Inflammation Flashcards
What do diseases which cause inflammation end in?
itis
How does inflammation help stop infection: Delivery system?
Deliver effector molecules, drugs and cells to infection site or injury
How does inflammation help stop infection: clotting
Induce local blood clotting
How does inflammation help stop infection: immune response?
stimulate adaptive immune response
How does inflammation help stop infection: repair?
Promote repair of injured tissue
What injuries do the host respond to e.g. catagory?
Infection
Trauma/overuse
Exposure to noxious chemicals or allergens
What are common signs of inflammation?
Redness
Swelling
Heat
Pain
Loss of function
What is the initial sign of inflammation?
vasodilation and nitric oxide flow
Where does nitric oxide flow and what does it do?
flow from arterioles into capillary beds close to the site of injury. This is responsible for the heat and redness
What does vasodilation do to blood flow?
blood rate to slow
What is margination?
Vasodilation causes blood rate to slow meaning the white blood cells can move towards the walls of the cell
What happens after margination of white blood cells to endothelial walls?
Chemical signals are released causing changes to endothelial wall
What do chemicals cause the cell wall to do?
causing them to contract and allow fluid into surrounding tissues causing swelling
What surface proteins are increased in the endothelial cells by chemical signals caused by margination?
selectin and ICAM
What does selectin bind to?
Selectins bind to glycoproteins on the surface of passingcells
What does ICAM bind to?
ICAM binds to integrin which is expressed on leukocytes
What does binding of selectin and ICAM do to leukocytes?
slowly roll along vessel wall as the binding is not strong
What binds to leukocytes to change the structure of integrin on them?
Chemokines
What does change of Integrin structure do to the leukocyte?
binds to ICAM strongly so stops rolling and flattens against cell wall
How does the leukocyte get through the cell wall after flattening and what is this called?
extending pseudoposa through the gaps and pull themselves through into the extravascular space – this is diapedesis
Once in the extravascular space how does the leukocytes get to the site of injury? (chemotaxis)
following a chemical gradient (C5A or the complement system)
is C5A high at site of injury?
yes
What does the leukocyte do at the site of injury?
clears or prevents infection by releasing cytokines or phagocytosing material
What is the key leukocyte here which acts through phagocytosis?
Neutrophils
What are inducers of inflammation? list :(
Cell lysis,
virulence factors (LPS, exotoxins ect.),
PAMPS,
cellular necrosis and release of intracellular contents, degradation of basement membrane
loss of epithelial/endothelial integrity
what does vasodilation lead to?
increased blood supply and increased vascular permeability (entry of plasma proteins)
When does loss of function occur?
if inflammation is severe
What are mast cells and what do they do?
release granulaes of inflammatory mediators
What do mononuclear phagocytes (macrophages) do?
Phagocytose and produce pro-inflammatory cytokines
What so neutrophils do?
Phagocytes which release proteases
What are main components of inflammatory response?
Fibroblasts, epithelial and endothelial cells
Platelets
NK cells
What are vasoactive inflammatory mediators?
Histamine, kinins
What are lipid inflammatory mediators?
Eicosanoids - Leuko tire service and prostaglandins
What are some protein inflammatory mediators?
Complement components and cytokines (TNF-alpha, IL-1, IL-6) and chemokines (IL-8)
How do mast cell’s activate and work?
IgE antibodies are inserted into the mast cells membrane and cross links of antibodies by antigens signal the release of inflammatory mediators.
What activates mass cells?
C3a and C5a, cytokines or direct mechanical damage
What do mast cells release?
TNF-alpha
What does the TNF-alpha secreted by mast cells do?
Activate macrophages, increase proteins which triggers clotting, endothelial cells increase adhering surface, induce IL-8, induce contraction and gap formation making it more permeable
What two molecules to mast cells secrete?
prostaglandins and leukotrienes
What enzyme converts prostaglandins from arachidonic acid?
COX1 and COX2
What do prostaglandins do?
Increase body temp and cause vasodilation
What molecule is a potent potentiators of the activity of histamine and kinins?
posteglandins
What enzyme drives the formation of Leukotrienes from arachidonic acid?
5-lipo-oxygenase
What do Leukotrienes do?
upregulate the expression of adhesion molecules on neutrophils, increase their toxic oxygen properties proliferation, cytokine release of macrophages, are chemotaxins factors for neutrophils and macrophages.
What do macrophages secrete?
TNF-alpha, IL-8, IL-6 and IL-1
What is IL-8?
chemotaxis agent
What does IL-1 and IL-6 help the macrophages do?
secrete IL-8 and upregulate cell adhesion molecules on the surface of the endothelial cells.
What are kinins derived from?
precursors proteins
what enzyme converts precursor proteins into kinins?
kallikrein
what triggers kallikrein to convert?
clotting cascade and tissue damage
What 2 molecules are made by Kallikrein from precursor protiens?
bradykinin and kalidin
What do bradykinin and kalidin do?
increase vascular permeability, dilate venules and cause contraction on smooth muscles in airways
What does bradykinn do specifically?
directly on pain nerve endings
What is ICAM1’s ligand?
LFA-1
What concentration gradient does neutrophils follow to the site of injury?
IL-8
What three ways does pain develop?
Inflammatory mediators affect nocioceptors, Bradykinin and exudation of plasma increases tissue pressure.
Why is it good you get a fever?
defenses work better, faster lymphocyte division, increases cell migration, inhibits microbial replication
What mediates the resolution of inflammation?
strict temporal and spatial synthesis
What is M1?
pro-inflammatory
What is M2?
anti-inflammatory
How do macrophages reduce actute inflammation?
they take on different phenotypes
How do neutrophils resolve inflammation?
apoptose
What are the sepcific molecules for resolution of inflammation?
lipoxins and resolvins
what secretes lipoxins and resolvins?
macrophages, neutrophils and structural cells
what needs to be reduced in inflammation?
diapedesis, neutrophil chemotaxis, production of pro-inflammatory cytokines and vascular permeability
what does the resolution mediator TGF-beta do?
mediates wound healing, angiogenesis, fibroblast proliferation, collagen synthesis and deposition, remodelling of ECM.
what is Efferocytosis?
Is the clearance of apoptotic cells by phagocytes.
What are the three signals neutraphils show?
find me - attract macrophages
Kepp-out - deter other neutrophils
Eat-me/do no eat-me - help phagocytes distinguish viable/apoptotic cells
genetic predisposition to developing these allergies
What does histamine secreted by mast cells
