L13 - Review of the Innate Immune System Flashcards
Why do we need an innate immune system?
the adaptive immune response is too slow to protect us from new pathogens.
Allows survival until adaptive immune response kicks in.
What is the Innate immune system?
The unspecific Immune system, that is present from birth
Describe the differences in specificity between adaptive and innate immunity?
Adaptive immunity – involves very specific recognition of infectious agent (usually sees a protein = antigen)
Innate immunity – no specific antigen recognition
Innate immunity involves recognition of broadly conserved features of different classes of pathogens
What are PAMPs?
Pathogen associated molecular patterns
Molecules present only on pathogens and not on host cells
Essential for survival of pathogens
Invariant structures shared by entire class of pathogens
Give examples of PAMPs on Gram positive and negative bacteria as well as in general?
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
What are PRRs?
Pattern Recognition Receptors
Host factors that specifically recognise a particular type of PAMP
They are germ-line encoded
What are Extracellular PRRs?
Extracellular – they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen
What are Intracellular PRRs?
Intracellular (cytoplasmic) – they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen
What are Secreted PRRs?
Secreted – they act to tag circulating pathogens for elimination
Briefly state some of the components of the Innate Immunity?
The inflammatory response Phagocytes Monocytes/granulocytes/neutrophils Complement Cytokines, chemokines and anti-microbial peptides (AMPs) Natural Killer cells
Describe the Inflammatory response as a component of Innate Immunity?
A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components
Enhanced permeability and extravasation
Neutrophil recruitment
Enhanced cell adhesion
Enhance clotting
Triggered by the release of pro-inflammatory cytokines and chemokines at the site of infection
Describe Phagocytosis as a component of Innate Immunity?
Phagocytes have to be able to recognise what to eat
Phagocytes need know when they are infected in order to produce cytokines and chemokines
The molecular recognition events are distinct – i.e. they use different pattern recognition receptors
What are the roles of Macrophages and Dendritic cells?
Phagocytosis; material is destroyed in lysosomes
Infections can trigger macrophage activation - activated macrophages produce cytokines and chemokines to stimulate both innate and adaptive immune responses – this triggers the inflammatory response and can promote a local anti-microbial state
Dendritic cells - Peptides from broken down pathogens can be presented through MHC and promote the development or recall of an adaptive T cell response
How do Phagocytes know what to engulf?
Material to be “eaten” is recognised in a number of ways:
By detecting phosphatidylserine on exterior membrane surface (cells undergoing apoptosis)
By detecting “atypical sugars” (e.g. mannose, fucose, b-glucan) on cell surfaces
By Scavenger receptors
By “passive sampling”
By detecting complement proteins bound to the pathogen surface
Describe the complement system as a component of Innate Immunity?
Originally described as a heat-sensitive component of serum that could augment the ability of antibodies to inactivate antigen
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)
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”
What PAMPs are recognised by Toll-like receptors, and what cytokines/chemokines are produced as a result?
PAMPs: LPS (together with CD14) lipoproteins Unmethylated CpG Flagellin ds RNA; ss RNA (in endosomes)
Produce:
inflammation: cytokine release
(TNF, IL-1, IL-12)
enhanced killing: reactive oxygen species, NO)
What PAMPs are recognised by Nod-like receptors, and what cytokines/chemokines are produced as a result?
PAMPs:
Peptidoglycan from Gram positive and negative bacteria
Some viral DNA and RNA (indirect?)
Produce:
inflammation: cytokine release (IL-1, IL-8)
What PAMPs are recognised by RIG-like receptors, and what cytokines/chemokines are produced as a result?
PAMPs:
Viral dsRNA and 5’-triphospho RNA
Produce:
type I interferon production
What are Cytokines and Chemokines?
They are both Glycoprotein hormones that affect the immune response
Cytokines:
Act to modify the behaviour of cells in the immune response
Most of these are called interleukins (eg. IL-1)
Chemokines:
Act as chemotactic factors – i.e. they create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection
What are Interferons?
The main Anti-viral Cytokines
Secreted factors (type I and type III)
Type 3 protects epithelial surfaces and type 1 protects other surfaces
Induced by viral infection
Offer cross-protection
Widely distributed in evolution, from fish upwards, but species-specific
What are Defensins?
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
What are NK cells?
Natural killer cells
Make up 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
via surface contact
How are NK cells activated?
Activated by loss-of-self.
NK cells have an MHC receptor that recognisesMHC class 1 peptide on the surface of uninfected cells. If it recognises this pepetide, it does nothing.
In an infected cell, MHC 1 peptide is lost.
If NK cells cannot detect the MHC 1 peptide, it engages the cell and induces cell death via perforins and cytotoxic granules
State some diseases that are associated with defects in Innate Immunity?
Complement – core defects (e.g. C3) linked to development of autoimmune diseases such as lupus
Complement – non-core defects linked to suseptibility to specific types of pathogens such as Neisseria
Macrophage deficiencies - Chronic granulomatous disease (CGD); No oxidative burst for bacterial killing
Macrophage deficiencies – IRF8 mutations linked to susceptibility to TB
Aicardi–Goutières syndrome associated with constitutive production of inflammatory cytokines
Lack of interferon-responsiveness – sensitivity to viral infection (e.g. measles)
