primary immunodeficiency disorders Flashcards
what are hallmarks of immune deficiency
recurrent infections
what does SPUR stand for
serious, persistent, unusual, recurrent infections
Classification of immunodeficiency disorders: secondary
Common
Often subtle
Often involves more than one component of immune system
Conditions associated with secondary immune deficiency
physiological immune deficiency, infection, treatment interventions, malignancy, biochemical and nutritional disorders
physiological immune deficiency
extremes of life - ageing, prematurity (first few months of life if not breastfeeding baby only has placental IgG until immune system kicks in)
infection related secondary immune deficiency
HIV, measles
treatment intervention related secondary immune deficiency
Immunosuppressive therapy, anti cancer agents
malignancy secondary immune deficiency
cancers of immune system - lymphoma, leukaemia, myeloma
biochemical and nutritional disorder related secondary immune deficiency
malnutrition, renal insufficiency, diabetes, mineral deficiencies
primary immunodeficiency disorders
300 primary immune deficiencies now described:
Immune dysregulation, Autoinflammatory disorders
Defects in innate and adaptive immunity. gene mutation
what are the most common initial manifestations of PIDs
Respiratory diseases are the main and initial manifestation. Pulmonary complications cause significant morbidity and mortality in patients with PIDs. Early diagnosis and appropriate treatment can prevent or at least slow the development of respiratory complications
examples of upper respiratory complications
sinusitis, otitis media, laryngeal angiodema
examples of lower respiratory complications
malignancies, interstitial disease, pneunomia, bronchitis. these are more significant problems than the upper respiratory complications
defects in neutrophils 1
severe congenital neutropenia. person has precursor cells but no mature neutrophils. example = kostmann syndrome
defects in neutrophils 2
endothelial migration. adhesion molecules > mutation > nonfunction > neutrophils cant stick and leave blood stream to get to infection
what would you expect to happen if patients phagocytes were unable to bind to adhesion molecules
recurrent bacterial and fungal infections, high neutrophils in blood, pus
leukocyte adhesion deficiency
Very rare autosomal recessive primary immunodeficiency. Results in failure of neutrophil adhesion and migration, different types of deficiency effect different adhesion molecules.
what is the first sign of leukocyte adhesion deficiency
umbilical cord never heals. need a stem cell transplant
defects in neutrophil killing
Chronic granulomatous disease. Deficiency of the intracellular killing mechanism of phagocytes - absent respiratory burst. Inability to generate oxygen/nitrogen free radicals
Impaired killing of intracellular micro-organisms
clinical features of CGD
Recurrent deep bacterial infections. Recurrent fungal infections. Failure to thrive. Lymphadenopathy and hepatosplenomegaly. Granuloma formation
treatment of phagocyte deficiencies
immunoglobulin replacement therapy, aggressive management management of infection, definitive therapy (stem cell transplantation)
what is SCID
severe combined immunodeficiency - failure of production of lymphocytes
causes of SCID
Deficiency of cytokine receptors
Deficiency of signalling molecules
Metabolic defects
Defective receptor rearrangements
whats the commonest form of severe combined immunodeficiency
X-linked SCID, mainly effects males. Mutation of a component of the IL-2 Receptor. very low or absent T cells
