Review of The Innate Immune System Flashcards
Resolution of infection requires what
Resolution of infection requires both adaptive and innate immune responses
Compare specificity of adaptive/innate immunity
Adaptive immunity – involves very specific recognition of infectious agent (usually sees a protein = antigen)
Innate immunity – no specific antigen recognition
Innate involves recognition of broadly conserved features of different classes of pathogens
List the components to innate immunity
Phagocytosis The Inflammatory Response Cytokines, Interferons and Antimicrobial peptides (AMPs) Complement Intrinsic Defences – “the hostile cell” NK cells
Phagocytosis - where and by what
Carried out in vertebrates by Dendritic cells, macrophages and neutrophils
Phagocytosis - purpose
Phagocytosis clears pathogens but also presents peptides on MHCs – this promotes development or reactivation of the adaptive immune response
Macrophages have two distinct roles in innate immunity - describe
Phagocytosis; material is destroyed in lysosomes
Captured material can trigger macrophage activation - activated macrophages produce cytokines and chemokines
=
to stim innate/adaptive immune responses = inflammatory response + can promote a local anti-microbial state
The Inflammatory Response - purpose
A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components
The Inflammatory Response - effects
Enhanced permeability and extravasation
Neutrophil recruitment
Enhanced cell adhesion
Enhance clotting
Cytokines - function and examples
Act to modify the behaviour of cells in the immune response
Most of these are called interleukins (eg. IL-1)
Chemokines - function
Act as chemotactic factors – i.e. they create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection
How do Phagocytes know what to eat?
Material to be “eaten” is recognised in a number of ways:
By detecting phosphatidylserine on exterior membrane surface (cells undergoing apoptosis)
By Scavenger receptors
By some Toll-Like Receptors (TLRs)
By passive sampling
Pattern recognition is through Pathogen-associated Molecular Patterns (PAMPs) - present where
Molecules present only on pathogens and not on host cells
Pattern recognition is through Pathogen-associated Molecular Patterns (PAMPs) - essential for what
Essential for survival of pathogens
Examples of Pathogen-associated Molecular Patterns (PAMPs)
Gram-negative bacteria; lipopolysaccharides (LPSs) found in outer membrane
Gram-positive bacteria; teichoic acid, lipoteichoic acid, peptidoglycan found in outer membrane
Bacterial flagellin
Abnormal protein
glycosylation
Abnormal nucleic acids - viruses
Pattern recognition receptors (PRRs) - define + describe function
Host factors that specifically recognise a particular type of PAMP
They are germ-line encoded
There are several classes of PRR, but functionally they are either:
There are several classes of PRR, but functionally they are either:
Extracellular – they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen
Intracellular (cytoplasmic) – they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen
Secreted – they act to tag circulating pathogens for elimination
Receptor - lectin receptors
- describe the:
Ligand (PAMP)
Outcome
Lectin receptors
Ligand (PAMP) = Terminal mannose and fucose
Outcome = phagocytosis
Receptor - Scavenger receptors
- describe the:
Ligand (PAMP)
Outcome
Ligand (PAMP) = Bacterial cell walls
Modified low-density lipoproteins
Outcome = phagocytosis
Receptor - Toll-like receptors (TLRs) (surface and endosomal)
- describe the:
Ligand (PAMP)
Outcome
Ligand (PAMP) = LPS (together with CD14) Lipoproteins Unmethylated CpG Flagellin dsRNA; ssRNA (in endosomes)
Outcome = Inflammation: cytokine release (TNF, IL-1, IL-12)
enhanced killing: reactive oxygen species, NO);
phagocytosis
Receptor - NOD-like receptors (NLRs) (cytoplasm)
- describe the:
Ligand (PAMP)
Outcome
Ligand (PAMP) = Peptidoglycan from Gram-positive and Gram-negative bacteria
Outcome = Inflammation: cytokine release (IL-1, IL-8)
Receptor - RIG-like receptors (RIG-1 and MDA5) (cytoplasmic)
- describe the:
Ligand (PAMP)
Outcome
Ligand (PAMP) = dsRNA and 5’-triphospho-RNA
Outcome = Type I interferon production
Apoptosis
The Complement System - describe
Originally described as a heat-sensitive component of serum that could augment the ability of antibodies to inactivate antigen
The Complement System - function
Originally thought to be a biochemically complex antibody-dependent effector mechanism leading to:
Opsonisation
Recruitment of phagocytic cells, vasoactive function
Punches holes in target membranes (MAC)
The Complement System - role in action of pattern recognition receptors
Complement proteins act as secreted Pattern recognition receptors (PRRs) and can be activated by a range of PAMPs, and can also be activated by “altered self”
Interferons - define, distribution, induced by what and function
Secreted factors (type I and type III)
Induced by viral infection
Offer cross-protection
Widely distributed in evolution, from fish upwards, but species-specific
Anti-microbial peptides (AMPs)
(e.g. Defensins) - define and describe function
Secreted short peptides (18-45 amino acids)
Usually work by disrupting cell wall leading to lysis
Some are induced by bacterial infection
Offer broad protection
Intrinsic defences – “the hostile cell” - list
Apoptosis Restriction factors/Intrinsic Immunity Epigenetic silencing RNA silencing Autophagy/Xenophagy
Natural Killer (NK) cells (Large granular lymphocytes) - define and describe function
4% white blood cells
Lymphocyte-like but larger with granular cytoplasm
Kill certain tumour & virally infected cells
Target cell destruction is caused by cytotoxic molecules called granzymes & perforins
Natural Killer (NK) cells are activated by loss-of-self - explain
NK cells possess the ability to recognise and lyse virally infected cells and certain tumour cells.
Selectivity is conferred by LOSS of “self” MHC molecules on target cell surfaces, AND up-regulation of activating ligands
Innate immunity, describe the:
Cell types Speed Memory Specificity Receptors
Innate first:
Cell types
Macrophages, Neutrophils, DCs
Speed
Fast
Memory
No
Specificity
Low
Receptors
Pattern Recognition
Adaptive immunity, describe the:
Cell types Speed Memory Specificity Receptors
Innate first:
Cell types
Lymphocytes
Speed
Slow
Memory
Yes
Specificity
High
Receptors
Ig, TCR
Innate immunity, describe the:
Pattern recognition
Small number of microbial ligands that are highly conserved between pathogens;
Germ-line encoded receptors evolved by natural selection
Adaptive immunity, describe the:
Receptor system
Billions of possible antigens.
Receptors generated randomly within individual; cannot be inherited
