Immuno: Case Studies in Immunology Pt.2 Flashcards
Explain the following clinical manifestations of serum sickness:
- Deterioration in renal function
- Disorientation
- Purpura
-
Deterioration in renal function
- Deposition of immune complexes in the glomeruli leads to complement activation and inflammatory cell recruitment
- This leads to glomerulonephritis resulting in a rise in creatinine, proteinuria and haematuria
-
Disorientation
- Small vessel vassculitis affecting the cerebral vessels can compromise the oxygen supply to the brain
-
Purpura
- Inflamed blood vessels are likely to leak resulting in local haemorrhage
How should serum sickness be managed?
- Stop penicillin
- Give corticosteroids
- Ensure appropriate fluid balance
List some features of immunodeficiency.
- Severe infections (hospitalisation)
- Persistant (difficult to treat)
- Unusual (e.g. opportunistic, unusual sites of infection)
- Recurrent
- Concomitant problems
eg. failure to thrive,
List some non-immunological causes of recurrent infections in children.
- Prematurity
- Allergic rhinitis, sinusitis, Asthma
- Cystic fibrosis
- Local factors (e.g. foreing body)
- Ciliary disorders
What is the point of testing people with recurrent infections for antibodies against infections that they have been vaccinated for (e.g. tetanus)?
To see whether they are capable of mounting an antibody response
eg. tetanus, HiB, PCV-13
General investigations in suspected immunodeficiency?
- FBC
- Serum Immunoglobulins
- HIV test
Immunologists will do the rest
(ie. antibody testing, Flow cytometry)
Which condition is characterised by a failure to produce any immunoglobulin?
X-linked agammaglobulinaemia - failure of pre-B cells to mature in the bone marrow leading to failure of production of antibodies
Lack of Bruton’s Tyrosine kinase
(overactive in haematological malignancies eg. CLL)
How is X-linked agammaglobulinaemia treated?
IgG Immunoglobulin replacement therapy - every 3 weeks
IV or SC
in hospital or trained to do it at home
Lifelong
includes Antibodies against pneumococcus and haemophillus
Why do XLA patients have predisposition to autoinflammatory disease
BTK tyrosine kinase (deficiency in XLA) also acts as an inhibitor to inflammasome
So unregulated immune responses
What are some classic presenting features of multiple myeloma?
CRABS
Bone pain and pathological fractures
Hypercalcaemia symptoms
Which investigation is used to diagnose multiple myeloma?
Serum protein electrophoresis - shows a monoclonal band (this can be stained to check whether it is composed of heavy or light chains)
Kappa : Lambda ratio of ligh chains in serum
Why are patients with multiple myeloma prone to infections?
Suppression of normal antibody production by the malignant clone of cells results in a functional antibody deficiency
NOTE: this is sometimes called immune paresis
How does multiple myeloma lead to aneamia?
- Expansion of malignant clone of cells into the bone marrow crowds out normal red and white cell precursors
- Cytokines produced by the myeloma cells inhibit normal bone marrow function
Why is ESR elevated in multiple myeloma?
- Normally, erythrocytes don’t clump together because the repellent negative surface charge is greater than the attractant charge of plasma constituents
- If the protein constituents of plasma change, it increases the attractant charge, causes erythrocytes to clump together and clumped erythrocytes fall more quickly through plasma
- This causes raised ESR
- Often normal CRP
Which red blood cell abnormality may you see in the blood film of a patient with multiple myeloma?
Rouleaux formation
NOTE: you may also see Bence-Jones protein in the urine
What are the key clinical features of rheumatoid arthritis?
Peripheral, symmetrical polyarthritis with stiffness lasting > 6 weeks
When does rheumatoid arthritis commonly present and what is a possible explanation for this?
Post-partum - Th2 cells predominate during pregnancy and this switches back to Th1 post-partum
What is Rheumatoid Factor?
- Antibody directed against the Fc portion of human IgG
- Assays mainly look for IgM but there are also IgG and IgA variants
- 60-70% sensitive and specific
Better test than rheumatoid factor?
Anti-CCP
How are citrullinated peptides implicated in rheumatoid arthritis?
- Arginine residues are deiminated to form citrulline by PAD enzymes
- Polymorphisms in PAD that increases the level of citrullination may predispose to rheumatoid arthritis
- Loss of tolerance to citrullinated peptides results in the production of antibodies against CCP
- Anti-CCP antibodies are highly specific (95%)
Describe how specific HLA alleles can predispose to the development of rheumatoid arthritis.
- HLA-DR4 (60-70%) and HLA-DR1
- These predisposing classes have a common sequence at positions 70-74 (this area encodes the peptide-binding groove)
- Peptide presentation by these HLA molecules may be involved in disease pathogenesis
Which PAD polymorphisms are associated with rheumatoid arthritis?
PAD 2 and PAD 4
What is the role of PTPN22 and which polymorphism is associated with rheumatoid arthritis?
- It is a lymphocyte-specific tyrosine kinase that suppresses T cell activation
- 1858T allele increases susceptibility to rheumatoid arthritis, SLE and T1DM
Outline the management of rheumatoid arthritis.
- First-line: methotrexate (DMARD)
- Other options: TNF-alpha antagonists, rituximab, abatacept (CTLA4-Ig fusion protein), tocilizumab (antibody against IL6 receptor)
List some risks of biological therapy for rheumatoid arthritis.
- TB
- Opportunistic infections
- Malignancy - skin protection
