Innate Immunity II PDF

Innate Immunity II Friday January 10 Dr. Rodney DeKoter Microbiology & Immunology  Learning Objectives 1) To learn the anatomy of the immune response – where in the body the cells and tissues are located 2) To learn the principles of recognition and response in the immune system 3) T...

Innate Immunity II Friday January 10 Dr. Rodney DeKoter Microbiology & Immunology  Learning Objectives 1) To learn the anatomy of the immune response – where in the body the cells and tissues are located 2) To learn the principles of recognition and response in the immune system 3) To learn the fundamentals of intracellular signaling pathways 4) To learn the fundamentals of extracellular signaling pathways (cytokines) Anatomy of the Immune Response The Human Lymphatic System Structure of a Lymph Node Structure of the Spleen  Pathogen Recognition and Detection How do cells Induce “sense” phagocyto the sis presence of pathogens ? Expand response Created with BioRender Overview of Intracellular Signaling Pathways Image from geeksforgeeks.org There is a large diversity of signal transduction pathways Pathways can overlap and ”talk” to each other Pattern Recognition Receptors (PRRs) PRRs are expressed at the surface and within many cell types (WBC, some lymphocytes, and some epithelial cells) Recognize evolutionarily conserved, invariant regions of pathogens Can also recognize damage or infection signals Specificity is germline-encoded Critical for initiating immune responses (signals danger) Pattern Recognition Receptors (PRRs) 4 Families of PRRs: Toll-like receptors (TLR) C-type lectin receptors (CLR) Nucleotide oligomerization receptors (NLR) RIG-I like receptors (RLR) https:// www.immunology.org/ Toll-Deficient Fruit Flies Cannot Prevent Infection Aspergillus fumigatus infection in Toll- deficient fruit fly (Cell 1996) Pattern Recognition Receptors (PRRs) Recognize Pathogen Associated Molecular Patterns (PAMPs) https:// www.immunology.org/ Transmission electron microscopy of hyperflagellated Salmonella enterica serovar Typhimurium Tomoyasu et al. 2002. J Bact. 184:3. Toll-Like Receptors Recognize a Wide Variety of PAMPs  Pattern-Recognition Receptors Induce Phagocytosis in Dendritic Cells and Macrophages To Initiate Immune Responses PRRs bind to PAMPs Pseudopods engulf pathogen Phagosome formation Illustration by Gary Kaiser https://bio.libretexts.org/Bookshelves/Microbiology/Book %3A_Microbiology_(Kaiser) Damage-Associated Molecular Patterns (DAMPs) Are Self-Molecules Released as a Consequence of Cellular Damage Schaefer, Journal of Biological Chemistry  Extracellular Signaling: Cytokines Cytokines are chemical “messages” (proteins that allow communication between cells of the immune system) Target cells can only respond to cytokines if they have the receptor for it Cytokine modes of action: - Pleiotropy: same cytokine act on different cells to evoke different responses - Redundancy: different cytokines evoke same response in cells - Cascade induction: action of a cytokine on a cell induces production of one or more additional cytokines  The Six Major Cytokine Families Family Name Representati Representati Receptor(s) ve Member ve Function Interleukin-1 IL-1 beta Inflammation IL-1R1, IL- Family 1RAcP (heterodimer) Class 1 IL-2 Promotes cell IL-2R alpha,IL- (Hematopoieti division of 2R beta, n) Family lymphocytes common gamma chain (heterotrimer) Class 2 Interferon- Antiviral IFNAR1, (Interferon) alpha responses IFNAR2 Family (heterodimer)  The Six Major Cytokine Families (continued) Family Name Representati Representati Receptor(s) ve Member ve Function Tumour TNF-alpha Inflammation TNFR1 (forms Necrosis trimer) Factor Family Interleukin-17 IL-17 Activates and IL-17RA, IL- Family Recruits 17RB Neutrophils (heterodimer) Chemokine IL-8 Chemoattracta CXCR1 Family nt for (monomer) lymphocytes Receptors Can Be Monomeric, Dimeric, or Multimeric Example: Interleukin-2 Receptor Interleukin-2 Signaling Pathway Activation of Cellular Responses Activation of Cellular Responses Image from geeksforgeeks.org Changes in gene expression (transcription) Changes in protein expression (translation) Cell division Cell movement Cell differentiation Cell survival (life/death)  Summary The lymphatic system is important for organizing the immune response. Lymph nodes and spleen play key roles. Pattern recognition receptors (PRRs) recognize PAMPs (pathogen associated molecular patterns) and DAMPs (damage associated molecular patterns) Cytokines and cytokine receptors mediate extracellular signals Cellular responses are activated by signal transduction pathways