Effect of uremia on structure and function of immune system.
End-stage renal disease (ESRD) is simultaneously associated with immune activation, marked by systemic inflammation, and immune deficiency. Systemic inflammation contributes to atherosclerosis, cardiovascular disease, cachexia, and anemia, whereas immune deficiency leads to impaired response to vaccination, and increased incidence and severity of microbial infections. ESRD-associated inflammation and immune deficiency are associated with the following: (a) general expansion of monocytes and elevations of their basal integrin, Toll-like receptor (TLR)-2, TLR-4 expression, cytokine production, and reactive oxygen species (ROS) generation and reduced phagocytic capacity, (b) depletion and impaired inhibitory activity of regulatory T cells, (c) spontaneous activation, degranulation, increased basal ROS production, decreased phagocytic capacity, and increased apoptosis of the circulating polymorphonuclear leukocytes, (d) upregulation of ROS production machinery and chemokine expression in the cellular constituents of various tissues, highlighting participation of nonimmune cells in the prevailing inflammatory state, (e) depletion of the antigen-presenting dendritic cells, (f) reduced CD4/CD8 T cell ratio and depletion of naïve and central memory T cells, (g) diffuse B cell lymphopenia leading to impaired humoral immunity, and (h) increased proinflammatory activity of low-density lipoprotein and reduced anti-inflammatory capacity of high-density lipoprotein. Thus, ESRD-associated inflammation is due to activation of innate immune system, orchestrated by monocytes, macrophages, granulocytes, and cellular constituents of other organs/tissues. This is coupled with immune deficiency that is caused by depletion of dendritic cells, naïve and central memory T cells and B cells, and impaired phagocytic function of polymorphonuclear leukocytes and monocytes.
Division of Nephrology and Hypertension, University of California, Orange, California, USA. ndvaziri@uci.edu
Nosratola D
ND
Vaziri
Madeleine V
MV
Pahl
Albert
A
Crum
Keith
K
Norris
D001402:B-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D007153:Immunologic Deficiency Syndromes / Q000209:etiology; D007249:Inflammation; D007676:Kidney Failure, Chronic / Q000150:complications / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D018384:Oxidative Stress; D013601:T-Lymphocytes / Q000276:immunology; D014511:Uremia / Q000150:complications / Q000276:immunology*