Innate immune protection Flashcards
Innate vs Adaptive immunity
Features of the innate and adaptive immune response
Innate:
-Epithelial barriers
-Phagocytes
-Complement
-NK cells
Adaptive:
-B lymphocytes
-T lymphocytes
-Antibodies
-Effector T cells
Innate immunity definition
-A non specific defence mechanism that a host uses immediately or within several hours after
exposure to antigen
Timespans for innate vs adaptive immunity
Characteristics of innate immune system
-Designed to be very fast - within hours
-Ancient evolution - components of the innate immunity found in invertebrates (amoebae, snails, fruit flies)
-Responds exactly the same way each time
-Induces and directs the acquired/adaptive immune response
Physical/anatomical barriers of innate immune system
Skin:
-Produces anti-microbial compounds
Respiratory tract:
-Tight junctions between cells
-Cilia brush away pathogens
-Mucus production
GI tract:
-Peristalsis
-HCL production (low PH)
Eyes:
-Blinking
-Tears, sweat and saliva contains lysozyme
Internal protection:
-Microbial competition on skin and in gut
How does innate immune system recognise pathogens?
-Doesn’t recognise every pathogen
Recognises a few highly conserved molecular structures present in many different microorganisms (PAMPs)
-Pathogen, Associated, Molecular, Patterns
PAMPs are:
-Present in the microorganism but not the host
-Essential for the survival of the pathogen
PAMPs in Gram positive and Gram negative bacteria
Gram negative bacteria:
-Lipopolysaccharide (LPS)
Gram positive bacteria:
-Lipoteichoic acid
What recognises PAMPs
Pattern Recognition Receptors (PRRs):
-Collectins (serum)
-Toll like receptors (membrane)
-Nod like receptors (cytoplasm)
Collectins
-Family of proteins present in solution
-Collagen-like region interacts with
effector parts of
immune system
-Lectin region binds to sugar
molecules on surface
of pathogen
eg. mannose
-Doesn’t bind to host mannose due to incorrect spacing
Toll like receptors
-Membrane bound and cover cell surface
-TLR5 binds to flagellin
-TLR7/8 binds to single stranded RNA virus
NOD like receptors
-Nucleotide-binding oligomerization domain-like receptors sit in cytoplasm
-Recognise components of gram positive and negative bacteria
What are complements
-Series of proteins that circulate in blood and tissue fluids
-Operates via cascade
-3 ways of complement activation all lead to generation of C3 convertase
-C3a, C4a, C5a recruitment phagocytosis
-C3b opsonisation
-C5b, C6, 7, 8, 9 membrane attack complex causing lysis
What performs phagocytosis
Monocytes/macrophages:
-Macrophages mature from circulating monocytes
-Found in large numbers in GI tract, lung, liver, spleen
-Relatively long lived
Neutrophils:
-Found only in blood
-Short lived
Phagocytosis definition
-Recognition of the pathogen by receptors on the phagocyte leads to the ingestion and destruction
Phases of Phagocytosis
Killing mechanisms of macrophages and neutrophils (oxygen radicals)
-Reactive oxygen intermediates
(more in neutrophils)
-Following phagocytosis there
is an increase in O2 uptake
(respiratory burst)
-Oxygen is reduced by NADPH
oxidase to form hydroxyl
radicals and hypochlorite
-DNA damage and alterations
in bacterial membranes
-Oxygen radicals cause DNA damage and alterations in bacterial membranes
Killing mechanisms of macrophages and neutrophils (nitrogen radicals)
-Reactive nitrogen intermediates (more in macrophages)
-L-arginine to L-citrulline generates
NO radicals
-Catalysed by enzyme inducible
nitric oxide synthase (iNOS, NOS2)
induced by cytokines and
bacterial components
-2 most potent inducers are interferon gamma and tumour necrosis factor
-Nitrogen radicals cause DNA damage and alterations in bacterial membranes
Features of cytokines
-Proteins
-“Intercellular messengers”
-Bind to specific receptors
-Can be activating or deactivating
-In innate immune response they are
mainly activating:
* IL-1 (interleukin 1)
* IL-6 (interleukin 6)
* TNFa (tumour necrosis factor a)
Features of chemokines
-Class of cytokines with chemoattractant properties
-Promote inflammation by enabling cells to adhere to the surface of
blood vessels and migrate to infected tissue
-Eg. IL-8 produced by macrophages and endothelial cells MCP (monocyte chemotactic protein)
Features of interferons
-Class of cytokines
-Type 1 interferons (IFNa and IFNb) produced in response to virally infected cells
-Type 1 interferons activate NK cells
What do NK cells do?
-Kill virally infected cells and tumour cells
-Responsive to TNFa, IL-12
-Produce IFNy
Cytokines and chemokines summary
-Direct cells to where bacteria are
-Tell cells what they need to do
-Activate cells for killing
-Mount inflammatory immune response
What cells can act as antigen presenting cells?
-Macrophage
-B cell
-Dendritic cell
What do dendritic cells do?
-Mature dendritic cells present antigens to activate naive T cells
Innate immunity to adaptive immune response
-For naive T cell to become effector T cell, 2 signals are required:
-Recognition of pathogen fragments (from phagocytosis) and MHC on antigen presenting cell
-Co-stimulatory signal generated following recognition of pathogens by PRRs (e.g. TLRs)
-Upon recognition, APC up-regulates stimulatory signal
-Cytokines produced by innate immunity determine the flavour the T cell becomes
