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
describe treatment of primary immunodeficiencies
prevent infection
prophylactic antibiotics (mild immunodeficiency)
immunoglobulin replacement therapy (antibody deficiency)
stem cell transplantation (SCID, T cell deficiency)
gene therapy
how to prevent infections
avoid live vaccines (measles, mumps, rubella, polio)
prophylaxis against opportunistic infections
what is gene therapy
uses recombinant technology to correct the genetic defect in patient’s own stem cells which can then reconstitute the immune system
