Immunity to Infections PDF

Immunity to Infections Jan 8, 2025 Ken Hirasawa Immunity to Infections Immunity to Infections 1) Innate Immunity physical and chemical barriers, interferon (IFN) system, complement system, phagocytosis/opsonization, NK cells 2) Adap...

Immunity to Infections Jan 8, 2025 Ken Hirasawa Immunity to Infections Immunity to Infections 1) Innate Immunity physical and chemical barriers, interferon (IFN) system, complement system, phagocytosis/opsonization, NK cells 2) Adaptive Immunity neutralizing antibody, antibody-mediated phagocytosis, antibody- dependent cell-mediated cytotoxicity (ADCC), cytotoxic T lymphocytes (CTL) 3) Immune memory resistance for long period of time after infection, memory cells Immunity to Infections Infectious Diseases Immunity to Infections 1) Immunity to viruses 2) Immunity to bacteria 3) Immunity to parasites 4) Immunity to fungi Immunity to Infections -Immunity to viruses Diseases induced by viruses Influenza virus - 1918 Spanish flu (50 million death, 3% of world population) - 2009 swine flu (294K to 579K death) - seasonal epidemic (3-5 million illness and 250-500K death/year) HIV (Human immunodeficiency virus) - AIDS (acquired immune deficiency syndrome) - 1.8 million death (2010) > 0.6 million death (2023) -Antiviral drugs, but no vaccine Human coronaviruses - SARS outbreak (2002-4): 8,000 infected, 774 deaths - SARS-CoV-2 (COVID-19) pandemic (2019-23): 18-33 million deaths - Effective vaccines Oncogenic virus - viruses are involved in 30% of cancer development - cervical cancer vaccine = human papilloma virus vaccine Immunity to Infections -Immunity to viruses Immunity to Viruses Immunity to Infections -Immunity to viruses Immunity to Viruses Innate response 1) Anti-viral effects induced by interferon (IFN) -Innate Immunity & Inflamation 2) Lysis of viral infected cells by NK cell -Innate Immunity & Inflamation Antibody-mediated response 3) Neutralization – free virus 4) ADCC by NK cells, macrophages and neutrophils Cell-mediated response 5) Cytotoxic T lymphocytes (CTL) (CD8 T cells) Immunity to Infections -Immunity to viruses Innate Response Infected cells Type I IFN (IFN-, ) Type II IFN (IFN-) Interleukin 12 (IL-12) NK cell Cell lysis Adaptive Immunity Non infected cells Antiviral State Macrophage Immunity to Infections -Immunity to viruses Natural Killer (NK) cells Instead of attacking the invaders, they attack the body’s own cells infected with viruses. Immunity to Infections -Immunity to viruses Immunity to Viruses Innate response 1) Anti-viral effects induced by interferon (IFN) -Innate Immunity & Inflamation 2) Lysis of viral infected cells by NK cell -Innate Immunity & Inflamation Antibody-mediated response 3) Neutralization – free virus 4) ADCC by NK cells, macrophages and neutrophils Cell-mediated response 5) Cytotoxic T lymphocytes (CTL) (CD8 T cells) Adaptive Response Immunity to Infections -Immunity to viruses Adaptive Response Neutralization Fc receptor antibody-dependent cell-mediated cytotoxicity (ADCC) TCR cytotoxic T lymphocytes (CTL) MHC class I Immunity to Infections -Immunity to viruses Viral Immune Evasion Viruses know how to escape from immune system. 1) Virus infection of immune cells B lymphocytes: Epstein-Barr Virus T lymphocytes: HIV Human T lymphotropic virus (HTLV) Measles virus Macrophages: HIV Cytomegalovirus Immunity to Infections -Immunity to viruses Viral Immune Evasion 2) Vaccinia virus encodes IFN- and  receptor homolog. 3) Adenovirus E3 protein blocks transport of MHC to cell surface. E3 IFN Immunity to Infections -Immunity to bacteria Diseases induced by bacteria Tuberculosis (TB) - caused by a bacterium called Mycobacterium tuberculosis - 8.8 million new cases and 1.5 million death/year in the world - vaccine (BCG) and antibiotics - multiple drug-resistant tuberculosis (MDR-TB) E.Coli (Escherichia coli) - commonly found in the gut,most strains have no harm to human health - have beneficial functions (barrier, production of vitamins) - certain strains cause food poisoning (ie 0157:H7) - produces a potent toxin to damage the small intestine Immunity to Infections -Immunity to bacteria Innate Response 1) Antimicrobial peptide 2) Complement-mediated lysis 3) Phagocytosis -pattern recognition receptors (PRRs) & pathogen-associated molecular patterns (PAMPs) 4) Opsonization Complement-mediated lysis Phagocytosis & Opsonization Immunity to Infections -Immunity to bacteria Innate Response Immunity to Infections -Immunity to bacteria Adaptive Response Antibody-mediated response 4) Agglutination, blocking and neutralization of toxins 5) Phagocytosis (Ab-mediated) Fc receptor Cell-mediated response 6) Cytotoxic T lymphocytes (CTL) -intracellular infection Phagocytosis (Ab-mediated) Ab-mediated agglutination/blocking Neutralization of bacterial Cell-mediated response toxins Immunity to Infections -Immunity to bacteria Immunity to Bacteria Gram-positive Bacteria -resistant to lysis by complement system -neutralizing antibody, opsonization, phagocytosis Gram-negative Bacteria -complement system, neutralizing antibody, phagocytosis Mycobacteria (tuberculosis) -phagocytosis by macrophages, cell-mediated response Spirochetes (Lyme disease, some STDs) -complement, neutralizing antibody, cell-mediated response Immunity to Infections -Immunity to parasites Diseases induced by parasites Malaria - mosquito-borne disease caused by Plasmodium - 216 million cases, nearly1 million death/year (2010) - no effective vaccine - 2.3 million mosquito nets sent by Bill & Melinda Foundation Immunity to Infections -Immunity to parasites Innate Response 1) Complement-mediated lysis 2) Phagocytosis -pattern recognition receptors (PRRs) & pathogen-associated molecular patterns (PAMPs) 3) Opsonization Complement-mediated lysis Phagocytosis & Opsonization Immunity to Infections -Immunity to parasites Adaptive Response Antibody-mediated response 3) Agglutination and blocking 4) Phagocytosis (Ab-mediated) 5) Antibody-dependent cell-mediated cytotoxicity (ADCC) ADCC Immunity to Infections -Immunity to parasites Adaptive Response Antibody-mediated response 6) IgE/Mast cell/Eosinophill response degranulation histamine, heparin, cytokines Mast cell recruitment activation Eosinophill IgE detection of parasite antigen major basic protein crosslinking reactive oxygen intermediates ADCC Immunity to Infections -Immunity to fungi Diseases induced by fungi Candidiasis - Caused by Candida albicans - Normal flora of oral, skin and intestine - Immunocompromised host, AIDS patients and organ transplant receivers - Thrush, infection of the mucus membrane lining the mouth and tongue Immunity to Infections -Immunity to fungi Diseases induced by fungi Immunity to Infections -Immunity to fungi Innate response 1) Barriers - Skin, normal bacterial flora 2) Phagocytosis -neutrophils (neutropeia > susceptible to fungal infection) 3) Complement -complement mediated lysis -opsonization Immunity to Infections -Immunity to fungi Adaptive response Not well characterized believed to have roles in defending fungal infection -presence of antibodies against fungi -C. albicans infection among AIDS patients