Term
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Definition
Complete loss of activity (in either RAG-1 or -2) due to arrested lymphocyte development
an inherited immunological deficit in which there is an absence of mature T cells. Because T cells play an important role in the development of B cell responses, these patients exhibit defective B cell responses.
Has multiple genetic causes that profoundly affect
B and T cell development and/or function
-Mutations impair B and T cell maturation, causing severe defects in immune responses to all microorganisms
susceptible to infections, mostly opportunistic.
-Cytomegalovirus (CMV): causes pneumonia in the lung, but may also cause
serious disease in the brain, GI tract, and eyes (retinitis and blindness)
-Pneumocystis carnii [jeroveci] (fungus): causes pulmonary infection (pneumonia)
-Candidia spp. (fungus- causes candidiasis): often oral infection
Treatment
-by bone marrow transplantation, but often requires additional IvIg supplementation
-gene replacement using retrovirus (in the works)
T cells are reduced, but B and NK cells may or may not be, depending on the underlying mutation
--> T-B+NK+ -> defect in IL-7 receptor alpha chain
--> T-B+NK- -> defect in gamma common chain (X-LINKED SCID**know!!)
--> T-B-NK+ -> RAG, artemis, or ADA deficiency
--> T-B-NK- -> ADA deficiency |
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Term
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Definition
Partial loss of activity (in either RAG-1 or -2) due to arrested lymphocyte development
-No B cells, variable poorly functioning T cells
-Mutation in RAG1 or RAG2
-Leaky, Alloreactive, clonally restricted T cells; poorly proliferative
-Eosinophilia
-IgE elevated
-Failure to thrive |
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Term
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Definition
Superantigen activates large numbers of T cells (10-20%), whereas
conventional antigen presentation activates only around 0.01% of host T-cells
Associated with rapid increase in inflammatory cytokines such as TNF-α and -β,
IL-2, and INF-γ (“cytokine avalanche”)
Sudden increase in TNF-α results in endothelial and vascular smooth muscle
changes, which manifests as hypotension, shock, and features of sepsis.
Followed by T cell clonal deletion, resulting in impaired T cell responses |
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Term
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Definition
certain MHC alleles are associated with this set of diseases
-HLAB27 and ankylosing spondylitis is an example
additionally, certain MHC alleles are associated with susceptibility to particular infectious diseases |
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Term
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Definition
thymic aplasia
Severely Immunocompromised
devoid of T cell immunity |
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Term
APECED (autoimmune polyendocrinopathy–
candidiasis-ectodermal
dystrophy) |
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Definition
lack of AIRE (autoimmune regulator)
often have anemia, GI problems, TI diabetes, malabsorption problems |
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Term
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Definition
absence of FoxP3 in T regulatory cells
results in a wide variety of autoimmune disease syndromes -> malabsorption, diarrhea, T1 diabetes, eczema -> very serious disease |
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Term
| Bare Lymphocyte Syndrome Type 1 |
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Definition
Group 1 – most severe
-Death by age 3
-Antibody production lacking
-Class I, β2 transcription normal
Group 2 – asymptomatic
Group 3 – best characterized
-Normal Class I , β2 transcription
TYPE 1 is autosomal recessive
characterized by a defect in TAP1 or TAP2
Severe viral infections rare
Lungs
– Chronic spastic bronchitis
– Recurrent bacterial pneumonia; bronchiectasis
Ear/Nose/Throat
– Chronic sinusitis
– Postnasal drip
– Otitis media
– Erosion of tissue around nose
Skin
– Necrotizing granulomatous disease
Signs
• Normal antibody titers
• Increased NK cell levels
• Increased γ/δ T cell levels
• CD8+ T α/β T cell levels decreased
• Lack of Class I – activation of NK cells
inappropriately
Treatment
• Goal – early recognition, prevent brochiectasis
• Antibiotics
• Surgical intervention for chronic intervention –
discouraged (promotes progression of nasal disease)
• Immunosuppression not recommended
• Immunomodulation discouraged (IFNα, IFNγ)
• BMT – probably not advised (NK-mediated GvH) |
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Term
| Bare Lymphocyte Syndrome Type 2 |
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Definition
• AUTOSOMAL RECESSIVE
• Originally described as defect in MHC Class
II expression
• Class II genes intact
• Defects in RFXANK (19), CIITA (16), RFXAP
(13), RFX5 (1) -> these are transcriptional regulators for Class II MHC genes
• Clinically homogeneous
• Disease of regulation
• First reported in late 1970’s, early 1980’s
• Majority of families: North African, Spain,
Turkey
• RFXANK mutations most common (26
families)
Signs/Symptoms
• Severe defects in cellular and humoral
immunity
• Infections begin in first year of life
• Increase in viral, fungal, protozoal, bacterial
infections
• Recurrent GI, bronchial infections;
septicemia
• Death typical by age 10
• No correlation between genetic defect and
symptoms
• Hypogammaglobulinemia
• T and B cell numbers normal
• CD4+ T cells reduced
BLS Type 2 Variant
• Less severe deficiency
• HLA genes affected unequally
• HLA-DRB, HLA-DQB, HLA-DPA silenced
• HLA-DRA, HLA-DQA, HLA-DPB expressed
• Molecular defect not characterized
Therapy
• Bone marrow transplant
• Oddly – lack of class II on recipient cells does not change GvHD rates |
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Term
| Bruton’s agammaglobulinemia (XLA) |
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Definition
• X-linked disorder
• characterized by the very low or absent levels of serum immunoglobulins, all classes, with correspondingly low or absent CD19+ B cells. Usually diagnosed in early childhood.
• Bruton’s tyrosine kinase (Btk) is required for signaling through the pre-BCR
• Bruton’s agammaglobulinemia (XLA) is
caused by an inactivating mutation in Btk
found on the X chromosome
• Arrests B cell development
-patients have low
-serum antibody caused by defective B-cell maturation secondary to mutations in the btk (Bruton's/B-cell tyrosine kinase) gene
-B-cells (CD19, HLA-DR+) are severely decreased or
absent in the peripheral blood.
-T-cells (CD3) are normal or increased in number.
no Igs, B-cells, infections (haemophilus, strep., gram+) begin 6-9mo, pneumonia, sinusitis, otitis, no attenuated vaccines. Mutated BTK, pre-B-cell development inhibited |
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Term
| Common variable immunodeficiency (CVID) |
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Definition
-a heterogeneous group of disorders with
defective antibody formation.
-B-cells (CD19, HLA-DR+) and T- cells (CD3) are usually normal in number.
diagnosed 1-5yr, 15-35yr. Low IgG, IgA, IgM, pneumonia, sinusitis, GI infec.. Weakened cellular immunity, bunch of other stuff |
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Term
| HIV/Acquired Immune Deficiency Syndrome (AIDS) |
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Definition
-Disease associated with infection with human immunodeficiency virus (HIV)
-Marked by loss of CD4+ T cell population
-GP120 and GP41 are glycoproteins on HIV important for getting into cell
-CD4, CCR5 (on macrophages), and CXCR4 (T cells) are receptors on cell important for causing infection
Course of infection
-Primary Infection: High viral load, antibodies have not developed, ~50% of patients have symptoms (flu-like)
-Asymptomatic: Viral load drops, antibodies
develop,
-Early symptomatic: Mid-level viral loads, CD4+ T cells begin to drop
-Late symptomatic: High viral loads, low CD4+ levels
Treatment
-Drugs target RT, integrase, protease (virus assembly), and binding/fusion/entry
Immune response to HIV
-Antibody: neutralizes virus, but may make cells more susceptible to infection (Fc interactions)
-CD4+ T cell: important for CTL function, but expansion of infected cells can activate HIV production
-CD8+ T cells: kill infected cells, reduced CD4 help; CTL activity decreases before CD4 levels drop |
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Term
| Flow cytometry -> B cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) |
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Definition
| CD5+/CD23+/CD45++/Surface Ig+ |
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Term
| Flow cytometry -> Mantle Cell Lymphoma (MCL) |
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Definition
| CD5+/CD23-/CD45++/Surface Ig+ |
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Term
| Flow cytometry -> Follicular lymphoma (FL) or diffuse large B cell lymphoma (DLBCL) |
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Definition
| CD5-/CD10+/CD45++/Surface Ig+ |
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Term
| Flow cytometry -> hairy cell leukemia (HCL) |
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Definition
| CD11c+/CD103+/CD45++/Surface Ig+ |
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Term
| Flow cytometry -> pre-B acute lymphoblastic leukemia (ALL) |
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Definition
| CD10+/CD34+/low SSC/CD45 low/surface Ig- |
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Term
| Flow cytometry -> B acute lymphoblastic leukemia (ALL) |
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Definition
| CD10+/CD34-/CD22+/low SSC/CD45 low/surface Ig+ |
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Term
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Definition
| atopic dermatitis (excema) |
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Definition
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Definition
| autoimmune hemolytic anemia |
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Definition
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Definition
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Definition
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Term
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Definition
| streptococcal glomerulonephritis |
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Term
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Definition
| nephritis (caused by glomerulonephritis) |
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Term
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Definition
| nephrotic syndrome (caused by glomerulonephritis) |
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Definition
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Definition
| penicillin (drug) induced hemolytic anema |
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Definition
| schistosomiasis is a trigger |
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Term
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Definition
| hep b virus can be a trigger |
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Definition
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Definition
autosomal dominant
complement activation uncontrolled; large amts of vasoactive peptides;fluid accumulation Hereditary angioedema |
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Term
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Definition
| increase RBC lysis leads to Paroxysmal nocturnal hemoglobinuria |
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Term
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Definition
| (x-linked) susceptible to meningeococcal disease |
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Term
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Definition
| all pathways affected, serious gram-negative infections |
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Term
| Chronic Granulomatous Disease (CGD) |
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Definition
| caused by NADPH oxidase defect, most common is X-linked from gp91phox gene mutation |
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Term
| Leukocyte adhesion disorder (LAD) |
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Definition
autosomal recessive
caused by CD18 defect, leading to LFA-1 defect and impaired extravasation. High neutrophil count, normal T-cells, normal antibodies |
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Term
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Definition
| AR, defective CHS gene leading to problems with intracellular vacuole and granule fusion. Clumped albinism, abnormal granules, defect in lysosomal transporter, treat with BM transplant |
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Term
| Congenital/cyclical neutropenia |
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Definition
| mutation in neutrophil elastase gene (required for neutrophil differentiation). Can't localize infection, and have severe bacterial infections. |
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Term
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Definition
| repeated bacterial infections and reduced proinflammatory mediator levels |
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Term
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Definition
| sparse hair/eyebrows (XL most common -> defect in nemo, but AD also -> gain of function in IKBA), related to NF-kappaB, decreased proinflammatory mediators |
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Term
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Definition
| strikingly low levels of TNF-α, IL-6, autosomal recessive, disseminated bacterial infections are common |
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Definition
| increased HSV susceptibility, extremely rare |
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Definition
| most common immunodeficiency, no serum/mucosal antibody, GI/resp. infection, IV-IgA infusions |
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Term
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Definition
| type 1 XL has CD40L defect so B-cells can't be activated, other types have other problems |
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Term
| Wiskott-Aldrich Syndrome (WAS) |
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Definition
| WAS protein is important for creating immunologic synapse. Symptoms include thrombocytopenia, purpura, and eczema |
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Term
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Definition
| AR, silvery gray hair. Pyogenic bacterial infection, 3 types. Type 2 has hypogammaglobulinemia NK defects and suppressed DTH response |
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Term
| Myeloperoxidase deficiency |
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Definition
| AR and most common phagocyte disorder, no disease association except diabetes, |
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Definition
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| associated with Burkitt's lymphoma and nasopharyngeal carcinoma |
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Definition
| associated with Kaposi's sarcoma |
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Definition
| associated with T-cell malignancies |
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Definition
| defect in AIRE which is responsible for expressing non-thymic antigens during negative T-cell selection |
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Term
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Definition
| -gluten broken down gliadin fits in HLA-DQ2 because its glutamine residues are converted to glutamic acid |
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Definition
| autoantibodies to ACh receptor neuromuscular junction preventing muscle contraction |
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Definition
| autoantibodies to TSH receptor leading to thyroid hormone release and hyperthyroidism |
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Definition
| donor DC cells in graft carried to lymph where they activate CD8+ T-cells which attack the grafted organ. host CD4+ and B-cells respond to graft antigens and promote antibody production which destroy graft ADCC or classical cascade |
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