Collection of proteins that are important in defence against microbes.
• partipate in cascade of enzymatic reactions which hugely amplifys
Three pathways: alternative, lectin - both of which are innate and classical which is
adaptive.
• Central component of both pathways is C3 plasma protein. when cleaved (C3b)
binds to microbes and recruits and activates downstream complement
proteins.
3 main functions:
1. opsoninasion and phagocytosis - C3b coats microbes which phagocytes can bind to.
2. inflammation - proteolytic fragment especially C5a and C3a are chemoattractants for leukocytes
(neutrophils and monocytes). also activates endothelial cells and mast cells
3. Cell lysis: complements can accumulate into polymeric protein complex (membrane attach
complex) that inserts itself into microbial cell membranes. this disrupts the permeability barrier
and cause osmotic lysis.
Recognising between self and other:
The innate immune system recognises structures that are shared by various microbes not present on
normal host cells.
The microbial molecules that stimulate the innate immunity are called PAMPs - pathogen-associated
moloecular patterns and those on damaged or necrotic host cells are DAMPs - damage-associated
molecular patterns.
Receptor types:
Pattern-recognition receptors recognise these PAMPs and DAMPs.
• These are encoded by inherited genes so are identical in all cells and they are non-clonally
distributed - this means that they all recognise the same PAMPs / DAMPs
• Estimated to be 100 receptors which can recognise 1000s of PAMPs / DAMPs
• Expressed on many immune cells and epithelial barriers on found on cell surface and
intracellularly
Toll-Like Receptors - TLRs
• in humans their are 10 TLR proteins which make up 9 TLR recpetors
• signals generated by TLRs activate transcription factors which stimulate expression of cytokines
and inflammatory and antiviral proteins.
NOD-Like Receptors - NLRs
• large family which sense DAMPs and PAMPs in cytosol of cells
• They initiate signalling events which promote inflammation
• NOD1 and NOD2 are expressed in many cells including mucosal barrier epithelial cells and
phagocytes. They recognise dipeptides from bacterial cell wall peptidoglycan.
Cytosolic RNA and DNA sensors
• molecules in the cytosol which recognise microbial RNA and DNA - generate signals that lead to
inflammatoru and antiviral cytokines.
• RIG - like receptors sense viral RNA - induce production of type 1 interferons
• Cytosolic DNA sensors - CDSs - recognise microbial dsDNA - again induce production of type 1
interferon
• Also have ability to recognise self DNA if it accumulates in the cytosol.
Reaction Types:
1. Inflammation
Acute inflammatory response: injury results in barrier break, activate sentinel cells, secetions of
infalmmatory mediators, increased vascular permeability, fluid and proteins enter tissues, start killing of
microbes, migration of leukocytes into tissues, phagocytosis of the microbes.
2. Anti-Viral defence
Defence against viruses which involved type 1 interferons and NK cells.
Type 1 interferons:
• intefere / inhibit viral replication and induce antiviral state - cells become resistant to the
infection
• mainly secreted by plasmacytois dendritic cells (pDCs) and their are multiple subtypes - IFNa
(alpha) and IFNb (beta)
• specifically pDCs secrete type 1 IFN in response to viral nucleic acid by TLRs
• Type 1IFN activates signalling pathways which inhibit viral replicaiton, destroy viral genomes
and increase ability of NK cells to eliminate the virally infected cells.
Innate Memory:
Has limited memory - responds in the same way to the same microbe - resets to baseline after each
encounter.
Some cells such as macrophages and NK cells may be altered by encounters and thus have some
capability to respond better next time.
