Ch 18 Immunodeficiencies Flashcards
What are the five categories that immunodeficiencies are broadly divided into?
- humoral
- complement
- Cell-mediated
- phagocytic
- combined
reticular dysgenesis
defect in mitochondrial adenylate kinase; no development of myeloid or lymphoid lineage
ADA deficiency
adenosine deaminase; build up of toxins prevents lymphoid lineage
RAG1/RAG2
no V(D)J rearrangement; no pre-BCR/TCR
Common cytokine receptor y-chain or JAK3 deficiency
no T or NK cells
CD3 chain deficiency
no TCR signaling; no T cells
Bare lymphocyte syndrome
defect in MHC I: no pos selection of CD8 cells
defect in MHC II: no pos selection of CD4 cells
DiGeorge syndrome
TBX1 defect; no thymus= decreased immunity and no T cells
tx with passive Ig or transplant
Wiskott-Aldrich syndrome
defect in WASP; cytoskeleton malformation= no phagocytosis or chemotaxis
tx= abs and antibiotics, HSC transfer
Hyper IgM syndrome
no CD40/CD40L–> APCs and TH cells can’t communicate. no Ab to T dpdt Ag, only IgM
Hyper IgE syndrome
STAT3 defect impairs IL-6/TGF-B and decreases B cell memory but increases IgE levels
X-linked agammaglobulinemia
- low levels of IgG
- defect in Btk
- no development past pre-B stage
- tx with antibiotics and passive Abs
Selective IgA deficiency
- substitution of IgM for IgA as primary mucosal antibody
- IgA secreting B cells unable to differentiate to the plasma cell stage
Leukocyte adhesion deficiency (LAD)
- abnormality in LFA-1, Mac-1, and gp150/95 integrin adhesion molecules
- limits leukocyte recruitment
Chronic granulomatous disease
- defect in NADPH oxidative pathway used by phagocytes
- higher inflammation= granulomas
- tx IFN-y to induce TNF-a and nitric oxide
APECED
- mutation in AIRE gene
- escape of autoreactive T cells from thymus causing organ-specific autoimmunity
- adrenal and thyroid
IPEX syndrome
- mutated FoxP3 preventing development of TREG cells
- autoreactive t cells
- death before 2 years of age due to sepsis and attacks on key organs
Immunodeficiency disorders are treated by replacement therapy:
- replacement of missing protein
- replacement of missing cell type or lineage
- replacement of messing defective gene
Nude mice
- vestigial thymus (no T cells)
- study effects of transplantation and cancer
SCID mouse
- no mature T, B, and NK cells
- generate humanized immune systems following transfer of human HSCs
RAG knockout mice
- T and B cells absent
- experimental cancer or infectious disease research
Ways to acquire secondary immunodeficiency
- acquired hypogammaglobulinemia
- agent-induced immunodeficiency
- extremes of age
- malnutrition
Makeup of HIV
2 RNA genome segments + reverse transcriptase enzyme
R5 variants are the ____ form
infective
