Innate Immune Response (Ch14) Overview of Innate Defense System First lines of Defense • Physical Barriers – Skin – Mucous membranes • Antimicrobial substances – – – – Lysozyme Peroxidase enzyme Lactoferrin Defensins • Normal Flora Epithelial Barriers Skin as the first line of defense • Intact skin protects – Epidermis – Dermis Mucous membranes line the interior of the body Ciliated cells are important…where? Antimicrobial Substances Microbial Barriers • Normal flora (biota) play a role in keeping the body protected – Competitive exclusion – E. coli produce bacteriocins which kill Salmonella and Shigella Cells of the Immune System • Cells move from one system to the next • Found in blood, developed from bone marrow • What are some of these cells?? – Granulocytes (neutrophils, basophils, eosinophils) – Mononuclear phagocytes – Dendritic cells – Lymphocytes Dendritic cells • Branched cells, important in adaptive immunity • Develop from monocytes, engulf material and bring it to other cells for analysis How do cells of the immune system communicate? • Cytokines – – – – – Chemokines Colony-stimulating factors Interferons Interleukins Tumor Necrosis factors Cytokines and their function Interferons • Three types of glycoproteins – Alpha – Beta • Produced by virus infected host cells, induce mRNA for antiviral proteins – Gamma • Produced by lymphocytes Interferons inhibit viral replication Sensor systems in the blood, tissues and cells • Can detect signs of tissue damage or microbial invasion • Respond by – Detecting parts of bacteria/viruses using pattern recognition receptors (PRRs) – Directly destroy bacteria using complement – Recruit other components of host defense Pattern Recognition Receptors • Toll-Like receptors (TLRs) – Membrane bound receptors which detect bacterial parts • NOD-like receptors (NLRs) – Cytoplasmic proteins detect bacterial parts • RIG-like receptors (RLRs) – Cytoplasmic proteins detect viral RNA Toll-like receptors (TLRs) • A type of PRR • Recognize peptidoglycan, lipopolysaccharide, flagellin, certain nucleotide sequences unique to bacteria Toll-like receptors NOD-like receptors (NLRs) RIG-like receptors • Cytoplasmic proteins which detect viral RNA in a cell • Activate secretion of interferon and inflammatory response chemicals • Overall goal is to inhibit viral replication Complement Proteins are part of the Complement system • Consists of a collection of 9 interacting proteins found in blood and tissues • Activation of these proteins promote – Opsonization – Inflammatory response – Lysis of foreign cell How are the complement proteins activated? Regulation of the complement system What have we covered so far? • The innate immune system is composed of – Cells – Chemicals released by cells to communicate with each other – Receptors to recognize invaders • We need to look at the processes of phagocytosis and inflammation How do phagocytes work? Fever is a nonspecific response • Il-1 increases T lymphocytes • Decreases available iron • Increases cellular reactions Inflammation response • What are the key cells involved? • What are the four key symptoms of inflammation? • What activates the inflammation response?