Theme 2- innate 2c Flashcards
what are the 4 interconnected enzyme cascades
- Kinin
- Clotting
- Fibrinolytic
- Complement
describe the kinin system
what does it form
enzyme cascade
- HAGEMAN FACTOR activated following tissue injury
- Activates pre-kallikrein to form kallikrein which cleaves kininogen to form BRADYKININ
BRADYKININ- basic protein that inc VASCULAR PERMEABILITY, causes VASODILATION, PAIN and CONTRACTION of smooth muscle
describe the CLOTTING system
what does it form
enzyme cascade
- HAGEMAN factor activated after tissue injury
- activated by DAMAGE TO BLOOD VESSELS which causes high amounts of THROMBIN
- Thrombin then acts on SOLUBLE FIBRINOGEN to inc vascular permeability and neutrophil chemotaxis
describe the FIBRINOLYTIC system
what does it form
what does it activate
- enzyme cascade
- triggered by HAGEMAN factor and endothelial damage
- REMOVES clots
- produces PLASMIN
- PLASMIN = potent proteolytic enzyme that breaks down clots
- contributes further to inflammation by activating CLASSICAL COMPLEMENT PATHWAY
- blocks leakage and repair
what is complement
what are the 3 activation pathways
what are the 3 major outcomes
group of serum and cell surface proteins present as INACTIVE precursors in blood
- if activated, form an enzymatic cascade
Pathways: CLASSICAL, LECTIN, ALTERNATIVE
Outcomes:
1 OPSONISE particles to inc phagocytosis
2 ACTIVATE inflammation and immune response
3 LYSE target cells and microorganisms
what is complement factor C3b
important in
- important in the COMPLEMENT PATHWAY
- attaches to PATHOGENS (opsonisation) leading to INC PHAGOCYTOSIS via COMPLEMENT RECEPTORS on phagocytosis
- leads to formation of MEMBRANE ATTACK COMPLEX (MAC)
what is MAC
membrane attack complex
describe the classical pathway
- ANTIBODY (IgG/IgM) or CRP binds target antigen/PAMP/DAMP on cell surface
- attracts and bind C1 activating LATENT PROTEOLYTIC ACTIVITY
- C1 attracts C4 which is cleved to form C4b
- C4a released
- C4b transfers to the SURFACE of microbe/cell
- in prescence of Mg2+, C2 binds C4b and is cleaved by C1s and C2b released
- C3 convertase remains on cell surface
- a lot of C3 is attracted and binds to C3 convertase and is cleaved by it (AMPLIFICATION)
- C3a is released and C3b bind to complex forming C5 CONVERTASE
- C5 is recruited, C5 cleaved to C5b forms first part of MAC
- C6, C7, C8 and polyC9 attach, MAC forms
what is the alternate pathway
SPONTANEOUS cleavage of C3 to C3a and C3b
Mech:
- C3b binds to microbial cell surface
- C3b associates with factor B in the prescence of Mg2+ and is CLEAVED by factor D
- forms C3 convertase, which is stabilised by PROPERDIN and can amplify C3 cleavage
- this attracts more C3 O AMPLIFICATION
what happens in the lectin pathway
(MBL) mannose binding lectin is an OPSONIN, it attracts SERINE PROTEASES
- attracts C4
what is the role of C3a and C5a
inflammatory
- stimulate respiratory burst in NEUTROPHILS
- C3a (EOSINOPHILS) and C5a (NEUTROPHILS) can act as CHEMOKINES
what do Anaphylotoxins do
trigger mediator release by MAST CELLS
cell mediated (innate) immunity uses what
- innate Lymphoid Cells (including Natural Killer cells)
- Natural Killer T cells
- gammadelta T- cells
- B1 B cells
As well as Macrophages,Neutrophils, Eosinophils, Basophils and Mast cells
what is an ILC
innate lymphoid cell
describe ILCs and NK cells
what do they secrete
found where
what are the 3 groups
- no TCR
- most have no PRRs
- NK cells have activatory and inhibitory receptors
- activated by local mediators
- secrete cytokines
- found in skin and mucosa during innate immune reactions
3 groups:
ILC1 and NKs
ILC2
ILC3
what does the ILC1 and NK group of ILCs do
- secrete PRO-INFLAMMATORY TH1-like cytokines
ILC1- extracellular pathogen
NK- intracellular and tumour
what does the ILC2 do
immunity to worms and wound healing
secrete TH2 that activates eosinophils
what does the ILC3 do
lymphoid tissue development
intestinal health, immunity to extracellular bacteria and fungi, secrete regulatory cytokines
what do NK cells do
Have a range of surface activatory/inhibitory molecules to recognise infected cells (no MHC required)•Immunity to intracellular pathogens by killing infected target cells and able to destroy a range tumour cells•3 mechanisms of target cell killing
what are the NK cell mech of cell killing
(1) Kill target cells using perforins and granzymes in similarmechanisms to Cytotoxic T cells by inducing pore formation intarget cell membranes - necrosis and apoptosis
(2) Also express Fas ligand on surface, so can induce apoptosis
(3) Antibody Dependent Cellular Cytotoxicity killing relies on Ab binding to surface of cells – often virally infected or tumour cells – necrosis
what do NKT cells do
bridge bwteen innate and adaptive immunity
- have TCR but recognise antigen peptides presented by MHC
- kill infected targets mainly via apoptosis via Fas : Fas ligand
Make lots of cytokines (signalling/activating/growth factors) such as IL-2 and TNFa
- useful in low dose bacterial infections and against self tumour cells
what do eosinophils granules cont
Granules contain Cationic peptides, Major
basic protein and Peroxidase all of which
can be released directly onto the surface
of extracellular pathogens (worms)
what do neutrophil granules cont
Primary (azurophilic) granules: Lysosome & myeloperoxidase
Secondary (specific granules): Defensins, Lactoferrin
Higher production of RNI than other phagocytes
NETosis
describe g/d T cells
Slightly higher numbers in the mucosal associated lymphoid tissue and skin when compared to peripheral blood
Important in gut antigen recognition of bacterial antigens (particularly lipids) through non MHC restricted means (CD1)
Express Toll-like receptors and may phagocytose and process and present antigens to a/b T cells
Also express some NK cell activatory
receptors…….able to kill target cells
(via release of perforin/granzyme)
Over represented in some veterinary
species (such as pigs)
Emerging role in anti-tumour activity
= potential target for cancer
immunotherapy
what do B1 cells do
Sub group of B cells expressing CD5 High frequency in pleural and peritoneal cavity Mainly produce low affinity antibody (IgM) mostly against bacterial antigens (particularly carbohydrates) and are called natural antibodies No T cell help required Very little memory Important in fetal and neonate immunology hence part of innate immunity
