Please enable JavaScript.
Coggle requires JavaScript to display documents.
Innate Immunity and Complement (1.18.3.11) - Coggle Diagram
Innate Immunity and Complement (1.18.3.11)
Non- Cellular Components of the Innate Immune System
Lactoferrin
Mainly produced by epithelial cells of mucus membranes and neutrophils
Iron binding protein- particularly abundant in milk
Antibacterial
direct damage to bacterial membrane
deprives bacteria of iron- essential for bacterial growth
Acute Phase Proteins
Complement Cytokines
The complement system
30 Plasma proteins
Circulate in blood as inactive precursors
Activated in response to infection - cascade reaction: rapid amplification of activated proteins
Main roles
Inflammation: by stimulation of histamine release from mast cells (mast cell degranulation)
Chemotactic agents: recruitments of neutrophils and macrophages to site of infection
Cell lysis: through pore formation in cell membranes including bacteria
Opsonisation: coating of surface area leading to increased phagocytosis
3 Types of complement
Classical pathway
antibody dependant
Antigen-antibody complexes = complement activation
Triggers killing of pathogens and recruitment of inflammatory cells
Linking innate and adaptive immunity
Alternative pathway
Pathogen surfaces = complement activation
Lectin pathway
Lectin binding to pathogen surfaces= complement action
The Central Role of C3
Highest concentration of serum complement proteins in any species we can measure
C3 breaks down naturally into C3a and C3b
C3b
can bind microbes to the surface via carbohydrates
Can bind Factor H on host cells taking C3b out of circulatiom
Function
binds with C4 to microbial surface and tag it for phagocytosis
Complement receptors expressed on multiple types of phagocytes
C3a
acts as a anaphylotoxin or chemoattractant
Role in triggering inflammation
C3a, C4a and C5a are anaphylotoxins
change smooth muscle
Increase vasodilation
activates mast cells or neutrophils
Increases fluid in the tissue and speeds up lymph flow
Made by macrophages of the liver
membrane attack complexes
central effector mechanism
endpoint of all three pathways
forms a pore in the membrane
opens the bacterial cell
ctyosol
dramatic loss of cellular homeostasis
disrupts signalling
penetration of host lysozyme/proteases
complement components may form a membrane attack complex to punch holes in microbes
Canine C3 deficiency
Increased suscebtibility to infection
Inherited disorder
Homozygote dogs have no serum C3 - it is 126mg/mL in normal animals
Have trouble making antibodies against certain pathogens
Leads to increased pyometra, pneumonia, sepsis etc, due to the lack of antibodies.
Porcine Factor H deficiency
Inherited recessive autosomal disease
Facor H stops C3b activation
Carries born normal and up to a few weeks they stay normal. but after that production problems start occuring.
In animals, C3 accumulates on surface and basal membranes of kidneys as there is no serum C3 here.
The animal will eventually die of anaemia and renal failure
summary
complement inactive precursor are found in normal serum
complement system is activated by two innate pathways - alternative & lectin, and one acquired pathways - classical
all pathways converge on C3
complement components esp. C3b opsonize bacteria
complement system plays a key role in triggering inflammation
deficiencies in some complement components lead to increased susceptibility to infection
complement components may form a MAC to punch holes in microbes