Theme 2- innate 2c

Question 1

what are the 4 interconnected enzyme cascades

Answer 1

• Kinin
• Clotting
• Fibrinolytic
• Complement

Question 2

describe the kinin system

what does it form

Answer 2

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

Question 3

describe the CLOTTING system

what does it form

Answer 3

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

Question 4

describe the FIBRINOLYTIC system
what does it form

what does it activate

Answer 4

• 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

Question 5

what is complement
what are the 3 activation pathways
what are the 3 major outcomes

Answer 5

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

Question 6

what is complement factor C3b

important in

Answer 6

• 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)

Question 7

what is MAC

Answer 7

membrane attack complex

Question 8

describe the classical pathway

Answer 8

• 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

Question 9

what is the alternate pathway

Answer 9

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

Question 10

what happens in the lectin pathway

Answer 10

(MBL) mannose binding lectin is an OPSONIN, it attracts SERINE PROTEASES
- attracts C4

Question 11

what is the role of C3a and C5a

Answer 11

inflammatory

• stimulate respiratory burst in NEUTROPHILS
• C3a (EOSINOPHILS) and C5a (NEUTROPHILS) can act as CHEMOKINES

Question 12

what do Anaphylotoxins do

Answer 12

trigger mediator release by MAST CELLS

Question 13

cell mediated (innate) immunity uses what

Answer 13

• 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

Question 14

what is an ILC

Answer 14

innate lymphoid cell

Question 15

describe ILCs and NK cells
what do they secrete
found where

what are the 3 groups

Answer 15

• 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

Question 16

what does the ILC1 and NK group of ILCs do

Answer 16

• secrete PRO-INFLAMMATORY TH1-like cytokines
  ILC1- extracellular pathogen
  NK- intracellular and tumour

Question 17

what does the ILC2 do

Answer 17

immunity to worms and wound healing

secrete TH2 that activates eosinophils

Question 18

what does the ILC3 do

Answer 18

lymphoid tissue development

intestinal health, immunity to extracellular bacteria and fungi, secrete regulatory cytokines

Question 19

what do NK cells do

Answer 19

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

Question 20

what are the NK cell mech of cell killing

Answer 20

(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

Question 21

what do NKT cells do

Answer 21

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

Question 22

what do eosinophils granules cont

Answer 22

Granules contain Cationic peptides, Major
basic protein and Peroxidase all of which
can be released directly onto the surface
of extracellular pathogens (worms)

Question 23

what do neutrophil granules cont

Answer 23

Primary (azurophilic) granules: Lysosome & myeloperoxidase
Secondary (specific granules): Defensins, Lactoferrin
Higher production of RNI than other phagocytes
NETosis

Question 24

describe g/d T cells

Answer 24

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

Question 25

what do B1 cells do

Answer 25

``` 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 ```