Primary Immunodeficiency 2 (IMMUNOLOGY) Flashcards
What is reticular dysgenesis?
Failure of haematopoietic stem cells in the thymus to produce neutrophils/lymphocytes/macrophages/platelets
Reticular dysgenesis is fatal unless…
Stem cell transplant
What is severe combined immunodeficiency (SCID)?
Failure of haemotopoietic stem cells in the thymus to produce lymphocytes
How do patients with SCID present?
Unwell by 3 months Persistent diarrhoea Failure to thrive All types of infection (common/unusual/opportunistic) Vaccine-associated diseases Graft vs. Host Disease
Why do neonates with SCID only become unwell by 3 months?
Maternal IgG protects the SCID neonate in the first 3 months
What is the commonest form of SCID?
X-linked
Which mutation causes X-linked SCID?
Mutation of IL-2 receptor component
What is the clinical phenotype of X-linked SCID?
Very low or absent T cells
Normal or increased B cells
Poorly developed lymphoid tissue & thymus
How can X-linked SCID be treated prophylactically?
Avoid infection through prophylactic antibiotics and no vaccines + aggressive treatment of existing infections + antibody replacement by iv immunoglobulin
How can X-linked SCID be treated definitively?
Stem cell transplant
Gene therapy - stem cells treated ex vivo to express missing component
What is DiGeorge syndrome?
Genetic condition caused by a deletion at 22q11
Developmental defect of 4rd and 4th pharyngeal pouch
What are the clinical features of DiGeorge syndrome?
Failure of thyme development - T cell immunodeficiency Congenital heart defects Cleft palate Hypocalcaemia second to hypothyroidism Developmental delay Psychiatric disorders Lowest ears Abnormally folded High forehead Small mouth & jaw Oesophageal atresia
How can DiGeorge syndrome be detected through lab investigations?
Low or absent T cells
Normal or increased B cells
Normal NK cell numbers
How can DiGeorge syndrome be managed?
Correct metabolic & cardiac abnormalities Prophylactic antibiotics aggressive treatment of infection Possibly immunoglobulin replacement T cell function improves with age
What are the clinical features of T cell deficiencies?
Recurrent + opportunistic infections
Malignancies at young age
Autoimmune disease
What are 1st line investigations for T cell deficiencies?
Total white cell count & differential
Serum immunoglobulins & protein electrophoresis
Quantitation of lymphocyte subpopulation
What are 2nd line investigations for T cell deficiencies?
Functional tests of T-cell activation & proliferation
Additional tests of lymphocyte lineage
HIV Tests
How do antibody deficiencies present?
Recurrent bacterial infections
Antibody-mediated autoimmune disease
What is Bruton’s X-linked hypogammaglobulinaemia?
Failure to produce mature B cells resulting in no circulating B cells / no plasma cells / no circulatory antibodies after 6 months
How do patients with selective IgA deficiency present?
2/3 asymptomatic
1/3 recurrent RTIs
What is common variable immune deficiency (CVID)?
Heterogenous group of disorders causing low IgA, IgG and IgE / recurrent bacterial infections / often associated with autoimmune disease
What are the clinical features of CVID?
recurrent bacterial infections Bronchiectasis Persistent sinusitis Recurrent GI infection Auto-immune & granulamotous disease
What are 1st line investigations of B cell deficiencies?
Total white cell count & differential
Serum immunoglobulins
Serum & urine protein electrophoresis
What are 2nd line investigations of B cell deficiencies?
Quantitation of B and T lymphocytes
Specific antibody responses to known pathogens
