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)
In which type of immunity is there no specific recognition and what does it involve?
Innate immunity has no specific ANTIGEN recognition. Innate immunity involves the recognition of broadly conserved features of different classes of the pathogen.
What are the components of the innate immune system?
- Phagocytosis
- The inflammatory response
- Cytokines, interferons and antimicrobial peptides (AMPs)
- Complement (enhances the ability of the immune system to work)
- Intrinsic defences- “the hostile cell”
- NK cells
What cells in vertebrates carry on phagocytosis?
Phagocytosis is 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 and why is this critical for innate immunity?
Macrophages are tissue-resident or infiltrated immune cells critical for innate immunity and repair of damaged tissues.
What cells do most of the phagocytosing?
Neutrophils do most of the phagocytosing
What does phagocytosis clear and present and what does this in turn promote?
Phagocytosis clears the pathogen but also presents peptides on MHCs. This promotes development or reactivation of the adaptive immune response BY selecting and stimulating division of naive T and B cells,
What are the two 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, which can both stimulate the innate and adaptive immune responses. They can also stimulate the inflammatory response and can promote a local anti-microbial state
What is the inflammatory response?
A generic defence mechanism whose purpose is to localise and eliminate injurious agents and to remove damaged tissue components.
What does the inflammatory response localise?
Localises the infection
What does the inflammatory response remove and repair?
It removes infectious agents i.e. by phagocytosis and 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 is the role of cytokines?
A very defined narrow role that helps the immune system by modifying the behaviour of cells in the immune response
What are most of the cytokines called?
Majority of the cytokines are interleukins (e.g. IL-1)
Where are chemokines secreted?
They are secreted at the site of infection
What do chemokines act as and create?
They act as chemotactic factors and create concentration gradients which attract (or occasionally repel) specific cell types to production/infection
What are the 4 ways pathogens recognise material to ingest?
- By detecting phosphatidylserine on the exterior membrane surface (present on cells undergoing apoptosis)
- By scavenger receptors
- By some Toll0like receptors (TLRs)
- By passive sampling carried out by neutrophils
What carries out passive sampling?
passive sampling is carried out by neutrophils
Why does passive sampling need to be controlled?
Can do a lot of damage so need to be controlled?
What are PAMPs and where are they present?
Molecules/markers present only on pathogens and not on host cells
What are PAMPs essential for?
Essential for the survival of the pathogen
What are examples of PAMPs?
- Gram-negative bacteria; Lipopolysaccharides (LPSs) found on the outer membrane
- Gram positives bacteria; teichoic acid, lipoteichoic acid and peptidoglycan found in the outer membrane
- Bacterial flagellin
- Abnormal nucleic acids in viruses
What are PRRs?
Host factors that specifically recognise a particular type of PAMP
What does extracellular PRRS do?
They can recognise PAMPs outside a cell and trigger a coordinated response to the pathogen.
What does intracellular PRRS do?
They can recognise PAMPs inside a cell and trigger a coordinated response to the pathogen.
What does secreted PRRS do?
They act to tag on 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 antigens.
What does the complement system lead to and how?
Opsonisation, this is done by complement getting recruited and forming a hard shell complement protein around the pathogen
What are the effects of opsonisation on the pathogen?
Opsonisation makes it hard for the pathogen to exert its effects as it cannot bind to its receptor
What do complement proteins act 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 reactivated by “altered self”
Describe the classical pathway of the complement system?
- It works through the antigen-antibody pathway
- Triggering protein is C1Q in the classical pathway. This protein recognises polysaccharides
Describe the lectin pathway of the complement system?
There to recognise abnormal glycosylation of proteins. Any abnormally glycosylated pathogen will activate the lectin pathway of the complement system.
What will trigger the alternate pathway of the 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?
Viral infections
What are interferons 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?
They are antimicrobial peptides which are secreted. These are short peptides 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 defensins can be induced by bacterial infections
What are examples of intrinsic defences?
- Apoptosis
- Restrictopm factors/Intrinsic immunity
- Epigenetic silencing
- RNA silencing
- Autophagy/Xenophagy
What are NK cells?
Natural killer cells are large granular lymphocytes
What percentage of WBCs are NK cells?
4%
What do NK cells kill?
They kill certain tumour and amp; virally infected cells
What do NK cells target?
They target cell destruction caused by cytotoxic molecules called granzymes and amp perforins
What are NK cells activated by?
Activated by loss of self
What ability do NK cells possess?
The ability to recognise and lyse virally infected cells in certain tumour cells
Why do natural killer cells not kill healthy/uninfected cells?
- They recognise the MHC peptide complex on uninfected cells
- There would be no activating ligand present
This is an inhibitory signal to stop NK cells targeting healthy cells
Why do pathogens try and downregulated MHC class 1 and what do NK cells do in response
When downregulated the antigens will not be presented, however, NK cells are still able to kill such pathogens since they will recognise the absence of an inhibitory signal and lyse the cell by injecting perforins.
