@source: http://www.cram.

com/flashcards/gsse-pathology-inflammation-7714832
@title: GSSE pathology inflammation
@subject: inflammation
@language-hint:

Front (Term) Back (Definition)

arterial vasodilation
vessel permeability
pavmenting
chemotaxis
phagocytosis
killing
Describe the steps in inflammation collateral damage
mast cells - histamine
endothelium (no) + prostatcylin
Name 3 cells and their products that cause arterial dilatation (no)
macrophages
immediate - transient (acute phase)
immediate - prolonged cytokines (hours)
What are the 3 ways of dividing mediators of vascular
delayed permeability?
- prolonged - direct endothelium injury (days)
1. amines - mast cell and platelet degranulation
2. Blood plasma c3a -c5a, bradykinins and coagulation
arachidonic acid derivatives (substance p)
What are the mediators of immediate- transitantCOXpermeability
or lipoxygenase
increase
Endothelial cell adhesion molcules (integrins)
What are the 2 subclasses of pavmenting molecules?
Leukocyte adhesion molecules (igG) (interleukins/selectins)
complement 5a
lipoxygenase:
platelet activating factor
leukotriene B4
12-hydroxyeicosatetraenoic acid or 12S-HETE

Chemotaxis of pmn leukocytes is infleunces by Cytokines IL-8

monocyte chemoattractant protein-1

complement/lipoxygenase/cytokines

AND

matrix products (collagen) + fibronectin

Chemotaxis of monocytes/macrophages (MCP-1) is a B - chemokines (which are just CC - chemokines

Chemotaxis of lymphocytes Y - chemokines (C chemokines); lymphotactin
LTB4
eosinophil chemotaxis factor
c5a
b - chemokines
Chemotaxis of eosinophils eotaxin
What is the main chemotaxin? Platlet Activating Factor, it can produce most of the seperate steps
How is platelet activating factor...activated? activated by phospholipase a2
Attachment - requires opsonisation
What are the steps of phagocytosis, and what doesEndocytosis
the first relie on?
igG
What are the two best opsonins for the process ofC3bphagocytosis?
igG-FC
Once engaged, how does the process of phagocytic C3Bendocytosis
- laminin/fibronectin
procedde orforcomplement
the two attachment
receptoropsonins?
Oxygen dependant killing
What are the two subcategories of bacterial cell Oxygen
killing once
independant
the bacteria
killing
has been endocytosed?
hexose-monophosphate shunt produces reactive free radicles:
Myeloperoxidase dependnat: HOCL
Describe oechanisms in oxygen dependnat killing:
myleoperoxidase independant: superoxide/oh-
permeability increases proteins
lactoferrin (deprives of iron)
lysozyme
major basic protein
Desribe oxygen independant machnisms for killing bacteria
proteases
What inhibits phospholipas a2 Corticosteroids
endothelial activation
il1/tnf both contribute to neurotrphils priming
The hallmark of acute inflammation is increased vascularity
The most common method of vascular leakage information
inflammation
of endothelial
is? gap in venules
The immediate transient response in inflammation
VENULESSSSS
occurs in capillaries, arterioles, veins or venules?
Cytoskeleton reorganisation in inflammation is due
Tissue
to? necrosis factor
in inflammation, transcytosis occurs across the vesiculovacuolar organelle of endothelium
The selectin subgroup that loves leukocytes is L - selectin
In Lung, leukocyte diapedisis occurs across what Not
partvenules,
of the vascular
capillaries
system?
What cells predominate in the first 24 hours of acute
Neutrophils
inflammation?
What cells predominate in the second 24 hours of monocytes
acute inflammation
The most effective bactericidal system in neutrophils
The myeloperoxidase
is? system
Phagocytosis induced cell death is dependant onintegrin Mac1
Histamine is found in abundance in? Mast cells
Complement system how many proteins 20
The anaphylatoxins are c3a,c4a,c5a
Which complement activates the lipoxegensase pathway?
C5A
Which complment is the most powerful compared c5awith other complments at attracting neutrophils
C3A - vasodilation/permeability
C5B - phagocytosis
Name 3 crucial complement proteases and their C5Aroles- adhesion/activation-lip oxygenate system/strongest chemotaxin
Hereditary angioedema is due to C1 complement deficiency
Eicosanoid mediators are produced where in theLipid
intracellular
bodies envionrment?
Prostaglandins are generated via lipoxygenase orcycloxygenase
cyclooxygenase pathways
Thromboxane is produced in what cells PLATELETS
Prostaglandin D2 is produced in what cells Mast cells
Leukotrienes are produced by which pathway Lipoxygenase Pathway
5-lipoxygenase is present in which cells Neutrophils
made by haemopoetic stem cells!
Define: interleukins act on leukocytes
What cytokine plays a role in body mass regulation?
TNFa
IL8 belongs to which chemokine family CXC chemokine
Eotaxin belongs to CC chemokine
serpentine receptors belong to CXCR
azurophil granules are present in NEUTROPHILS
The specific granules are produces in Neutrophils
Which cell plays a central role in chronic inflammation?
Macrophage!
half life of blood monocyte 1 day
Eotaxine binds with only what receptor exclusively,
CCR3!
which
- eosinophils!
is expressed by what cells
major basic protein granules are present in... think
ok about
so as they
it thisare
makes
basic,sense
they take acidic stains, hence eosinophils!
The factor which transforms macrophages into epitheliod
inf -Y cells is
What factor produces fever? TNF ALPHA!
iNTERLEUKIN CAUSING FEVER? IL6!
Azurophile granules contain? Myeloperoxidase!!!
Myeloperoxidase is contained within? Azurophile granules
Whats one way that non-human cells for example Toll
in like
the receptors
gut, are recognised?
How does endothelium increase permeability? Via endothelial contraction
interplay between E selectin on endothelium and L-selectin on Leukocytes

What regulates bacterial rolling (first step in transmigration

integrins aretoinvolved
tissues) in next step
What does myeloperoxidase do? Produces hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride anion (Cl−) in the respiratory burst
What is the relationship between monocytes/macrophages
interferon-Yand
stimulates
interferon-Y?
them to cause Nitric Oxide
stop COX, stop prostaglandin production,
How do most anti- inflammatories work? hence stop vasodilatation
"put it on you CV"
Protein C antagonises which coagulation factor? C antagonises V
CELLS:
1. Preformed + hence stored in vesicles
2. On demand

PLASMA
Summary of Inflammatory Chemicals 1. Activation
 Histamine - MAST cells (small amount in basophils)
vasodilation/permeability + bronchospasm
stimulate cells to produce eotaxins

Serotonin - like histamine but less potent

What inflammatory mediators are preformed, what
platelets
secrete
and
them,
enterochromaffin
what do they cells
do?

mnemonic - they must come from granules!! Lysosomes - phagocytic cells

prostaglandins
platelet activating factor
leukotrienes - all leukocytes
nitric ox - made by macrophages!
What inflammatory mediators are made on demand, what secrete them, what do they do?
What are secreted by all leukocytes and all endothelial
Plateletcells?
activating factor and prostaglandins
-> one change per each class alphabetical)
pgd2/e2 vasodilate, bronchodilate
pgf2, vasodilate, bronchoconstrict
TXA2, vasoconstrict, bronchoconstrict, platelet agregation

pgI2 - exact opposite of TXA2

Summarise prostaglandin functions vasodilate, bronchodilate, platelet inhibitor
LTB4: chemotaxis

VS

Summarise leukotriene function LTC4,LTD4,LTE4: bronchospasm, vasoconstriction

arachidonic acid derivatives.
Leukocytes and prostacyclins are? both decreased in steroids; they inhibit
Whats the mildest form of acute inflammation? Serous inflammation
Macrophages - as these are lying senescent in the tissue.

Causes Fever
increases slow wave sleep
Interleukin 1 comes from? Function activates t cells
1. impaired neutrophil chemotaxis
2. microvascular sclerosis
Inflammation and repair are often defective in persons with diabetes
3. diminished mellitus
neutrophil because of
phagocytosis
c5a
IL8
LTB4 & LTC4

Neutrophil chemotaxins lipopolysacharides

(IL-8 family)
(C5a) are chemotactic for PMN and monocytes.

Macrophage chemotaxins TH1 secretionsinclude the ‘lymphokines’ of which MCF is a prominent member!
Do any cytokines have any opsonic activity? No, they can active leukocytes, but no opsonisation. c3b and igg do opsoniation
What phagocyte receptor locks with the igG opsonin?
its FcGr - recognises the Fc fragment of igG receptor!
What phagocyte receptor locks with the c3B opsonin?
its complement 1, 2 or 3 receptor
What 2 other molecules are opsonins - what receptor
laminin
areand
they
fibronectin
bound by?both stimulate complment 3 receptor!
collagen
ADP
thromboxane A2
What are the 4 platelet activators? thrombin
ADP is released from what granules in platelets?ADP = Dense granules
1. sub-endothelial collagen binds glycoprotein receptors
What is the first step in platelet activation? 2. phospholipase a2 pathway activated
What is the initial role of vonwillebrand factor? Helps slow down platelets whizzing past endothelium disruption
GPIIb/IIIa binds fibrinogen:
pulls platelets together
GPIIb/IIIa binds vWF;
What are the mechanisms of platelet aggregation? anchors to vessel wall
Why are aspirin and clopidogrel irreversible? Because platelets have no NUCLEUS!!
What is the most potent chemotactic agent known?
Leukotriene (i.e LTB4)
 Capture+Rolling; P selectin (on endothelial cells)

Slow rolling+firm adhesion (pavementing);

E selectin (on endothelial cells)
CD18 integrins (LFA-1+MAC-1) on leukocytes

Summarise the process of leukocyte adhesion cascade

transmigration: IL8
Histamine/prostaglandins/NO
Vasodilation is mediated by? "his vas is no pro"
Transiently;
stored amines
plasma products -
Increased permeability is mediated by? phopholipid derivatives
Myeloperoxidase system;
What is the most powerful killing pathway and chemical
makes hypochlorite
of granulocytes?
What is another powerful killing pathway in bacteria,
NADPH which
mediated
when absent
superoxide
causes
radical
chronic
generation
granulomatous disease