The Immune System, Allergy, and Cancer - UCLA School PDF
Preview The Immune System, Allergy, and Cancer - UCLA School
The Immune System, Allergy, and Cancer EPI 295 October 16, 2009 Sam S. Oh, MPH Outline Immune system • Brief overview – Immunosurveillance and editing – Allergy • Atopic dermatitis, allergic rhinitis, asthma – Allergy and cancer • Inflammation and cancer • Potential mechanisms • Study #1 – Study #2 – 2 Immune system Allergy Immune System Allergy and cancer Inflammation and cancer Potential mechanisms Human body is ideal environment for many microbes • Purpose: to discriminate and protect self from non-self • Cell surface proteins recognized by immune cells help • distinguish between self/non-self What happens if a mass of self cells grows • uncontrollably, survives immune assault, and spreads? Can also consider cancer as a progressive disruption of • the immune system to keep tumor growth in check 3 Markers of Self Epithelial Muscle cell cell Leukocyte Nerve cell Class I MHC self-marker protein R 4 Immunity and Cancer Antibody Macrophage Cancer cell Helper T cell Natural killer cell Cytotoxic T cell R 5 Immunosurveillance Hypothesis proposed as early as 1909 • – Transformed cells continuously form in vivo – Immune system scans and eradicates transformed cells before clinical manifestation Hypothesis not widely accepted for many decades • Animal models in 1990s suggested existence of tumor- • associated antigens – Supported idea of immunosurveillance for protection of host from transformed cells Studies of immune-suppressed humans lent further • support for the hypothesis But why does cancer occur in immune-competent people? • Kim et al. Immunology 2007 6 Cancer Immune Editing Elimination of transformed cells (immuno-surveillance) • results in immune selection and sculpting – Highly immunogenic tumor variants are selected out, favoring variants with decreased immunogenicity or other mechanisms to evade/suppress immune attack – Provides tumors mechanism to escape detection and elimination by immune system Preferred term over immunosurveillance • – Addresses host-protecting and tumor-sculpting actions (Dunn et al. Nat Immunol 2002;3:991-8) Experimental evidence • – Tumors grown in mice with incompetent immune systems are more immunogenic compared to tumors grown in immunocompetent hosts (Shankaran et al. Nature 2001) 7 •Growth self-sufficiency •Insensitivity to anti-growth signals •Evasion of apoptosis •Limitless replication potential •Sustained angiogenesis •Tissue invasion and metastasis Zitvogel et al. Nature Reviews Immunology 6, 715–727 (October 2006) | doi:10.1038/nri1936 8 Elimination Phase (Immunosurveillance) Once tumors reach a certain size, invasive growth • disrupts surrounding tissue, inducing localized inflammation Immune cells (e.g., natural killer cells) recruited • to the tumor site release interferon (IFN)-γ IFN-γ production leads to • Increased chemokine production – • Some induce cell death by preventing angiogenesis Recruitment of additional immune cells – • Produce cytotoxins such as tumor necrosis factor, perforin, and reactive oxygen species 9 The 3 Es of Cancer Immunoediting Dunn et al. Immunity 2004 10
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