Review of the innate immune system Flashcards
What does a resolution of infection require?
• Resolution of infection requires both adaptive and innate immune responses
What does adaptive immunity involve?
Involves very specific recognition of infectious agent (usually sees a protein = antigen)
What is there no specific recognition in innate immunity and what does it involve?
• Innate immunity – no specific antigen recognition
§ Innate involves recognition of broadly conserved features of different classes of pathogens
What are the components of the innate immune system?
• Phagocytosis
• The Inflammatory Response
• Cytokines, Interferons and Antimicrobial peptides (AMPs)
• Complement
○ Enhances ability of immune system to work
• Intrinsic Defences – “the hostile cell”
• NK cells
What is phagocytosis carried out by in vertebrates?
Carried out in vertebrates by dendritic cells, macrophages and neutrophils
What are macrophages never involved in?
○ Macrophages are never involved in triggering new immune response but can reactivate memory
Where are macrophages found?
Macrophages are tissue-resident
What cells do most of the phagocytosing?
Neutrophils do most of the phagocytosing
What does phagocytosis clear and present and what does this promote?
• Phagocytosis clears pathogens but also presents peptides on MHCs – this promotes development or reactivation of the adaptive immune response
§ Selects and stimulates division of naïve T and B cells
What are the 2 distinct roles of macrophages in innate immunity?
- Phagocytosis; material is destroyed in lysosomes
2. Captured material can trigger macrophage activation
What do activated macrophages produce and what does this trigger?
○ 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
What is the inflammatory response?
A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components
What does the inflammatory response localise?
Localizes the infection
What does the inflammatory response remove and repair?
- Removes infectious agent i.e. by phagocytosis
* Repairs tissue damage
What does the inflammatory response enhance?
Enhanced permeability, extravasation, cell adhesion and clotting
What does the inflammatory response recruit?
• Neutrophil recruitment
What are cytokines and chemokines?
Glycoprotein hormones that affect the immune response
What do cytokines act as?
○ Act as a very specific signal for a component of the immune system
What does the role of cytokines help?
○ Very defined narrow role that helps the immune system
What do cytokines act to modify?
○ Act to modify the behaviour of cells in the immune response
What are most of the cytokines called?
○ Most of these are called interleukins (eg. IL-1)
Where are chemokines secreted?
○ Secreted at site of infection
What do chemokines act as and create?
○ Act as chemotactic factors
§ Create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection
How do pathogens recognise material to ingest?
○ By detecting phosphatidylserine on exterior membrane surface (cells undergoing apoptosis)
○ By Scavenger receptors
○ By some Toll-Like Receptors (TLRs)
○ By passive sampling
What can passive sampling be done by?
§ Done by neurophils
Why does passive sampling need to be controlled?
§ Can do a lot of tissue damage so need to be controlled
What are PAMPs and where they present?
• Molecules present only on pathogens and not on host cells
What are PAMPs essential for?
• Essential for survival of pathogens
What are examples of 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
What are PRRs?
• Host factors that specifically recognise a particular type of PAMP
What do extracellular PRRs do?
they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen
What do intracellular PRRs do?
they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen
What do secreted PRRs do?
they act to tag circulating pathogens for elimination
What is the complement system originally described as?
Originally described as a heat-sensitive component of serum that could augment the ability of antibodies to inactivate antigen
What does the complement system lead to and how?
○ Opsonisation
§ Complement gets recruited and forms a hard shell complement protein around the pathogen
What does opsonization make harder?
§ Opsonisation makes it hard for the pathogen to exert its effects as it cannot bind to its receptor
What do complement proteins act as and what can they be activated by?
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”
Classical pathway of complement system
○ Works through antigen-antibody pathway
○ Triggering protein C1Q in classical pathway and this recognizes polysaccharides
Lectin pathway of complement system
○ There to recognise abnormal glycosylation of proteins
○ Any abnormally glycosylated pathogen will attract the lectin pathway of complement system
Alternative pathway of complement system
○ Any pathogen surface which is not of host origin
What are interferons?
Secreted factors (type I and type III)
What are interferons induced by?
Induced by viral infection
What are interferons secreted by?
Secreted by proteins
How does the interferon system work?
§ Interferon is produced during primary infection
§ Interferon binds to neighbouring cells that have the receptor for it
§ Triggers antiviral state in neighbouring cells
What are defensins?
- Anti-microbial peptides
- Secreted short pepitdes about 18-45 amino acids long
How do defensins work?
• Usually work by disrupting cell wall leading to lysis
What are defensins induced by?
• Some are induced by bacterial infection
What are example of intrinsic defences?
○ Apoptosis ○ Restriction factors/Intrinsic Immunity ○ Epigenetic silencing ○ RNA silencing ○ Autophagy/Xenophagy
What are natural killer cells?
Large granular lymphocytes
What percentage of WBC’s are natural killer cells
• 4% white blood cells
What do natural killer cells kill?
• Kill certain tumour & virally infected cells
What do natural killer cells target?
• Target cell destruction is caused by cytotoxic molecules called granzymes & perforins
What are natural killer cells activated by?
• Activated by loss-of-self
What ability do natural killer cells possess?
• NK cells possess the ability to recognise and lyse virally infected cells and certain tumour cells.
Why do natural killer cells not kill uninfected cells?
• NK cells do not kill uninfected cells because they recognize the MHC-peptide complex as well as the fact that there is no activating ligand
§ This is an inhibitory signal so stops NK from targeting healthy/unifected cells
Why do pathogens try and downregulate MHC class 1 and what do the natural killer cells do in response?
• Pathogens try and downregulate MHC class I because if it is downregulated, the antigens will not be presented § NK cells however, detect the absence of MHC and as there is no inhibitory signal, they lyse the cells by injecting perforins
INNATE VS ADAPTIVE
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