Lecture 4: Inflammation Flashcards
__ is the process of reaction of living vascularized tissue to injury
inflammation
Sometimes inflammation can induce tissue damage but normally it is beneficial in what 2 ways
destroys invaders and prepares injured tissue for repair
3 main events of blood vessels during inflammation
- increased blood flow
- increased vascular permeability
- leukocytic exudation through vessels
2 types of repair
regeneration and scarring/fibrosis
__ is the replacement by cells of the same type and __ is the replacement by c.t.
regeneration, scarring/fibrosis
5 signs of acute inflammation
- rubor (redness)
- tumor (swelling)
- calor (heat)
- dolor (pain)
- loss of function (functio laesa)
the calor/heat is due to the release of mediators __ and __
IL1 and prostaglandin
what causes the rubor/redness of inflammation
hyperemia
what causes the tumor/swelling during inflammation
increased vascular permeability
what causes the dolor/pain during inflammation
stimulation of free nerve endings
What regulates the process of inflammation
chemical mediators
3 mediators of inflammation from PLASMA
- kinins; bradykinin
- complement fragments: C5a
- coagulation/fibrinolytic products
4 mediators of inflammation from TISSUE/CELLS
- Vasoactive amines: histamine, serotonin
- prostaglnadins and leukotrienes: PGE2 and LTB4
- Cytokines/chemokines: TNFalpha, IL1, IL8, MIP1
- nitric oxide
3 steps to leukocytes exiting a BV
- Margination
- adhesion and migration
- chemotaxis and activation
What initially happens to blood vessel after damage occurs
transient vasoconstriction (neurally mediated, lasts only seconds)
Post injury, After neural vasoconstriction of BV that last only a few seconds what happens next?
chemical mediated vasodilation that lasts minutes to days
chemical mediators of vasodilation
PGE2, Histamine, NO
5 mechanisms to increased vascular permeability
- endothelial contraction (histamine)
- direct endothelial injury (burn)
- leukocyte-endothelial injury
- increased transcytosis
- endothelial prolif and leak
__ is the most common way permeability is increased
endothelial contraction
edothelial cells contract when stimulated by histamine and leukotrienes causing __in venules = increased perm
gaps
__ is mostly in venules and pulmonary capillaries, it is a late response and is long-lived 9hours)
leukocyte-dependent injuy
transcytosis increasing vascular perm is caused by
VEGF (vascular endothelial derived growth factor)
describe the 4 steps in leukocyte migration
- margination
- rolling
- adhesion
- transmigration
leukocytic events during acute inflammation occur in
venules and capillaries
Leukocyte margination and rolling is mediated by expresson of __ on endothelial cells and ___ on leukocyte
selectin (E and P), sialyl-lewis X modified glycoprotein
mediators like __ and __ upregulate expression of e-selecting and activate leukocytes to express high affinity integrins (LFA or MAC)
TNF alpha and IL1
important factors involved in leukocytic margination and rolling
- selectins
- sialyl-lewis X mod glycoprotein
- TNF alpha
- IL1
leukocyte adhesion is mediated by
adhesion molecules
endothelial cell adhesion molecules
ICAM1 and VCAM1 (Ig superfamily proteins)
leukocyte integrins that allow for adhesion to ICAM and VCAM
LFA-1 (CD11a/CD18)
Mac-1 (CD11b/CD18)
VLA4
(Heterodimeric proteins)
cytokines like __ and __ and chemokines like __ upregulate high-affinity integrin expression on leukocytes
TNF alpha, IL1, IL8
What mediates leukocyte transmigration?
PECAM1 (CD31) (homophilic adhesion molecule)
Stopped at
video of rolling p. 13
summary of neutrophils: __ allows rolling, __ allows firm attachment, and __ allows transmigration
selectins, integrins, CD31 (PECAM)
2 leukocyte adhesion deficiencies due to genetic mutations in integrins and selectins? which one is recognized in animals?
LAD1 Integrins and LAD2 selectins
LAD1 has been identified in animals!
In holstein cattle __ is mutation in CD18 integrin that binds to intercellular adhesion molecule = altered expression of CD18 so neutrophils cannot adhere and transmigrate, these calves die quickly
BLAD - bovine leukocyte adhesion deficiency
BLAD in cattle is a mutation in __ causing neutrophils to be “trapped” in bloodstream unable to adhere and exit
CD18 integrin
BLAD causes decraesed survival due to __ and __ as neutrophils cannot respond to infection by bacteria and fungi
enteritis and pneumonia
There is a similar disease to BLAD that is a CD18 missense mutaiton in __ dogs
irish setter dogs
__ is cell migration along a concentration gradient of chemical mediator
chemotaxis
__ is random migration stimulated by a mediator
chemokinesis
most inflammatory reactions in the early stages are characterized by infultration of
neutrophils - fast, release and respond to wide array of mediators, very motile, effective killer of bacteria
what are the first cells to respond?
neutrophils
neutrophils and macrophages release ___ and __ which can induce tissue damage
superoxide anion and lysosomal enzymes
__ are less motile, long lived cells derived from monocytes or local division
macrophages
macrophages form __ and __ cells
epithelioid and multinucleated
__ move from the blood and develop into macrophages in the tissue
monocytes
__ modulate inflammatory, immune, and repair through lots of mediators and cytokines
macrophages
eosinophils have protein __ that can kill helminths
major basic protein
eosinophils are important in many __ diseases and __
hypersensitivity dz and mediates tissue damage in chronic reactions
__ prolongs eosinophil tissue survival
IL5
__ are derived from BM and local division, they are important mediators of hypersensitivity dz
mast cells
mast cells contain important mediators __ and __ and are a major source of
histamine, serotonin, leukotrienes, cytokines, chemokines
__ are critical regulatro/effector of Ag driven inflammatory process, they produce Ab and cytokines
lymphocytes
6 inflammatory cells
- neutrophils
- macrophages (multinucleated giants, epithelioid)
- eosinophils
- lymphocytes
- mast cells
- platelets - the forgotten one!
3 important things platelets release to aid in inflamm response
- vasoactive amine: serotonin
- PAF
- Growth factors: PDGF, TGF beta, FGF
__ ddx is based solely on morphology
morphologic (chronic diffuse granulomatous enteritis)
___ ddx includes causative agent
etiologic (intestinal mycobacteriosis, intestinal paratuberculosis)
__ is the specific agent causing the dz
cause (mycobacterium avium subspp paratuberculosis )
name of the disease caused by mycobacterium avium subspp paratuberculosis
Johne’s dz
4 things needed for morphological classification
- duration: acute, subacute, chronic
- distribution: focal, multifocal, locally-extensive diffuse
- type of exudate: serous, fibrinous, suppurative, eosinophilic, hemorrhagic, necrotizing, mixed etc.
- tissue involved: hepatitis, nephritis, etc.
__ is considered hours to days in duration, there are changes in vessel perm and flow allowing leukocyte exudation
acute
__ takes 7-10 days, tissue cells proliferate, but ther is no fibrosis or scarring
subacute
__ is beyond 10 days and is marked by firbosis or scarring
chronic
__ refers to an exudate dominated by fibrin, __ refers to scarring/repair marked by firbosis (proliferation of fibroblasts laying down collagen) (i.e. pig with
fibrinous exudate, fibrous
__ exudates are dominated by large number of neutrophils responding to bacterial infection (i.e. rabbit uterus or brain abscess caused by Pasturellosis)
suppurative (similar to purulent) see lots of neutrophils microscopically
__ is a collection of suppurative or purulent exudate (ie. rabbit with chronic focal suppurative encephalitis due to pasturellosis)
abscess
__ exudate occurs commonly on peritoneal pleura or mucosal surfaces, hyperemia of surosal surfaces with red to grey thick exudate with sheets of fibrin. commonly seen with bacterial infections
fibrinopurulent exudate
__ exudate may result in a green sheen grossly and histologically is seen with parasite or allergic reactions
eosinophilic
__ exudate is characterized by hemorrhaging and inflammatory cells (i.e. pig intestine with lisonia infection or dog with parvo)
hemorrhagic
__ has a characteristic segmental hemorrhagic enteritis associated with it
parvovirus
__ exudate is associated with dry pale muscle (ie. clostridium infection)
necrotic
__ infection you see necrotic exudate and GAS BUBBLES which are characteristics of this infection due to bacteria exotoxins lysing cell membrane and causing necrosis
clostridium
multi-focal necrotic and hemorrhagic exudate lesions that look like “bullseyes” characteristic of __ infection in ruminants
mycotic rumenitis/omasitis/abomasitis
__ exudate involves all modifiers of tissue, clotting factors leak from vessels (salmonella)
fibrinonecrotic
fibrinonecrotic exudate casts passed in feces of cattle is characteristic for _ infection
salmonella
__ is an injury that damages the overlying epithelium but does not go through the basement membrane
erosion
__ is an injury that damages the epithelium and goes through the basement membrane
ulcer
cow with acute multifocal erosive stomatitis and esophagitis would be an example of ___ infection
bovine viral diarrhea infection
an example of ___ exudate can be seen with viral and parasitic dz in cattle where Ag reaction causes raised multifocal bumpy lesions. An example of this is the paraiste __ in cattle which burrows and causes chronic multi focal abomasitis
lyphocytic, ostertagia
__ inflammation is seen with parasitic infections with __ where there is an acute inflammatory response causing TISSUE PROLIFERATION
hyperplastic, coccidiosis (raised bumps like ostertagia)
__ inflammation is macrophage dominated and almost always is chronic
granulomatous (hamburger/brain looking intestines and enlarged ln’s)