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Adaptive Immunity Big Picture, -we are not 'tolerized' to bacteria -don't want to activate complement Microfold (M) cells-microfolds on luminal surface -no microvilli, glycocalyx, mucus -overlie Peyer's patches ->interacts directly w/ luminal molecules -take up gut lumen Ags via endocytosis -Ags released beneath M cells to APC DCs Effector T cells disseminate to all mucosa -naive T cells home via CCL21, CCL17 -effector home via MAdCAM:L-selectin/a4:b7 (T) MAdCAM on endoth -anchor to epith via CCL28:CCR10(T) Commensal Bacteria Can prevent proliferation of other bac. -C. difficile can thrive w/out commensal ->neutrophils, RBCs leak into gut, Immunization Vaccine ISCOMs-Immune Stim COMplexes -lipid micelles that fuse w/ cell memb. -enclosed peptide xferred to APC ->to MHC-I-> to CTL, Live-Attenuated Advs-more potent -need just one admin -relatively inexpensive -induce humoral & CMI Disadvs-can revert to virulence (in immunocompromised) -must select for avirulence -less reliable in tropics Attenuate by: -growing virus in monkey -delete virulence gene from DNA -or just mutate it -or use viruses to carry peptides Bacterial Vaccines Use live bac w/ defective enz -can also use as vector for other bac, Immunization Vaccine Humoral Immunity -Tetanus, Diphtheria-powerful exotoxin->need lots of pre-existing ABs in circulation to neutralize (polio too) -Influenza-incubation period too short for memory to kick in -need lots of preformed ABs, so repeat immunizations -HIV-ABs don't clear HIV, Immunization Target Population Newborns can't mount good LPS response -Therefore H. influenza B vaccine not effective -However, linked recognition w/ joined LPS and tetanus toxoid -Previous tet exposure->TH2 activate B cell against LPS, Mucosal Associated Lymphoid Tissue (MALT) GALT -we are not 'tolerized' to bacteria -don't want to activate complement Microfold (M) cells-microfolds on luminal surface -no microvilli, glycocalyx, mucus -overlie Peyer's patches ->interacts directly w/ luminal molecules -take up gut lumen Ags via endocytosis -Ags released beneath M cells to APC DCs Effector T cells disseminate to all mucosa -naive T cells home via CCL21, CCL17 -effector home via MAdCAM:L-selectin/a4:b7 (T) MAdCAM on endoth -anchor to epith via CCL28:CCR10(T), Pathogens Extracellular Interstitial Spaces, blood, lymph -Viruses, bac, Protozoa, Fungi, worms Protection-ABs, complement, phagos, neutrolization, Immunization Vaccine DNA Vaccination-inject DNA of specific Ag and cytokines into mm. -via "biolistic gun" to TLR9 on DCs (unmethylated CpG of DNA) -enhance by adding GM-CSF plasmid -could lead to malaria, HIV vaccs, Pathogens Extracellular Epithelial Surfaces -N.gonorrhea, Mycoplasm spp., Strep. pneumoniae, Vibrio cholerai, E.coli, H. pylori, C. albicans, worms Protection-ABs (esp IgA), antimicrobial peptides, Immunization Therapy of Existing Infections Cytokine Therapy-must be at time of initial exposure -anti-IL-4 AB at infection ->converts to Th1 response -IL-12+antiparasitic Rx+Leishmania ->convert to Th1 and clear infx Unknown success of therapeutic vaccination