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Aplasia/hypoplasia of the thymus + cardiac and parathyroid abnormalities
low/absent T cells with possibility of autoimmune disease
susceptible to opportunistic infections
DiGeorge Syndrome
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boys more than girls
failure to thrive, candidiasis, chronic diarrhea, opportunistic infections, dermatitis/eczema
T cell dysfunction, T cell lymphopenia, lack of B cell number and/or function
small, dysplasia of thymus
Severe combined immunodeficiency
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T cells absent
B cells present in normal numbers but not functional
- Common gamma chain deficiency
- X-SCID (T- B+ NK-)
- could also be JAK3 CD45 IL-2Ralpha
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T cells absent with normal B and NK cell numbers
- TCR specific or important for T cell proliferation:
- IL-7R or CD3
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T and B cells absent
NK cells present in normal numbers
- RAG1 RAG2 Artemis or Cernunnos
- genes involved in TCR and BCR gene rearrangement
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ADA, reticular dysgenesis, PNP often with skeletal findings, hearing loss, and behavioral issues
- Total lymphopenia (T, B, and NK cells)
- defect in purine salvage leads to lymphocytotoxic accumulation of adenosine and deoxyadenosine
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Partial defect in RAG1/RAG2, Artemis, IL-7R
- Atypical SCID or Omenn Syndrome
- Oligoclonal T cells present
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MHCI deficiency, Bare Lymphocyte Syndrome I
- TAP1, TAP2, mutations lead lack of intrathymic maturation of CD8+ t cells
- chronic upper respiratory diseases (viral) without opportunistic infections
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MHCII deficiency, Bare Lymphocyte Syndrome II
- Transcription factor defects lead to lack of MHCII expression
- defective maturation of CD4+ T cells
- low Ig levels, susceptible to opportunistic infections
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X linked defect in WASP (regulates actin in T cells and megakaryocytes)
petechiae, thrombocytopenia, small platelets, eczema (severe in infancy), sinopulmonary and opportunistic infections
Wiscott-Aldrich
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Cerebellar gait, occulocutaneous (bloodshot eyes), radiation sensitivity, dysgammaglobulinemia, lymphopenia, lymphoma, increased sinopulmonary infections
Ataxia-telangiectasia, ATM gene defect, no dsDNA break repair
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Well for first few months then constant otitis, sinusitis, pneumonia, and diarrhea
small or absent lymph nodes, tonsils and adenoids
low or absent B cells
X linked agammaglobulinemia (XLA)
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Recurrent respiratory tract infections, more prone to autoimmune disease and lymphomas, reduced levels of one or more Ig and impaired antibody production
- Common Variable Immunodeficiency
- TACI mutations
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recurrent infections, autoimmunity, allergy
common disease, most people are asymptomatic
Selective IgA Deficiency
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Transient hypogammaglobulinemia of Infancy
- Commonly corrects by 2 years
- IgA and IgM can also be low
- Antibody responses are usually ok
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Recurrent and severe infections with Staph aureus, Serratia, Burkholderia, Nocordia, Candida, Aspergillus
Gastric outlet obstruction, colitis, hydronephrosis
Dx with dihydrorhodamine oxidation
- Chronic Granulomatous Disease
- defects in NADPH oxidase complex (gp91phox)
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Impaired wound healing, severe periodontitis, omphalitis with delayed separation of the umbilical cord, no pus, leukocytosis
- Leukocyte Adhesion Deficiency
- LAD 1 mutation in CD18 (LFA-1)
- LAD 2 defect in fucosylation leads to lack of E selectin ligand
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mast cell and basophil activation
systemic anaphylaxis, localized anaphylaxis
ex. Hay fever, asthma, hives, food allergies, eczema
Type I (IgE mediated) hypersensitivity reaction
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complement or ADCC effectors against cell surface antigens
ex. Blood transfusion reactions, erythroblastosis fetalis, and autoimmune hemolytic anemia
Type II (IgG or IgM mediated cytotoxic) hypersensitivity reaction
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Antigen-antibody complexes deposit in tissu and induce complement activation with ensuing inflammatory response, esp. neutrophils
ex. Localized arthrus reaction, serum sickness, necrotizing vasculitis, glomerulonephritis, rheumatoid arthritis, and SLE
Type III (Immune complex mediated) hypersensitivity reaction
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Sensitized Th1 cells activate macrophages or Tc cells which mediate cellular damage
ex. Contact dermatitis, tubercular lesions, and graft rejection
Type IV (Cell mediated) Hypersensitvity reaction
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graft rejection cannot be treated, occurs within minutes to hours, by type II and type III Hypersensitvity (antibody dependent)
Hyperacute rejection
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graft rejection mediated by T cells (type IV) and B cells that produce alloantibodies (type III)
trested with immunosuppression, steroids, T cell depletion, and plasmapheresis
Acute rejection
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graft rejection months to years after transplant, main target endothelium, fibrosis and extensive tissue damage
inflammation, cytokines, anti-HLA
- Chronic rejection
- diagnosed with biopsy
- often confused with maintenance drug toxicity
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Red painful swelling, especially in toes/1st MTP joint
links to hypertension, obesity, and alcohol consumption
intracellular and extracellular negatively birefringent (yellow) needle shaped crystals
Acute gout
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Red, painful joint swelling
more common in knees and wrists
associated with osteoarthritis, hyperparathyroidism, hemochromatosis, hypophosphatemia, osteodystrophy
intracellular and extracellular positively birefringent (blue) rhomboid shaped crystals
fluffy white radio-opaque chondrocalcinosis
Calcium Pyrophosphate Deposition Disease (CPPD) or Pseudogout
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Probenecid
Blocks Uric acid transporters which reuptake urate from urine
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Kineret (anakinra), Rilonocept, Canakinumab (Ilaris)
IL-1 or receptor antagonist
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Colchicine
blocks Uric acid activation of the inflammasome
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allopurinol febuxostat pegloticase
- Chronic treatment of gout
- first 2 are xanthine oxidase inhibitors, uroticase breaks down Uric acid
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