Review of innate system Flashcards
What is the difference between innate and adaptive immunity with regards to specificity?
→ 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
How does pattern recognition occur within innate immunity systems?
Pattern recognition is through Pathogen-associated Molecular Patterns (PAMPs)
→ Molecules present only on pathogens and not on host cells
→ Essential for survival of pathogens
→ Invariant structures shared by entire class of pathogens
What are pattern recognition receptors? (PRRs)
→ 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:
- 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
What are the components to innate immunity?
→ The inflammatory response
1. Phagocytes
2. Monocytes/granulocytes/neutrophils
3. Complement
4. Cytokines, chemokines and anti-microbial peptides (AMPs)
5. Natural Killer cells
What is the inflammatory response?
→ 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
What 3 distinct roles do macrophages and dendritic cells have in immunity?
- 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
- 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 eat?
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
What is the complement system?
→ 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:
1. Opsonisation
2. Recruitment of phagocytic cells, vasoactive function
3. Punches holes in target membranes (MAC)
→ The complement system is an evolutionarily ancient system, which predates the development of the adaptive response
→ The use as an effector mechanism for the latter is therefore an adaptation grafted onto the original purposes of complement as a vital part of innate immunity
→ 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 are cytokines and chemokines?
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?
Interferons; the main anti-viral cytokines
→ Secreted factors (type I and type III)
→ Induced by viral infection
→ Offer cross-protection
→ Widely distributed in evolution, from fish upwards, but species-specific
→ No antibodies are involved so the interferon system is not related to prior infection etc
→ So if you have a cell that is infected by a virus, that virus replicates and attempts to spread, the viral progeny tries to infect new cells.
→ If the interferon system is working properly, when initial cell that has been infected dies, it releases interferons, which bind to receptors in neighbouring cells, triggering the turn on of transcription and translation of anti-viral genes so in next cell, these would stop virus replicating in more cells
(so viral and cellular proteins are not translated to avid virus being replicated in more cells)
What are anti-microbial peptides(AMPs eg defensins) and what do they do?
→ 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 do natural killer cells do? (NKs)
How are they activated?
→ 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
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
MHC class 1 is on most cells in your body, NK cells have a mechanism for recognising MHC class 1 cells, if they detect MHC Class 1, they do nothing however if they dont sense these MHC class 1, they infect cell with proteases causing cell death
What diseases are associated with inherited 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 susceptibility 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)
