What is a primary immunodeficiency?
- inherited disorders with defects in 1+ components of the immune system
- infections are hallmarks
What are secondary immunodeficiencies?
- non-inherited, acquired
- caused by environmental facotrs
- infections are hallmarks
What are combined immunodeficies
- impairments in both B- and T-cell function
- inherited mutations
What defect causes pyogenic (pus-forming) bacterial infection in primary immunodeficiencies?
defect in antibody, complement or phagocyte function
What defect typically causes persistent fungal or viral infection in primary immunodeficiencies?
defect in T-cell function
What are Combined Immunodeficiencies limited to the immune system? (give examples, cells affected, immune defect and antibody level)
- Yc and RAG-1/2 deficiency
- T, B and NK cells
- deficient T, B and NK cell development
- low antibody
What are Combined Immunodeficiencies with defects in tissues outside the immune system? (give examples, cells affected, immune defect and antibody level)
- FOXN1 and Job syndrome
- thymic epithelium, TH17 and TFH cell development affected
- Deficient/defective T cell, TH17 and TFH cell development
- decreased antibody / high IgE
What areantibody deficiencies? (give examples, cells affected, immune defect and antibody level)
- Bruton’s X-linked agammaglobulinemia, AID deficiency, Selective IgA deficiency
- B cells affected
- defective Ig class-switching and somatic hypermutation / absent mature B cells
- low antibody, IgG/IgA low + IgM increased, low-absent IgA
What is immune dysregulation? (give examples, cells affected, immune def
- perforin deficiency, IL-10 deficiency
- CTLs, NK cells and multiple others
- impaired CTL and NK-cell cytotoxicity and no IL-10
- normal antibody
What are phagocyte defects? (give examples, cells affected, immune defect and antibody level)
- Elastase deficiency, GATA2 deficiency
- neutrophiles, monocytes, DCs
- neutrophil, monocyte, DC deficiency
- normal antibody
What are innate immunity defects? (give examples, cells affected, immune defect and antibody level)
- IL-12p40 deficiency, IFN-y receptor 1 deficiency
- DCs, monocytes, macrophages and multiple others
- IFN-y secretion and signaling
- normal antibody
What are Autoinflammatory disorders? (give examples, cells affected, immune defect and antibody level)
- Muckle-Wells syndrome
- neutrophils, monocytes
- inflammasome hyperactivity
- normal antibody
What are Complement deficiencies? (give examples, cells affected, immune defect and antibody level)
- C1q deficiency, MASP deficiency
- apoptotic cells / none
- deficient activation of classical / lectin complement pathway
- normal antibody
What are phenocopies of inborn errors of immunity? (give examples, cells affected, immune defect and antibody level)
- APECED deficiency
- T cells
- impaired negative selection of T cells
- normal with autoantibodies
What does adenosine deaminase deficiency disrupt and subsequently cause? what can it be treated with?
- disrupts S-phase of cell cycle
- lack of circulating T and B cells
- causes SCID in infancy, can be treated with bone marrow transplantation
What does Omenn syndrome cause?
- partial loss of V(D)J recombinase activity through mutations in RAG1 or RAG2 alleles
- peripheral T cells are autoreactive
How does FOXN1 mutation affect T cells?
lack of thymic function, leads to abnormal T-cell development
How does DiGeorge syndrome affect T cells?
- thymus is absent
- abnormal T-cell development and function
How does Bare Lymphocyte Syndrome affect T cells?
- MHC class I or II deficiency
- improper activation of CD8 (MHC class I)
- mutation in TFs responsible for MHC II expression
How does X-linked Agammaglobulinemia affect B cells?
- failure of B cell precursors to mature into B cells and then plasma cells
- low levels of all isotypes
- reduced B cell #s
What is Hyper IgM syndrome?
- affects Igs
- only males
- caused by mutation in CD40 ligand
- low levels of IgG, IgA and IgE (IgM might be low, normal or elevated)
What is chronic granulomatous disorder?
- defects in phagocytes where they cannot kill certain pathogens
- vulnerability to severe recurrent bacterial and fungal infefctions
what is leukocyte adhesion deficiency?
- defects in migration of phagocytes
- patients are deficient in the expression of 3 integrins containing CD18 (LFA-1, Mac-2, Gp 150/195
What is Chediak-Higashi syndrome?
- defects in phagocytes
- impaired lysis of phagocytosed bacteria
- abnormal NK cell function
- defective lysosomal function in macrophages, DCs and neutrophils
