Week 6 Flashcards
(18 cards)
What is primary immunodeficiency?
- Congenital/inherited
- results from genetic defects
- deficiency causes disease
What is secondary immunodeficiency?
- acquired
- result of other disease or conditions e.g. HIV, malnutrition, immunosuppression
List some categories of primary immunodeficiencies.
- combined IDs
- combined with syndromic features
- antibody deficiencies
- phagocyte defects
- defects in innate immunity
- autoinflammatory disorders
Give examples of combined IDs
- SCID (x-linked)
- ADA-SCID
- hyper IgM syndrome
Discuss X-linked SCID
- mutation in cytokine receptors, IL-2Ry/common y chain
- T cells and NK cells fail
- B cells normal but no help from T cells so immune response affected
Discuss ADA-SCID
- adenoside deaminase deficiency
- depletes T, B and NK cells
- cells will have basal expression of ADA but needs to be enhanced in thymocytes
- mostly recessive
How can ADA-SCID now be treated?
- Take patients bone marrow cells
- Virus is altered ex vivo so it can’t reproduce
- A gene is inserted into the virus
- Altered virus is added to cells ex vivo
- Cells genetically altered ex vivo
- Patient conditions with chemo/radiotherapy
- Altered cells transplanted back into patient
- Altered cells expand and exert biological effect in vivo.
Discuss hyper IgM syndrome
- high levels of IgM and low levels of other Igs so unable to class switch
- deficient in CD40L on T cells
- so B cells cannot switch from IgM to other class
Give examples of combined IDs with syndromic features.
- FoxN1 deficiency
Discuss FoxN1 deficiency.
- FoxN1 molecule important in immune response but also in epithelial cells
- athymic = no thymus > no T cells, alopecia
- B cells are normal but lack of T cells still affects immune system
Give examples of antibody deficiencies.
- Bruton’s tyrosine kinase deficiency
- CD40L deficiency (hyper IgM)
- IgA deficiency
What happens if you have a humoral or B cell defect?
- recurrent sepsis
- bacterial infections (often in airways)
- chronic gastroenteritis
- failure to thrive as an infant
Discuss Bruton’s tyrosine kinase deficiency.
- mutation in Bruton’s tyrosine kinase gene
- prevents B cell development
- few follicles in lymph nodes
- results in low serum antibody levels
- X linked
Discuss IgA deficiency
- very common
- possibly due to interleukin deficiency
- many people asymptomatic
- IgG can help e.g. protect mucosal immune system
Give examples of phagocyte defects.
- defects of neutrophil function
- defects of respiratory burst
- Mendelian susceptibility to mycobacterial disease (MSMD)
Discuss chronic granulomatous disease (defects of respiratory burst)
- no superoxide burst
- multiple granulomas form as a result of defective elimination of bacteria
- defects in the NADPH enzymes that generate the superoxide radicals involved in bacterial killing
Give examples of autoinflammatory disorders.
- familial Mediterranean fever
- IL-10/10R deficiency
Discuss familial Mediterranean fever
- an inflammasome converts pro-IL-1 to IL-1
- In FMF inflammasome regulators are mutated
- inflammasome activate so increased IL-1
- inflammation can respond to anti-IL-1 antibody for treatment
