Review of the Innate Immune System Flashcards
Why do we need an innate immune response?
Adaptive Immune Response is too slow to protect us from some new pathogens
Describe the speed of action of the adaptive immune response
Cytotoxic T cells activated for new infection after 3-4 days and antibodies after 5 days
Sufficient for slow growing bacteria (may take upto 6 days) before they start replicating at a dangerous level by which time the specific immune response will be under way
Why is adaptive immunity not sufficient for Influenza?
Influenza replicates every 4hrs - produce thousands of products rapidly
- requires innate immunity
Which type of immunity is required to resolve infections?
Resolution of infection requires both adaptive and innate immune responses
How does adaptive immunity work?
Adaptive involves very specific recognition of infectious agent (usually sees a protein = antigen)
Outline the specificity of innate immunity
Involves recognition of broadly conserved features of different classes of pathogens
- no specific antigen recognition
What are the components of innate immunity?
- Phagocytosis
- Inflammatory Response
- Cytokines, Interferons + Antimicrobial peptides (AMPs)
- Complement
- Intrinsic Defences – “the hostile cell”
- NK cells
Which immune cells carry out phagocytosis?
Carried out in vertebrates by Dendritic cells, macrophages and neutrophils
What is the role of phagocytosis?
Phagocytosis clears pathogens but also presents peptides on MHCs – this promotes development or reactivation of the adaptive immune response
How do macrophages carry out phagocytosis?
Material is destroyed in lysosomes
How do macrophages trigger an inflammatory response?
- Captured material triggers macrophage activation
- Activated macrophages produce cytokines and chemokines
- Stimulates both innate + adaptive immune responses
- Inflammatory response triggered; can promote a local antimicrobial state
What is an inflammatory response?
Generic defence mechanism
- Localises + eliminates injurious agents
- Removes damaged tissue components
What changes occur during an inflammatory response
- Enhanced permeability and extravasation
- Neutrophil recruitment
- Enhanced cell adhesion
- Enhance clotting
What 2 hormones do activated macrophages release?
Infected macrophage sends out 2 types of polypeptide hormones - cytokines and chemokines
How does the bloodstream aid inflammatory response?
Bloodstream supplies neutrophils and macrophages as well as normal RBCs etc.
Allows breakdown of capillary wall to allow more immune cells to get in to help break down pathogens
What are chemokines and cytokines?
Glycoprotein hormones that affect the immune response
What is the role of cytokines?
Act to modify the behaviour of cells in the immune response
Interleukins (eg. IL-1)
What is the role of chemokines?
Act as chemotactic factors
i.e. create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection
How are pathogens recognised by phagocytes?
- Detecting phosphatidylserine on exterior membrane surface (cells undergoing apoptosis)
- By Scavenger receptors
- By some Toll-Like Receptors (TLRs)
- By passive sampling
How do phagocytes recognise pathogenic patterns?
Pattern recognition is through Pathogen-associated Molecular Patterns (PAMPs)
Why is PAMP recognition a good way to recognise pathogens?
PAMP molecules present on pathogens only; not on host cells
Essential for survival of pathogens
Invariant structures shared by entire class of pathogens
Outline common PAMPs
- Gram-ve bacteria; LPSs
- Gram+ve bacteria; teichoic acid, lipoteichoic acid, peptidoglycans
- Bacterial flagellin
- Abnormal protein glycosylation
- Abnormal nucleic acids - viruses
What are PRRs?
Pattern Recognition Receptors are host factors that specifically recognise a particular type of PAMP
How are PRRs encoded?
They are germ-line encoded
What are the the different functional classes of PRRs?
There are several classes of PRR, but functionally they are either:
- Extracellular
- Intracellular
- Secreted
How do extracellular PRRs work?
Recognise PAMPs outside of a cell and trigger a coordinated response to the pathogen
How do intracellular PRRs recognise PAMPs?
Recognise PAMPs inside a cell and act to coordinate a response to the pathogen
How do secreted PRRs recognise PAMPs?
They act to tag circulating pathogens for elimination
How do Toll-like receptors recognise pathogens?
Toll-like receptors recognise pathogens and flag them for cytokine and inflammatory cell release
Where are NOD-like / RIG-like receptors found?
NOD-like and RIG-like receptors are cytoplasmic
What is the complement system?
Effector mechanism for development of adaptive response
An adaptation grafted onto the original purposes of complement as a vital part of innate immunity
How are complement proteins activated?
Complement proteins act as secreted PRRs and are activated by a range of PAMPs
Can also be activated by “altered self”
What are interferons?
Secreted factors (type I and type III)
Induced by viral infection
Offer cross-protection
Outline the interferon system
- During primary infection IFN produced and secreted
- IFN binds to neighbouring cells that has receptors for it
- Antiviral state triggered
- Virus ineffective in infecting other cells when undergoes apoptosis
- IFN causes expression of antiviral genes
How do interferons produce an antiviral state?
IFN arrives from infected cell, binding a receptor and sets up a signal transduction system causing lots of gene expression
Which protein is upregulated by IFNs?
Protein Kinase R (PKRI) not expressed at high levels but is upregulated by IFN (at protein level) Requires cofactor (dsDNA) to activate it.
Describe the effect of virus on IFN upregulated PKR
If virus gets in and replicates, it produces lots of dsDNA that is now able to activate PKRa - immediately switches off ribosome function
What are AMPs?
Antimicrobial Peptides (AMPs) E.g. Defensins Secreted short peptides (18-45 amino acids)
How do AMPs work?
Usually work by disrupting cell wall leading to lysis
Some are induced by bacterial infection
Offer broad protection
Outline the intrinsic defences of cells
The hostile cell contains biochemical mechanisms that discourage viral replication
- Apoptosis
- Restriction factors / Intrinsic Immunity
- Epigenetic silencing
- RNA silencing
- Autophagy/Xenophagy
What are NK cells?
Natural Killer (NK) Cells
> large granular lymphocytes
4% white blood cells
Lymphocyte-like but larger with granular cytoplasm
What is the role of NK cells
Kill certain tumour & virally infected cells
Target cell destruction is
caused by cytotoxic molecules called granzymes & perforins
How are NK cells activated?
Natural Killer (NK) cells are activated by loss-of-self
What effect do NK cells have on infected cells?
NK cells possess the ability to recognise and lyse virally infected cells and certain tumour cells
How do NK cells obtain selectivity for infected cells?
Selectivity is conferred by LOSS of “self” MHC molecules on target cell surfaces, AND up-regulation of activating ligands
