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INNATE IMMUNITY/ MUCOSAL IMMUNOLOGY REVIEW

INNATE IMMUNITY/ MUCOSAL IMMUNOLOGY REVIEW. April 23, 2009. Immediate Response. Induced Response. TWO PHASES OF INNATE IMMUNE RESPONSE. Cells and proteins involved reside at sites of pathogen entry. Proteins produced during the immediate response

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INNATE IMMUNITY/ MUCOSAL IMMUNOLOGY REVIEW

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  1. INNATE IMMUNITY/ MUCOSAL IMMUNOLOGY REVIEW April 23, 2009

  2. Immediate Response Induced Response TWO PHASES OF INNATE IMMUNE RESPONSE Cells and proteins involved reside at sites of pathogen entry Proteins produced during the immediate response recruit help. Cells do not reside at the site, but rather respond to the cry for assitance

  3. Figure 8-6 EPITHELIUM IS AN ACTIVE BARRIER

  4. Figure 8-9 MICROBES ACTIVATE COMPLEMENT VIA THE ALTERNATIVE PATHWAY occasionally lyse a pathogen promotes inflammation makes the pathogen more appealing to macrophages

  5. TISSUE MACROPHAGES RECOGNIZE THE PATHOGEN Complement Receptors: CR3 a.k.a. Cd11 and CR4 Pattern Recognition Receptors LPS, mannose, glycan, scavenger receptors recognize bacterial carbs. TLR (don’t bind pathogen)

  6. THE ACTIVATED MACROPHAGE INGESTS PATHOGENS generates toxic oxygen species..respiratory burst anti-microbials..eat or destroy pathogens (Immediate Respones) makes cytokines and chemokineswhich are responsible for the induced response

  7. IL-1, IL-6 ( antibody secretion), IL-12 (T cells and NK cells) THE ROLES OF CYTOKINES AND CHEMOKINES Local Effects: Alterations in vascular endothelium: TNFa, IL-1 Influx of neutrophils and lymphocytes: IL-8 Activation of Lymphocytes: Systemic Effects Fever IL-1, IL-6, TNFa Shock TNFa Acute Phase Response IL-6

  8. INFLAMMATION RECRUITS CELLS TO THE SITE Vessel dilation affects blood flow TNFa/leukotrienes increases expression of adhesion molecules (selectins) IL-8 summons neutrophils to site

  9. ACTION OF CYTOKINES LEADS TO FEVER Increased temperature decreases the rate of pathogen replication At higher temperatures, human cells become resistant to TNFa Antigen processing and presentation is increased (degradation of proteins to peptides and association with MHC proteins)

  10. Il-6 INDUCES THE ACUTE PHASE RESPONSE 3 PROTEINS (C-reactive protein, fibrinogen, Mannose binding protein) 2 EFFECTS (opsonization and Complement fixation)

  11. THE INNATE IMMUNE RESPONSE TO VIRUSES

  12. VIRUS INFECTED CELLS PRODUCE TYPE I INTERFERONS ds RNA stimulates IFN production and produce IFNg Oligoadenylate synthetase degrades viral RNA Activation of Adaptive Immunity

  13. RECOGNITION BY NK CELLS: TO KILL OR NOT KILL Healthy cells express MHC class I which interacts with an NK cell receptor issuing a “don’t kill” signal that counteracts the “kill signal” Viruses decrease MHC class I expression so there is no “don’t kill” signal Viruses stimulate production of type I IFNs which increase MHC class I on neighboring healthy cells

  14. MUCOSAL IMMUNOLOGY

  15. THE MUCOSAL IMMUNE SYSTEM Divided into inductive and effector sites Inductive sites: lymphocytes are sensitized to antigen Effector sites: lymphocytes respond to antigen GALT IS THE MAJOR INDUCTIVE SITE PP are major source of IgA secreting cells

  16. ANTIGEN ACCESS TO PEYER’S PATCHES Specialized epithelium: M Cells Microfolds Antigen uptake but NOT APC Target for bacterial cells

  17. A COMMON MUCOSAL IMMUNE SYSTEM Mucosal and systemic immune systems are compartmentalized Lymphocytes recirculate based on integrin and adhesion molecule expression l-selectin: naïve lymphocytes, unrestricted access Integrin a4b1: systemic and upper respiratory tract access Integrin a4b7: gastrointestinal tract access MAdCAM is expressed on mucosal vasculature and is the receptor for a4b7

  18. MUCOSAL IMMUNE RESPONSES B cells: hallmark of effective mucosal immunity is a secretory IgA response T cells: conventional ab TCR gd TCR or abTCR/CD8aa develop locally direct TH1 responses interface with innate immune system ORAL TOLERANCE Non-living antigens encountered in the gi tract do not cause local response Also will not respond to subsequent systemic challenge

  19. Surgeons must be very careful when they take the knife For underneath their fine incisions Stirs the culpritlife Emily Dickinson THE IMUNE SYSTEM

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