10. Immunocompromised host Flashcards
“immunocompromise” is?
state in which the immune system is unable to respond appropriately and effectively to infections microorganisms
“immunodeficiency” is?
immunocompromise caused by defect in 1 or more components of immune system
describe the 2 types of immunodeficiency
1. primary - congenital due to intrinsic gene defect (275 genes) - missing protein - missing cell - non-functional components
- secondary - acquired
due to underlying disease/treatment
- decreased production/function of immune components
- increased loss or catabolism of immune components
Which 4 characteristics of infections suggest underlying immune deficiency?
SPUR:
Severe
Persistent (despite treatment)
Unusual (site or microogranism)
Recurrent
10 warning signs of PIDs in children?
- 4+ new ear infection <1yr
- 2+ serious sinus infections <1yr
- 2+ pneumonias <1yr
- recurrent, deep skin or organ abscesses
- persistent thrush in mouth or fungal infection on skin
- 2+ deep-seated infections inc. septicaemia
- 2+ months on antibiotics with little effect
- need for IV antibiotics to clear infections
- failure of infant to gain weight/grow normally
- family history of PID
10 warning signs of PID in adults?
- 2+ new ear infections <1yr
- 2+ new sinus infections <1yr
- 1 pneumoniae/yr for >1yr
- recurrent viral infections
- recurrent deep abscesses of skin or internal organs
- persistent thrush or fungal infection on skin or elsewhere
- infection with normally harmless tuberculosis-like bacteria
- recurrent need for IV antibiotics to clear infections
- chronic diarrhoea with weight loss
- family history of PID
what are the limitations of the 10 warning signs
- lack of pop-based evidence (e.g. family history, failure to thrive)
- PID patients with diff. defects/presentations (infections with subtle presentation, T cells/ B cells/ phagocytes/ complement)
- PID patients with non-infectious manifestations (autoimmunity, malignancy, inflammatory responses)
which malignancy is common in PIDs
lymphoma
name the 4 main types of PID in commoness order, and give an example of each
- predominantly antibody deficiencies (65%)
- COMMON VARIABLE IMMUNODEFICIENCY (CVID)
- X-LINKED AGAMMAGLOBULINAEMIA (BRUTON’S DISEASE)
- SELECTIVE IgA DEFICIENCY (usually asymptomatic) - combined B and T cell
- SEVERE COMBINED IMMUNODEFICIENCY (SCID) - phagocytic defects
- CHRONIC GRANULOMATOUS DISEASE - other cellular immunodeficiencies
what PIDs do different ages of symptom onset suggest
- <6 mths = T cell or phagocyte defect
- > 6 mths - <5 yrs = B cell/antibody or phagocyte defect
- > 5 yrs = B cell/antibody defect, complement defect or secondary immunodeficiency
which microbes are commonly associated with complement deficiency
encapsulated bacteria, e.g. Neisseria spp, streptococci, H. influenzae
which infections are associated with C3 or C5-C9 deficiency?
C3 = pyogenic infections
C5-C9 = meningitis, sepsis and arthritis
which condition results from C1 inhibitor deficiency?
angioedema
which microbes are associated with phagocytic defects?
Bacteria: S. aureus, P. aeruginosa, non-tuberculous mycobacteria
Fungi: Candida spp., Aspergillus spp.
which infections are associated with phagocytic defects?
- skin/mucous infections
- deep seated infections
- invasive fungal infections (ASPERGILLOSIS)
which specific infection is indicative of antibody deficiencies
giardia lamblia (protozoa) GI infection
which microbes are associated with antibody deficiencies?
Bacteria: streptococci, staphylococci, H. influenzae, P. aeruginosa, Mycoplasma pneumoniae (upper resp. infections)
Protozoa: Giardia lamblia
which infections are associated with antibody deficiencies
- sinorespiratory infections
- GI infections
which conditions are associated with antibody deficiencies
- arthropathies
- malignancies
- autoimmunity
which microbes are associated with T cell deficiencies
Bacteria: same as antibody deficiency + intracellular bacteria like S. typhi, L. monocytogenes, and non-tuberculous mycobacteria
All viruses
Fungi: Candida spp, Aspergillus spp, Cryptococcus neoformans, Histoplasma capsulatum
Protozoa: Pneumocystis jirovecii, Toxoplasma gondii, Cryptosporidium parvum
which conditions are associated with T cell defects?
- opportunistic infections
- deep skin and tissue abscesses
- failure to thrive
- death if not treated
what is supportive treatment for PID?
- infection prevention (prophylactic antimicrobials)
- treat infections promptly and aggressively (passive immunisation)
- nutritional support (vitamins A/D)
- use UV-irradiated CMVned blood products only
- avoid live attenuated vaccines in Ps with severe PIDs (SCID)
- avoid non-essential exposure to radiation
what is the specific treatment for antibody deficiencies?
regular immunoglobulin replacement therapy (IVIG or SCIG)
what is the specific treatment for SCID
Haematopoietic Stem Cell Therapy (90% success), but:
- need donor match
- must be performed within 3 1/2 mths
name commorbidities of PID
- autoimmunity
- malignancies (esp. lymphoma and leukaemia)
- organ damage (e.g. lungs) if untreated
what is immunoglobulin replacement therapy and when is it used
concentrated form of Igs given either IV every 3 wks or Sc (subcutaneous) in young patients
used to treat CVID, XLA and hyper-IgM syndrome
what are the main causes of secondary immune deficiencies?
decreased production of immune components
- malnutrition - main cause
- infection (HIV)
- liver diseases (as liver products acute phase proteins, etc.)
- lymphoproliferative diseases - i.e. cancer and chemotherapy (causes neutropenia)
- splenectomy
name possible causes for splenectomy/hyposplenism
- infarction (eg sickle cell anaemia)
- trauma
- autoimmune haemolytic disease
- infiltration (tumour)
- coeliac disease
- congenital
why is the spleen so important
largest lymphoid organ
- only organ to fight blood-borne pathogens, inc. encapsulated bacteria
- antibody production:
- acute response: IgM production (pentameric - 5 fold activation of complement)
- long term protection: IgG production (best opsonin)
- splenic macrophages:
- removal of opsonised microbes
- removal of immune complexes
what are the complications of splenectomy
- increased susceptibility to encapsulated bacteria: H. influenzae, Strep. pneumoniae, N. meningitidis
- OPSI (overwhelming post-splenectomy infection): sepsis and meningitis
describe the management of asplenic patients
- penicillin prophylaxis (life-long)
- immunisation against encapsulated bacteria
- medic alert bracelet
why does haematological malignancy increase infection susceptibility?
- chemotherapy-induced neutropenia
- chemotherapy-induced damage to mucosal barriers
- vascular catheters (e.g. Hickman line)
