Defence Against Extracellular Pathogens Flashcards
How do antibodies interact with defence components?
IgM and IgG activate the complement proteins
IgG and IgA interact with phagocytes via FcgR and FcgA
IgG interacts with NK via FcgR
IgE interacts with mast cells via FceR
What is the complement?
A collection of 30 proteins that complement the action of antibodies
Present in circulation inactivated and activates only when body is infected
What are the roles of the complement proteins?
Activation enzymes
Immune Defence molecules
Control proteins
What are the complement proteins pathways?
Classical pathway
Alternative pathway
MB lectin pathway
Briefly explain the MB lectin and classical pathway until C5 convertase production
The classical pathway needs presence of Igs bound to microbe in other to function. At least 2 tulip heads of C1q bind to Fc region of Ig therefore activating C1r and C1s which split C4 and C2 into C4a, C4b and C2a, C2b. The C4bC2a stick together to form the C3 convertase of this pathway which is C4b2a
The MB lectin pathway do not require antibodies. The MBL is composed of 6 units which bind to mannose head of microbial carbohydrates (behave like PRR) therefore activating MASP1 and 2 which split C4 and C2 to form C3 convertase.
The C3 convertase splits C3 into C3a (opsonisation) and C3b (mast cell activation and neutrophil recruitment)
Briefly explain the alternative pathway
Most ancient pathway, do not require antibodies nad interact directly with microbial surface. It uses the complement proteins to trigger its own activation.
It’s C3 convertase is C3bBbP. C3b comes form tick over pathway, tissue protease constantly split C3 into C3a and b allowing creation of C3b to feed this pathway. However, C3b is very unstable and need to bind to microbial surface to stabilise itself. (Ht3n cleavage of factor B and attachment of P)
What happen after C3 convertase formation?
C3 convertase in all the pathway bind to C3b to form C5 convertase which split C5 into C5a (mast cell activation) and C5b (starting material for membrane attack complex).
C5b stick to lipid membrane microbe, followed by C6 and C7. C8 then come anchor itself in lipid membrane and 12-14 molecules of C9 form a tubular structure in membrane therefore punching a hole in it.
How are phagocytes helped in their function?
Bacteria induce macrophages to produce IL6 which act in liver to secreted acute phase proteins ( MBL and CRP). They coat the surface of microbes to make them more tasty to phagocytes.
CRP binds to phosphorylcholine on bacterial surface to opsonise it
MBL binds to mannose residues on bacterial surfaces
Also through FCR and CR interacting with antibodies and C3b respectively, microbe gets more attached to phagocytes and facilitate phagocytosis
Explain extracellular digestion
When parasite is too big to be engulfed, eosinophils upon binding (via FCR and CR) release digestive proteins that externally digest the parasites.
Usually higher level of IgE for parasite infection
What triggers mast cell activation?
Cross-linking or bridging of the surface IgE (Ag binding to at least 2 different copies of IgE)
C3a and C5a complement proteins also trigger mast cell activation
Release of inflammatory mediators. Some preformed: histamine,heparin and tryptase. Some newly formed ( arachidonic acid, LKT, PG and cytokines)
What are the steps of local inflammation?
Vasodilatation
Leukocytes adhesion molecules expressed by endothelium to allow slower mot of leukocytes
Increase in vascular permeability to allow them to go to site of infection
Chemotaxis of leukocytes
Immobilisation
What are the molecules produced in acute phase response?
IL1, IL6 and TNF
They induce symptoms such as fever (by acting on hypothalamus to raise body temperature), leucocytosis (by increasing release of leukocytes from bone marrow), Acute phase proteins release from liver (CRP)
Bring about all symptoms of infection (lowsiness, tiredness, feeling like shit etc….)
