Immunodeficiencies Flashcards
immunodeficiency
impaired immune response resulting in increased susceptibility to opportunistic infections and obligate pathogens
primary immunodeficiency
inherited (due to mutations in genes related to the immune system)
secondary immunodeficiency
caused by disease, treatment, or other infection
physiological causes of secondary immunodeficiency
elderly: t-cell oligoclonality, reduced t-cell output, reduced B cell repetoire; decreased functional T cell responses
young: immature lymphoid organs; low IgG levels (especially from 3-12 months after birth when its mostly IgM), decreased neutrophil and NK function; no memory cells
iatrogenic- chemotherapy and radiation
decreased immune cell function (decreased cytokines, decreased phagocytosis, decreased chemotaxis) and decreased production of hematopoietic stem cells in the bone marrow
iatrogenic- glucocorticoids
decreased t cell function (decreased cytokine production and decreased proliferation); decreased macrophage function (decreased phagocytosis and decreased fc receptor expression); viability of immune cells decreased (decreased apoptosis); inhibition of transcription factors (NKFB, NFAT, AP1)
cyclosporin and tacrolimus are normally used for what
immunosuppresives (post organ transplant or to treat autoimmune inflammatory diseases like atopic dermatitis, psoriasis, eczema, rheumatoid arthritis, ulcerative colitis)
cyclosporin and tacrolimus cause secondary ID by
inhibiting the function of T cells by inhibiting calcineurin, causing a secondary immunodeficiency similar to AIDS. normally, MHC presents antigen to T cell and it activates a signaling pathway that results in increased Ca2+. Ca2+ activates calcineurin which is a phosphatase that removes phosphate from NFAT to allow it to enter the nucleus and activate transcription factors for IL-2, IL-4, IFN gamma, TNF alpha, and IL-10. So without calcineurin, this is blocked
iatrogenic: surgery
causes breaked in epithelial barrier–> inflammation (cytokines like Il-6 and TNF-alpha) and increased cortisol levels (a glucocorticoid)
iatrogenic: splenectomy
increased susceptibility to infection with encapsulated bacteria OPSI (thats why they vaccinate before surgery)
autoimmune diseases that cause secondary immunodeficiency
SLE, vasculitis
paraneoplastic syndrome/ tumors
leukemia, paraneoplastic syndrome, multiple myeloma
metabolic causes of secondary immunodeficiency
diabetes and kidney failure- cause increased fungal infections, increased bacterial and fungal respiratory infections and slow wound healing. This is because of hyperglycemia, impaired neutrophil and lymphocyte function, and vasculopathy that makes blood vessels thinner and decreases leukocyte mobility to site of infection
malnutrition causes of secondary immunodeficiency
causes = insufficient protein uptake and insufficient uptake of vitamins (zinc, iron, folate, pyroxidine, and vitamin A)
as a result of malnutrition….
diminished T cell number and function, specific B cell production impaired, and lack of cells in lymphoid organs