Core Concepts-L3-Complement and Coagulation

what is complement?

• set of proteins found in the blood serum which is made by the liver

• help antibodies by tagging microbes for destruction and help neutralise them and punch holes in microbial membranes

what is opsonisation and name an example

• complement proteins like C3b stick to microbe surfaces and flag them for phagocytes

• phagocytes have complement receptors like CR1 that bind C3b

what do antibodies do?

1. neutralise- bind directly

2. trigger opsonisation- antibody Fc can be recognised by phagocytes 

3. work with T cell subsets- Th17 recruit neutrophils and induce AMPs and CD8 T

name the complement outcomes from the pathway

1. C3b- used for opsonisation(CR1 receptors)

2. C5b- recruits C6-C9. C9 polymerises and forms a pore in membranes and lyses it

3. C3a and C5a- potent inflammatory mediators and cause vasodilation, permeability and cel recruitment

where is complement made?

• made in the liver during the acute phase

• during infection IL-6 cytokines are made- makes acute phase proteins

name some acute phase proteins

1. CRP- c reactive protein- complement activation

2. serum amyloid A- chemotaxis and recruit immune

3. mannose binding lectin- helps with lectin complement pathway activation

describe the classical pathway

• antibody mediated- triggered when IgG Fc portion binds to Fc receptor and triggers phagocytosis

• can interact with complement proteins and trigger C3 activation and cascade to drive inflammation (make C3b which opsonises)

describe the lectin pathway

• triggered when the mannose binding lectin binds mannose or sugar patterns on microbial surfaces

• interacts with C4/C2 to activate C3 convertase

• which targets formation of phagocytosis and lysis and inflammation

uses soluble pattern recognition receptors

describe the alternative pathway

• C3b from the classical or lectin pathways can bind to microbial surfaces directly and recruit Factor B which is cleaved by Factor D- forms an alternative C3 convertase

• C3b binds to exposed thiol groups on microbes and can interact with CR1 receptors

causes amplification: C3 converses cleaves more C3, more C3b made and more opsonisation and can produce C5a

what roles do C3a and C5a play in complement mediated inflammation?

induce inflammation via 2 pathways

1. endothelial cells- target local blood vessels at the site of infections. binds to receptors and up regulates adhesion molecules and down regulation of tight junctions. humeral proteins leaks into tissues which brings opsonins and antibodies to the site of infections.

2. mast cells- patrolling or recruited. have histamine rich granules and are important for vascular changes and inflammation. degranulations happens by 1) innate pathway and C3a binds mast cell receptors and triggers release of granules 2)adaptive/allergin pathway- antigens cross link IgE bound to mast cells

what are the things that cause inflammation?

1. complement proteins

2. cytokines

3. complement C5a

4. peptide hormones

5. lipid mediators like prostaglandins