - specifically, in meningicoccal septicaemia, it is C7 affected usually

Question 9

How can we test the function of complement (2)

Answer 9

CH50 - functional test of the integrity of the classical complement cascade
AP50 - functional test of the integrity of the alternative complement cascade

Question 10

how do you manage a patient with a complement deficiency

Answer 10

• Vaccines (increase R of encapsulated bacterial infections):
  
  • meningovax
  • penumocax
  • HIB vaccine
• daily prophylactic penicillin
• high level of suspicion

Question 11

what illness can you get after taking penicillin for an infection

Answer 11

serum sickness

• penicillin can bind to cell surface proteins
• acts as a neo-antigen which stimulates a very strong IgG response
• the individual is therefore sensitised to penicillin
• subsequent exposure to penicillin leads to - formation of immune complexes with circulating penicillin
• production of more IgG antibodies
• causes: renal dysfunction, arthralgia, purpura

Question 12

what are the investigations for serum sickness (3)

Answer 12

• low serum C3 + C4
• specific IgG to penicillin
• characteristic biopsy features (skin and kidneys) - infiltration of macrophages and neutrophils, deposition of IgG, IgM and complement

Question 13

Presentation of serum sickness

Answer 13

Immune complexes deposit into small vessels

• Glomerulonephritis: deposition in glomeruli (get loss of renal function - high creatinine, proteinuria, haematuria)
• arthralgia and a vasculitis rash
• disorientation: vasculitis affecting cerebral vessels may compromise oxygen supply to the brain
• purpura: blood vessels are likely to leak, so get local haemorrhage

Question 14

how do you manage serum sickness

Answer 14

• discontinue penicillin immediately
• decrease systemic inflammation via corticosteroids
• ensure appropriate fluid balance

Question 15

list 3 reasons for chronic infections in a 3 year old

Answer 15

• cystic fibrosis
• local factors eg foreign body
• ciliary disorders

Question 16

features of X linked agammaglobulinaemia

Answer 16

• failure of pre-B cells to mature in the bone marrow (so get low B cells - so can’t produce immunoglobulins)
• leads to failure to produce immunoglobulin

Question 17

how is X linked agammaglobulinaemia managed

Answer 17

immunoglobulin replacement therapy

• pooled serum Ig
• every 3 weeks
• indefinite

Question 18

features of Multiple Myeloma (7)

Answer 18

• unusual or vertebral fractures (lytic lesions)
• high ESR
• high calcium
• measure Ig/ electrophoretic strip
• urinary Bence Jone proteins
• anaemia (since malignant clone of plasma cells crowds out the normal RBC)
• more susceptible to infections (since suppression of normal immunoglobulin by the malignant clone results in a functional antibody deficiency)
• Rouleaux formation on blood film of RBCs

Question 19

features of rheumatoid arthritis (4)

Answer 19

• peripheral, symmetrical polyarthritis + stiffness
• persists for >6w
• may be associated with RF +/ anti-CCP antibodies
• post-partum presentation common

Question 20

what is rheumatoid factor

Answer 20

• antibody against Fc region of human IgG
• assays look for IgM RF usually
• also look at anti-CCP antibodies (highly specific)

Question 21

list genetic predispositions to rheumatoid arthritis (3)

Answer 21

HLA DR - DR4, DR1
PADI type 2 and 4
PTPN 22

Question 22

how is rheumatoid arthritis managed

Answer 22

1st line

• methotrexate (Disease Modifying Drugs)
• sulphasalazine/ hydroxychloroquine/leflunomide

further

• anti TNF alpha
• rituximab - anti CD20
• abatacept - binds CD80 and CD86
• tocilizumab - against IL6 receptor

Question 23

1. Pt has malar rash + tender joints + HTN + oedema. You then see the attached image. What is going on?
2. What effect does this have on complement pathway?
3. What would renal biopsy show?

Answer 23

1. SLE: pic shows dsDNA
2. Low C3 and C4: complement gets consumed since immune complexes bind to C1q and activate the classical pathway
3. Diffuse proliferative nephritis

Question 24

Rouleaux formation in which blood condition?

Answer 24

Multiple myeloma