Transcript Lecture 21
Figure 23.1 Figure 23.3 Human Microbiota – Respiratory Tract • The lungs and trachea are usually sterile. • The ciliated mucous lining of the trachea, bronchi, and bronchioles makes up the mucociliary escalator. • - Sweeps foreign particles up and out of the lung Figure 23.5 Human Microbiota – Stomach • Stomach has very high acidity. • - Few microbes survive. • - Helicobacter pylori • - Survives at pH 1 • - Burrows into protective mucus • - Causes gastric ulcers Figure 23.6 Decreased stomach acidity = Hypochlorydia - Caused by malnourishment - Vibrio cholerae survives stomach passage. - Establishes infection in less acidic intestine Overview of the Immune System • Nonadaptive (innate) immunity • - Barriers to infection • - Nonspecific responses to destroy invading cells • - Present at birth • Adaptive immunity • - Reaction to specific antigens • - Parts of foreign proteins, sugars, chemicals • - Body reacts to antigens when exposed. • - Retains “memory” of those antigens • - Faster response if exposed a second time Cells of the Immune System • Blood is composed of red blood cells, white blood cells, and platelets. WBCs are formed by differentiation of stem cells produced in the bone marrow. Figure 23.12 Figure 23.11 monocyte PMN lymphocyte Figure 23.13 Figure 23.14 Lymphoid Organs • Primary lymphoid organs • - Where lymphocytes mature • - e.g.: Thymus • Secondary lymphoid organs • - Where lymphocytes encounter antigens • - e.g.: Spleen and lymph nodes Figure 23.16 • The gastrointestinal system possesses an innate system called gut-associated lymphoid tissue (GALT). • - Includes tonsils and Peyer’s patches • - Specialized M cells take up microbes from the intestine and release on the other side for macrophages. Figure 23.17 Figure 23.22 Figure 23.23 Figure 23.24 The Acute Inflammatory Response • Animation: The basic inflammatory response Click box to launch animation Phagocytosis • Phagocytes must avoid attacking host cells. • - Host cell glycoprotein CD47 prevents attack. • Phagocytes is enhanced by opsonization. • - Microbial cells are coated with antibodies. Figure 23.27 Phagocytosis • Animation: Phagocytosis Click box to launch animation Natural Killer Cells • Destroy infected and cancerous host cells • Healthy cells make surface MHC class I antigens. • - Cancerous and infected cells stop making MHC I Figure 23.28 When an NK cell encounters a cell lacking these markers, it secretes perforins protein into the target cell. - Creates membrane pores to lyse cell Toll-Like Receptors • Microbes possess unique structures that immediately tag them as foreign. • - These pathogen-associated molecular patterns (PAMPs) are recognized by Toll-like receptors present on various host cell types. • Once bound to their ligands, the TLRs trigger an intracellular regulatory cascade. • - Cause host cell to release proteins called cytokines • - Bind to various immune cells, and direct them to engage the invader Toll-Like Receptors LBP LAM LPS Bacteria LBP Viral dSRNA LTA LPS Yeast Bacteria PGN BLP MycoBacterial 19KDa Protein MD2 T T L L R R 4 4 CD14 TRAM SIGIRR T L R 1 ST2 Uropathogenic Bacteria T L R 2 T L R 2 CD14 TRIF k NF- B Pathway k T L R 6 T L R 5 TIRAP Rac PI3K TIRAP PI3K Rac RIP2 TIRAP BTK DNA CpG MALP2 IRF8 NF- B IRAKM IRAK4 TRAF6 UEV1A Triad3 IKKs MKK6 MKK3 TAB2 TAB1 TAK1 MKK7 MEKK3 IKKs I B k IRF7 TRIF NF- B RIP3 TBK1 TRAF6 BTK e k IFN- IRF3 2009 ProteinLounge.com aIRF7 IFN-b TANK IKK p38 I B IRAK TRAF6 RIP C IRAK2 ECSIT ENDOSOME k IRAK1 TRAF6 k NF- B k NF- B JNK CREB SLAM,CD80, CD83 IRF8 TNF,COX2, IL-18 C-Jun IFN-Responsive Genes ATF2 iNOS Signaling 2009 ProteinLounge.com C LPS LBP Ribonucleotide Reductase SOD GSH ONOO- O2NF-kB IkBs Degradation NADPH Oxidase P NO P Viral Protease IRF1 P P NF-kB IRF1 HMGI/g Hu R Calm AP-1 Virus(Herpesvirus, Picornaviruses, Flaviviruses and Coronaviruses) Calm iNOS iNOS Viral Polyprotein iNOS mRNA L-Arginine+O2 Destabilization iNOS Viral RNA