primary immunodeficiency Flashcards
immunodeficiency
defects in the immune system
types of immunodeficiencies
primary: congenital
secondary: acquired
what is the major consequence of immunodeficiency
increased susceptibility to infection
(& cancer, autoimmunity)
primary immunodeficiency consequences
- infection
- tumour
primary immunodeficiency aetiology
genetic aberrations (mainly)
autoimmunity (few)
primary immunodeficiency abnormalities
innate immune system
- antibody deficiency
lymphocyte development
- defects in T and B cells
mature lymphocyte response to antigens
- defects in TCR
causes of primary immunodeficiency abnormalities
- mutations
- polymorphisms
- polygenetics
mutations
- rare
- permanent alteration in DNA sequence
- conditions: SCID
SCID
defective T cells and B cells → infections in first few weeks of life
- unusual/recurrent infections, diarrhoea, rashes
- very low lymphocyte count
treatment: SCT (asap), gene therapy
polymorphism
- common
- variation of DNA sequence
- increased risk of infections
- conditions: HLA, MBL
what is MBL
mannan binding lectin
collagen like protein that binds sugars in bacterial cell wall and activates classic complement pathway
polygenic disorders
- common
- combined action of more than one gene
- develop recurrent infections with pneumococcus and haemophillus
- affects antibodies, present later in life
- conditions: CVID, IgA deficiency, specific antibody deficiency
what is the most common primary immunodeficiency
CVID
primary immunodeficiency causes - autoimmunity
autoimmune polyendocrinopathy candidiasis ectodermal dysplasia (APECED)
defect in central tolerance leads to autoimmunity
- produce anti-IL17 → recurrent candida infection
- produce anti-IFN-y → recurrent mycobacterial infection
type of opportunistic infection gives clues about
degree and cause of immunodeficiency
T cell defects or macrophages
infection with intracellular organisms:
- protozoa
- viruses (herpes simplex/varicella zoster, kaposi sarcoma, EBV)
- intracellular bacteria (mycobacteria)
- fungi: candida
phagocyte defects
infections
- staphylococci
- gram-negative bacteria
- fungi
compliment defects
meningitis
- Neisseria meningitidis
B cell defects
antibody deficiency (IgG and IgA) leads to respiratory infection
- pneumococcus
- haemophilus spp
