Lecture 14.1 Flashcards
X-linked agammaglobulinemia
Results from mutation that renders Bruton’s Tyrosine Kinase non-functional.
Total lack of B-cells
Presentation: under-developed tonsils
Susceptible to extracellular bacteria and some viruses
Pre-B-cell Receptor Deficiency
Results from defect in surrogate light chain
Apoptotic death of B-cell during development
Susceptible to extracellular bacteria and many viruses
X-linked Hyper IgM Syndrome
Two causes: 1) Defect in CD40 ligand the prevents helper T-cells from activating B-cells and macrophages; and 2) AID deficiency, rendering B-cells unable to class switch
No germinal center formed in 1; yes in 2, but again, just no class switching
Selective IgA Deficiency
One of the most common immunodeficiencies, yet mutations unknown.
Leads to susceptibility of parasite pathogens. One example is Giardia lamblia, an intestinal parasite. IgA is the only antibody that can patrol mucosal areas such as the intestine, so lacking IgA would mean that the parasite would be able to attach to the host and colonize the GI tract because there would be no IgA to block it.
Patients are at risk for anaphylactic shock upon transfusion because they are not tolerant to the IgA that is transplanted in during a transfusion.
Selective IgG Deficiency
Genetic cause unknown
IgG1: rare, but susceptibility to bacterial and viral pathogens
IgG2: common in kids
IgG3: common in adults
IgG4: unknown significance
Common Variable Immunodeficiency (CVID)
A group of around 150 primary immunodeficiencies that have common features that typically include reduced levels of antibodies, but different etiologies, most of unknown genetic etiology.
Presentation: Recurring infections with mostly bacterial/viral pathogens and hypogammaglobulinemia.
Ataxia Telangiectasia
Disease caused by an inherited defect in the ATM gene; this gene encodes a DNA repair enzyme
Can cause B and T-cell deficiencies
Presentation: Triad of spider angiomas, ataxia, and IgA deficiency (common) or IgE deficiency.
IL-12 Signaling Deficiency
Patients can only make small amount of INF-gamma, which results in diminished ability to produce TH1 effector cells and inability to activate macrophages.
Patients are susceptible to disseminated mycobacterial infections.
Job’s Syndrome (hyper IgE syndrome)
This is caused by a genetic deficiency of STAT-3 function that results in reduced production of IFN-gamma by TH1 cells, causing polarized production of TH2 cells, which then results in high number of IgE.
Presentation: eczema, recurrent abscesses with Staph aureus, broad nose, frontal bossing, deep-set eyes, and retention of primary teeth.
Chronic Mucocutaneous Candidiasis
Idiopathic T-cell dysfunction that causes susceptibility to Candida sp.
Presentation: superficial infections of skin, mucous membranes, and nails.
TAP-1 or TAP-2 Deficiency
CD8 Alpha Chain Defect
Recall that MHC molecules are not stable unless a peptide is loaded into their binding groove. A deficiency in TAP means that very few proteins are transported out of the ER membrane and loaded onto MHC molecules; thus, very few T-cells receive positive selection in the thymus, resulting in very few CD8 effector T-cells
Patients are highly susceptible to viral and some intracellular bacterial infections.
Perforin Deficiency
Results in dramatically or totally reduced CTL activity, even though patients have a normal number of CD8 T-cells.
Patients are highly susceptible to viral and some intracellular bacterial infections.
