Innate Immunity Defects Flashcards
Chronic Granulomatous Disease (CGD) is cause by mutations in which important player of phagocytosis?
NADPH oxidase
What is the importance of NADPH?
Genetic defects of NADPH oxidase result in the inability of phagocytes (neutrophils, monocytes, and macrophages) to create reactive oxygen species and destroy certain microbes (catalase positive).
What is the clinical presentation of a person with Chornic Granulomatous disease given their NADPH oxidase isn’t doing its job to fight off microbes?
A patient would present with frequent and recurrent bacterial and fungal infections
What GTP-binding protein and GTPase are respectively important in creating the NADPH oxidase complex?
Rac2 and Rap1
Patients with CGD express lower levels of which receptors and CD’s associated with neutrophils and innate immunity as compared to someone without the mutation with pneumonia?
Decreased expression results in impaired neutrophil activation (TLR5), phagocytosis (CD11b/CD18), and chemotaxis (CXCR1)
Why is Leukocyte adhesion important and what results if leukocytes aren’t able to “adhere”?
Cells won’t bind and roll to the affected tissue where the leukocytes are needed to react.
What defects are responsible for Leukocyte adhesion defect 1 (LAD-1)
Absence of CD18 (expressed in LFA-1, CR3, and CR4)
What are the defects associated with LAD-2,3?
Defects in selectin or selectin ligand expression.
How would a C1, C2, or C4 deficiency present?
Bacterial infection or autoimmunity because there is defective clearance of immune complexes
What happens when there is a Factor I or H deficiency?
C3 gets used up because Factor H is an inhibitor and you can’t properly attack bacteria (look this up)
Mutations in genes encoding proteins in TLR or CD8 signaling would cause defects in innate immunity?
TLR: these are critical PAMPs in the innate immunity, CD8 cells are in the adaptive humoral branch.
