Review of the innate Immune system Flashcards
Why do we need the innate system when we have the adaptive immune response for an infection?
- Adaptive Immune Response (antibodies + T cells) are too slow to protect us from some new pathogens
- Especially for infections which have a high replication rate
- So innate provides first line of defence to keep infection under control until antibodies and T cells kick in
- Resolution of infection requires both adaptive and innate immune responses
State the key difference between adaptive and innate immunity?
- Adaptive immunity - involves very specific recognition of a particular infectious agent (usually sees a protein = antigen)
- Innate immunity - no specific antigen recognition + involves recognition of broadly conserved features of different classes of pathogens (PAMPS)
Pattern recognition of pathogens
What molecules does pattern recognition of pathogens occur by and describe it?
- 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
State examples of PAMPs for G -ve, G+ve, bacteria, and viruses?
- 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 pattern recognition receptors (PRs)?
- Host factors that specifically recognise a particular type of PAMP
- They are germ-line encoded: These receptors evolved to recognize conserved products of microbial metabolism produced by microbial pathogens,
State the 3 functional classes of PR’s
- Extracellular: They recognise PAMPs outside of a cell and trigger a coordinated 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
Components of the innate system
State the 5 key components of innate immunity?
- The inflammatory response
- Phagocytes: Monocytes/granulocytes/neutrophils
- Complement
- Cytokines, chemokines and anti-microbial peptides (AMPs)
- Natural Killer cells
- They’re all related as they all trigger each other
Describe the inflammatory response and it’s effects
- A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components
- Effects:
- Enhanced permeability and extravasation: Permeability, so cells can get to site of infection. Extravasation = cells from blood to tissue
- Neutrophil recruitment
- Enhanced cell adhesion
- Enhance clotting
How is the inflammatory response triggered?
Triggered by the release of pro-inflammatory cytokines and chemokines at the site of infection
How do phagocytes distingiush between recognising what to target and how to know when they are infected?
- Phagocytes have to be able to recognise what to eat, but they need know to as well 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 (PRRs)
State the type of phagocytes that can carry out phagocytosis in multicellular animals?
- Dendritic cells, macrophages and neutrophils
- Considered as professional phagocytes
State the 3 distinct roles of macrophages and dendritic cells 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 (more for D cell)
- The major histocompatibility complex (MHC) is a series of genes that code for cell surface proteins which control the adaptive immune response
State 5 ways pathogens use recognition for phagocytes to eat?
- By detecting phosphatidylserine on exterior membrane surface (cells undergoing apoptosis
- By detecting “atypical sugars” (e.g. mannose, fucose, beta-glucan) on cell surfaces
- By Scavenger receptors -> receptors that are non-self
- By “passive sampling”
- By detecting complement proteins bound to the pathogen surface
Describe what the complement system is used for
- 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)
- there are all an effector mechanism used as a vital part of innate system
Describe the role of complement proteins?
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”
