BIOL 318 Immunology Lecture 3 (20240911) PDF

BIOL 318 Immunology Lecture 3 Lecture by Andrea Verdugo Meza, PhD Candidate, MSc, BioEng Email: [email protected] September 11, 2024 Learning objectives Identify the physica...

BIOL 318 Immunology Lecture 3 Lecture by Andrea Verdugo Meza, PhD Candidate, MSc, BioEng Email: [email protected] September 11, 2024 Learning objectives Identify the physical, chemical, and biological components of the innate immune response Explain effector mechanisms of the immune response, describing: Recognition mechanisms PRRs Signaling mechanisms Cytokines & chemokines Effector mechanisms Antimicrobial substances Opsonization NETosis Phagocytosis Physical, chemical, and biological components of the innate immune response Epithelial layers produce protective substances Physical, chemical, and biological components of the innate immune response What can you tell from this experiment? Skin produces an anti-microbial peptide, Psoriasin, that kills Gram- negative microbes. Physical, chemical, and biological components of the innate immune response Antimicrobial peptides are constantly secreting as a preventative mechanism from the innate immune response Antimicrobial peptides (AMP) are short, cationic peptides Made by neutrophils and some epithelial cells (small intestines) Interact strongly with phospholipids & form pores in membrane Differentially active against different micro-organisms File:Modes of action.png Effectors Mechanisms of Innate Immune Responses to Infection Step 2.1→ Recognition of PAMPs Pattern recognition receptors (PRRs) PRRs bind and target invaders for clearance Present on epithelial cells Present on immune cells The ligands for PRRs are: Pathogen-Associated Molecular Patterns (PAMPs) found on microbes Antigen (conserved on both pathogens and commensals) Damage-Associated Molecular Patterns (DAMPs) found on aging, dead, or damaged self-structures Once a PRR engage with the corresponding PAMP or DAMP, a immune cascade is initiated Pattern recognition receptors (PRRs) Pattern recognition receptors (PRRs): TLRs recognize PAMPs on bacteria cell wall Pattern recognition receptors (PRRs): TLRs recognize PAMPs on bacteria cell wall Pattern recognition receptors (PRRs): TLRs recognize PAMPs on bacteria cell wall Localization linked to function Pattern recognition receptors (PRRs): TLRs recognize PAMPs on bacteria cell wall Localization linked to function Pattern recognition receptors (PRRs): NLRs recognize PAMPs on bacteria cell wall  Effectors Mechanisms of Innate Immune Responses to Infection Step 2.3→ Active elimination of pathogens Effectors Mechanisms of Innate Immune Responses to Infection: Phagocytosis Phagocytosis refers to the engulfment and internalization of materials such as microbes for their clearance and destruction Macrophages, neutrophils and dendritic cells are specialized phagocytic cells For a cell to phagocyte a microbe, this has to be recognized by a PRR i.e. a Macrophage can recognize E. coli LPS via TLR4 Effectors Mechanisms of Innate Immune Responses to Infection: Phagocytosis  Effectors Mechanisms of Innate Immune Responses to Infection: Phagocytosis Adherence Phagocyte membrane displays several surface TLRs that bind pathogens Ingestion Pseudopodia extend to engulf the attached pathogen Pseudopodia’s tips meet and fuse → phagosome Phagosome formation= internal vacuole of cell membrane containing engulfed particle(s) Phagosome separates from the cell membrane and becomes an internal structure Killing and Digestion Phagosome fuses with lysosome (containing microbiocidal chemicals) → phagolysosome Usually, bacterial death occurs in ~ 30 min with subsequent digestion of remains Expulsion Phagolysosome fuses with cell membrane and expels indigestible debris (exocytosis)  Effectors Mechanisms of Innate Immune Responses to Infection: Phagocytosis Destruction in phagolysosome occurs through enzyme degradation, antimicrobial proteins, and toxic effects of reactive oxygen (RO) and reactive nitrogen species (RNS)  Effectors Mechanisms of Innate Immune Responses to Infection: NETosis Early inflammation is rich in neutrophils Later it is more monocytes-macrophages Controlled by chemokines expressed by endothelial and epithelial cells Increased vascular permeability to recruit neutrophils and other leukocytes from the blood to the site of damage/infection Effectors Mechanisms of Innate Immune Responses to Infection: NETosis NETosis is the controlled death of neutrophils and leads to pathogen trap and degradation Macrophages, neutrophils, epithelial cells…all of this cells communicate and coordinate an effective immune response through cytokines and chemokines Molecules activated once the pathogen/harm signal was recognized Also enzymes like iNOS and COX2 25 Other effector mechanisms of the innate immune response Other effector mechanisms of the innate immune response Dendritic cells are a key bridge between the innate and adaptive immune response Other effector mechanisms of the innate immune response Natural Killer cells directly secrete granules full of pore- forming molecules that lyse infected cells Other effector mechanisms of the innate immune response Opsonization, which will be covered in Lecture 6  Summary Innate immunity is the frontline of immunity Innate immune responses depend on recognition of “general” pathogen molecules Responses are varied, but include: Phagocytosis Triggering of inflammatory responses Direct destruction by natural killer cells Initiation of adaptive immune responses