INNATE HOST DEFENSES CHAPTER 16 Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Host Defenses Innate Prior stimulation not needed (non-specific) Often needed to trigger adaptive defenses Adaptive Respond after stimulation by the pathogen or agent (specific defenses, immune response) Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Types of Innate Defense Physical Barriers Chemical Barriers Cellular Defenses Inflammation Response Fever Response Molecular defenses Interferon Complement Acute Phase proteins Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Barriers Physical Skin Stratified Close intercellular junctions Waterproof, dead cells Mucous membranes Simple epithelium Mucus layer Mechanical defenses Urine flow Secretions Chemical pH Salt Lysozyme Transferrin Serum Lactoferrin Saliva, milk, mucus Defensins Mucus and Extracellular fluid Lyse microbial cells Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Cellular Defenses - Granulocytes Basophils / Mast cells Histamine release Inflammatory response Eosinophils Modulate inflammation Peroxide release Neutrophils Early phagocytic cells Dendritic cells Phagocytic Antigen presenting cells, role in adaptive immunity Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Cellular Defenses - Agranulocytes Monocytes Phagocytic cells Later appearance than neutrophils Lymphocytes Cells of adaptive immunity Will be discussed in Ch. 17 Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Cells Found in the Blood Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Phagocytosis Cells Involved: PMNs, macrophages, eosinophils Order of appearance Neutrophils first Macrophages at the tail end Eosinophil presence highest when worms and protozoa cause disease Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Stages of Phagocytosis Chemotaxis Toll-like receptors on phagocytes (TLRs) Recognition of microbial surface molecules Cytokines, complement substances from damaged host cells Adherence Capsules, M proteins reduce this Complement proteins enhance this Ingestion Formation of phagosome Digestion Phagosome + Lysosome = Phagolysosome Formation inhibited by P. falciparum Enzymes and reactive oxides damage microbes Capsule protects microbes like Y. pestis Staph. Strep. release WBC degrading toxins - Leukocidins Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Inflammation Cardinal Signs 3 Stages in acute Inflammation Heat (calor) Redness (rubor) Pain (dolor) Swelling (edema) 3 Stages in acute Inflammation Vasodilation Phagocytosos Tissue Repair Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Chronic Inflammation Continuous pus formation, no drainage possible Healing never achieved Granulomatous tissue types: Gummas (syphilis) Tubercles (tuberculosis) Lepromas (leprosy) Steroidal anti-inflammatories can release microbes from granulomas Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Fever Response Benefits of Fever Systemic increase in body temperature Risks for some patients Convulsions, cardiac stress, dehydration may occur with v. high fevers Pyrogens Exogenous Endogenous Leukocyte Endogenous mediator Reduced microbial growth Toxin inactivation Increased metabolism and immune cell responses Increased phagocytosis Interferon Transferrin Lysosomal activity Rest for patient Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Molecular Defense: Interferons Type I IFN-α IFN-β Antiviral Adjacent uninfected cells affected Therapeutic Uses Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Complement System Serum proteins (10% by weight) Activation Ag/Ab complexes (Classical) Ag on pathogen surface (Alternate) General functions Enhanced inflammation Opsonization Cytolysis Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Summary Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.