Exam 1: Dr. Kaplan Inflammation: Mechanisms 2 Flashcards
What are the 3 ways on innate immune cell killing?
Phagocytosis
Release of antimicrobial products
Targeted destruction of infected host cells
What do the innate immune cell killings defend against?
A variety of pathogens without eliciting help from the adaptive system
How quickly can the innate immune cell killing mechanisms be deployed?
Immediately without previous exposure, but can continue to work after adaptive immune response has been mounted
What are 3 types of phagocytes?
Macrophages
Neutrophils
Dendritic cells
What are the 3 stages of phagocytosis?
Recognition and adhesion of particles on plasma membrane of phagocyte
Membrane and cytoskeletal reorganiztion to mediate particle engulfment and creation of a phagosome
Maturation of phagosome to microbicidal and degradative phagolysosome
What are examples of some PRRs?
MR/CD206
Dectin-1
Scavenger receptor A1
Phosphatidyl serine receptor
What does MR/CD206 recognize?
Mannose and fucose on bacteria, fungi, and viruses
What does dectin-1 recognize?
β-glucan residues on fungi
What does scavenger receptor A1 recognize?
Polyanionic ligands on various microbes
What does phosphatidyl serine receptor recognize?
Phosphatidyl serine on apoptotic cells
What is recognition mediated by?
PRRs and opsonic receptors
What is opsonization?
Process whereby particles are coated with a protein-binding enhancer to enhance phagocytosis
What are the 2 major opsonins that mammals have?
Complement (C3b)
Antibody (IgG)
What can also act as an opsonin when bound to microbes?
CRP
What are 2 examples of opsonic receptors?
CR3
FCγ1R/CD64
What does CR3 recognize?
C3b on an surface bound by C3b
What does FCγ1R/CD64 recognize?
The Fc portion of the IgG antibody on any surface bound by IgG
What does the phagocytosis of irregularly shaped microbes or several microbes require?
Alteration in morphology
What does recognition of particle by phagocytic receptors result in?
Tight adhesion of microbe to phagocyte and clusters the receptors together
How long does the phagosome last?
Only a few seconds, but quickly evolves to an acidic, oxidative, degradative, antimicrobial chamber
What does the evolution of the phagolysosome evolution involve?
Fusion of the phagosome with endosomes and lysosomes in the cell
What does the phagosome do?
Recruits protein complexes that actively pump protons into it, reducing pH
What can the lower pH reduced by the protein complexes recruited by phagosomes do?
Kill microbes and activate antimicrobial enzymes that have been delivered to the phagosome
What does a phagosome do in neutrophils?
It also fuses with a modified lysosome containing high concentrations of antimicrobial proteins
What is an oxidative or respiratory burst?
Assembly of NADPH oxidase on phagosomal membrane
What does NADPH oxidase do?
Transfers unpaired electrons from NADPH to molecular oxygen generating superoxide
What is superoxide?
Extremely reactive and damaging
Reacts with hydrogen ions to form hydrogen peroxide
What is hydrogen peroxide?
A powerful oxidant that can be converted to hydroxyl radicals in presence of ferrous ions, which is damaging to all macromolecules
What can neutrophils make?
The antimicrobial enzyme myeloperoxidase
What does myeloperoxidase do?
Combines hydrogen peroxide with chloride ion to make hypochlorite ion (bleach)
What are the antimicrobial enzymes, proteases, improtant for?
Bridging innate with adaptive immunity
What can the amino acid arginine be converted to?
Nitric oxide