Define Innate Immunity
A non-specific defence mechanism that a host uses immediately or within several hours after exposure to antigen.
True or False: Repeated exposure to the same antigen increases the strength and speed of the innate immune response
Innate immunity responds the eaxct same way each time as it does not confer immunological memory.
What are some of the innate barriers to pathogen entry?
Skin - Thick physical barrier makes it difficult for pathogens to penetrate. Also the secretion of sebum (fatty acids) can inhibit survival of microbes on the skin.
Cilia and Mucus in the Respiratory tract.
HCL/Low pH and Acid Hydrolases in the Stomach.
Tears, sweat and saliva - Contain lysozymes which cleave between sugars of the peptidoglycan layer within bacterial cell walls
Commensal Microbiota - Outcompete harmful pathogens for adhesion space and nutrients
What is the key protein in the complement cascade and what activates it?
C3 - activated by C3 convertase to produce C3a and C3b
What are the effector fates of C3a and C3b?
C3a stimulates a pro-inflammatory response with C5a by stimulating Mast cells to release Histamine, which increases vascular permeability enhancing chemotaxis
C3b along with other complement proteins (C5b,C6,C7,C8,C9) forms the Membrane Attack Complex (MAC) which causes cell lysis
C3b can also form thioester bonds with the surface of pathogens. Complement receptor CR1 on macrophages can recognise the C3b proteins and bind to them, leading to phagocytosis - Opsonisation
How do cells of the innate recognise pathogens?
They express Pathogen Recognition Receptors (PRRs) which can recognise Pathogen Associated Molecular Patterns (PAMPs)
PAMPs are found exclusively on non-host cells and thus provides the innate immune system with broad recognition specificity
Give examples of common PAMPs
LPS on Gram -ve bacteria
Lipoteichoic acid on Gram +ve bacteria
Give examples of common PRRs
Toll-like receptors - Membrane
Nod-like receptors - Cytoplasm
Collectins - Serum
How does the structure of Collectins aid their function?
Collectins are made up of a collagen-like region, which interacts with effector parts of the immune system, and a lectin region, which binds to sugar molecules on the pathogen's surface
How many mammalian TLR homologues exist?
At least .10
Which TLRs function as dimers?
What do NOD 1 receptors sense?
Gamma-glutamyl diaminoprimelic acid in peptidoglycan only in Gram -ve bacteria.
What do NOD 2 receptors sense?
Muramyl dipeptide in peptidoglycan (Both Gram bacteria)
True or False: Macrophages are short lived and Neutrophils are long lived cells
Neutrophils are short lived
Macrophages are relatively long lived
Describe the process of phagocytosis.
PRR on phagocyte recognises PAMP on pathogen.
Phagocyte extend psedopodia and engulfs the pathogen, forming a phagosome.
Lysosome fuses with phagosome to form a phagolysosome.
Digestive enzymes degrade the pathogen.
Peptide loaded onto MHC class II molecule and expressed on cell surface.
Indigestible remnants and waste materials are released from the cell by exocytosis.
What are some non-phagocytic oxygen-dependent killing mechanisms displayed by Macrophages and Neutrophils?
Generation of Reactive Oxygen Species (ROS):
Post-phagocytosis, there is an increase in O2 uptake - "Respiratory Burst".
Oxygen is reduced by NADPH oxidase to form Hydroxyl radicals and Hypochlorite.
What protects the immune cells from the ROS that they produce?
They have enzymes that catalyse the converion of ROS into less harmful intermediates.
Describe an oxygen-independent killing mechanism used by Neutrophils and Macrophages.
Production of Reactive Nitrogen intermediates
O2 + L-arginine --> NO + L-citrulline
This reaction is catalysed by the enzyme NO Synthetase (iNOS), which is induced by cytokines IFN-gamma and TNF, as well as bacterial components.
Cofactor used is tetrahydrobiopterin.
Name 2 pro-inflammatory cytokines.
IL-1 and IL-6
Name the cytokine involved in the activation of macrophages.
Name the cytokine involved in the activation and differentiation of CD4 T cells.
Name the other cytokine (not TNF-alpha) that activates macrophages.
Name 2 chemokine produced by macrophages and endothelial cells to stimulate chemotaxis.
Monocyte chemotactic protein (MCP)
Which interferons are involved in the response to virally infected cells and what immune cell responds to these interferons?
Type 1 interferons - IFN-alpha & IFN-gamma
NK cells respond by killing the infected cells and producing IFN-gamma, to activate macrophages, upregulate MHC expression and together with IL-12, stimulate differentiation of CD4 Th1 cells.
Which innate immune cells can undergo respiratory burst?
NOT NK cells
What are the activation signals required to stimulate inactive/naive T cells?
Signal 1 - TCR recognises antigen/peptide on MHC class II on APC.
Signal 2 - CD80/CD86 on APC recognises CD28 on T cell provides co-stimulation.