28 - Immunodeficiency Flashcards
what is immunodeficiency?
conditions caused by defects in one or more components of the immune system
list the two classifications of immunodeficiency
primary/ congenital
secondary/ acquired
describe the classifications of immunodeficiency
primary/ congenital
- condition resulting from a genetic or developmental defect
- present at birth, mostly inherited, though may not be observed until later
secondary/ acquired
- originate as a result of malnutrition, cancer, drug treatment, infection
- more common
- result in immunosuppression
describe the general clinical features of PIDs/ primary immunodeficiencies
recurring infections
- e.g. UTIs, otitis media, gastroenteritis = affecting the urinary tract, GI tract and ear
- thrush and fungal infections
failure to thrive for a baby
severe infections with unusual pathogens, occurring in unusual sites - wouldn’t occur in immunocompetent individuals
needing a higher dose or i.v. delivery of antibiotics
describe the different general causes of PIDs - innate? adaptive?
for innate immune system = caused by a defect in phagocytic or complement function
for adaptive immune system = disorders affecting T and/or B cells, antibody production and cell-mediated immunity
what is the relationship between haematopoiesis and PIDs?
defects in the earlier stem cells (e.g. HSCs, early progenitor cells) affect more of the immune system - greater downstream effects
defects in later stage haematopoietic cells show a more restricted pathology - e.g. affecting just T or B cell lineages
what are the four types of immune dysfunction?
phagocytic disorders - e.g. chronic granulomatous disease
disorders affecting B cell function and antibody production - e.g. XIA/ X-linked agammaglobulinemia
thymic epithelial cell mediated dysfunction - e.g. DiGeorge syndrome
combined T and B cell immune dysfunction - e.g. WAS/ Wiskott-Aldrich Syndrome, SCID`
examples of major B cell disorders?
XIA = X-linked agammaglobulinemia/ Bruton’s disease
common variable immunodeficiency/ CVID
Selective IgA deficiency
IgG2 subclass deficiency
specific Ig deficiency with normal Igs
examples of adaptive PIDs?
XIA = X-linked agammaglobulinemia/ Bruton’s disease
selective IgA immunodeficiency
SCID = severe combined immunodeficiency
DiGeorge syndrome
WAS = Wiskott-Aldrich syndrome
what is XIA?
X-linked agammaglobulinemia or Bruton’s disease
X-linked recessive immunodeficiency which affects B-cell development
what causes XIA? what effect does this have on immune cells?
BTK gene on X chromosome that encodes Bruton’s tyrosine kinase is mutated - BTK is needed for downstream signalling of B cells for development
BTK mutation blocks B-cell signalling = blocks B-cell development = stops at pre-B cell stage
lack of B cells and antibody production
clinical consequences of XIA
recurrent severe infections
- susceptible to resp, GI tracts & ear infections
risk of autoimmunity
symptoms appear early in life
diagnosis of XIA? immune cell levels, other tests?
immune cell levels:
- low/ absent B cells, plasma cells and Igs
- normal T cells, NK cells and T-cell mediated responses = this is a B cell restricted ID
diagnosis by flow cytometry or immunoglobulin immune-electrophoresis
- patient’s serum is placed on matrix of a small plate, and components of serum migrate according to charge, stimulated by electricity
- sample moves and separates components = absence of Igs indicates XIA
treatment for XIA?
i.v. administration of exogenous Igs - polyclonal Igs from donor
antibody therapy needed for severe infections but NO live vaccines
what is selective IgA deficiency?
absence of IgA - needed for protecting mucosal surfaces
selective IgA - diagnosis?
low serum and secretory IgA levels
selective IgA - presentation?
- mostly asymptomatic
- sometimes infections of respiratory, urogenital or GI tract, increased incidence of allergic reactions
what are combined immunodeficiencies? examples?
IDs affecting both T and B cells
examples:
- DiGeorge syndrome
- Wiskott-Aldrich syndrome/ WAS
- Ataxia-telangiectasia
