o Binds to pattern recognition receptor which causes immune cell activation and
pathogen elimination
Immediate response and non-highly specific
Cytokines and Chemokines
Cytokines initiate an inflammatory response on endothelium and activate an acute phase
response
Chemokines are secreted protein
Cytokine production is induced from binding of a ligand to receptor to stimulate signalling
pathways that activate transcription factors to allow gene expression
Acute Phase Response
The acute-phase response is the term given to the coordinated series of events that occur
non-specifically in response to infection, inflammation, or trauma
IL1 and IL6 enter liver hepatocytes and release acute phase proteins which activate
complement opsonisation
Complement System
3 Pathways for complement activation
o Classical
Antibody/antigen complexes
, o Lectin
Binding to mannose, glucose and lectin
o Alternative
C3b binds to pathogen
Opsonisation
o Enhancement of phagocytosis by coating with C3b to microbe
o Opsonisation of microbe by IgG
o Binding of opsonised microbes to phagocyte Fc receptors
o Fc receptor signals activate phagocyte and causes phagocytosis of microbe
Inflammation
o Increase of blood vessel permeability and chemotactic attraction of phagocytes
o Binding of C3b to microbe causes release of C3a, proteolysis of C5, releasing C5a
o Recruitment and activation of leukocytes by C6a and C3a
o Destruction of microbes by leukocytes
Cytolysis
o Bursting of microbe due to inflow of extracellular fluid through transmembrane
attack complex
o Binding of C3b to microbe activates complement components and forms membrane
attack complex
The complement system is regulated by a number of factors like factor I, H and C1 inhibitor
o A deficiency is C1 inhibitor causes an increase in classical pathway activation
Immune Recognition
The immune system recognises threats using microbial associated molecular patterns
The recognition of PAMPs is mediated by
o Toll like receptors
o NOD-like receptors
o RigI like receptors
o C-type lectin receptors
DAMPs (damage associated molecular patterns) are molecules released from necrotic
peptides
, Toll-Like Receptors
TLR5 recognises flagellin
TLR7 recognises viral ssRNA
TLR9 recognises CpG DNA
TLR4 recognises LPS
NFkB
NFkB regulates
o Inflammatory cytokines
o Chemokines
o Adhesion molecules
o Immune effector molecules
o Pro-survival molecules
Inflammation
In response to infection or injury, cells produce inflammatory mediators
o Inflammatory mediators act on blood vessels
o Immune cells and molecules in plasma enter the tissue
o Coagulation is initiated
o Inflammation switched off by anti-inflammatory mediators
Inflammation is regulated by
o Cytokines
o Receptor antagonists
o Lipids
o Drugs like NSAIDs
Inflammation is driven by the inflammasome
o PAMPs and DAMPs activate caspase 1 which activates IL1 beta and IL18 which drives
inflammation
Inflammation causes
o Vasodilation
Increases delivery, temperature and removes toxins
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