4-Innate Immunity I (Basics: Tissues, cells & molecules ) Flashcards
Pathogen enter through:
Mucosal surface
Epithelial surfaces – skin
(1st line of defence)
(part of innate immunity)
To cause infection
-Pathogen must enter the body – there are different routes of entry
-Need to break through these barriers
Epithelial surfaces of the body and give examples
-1st barrier against infection
Skin
Gut epithelium
Respiratory epithelium
Mucosal membranes
Saliva, hair, mucus, tears
Epithelial layers can also produce…
protective substances
-Acidic pH
-Antimicrobial peptides
(defensins secreted)
cellular elements of innate immunity (4)
Neutrophils & other granulocytes
Monocytes & macrophages
Dendritic cells
NK cells (Natural killer) & other innate lymphoid cells (ILCs)
Neutrophils & other granulocytes
Phagocytosis & activation of bactericidal mechanisms
Monocytes & macrophages
-Monocyte can differentiate into macrophages.
-macrophages are tissue resident: different name based on different location
Dendritic cells
-Antigen uptake in peripheral sites & antigen presentation
-Immature DC
-Mature DC
-Conventional DC –potent antigen presenting cells
-Plasmacytoid DC
Key molecules (3)
-Antimicrobial enzymes -catalytic
Lysozyme – digest peptidoglycan (in gram +)
Secreted by immune cells
-Antimicrobial peptides – short aa
Defensins – disrupt cell membrane & form a pore
-Complement
Infection & response – divided into stages
1.Pathogens adhere epithelium
2.Local infection & penetration of epithelium
3.Local infection of tissues
4.Adaptive immunity
one key function of innate immunity
Phagocytosis
what is Phagocytosis
engulfment & internalization of pathogens or their components upon binding to receptors on cell surface of phagocytes
phagocytes examples (3)
Macrophages
Granulocytes: Neutrophils
Dendritic cells
Phagocytosis can lead to
-Removal & killing of pathogens
-Clearing debris – PRRs recognize DAMP (damaged/soon dying cells)
-Generation of peptides (Antigen) for presentation to T cells by phagocytes
(only macrophages & DC)
Receptors in phagocytosis
MANY = PRR (but not all PRR induce phagocytosis)
Indirectly occurring phagocytosis by:
opsonization
Opsonization
Phagocytes recognize and bind opsonins/soluble pattern-recognition proteins (soluble proteins bound to microbial surfaces) – enhance phagocytosis
Opsonization examples
Antibodies -soluble proteins secreted by B cells
complement proteins
Phagocytosis steps - full version
-Phagocytosis initiates when – receptors interact with ligand/pathogen (PRR bind to PAMP)
-Prompts membrane protrusions that extends – pseudopodia
-PAMP bind to PRR on membrane evagination –pseudopodia
-Pathogen internalized in large membrane-enclosed endocytic vesicle – phagosome
-Phagosome fuses with one/or more lysosomes – phagolysosome – release lysosomal content
-Phagolysosome acidifies – acquire antimicrobial peptides & enzymes to kill pathogen
-Bacterium is killed & digested by low pH activated lysosomal enzymes
Phagocytosis steps - simple version
-PRR bind to PAMP
-pseudopodia
-forms first vesicle = phagosome
-phagosome fuse with lysosome = phagolysosome
Neutrophiles contain diff. Types of cytoplasmic granules
-Primary granules
-Secondary granules
-Granules fuse with phagosome (phagolysosome)
release additional enzymes & antimicrobial peptides – attack microorganism
Phagocytic cells & internalized vesicles
DC
Macrophages
Neutrophils
DC - phagolysosome
Macrophaes - phagolysosme
Neutrophils - granules (still called phagolysosome - pretty much same thing)
Process of killing phagocytosed pathogen
-Phagocytosis/ligand binding triggers signaling – result in change
-Phagolysosome – contain products able of killing microbes
what does phagolysosome contain that kills microbes?
-Low pH/acidification
-Hydrolytic enzymes –love low pH
Lysozyme & protease
-Oxidative attack
-Antimicrobial peptides
Defensins & cathelicidin
oxidative attack oh phagocytosed pathogen
-Employ ROS (reactive oxygen species)
Damage microbial membranes & intracellular components
-Generated by phagocytes unique NADPH oxidase enzyme complex/phagosome NADPH oxidase
-ROS production by NADPH oxidase -increase O2 consumption – respiratory burst (pump O2 in phagolysosome = toxic
-RNS (reactive nitrogen species)
why is phagolysosome important in immunity
Important organelle for innate & adaptive immunity
phagolysosome in Innate immunity
Innate – pathogen…
Killing
Processing
Presentation to sensory cytosolic PRRs (TLR, NOD)
Inside of cell
phagolysosome in adaptive immunity
Adaptive – antigen…
Degradation
Processing
Presentation onto MHC molecules
phagocytosis is a major mode for :
clearance of cells
what can phagocytosis do:
-can clear cells from apoptosis
-Dead/dying cells – express DAMPs (damage-associated molecular patterns) – “eat me” bind to PRRs
what does neutrophils do with phagocytosis:
-Ingest & kill microorganisms
-Not tissue-resident – recruited to site of infection
-Pus = result of dead/dying neutrophils
20%-60% of neutrophils can produce
Extracellular matrix called:
NETs (neutrophil extracellular traps)
Trap microorganisms & prevent spread
