Microbiology L16 Notes p. 390-407 Chapter 16 Innate Immune Defenses

Body's 3 antiinfection defenses: nonspecific surface, innate immune system (nonspecific interior), and adaptive immune defenses. Inflammation, phagocytosis, complement, interferon, natural killer cells.

Inflammation: Cornerston of innate immune defenses. Pain, redness, heat, swelling, vasodilation, permeability increase , phagocyte attraction (margination and diapedesis) and activation, release of inflammatory mediators.

Inflammatory mediators(6): Bacterial by-products, complement fragments, kinins, histamine, prostaglandins, leukotrienes

Pus: Mixture of dead microbes, leukocytes, microbes, and host cells oozing from infection site

Leukocytes: Phagocytes (nonspecific) and lymphocytes (specific)

Polymorphonuclear leucocytes (granulocytes) = neutrophils, eosinophils, basophils

Mononuclear leucocytes (agranulocytes) = monocytes and macrophages

Neutrophils (don't stain): Release from granules of antibacterial substances. Lysozyme (cleaves peptidoglycan), lactoferrin (binds iron), acid hydrolases, myeloperoxidase. Phagocytosis.

Eosinophils (eosin stains red): Granules release acid phosphatase, peroxidase, proteinases. Active against protozoa, fungi, worms. Phagocytosis. Lessen effects of inflammation.

Basophils (and mast cells) Granules blue from methylene blue. Degranulate, but no phagocytosis. Anti-parasitic.

Monocytes: circulatory macrophages. Active phagocytes

Macrophages: lifespan = weeks to months. Various forms in different tissues.

Phagocytosis: Indispensable

Complement cascades: Classical (Ab dependent), alternative (properdin; directly activated by bacterial surfaces) pathways. Pathways join at C3. Major function not lysis of targets.

Interferons: Name originated in Flash Gordon comic strip. Limit viral infections. Infected cell signals others to make antiviral proteins, increase production of class I MHC molecules. No class I: NK cells attack.

http://pls.atu.edu/biology/biology/people/bisk/micro/micro.htm Study Cards:C16

http://www.nidr.nih.gov/prog-ann/97079.htm

PURPOSEThe National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Dental Research (NIDR), National Institutes of Health (NIH), invite applications for research studies of the innate immune system. Two general systems of immune recognition have been selected through evolution: innate immunity and acquired immunity. The innate immune system provides broad, but relatively nonspecific host defenses that lack the properties of antigenic specificity and immunologic memory that characterize acquired immunity. However, recent discoveries point to many robust mechanisms of innate immunity and have highlighted important functional links between the innate and acquired immune responses. The purpose of the PA (Program Announcement) is to support basic and preclinical studies of the mechanisms of innate immunity in order to: a) develop new strategies to augment antimicrobial defenses; b) develop novel approaches for immunomodulation in chronic infectious and inflammatory disorders; and c) identify new methods, based on mechanisms of innate immunity, to modulate acquired immune responses (e.g., to enhance vaccine efficacy).

Background This PA will support studies of the mechanisms of innate or "natural" immunity. The innate immune system provides rapidly activated host defenses triggered largely by cell-surface carbohydrates found only on microoganisms. These carbohydrates are structurally and immunologically distinct from the surface carbohydrates of mammalian cells. Innate immunity is phylogenetically older and has often been viewed as a vestige of ancient antimicrobial systems made redundant by the evolution of acquired immunity. This notion is now being challenged by the elucidantion of key mechanisms of innate immunity and by the discovery of important functional connections between innate and acquired immune responses.

Research Objectives and Scope The objective of this PA is to support innovative research on mechanisms of innate immunity. The scope of research to be supported by this PA includes, but is not limited, the following broad areas; the role of the innate immune system in regulating the onset, duration, magnitude, and character of acquired immune responses; studies of the structure and function of antimicrobial products of the innate immune system; characterization of newly recognized mechanisms and effectors of innate immunity; and studies of the genetic control of innate resistance to infection. Examples of specific advances and promising areas for further investigation include, but are not limited to, the following:

studies to define the mechanisms by which complement binding promotes antigen trapping and antigen presentation and renders microbial antigens orders of magnitude more immunogenic for humoral immune responses; design and development of novel vaccine candidates incorporating complement components; studies of the antimicrobial activities of leukocyte and epithelial defensins and design and development of defensin-like antimicrobials; studies of the genetic regulation, structure, and function of mannose binding protein (MBP), a serum opsonin that promotes the ingestion and killing of bacteria and viruses; production of MBP is genetically controlled, varies widely in man, and correlates with innate resistance to infection; studies to determine the mechanisms of mast cell mediated antimicrobial defenses, a newly identified function of mast cells; and based on this knowledge, development of novel strategies to boost respiratory, gastrointestinal, and urogenital immunity; studies of a recently identified gene, called Nramp1, that regulates murine innate resistance to intracellular pathogens; Nramp 1 homologs have been found in species ranging from Drosophlia to man, but their role in determining susceptibility to human infectious diseases remains to be established.