Overview of the Immune Response and Regulation

INTRODUCTION Both cancer and autoimmune diseases are significant health burdens that pose tremendous financial strains on healthcare services worldwide. Nearly 1.7 million cases of cancer are expected to be diagnosed and 585,000 Americans are expected to die of the disease in the United States in 2014.¹ Furthermore, while the diagnosis of any individual autoimmune disease is relatively rare, as a collective disorder, autoimmune disease is estimated to afflict 1 in every 31 Americans² and is among the leading causes of death in young and middle-aged women (ages <65 years) in the United States.³ Numerous biological and biochemical factors are implicated in both cancer and autoimmune diseases, yet these two seemingly disparate diseases share a common thread: immunopathology.

The immune system can recognize a seemingly infinite repertoire of antigens and has evolved robust protective responses against foreign substances. Inevitably, a system that reacts against such a diverse set of antigens has the propensity to react against itself and is the basis for autoimmunity. Furthermore, the role of protective immunity is complicated since potent pro-inflammatory molecules and immune cells destroy invading organisms and cancer cells while also damaging the surrounding normal cells. As such, a means of restraining the immune system is essential to maintaining a homeostatic immune organization. This immune homeostasis encompasses a means to 1) discriminate self from non-self and regulate insufficient immunity to ensure that pathogens are eliminated and 2) suppress excessive immune responses such that autoimmunity is averted. This Focus series describes the physiological and pathological roles of…

ABBREVIATIONS: CTLA-4 - cytotoxic T-lymphocyte-associated protein 4, DAMPs - damage associated molecular patterns, FOXP3 - forkhead lineage-specific transcription factor, IFN-γ - interferon-gamma, IL – interleukin, MDSCs - myeloid derived suppressor cells, NK - natural killer, PAMPs - pathogen associated molecular patterns, PRRs - pathogen recognition receptors, Tregs - regulatory T cells, Th - T helper, TNF-α - tumor necrosis factor-alpha.