primary immunodeficiency disorders

Question 1

what are hallmarks of immune deficiency

Answer 1

recurrent infections

Question 2

what does SPUR stand for

Answer 2

serious, persistent, unusual, recurrent infections

Question 3

Classification of immunodeficiency disorders: secondary

Answer 3

Common
Often subtle
Often involves more than one component of immune system

Question 4

Conditions associated with secondary immune deficiency

Answer 4

physiological immune deficiency, infection, treatment interventions, malignancy, biochemical and nutritional disorders

Question 5

physiological immune deficiency

Answer 5

extremes of life - ageing, prematurity (first few months of life if not breastfeeding baby only has placental IgG until immune system kicks in)

Question 6

infection related secondary immune deficiency

Answer 6

HIV, measles

Question 7

treatment intervention related secondary immune deficiency

Answer 7

Immunosuppressive therapy, anti cancer agents

Question 8

malignancy secondary immune deficiency

Answer 8

cancers of immune system - lymphoma, leukaemia, myeloma

Question 9

biochemical and nutritional disorder related secondary immune deficiency

Answer 9

malnutrition, renal insufficiency, diabetes, mineral deficiencies

Question 10

primary immunodeficiency disorders

Answer 10

300 primary immune deficiencies now described:
Immune dysregulation, Autoinflammatory disorders
Defects in innate and adaptive immunity. gene mutation

Question 11

what are the most common initial manifestations of PIDs

Answer 11

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

Question 12

examples of upper respiratory complications

Answer 12

sinusitis, otitis media, laryngeal angiodema

Question 13

examples of lower respiratory complications

Answer 13

malignancies, interstitial disease, pneunomia, bronchitis. these are more significant problems than the upper respiratory complications

Question 14

defects in neutrophils 1

Answer 14

severe congenital neutropenia. person has precursor cells but no mature neutrophils. example = kostmann syndrome

Question 15

defects in neutrophils 2

Answer 15

endothelial migration. adhesion molecules > mutation > nonfunction > neutrophils cant stick and leave blood stream to get to infection

Question 16

what would you expect to happen if patients phagocytes were unable to bind to adhesion molecules

Answer 16

recurrent bacterial and fungal infections, high neutrophils in blood, pus

Question 17

leukocyte adhesion deficiency

Answer 17

Very rare autosomal recessive primary immunodeficiency. Results in failure of neutrophil adhesion and migration, different types of deficiency effect different adhesion molecules.

Question 18

what is the first sign of leukocyte adhesion deficiency

Answer 18

umbilical cord never heals. need a stem cell transplant

Question 19

defects in neutrophil killing

Answer 19

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

Question 20

clinical features of CGD

Answer 20

Recurrent deep bacterial infections. Recurrent fungal infections. Failure to thrive. Lymphadenopathy and hepatosplenomegaly. Granuloma formation

Question 21

treatment of phagocyte deficiencies

Answer 21

immunoglobulin replacement therapy, aggressive management management of infection, definitive therapy (stem cell transplantation)

Question 22

what is SCID

Answer 22

severe combined immunodeficiency - failure of production of lymphocytes

Question 23

causes of SCID

Answer 23

Deficiency of cytokine receptors
Deficiency of signalling molecules
Metabolic defects
Defective receptor rearrangements

Question 24

whats the commonest form of severe combined immunodeficiency

Answer 24

X-linked SCID, mainly effects males. Mutation of a component of the IL-2 Receptor. very low or absent T cells

Question 25

clinical phenotype of SCID

Answer 25

Unwell by 3 months of age
Persistent diarrhoea
Failure to thrive
Infections of all types
unusual skin disease
family history of infant death

Question 26

why do people with SCID get recurrent viral infections

Answer 26

CD8 + T cells are essential in killing off virally infected host cells. they lack them

Question 27

why do people with SCID have recurrent bacterial infections

Answer 27

effector CD4+Tfh cells are essential for helping B cells make antibodies

Question 28

why do people with SCID get frequent fungal infections

Answer 28

effector CD4+Th cells are essential for defence against fungal pathogens