L26- Immunodeficiencies Flashcards
Primary Immunodeficiency:
- (common/rare)- compared to secondary
- (2) age of onset
- (3) typical causes
1- rare
2- 6mo-2yr, once maternal immune system is not contributing (Igs)
3- genetic defects:
- B and or T cell development / function
- complement proteins
- phagocytes
Secondary Immunodeficiency:
- (common/rare)- compared to primary
- (2) age of onset
- (3) typical causes
1- common
2- depends on cause, but later than 2y/o typically
3:
- therapy (immunosuppression, chemotherapy)
- infections (HIV)
- malnutrition
- neoplasia
- renal disease (BV damage)
- metabolic disease (DM)
Immune deficiency via infections:
- (1) type pathogens can cause T cell defects
- (2) for B cell defects
- (3) granulocyte defect
- (4) complement defect
1- Bacteria (many, sepsis), Viruses (HIV, CMV, EBV, VZV), Fungi/Parasites (candida, P. jiroveci)
2- Bacteria (*Strep., Staph., Haemophilus), Viruses (enteroviral encephalitis), Fungi/Parasites (severe intestinal giardiasis)
3- Bacteria (Staph. Pseudomonas)
4- Bacteria (Neisseria, pyogenic infections)
list and categorize the common primary immune deficiencies
T-cell defect: DiGeorge syndrome
B-cell defect: Bruton’s agammaglobulinemia, Hyper IgM syndrome, IgA deficiency
T/B-cell defect: SCID, common variable immunodeficiency, Wiskott-Aldrich syndrom
Phagocytic cell defect: chronic granulomatous disease
Complement: C3 deficiency, C5-C9 deficiency
DiGeorge Syndrome:
- (1) age of onset
- (T cell/B cell/phagocyte/complement) defect
- (3) mechanism
- (4) features
1- birth
2- T cell
3- lack of thymic development – lack of T cell maturation
4- viral, fungal, protozoal infections
X-linked agammaglobulinemia:
- (1) age of onset
- (T cell/B cell/phagocyte/complement) defect
- (3) mechanism
- (4) features
1- 6mos
2- B cell
3- BTK mutation –> failed B cell maturation –> no Ig production
4- pyogenic bacteria, enteroviruses, giargia infections
Hyper IgM syndrome:
- (1) age of onset
- (T cell/B cell/phagocyte/complement) defect
- (3) mechanism
- (4) features
1- 1-4yrs
2- B-cell
3- lack CD40L –> no T cell - B cell / macrophage interaction –> no class switch in B cells
4- pyogenic bacteria infections // normal or elevated IgM, no IgG, IgA, IgE
IgA deficiency:
- (1) age of onset
- (T cell/B cell/phagocyte/complement) defect
- (3) mechanism
- (4) features
1- >6mos – may be asymptomatic
2- B-cell
3- impaired B cell differentiation to IgA producing cells
4- sinopulmonary infections, diarrhea, autoimmune dx, anaphylaxis with blood transfusion with foreign IgA
X-linked SCID:
- (1) age of onset
- (T cell/B cell/phagocyte/complement) defect
- (3) mechanism
- (4) features
(severe combined immuno-deficiency)
1- 6mos
2- T and B cell
3- γ chain mutation of CK receptors (mainly IL-7) – impaired signaling
4- bacterial, viral, fungal, protozoal infections
Autosomal SCID:
- (1) age of onset
- (T cell/B cell/phagocyte/complement) defect
- (3) mechanism
- (4) features
(severe combined immuno-deficiency)
1- 6mos
2- T and B cell
3- ~50% due to ADA (adenosine deaminase) deficiency mutation –> toxic metabolite accumulation
4- bacterial, *viral, *fungal, protozoal infections
Common variable immunodeficiency:
- (1) age of onset
- (T cell/B cell/phagocyte/complement) defect
- (3) mechanism
- (4) features
1- 10s-20s
2- T and B cell
3- unknown cause –> defective Ig production
4- pyogenic bacteria, enteroviruses, giardia infections, autoimmune disease
Wiskott-Aldrich syndrome:
- (1) age of onset
- (T cell/B cell/phagocyte/complement) defect
- (3) mechanism
- (4) features
1- early onset
2- T and B cell
3- mutation of proteins linking membrane receptors
4- thrombocytopenia, eczema, recurrent infections, T-cell depletion in blood / paracortical areas of LNs
Chronic granulomatous disease:
- (T cell/B cell/phagocyte/complement) defect
- (2) mechanism
- (3) features
- (4) is the diagnostic test
1- phagocyte
2- defective NADPH oxidase production and generation of superoxide anion (X-linked or autosomal)
3- catalase+ bacteria, fungi infections —> characteristic granuloma in response to inflammation
4- Nitroblue Tetrazoluim reduction:
- Pos. is normal, NADPH = purple
- Neg. is abnormal, absent NADPH = yellow
