Patho Inflammation (2) Review

Interleukins are produced by ___________ and ___________ and alter the adhesion molecules on many cells.

Macrophages

Leukocytes

Interleukins induce leukocyte ___________, proliferation and maturation in the ___________ ___________ and enhance or suppress inflammation.

chemotaxis

bone marrow

TNF - alpha and Il-1 are two major ___________ cytokines that mediate ___________ and are released by macrophages.

Il-1 is also produced by

-

-

-

cells.

proinflammatory

inflammation

Neutrophils

endothelial

epithelial cells

Secretion of TNF- alpha and IL-1 is often stimulated by ___________ and immune cells and injury. They can alter adhesion molecules on the endothelial surface and cause them to secrete

-

-

-

endotoxins

cytokines

chemokines

reactive oxygen species

__________ stimulates priming and aggregation of neutrophils - leading to enhanced response to other mediators.

TNF-alpha

Il-1 and TNF- alpha also affect our _______________

Temp

TNF-a produced in large quantities in response to _______ ___________ bacteria - can be lethal by indiction of ________, decreased synthesis of _______________ proteins by the liver, and ___________ wasting with intravascular ___________

gram negative

fever

inflammatory

muscle

thrombosis

IL-6 is _______________ cytokine produced by macrophages, lymphocytes, fibroblasts, etc. - induces _____________ to produce more inflammatory proteins and stimulates growth of blood cell __________ in the bone marroq

proinflammatory

hepatocytes

precursors

IL-10 is on of the ________________ cytokines produced by _____________ to control the inflammatory response

antiinflammatory

lymphocytes

_________________ protect us against viral infection by inducing production of ___________ proteins

Interferons

antiviral

IFN- a and b are produced by _____________ - IFN y is released by lymphocytes and helps with the _____________ immune response

macrophages

acquired

Chemokines serve to attract and direct migration of immune and inflammatory cells with a ___________ gradient

chemotactic

Inflammatory chemokines induced in response to inflam ___________ or bacterial toxins

cytokines

NO produced by ___________ cells - cause smooth muscle ___________ and stops platlet ___________

edothelial

relaxation

aggregation

Blocking NO production ____________ leukocute rolling and adhesion to capp venules

PROMOTES

With NO there will be less leukocyte ____________ - reduction in ___________

adhesion

inflammation

Impaired production of ______ is implicated in inflammatory changes associated with atherosclerosis

NO

Oxygen Free Radicals are often release by leukocytes after exposure to microbes, cytokines, immune complexes or during the ___________ process

phagocytic

ROS at low levels increases ___________ and ___________ adhesion molecule expression - increasing inflamm process

Cytokines

Adhesion

At high levels ROS can damage ______________ = increased permeability

endothelium

Two phases of inflammation

___________ - changes in vessel diameter = increased blood flow to injury

___________ - leukocytes and other cells migrate from circulation to tissue

vascular

cellular

With injury there is brief period of vaso___________ followed by vaso___________

constriction

dilation

With vasodilation increased vessel size leads to

- larger ___________ of blood to area

- decreased ___________ of blood

- increased ___________ pressure

volume

velocity

hydrostatic

Retration of endothelial cells by mediators means increased ___________ ___________ - proteins move into intracellular space and take ___________ with them - blood becomes more ___________ - flow further slows and ___________ start to stick to the endothelium

Vascular permeability

fluid

viscous

leukocytes

5 cardinal signs of inflammation are?

Heat

Redness

Swelling

Pain

Loss of function

5 signs caused by ___________ phase of inflammation

Main things that happen here are

Brief vaso___________ followed by vaso___________

Increased ___________ ___________

Migration of ___________

vascular

constriction

dilation

vasc. permeability

leukocytes

Organize the following in order

A - Endothelial cell retraction

B- Edema, pain, and impaired function

C- Low velocity flow

D- Leukocytes stick to the endothelium

E - Binding of mediators to endothelial receptors

F - loss of proteins and water into tissues

G - Decreased osmotic pressure

H - Increased blood viscosity

E

A

F

G

B

H

C

D

During inflammation, biochemical mediators are released from ___________ cells, ___________ proteins are activated from dying cells and ___________ molecules on the surface of many cells are added.

mast

plasma

adhesion

Some of the adhesion molecules are

-

-

- members of the Ig family like ___________, ___________, ___________

And are found on bothe the leukocyte AND the endothelial cell walls - they are COMPLEMENTARY

Selectins

Integrins

ICAM1

ICAM2

VCAM1

Through ___________ leukocytes are encouraged to move into the tissue where injury has occured

Chemotaxis

___________

Leukocytes move along the endothelial wall

Migration

___________

Leukocytes stick to the endothelium with the help of adhesion molecules

Adhesion

___________

Leukocytes cross the blood vessel wall into the tissues

Transmigration

___________

A response involving cell orientation or movement either towards (positive) or away (negative) a chemical stimulus

Chemotaxis

As blood volume near the area INCREASES, the velocity of the blood ___________ and the hydrostatic pressure _____________

decreases

increases

As leukocytes slow down - they adhere to the endothelial surface via intercellular adhesion molecules or ___________ - once attached the endothelial cells begin to separate and leukocytes move with ___________ like movements through junctions - this is ___________

ICAMS

pseudopod

transmigration

______________________ enhances recognition and binding activity of phagocytes - like glue between phagocyte and target

Opsonization

Major phagocytes include

-

-

-

- macrophages

- monocytes

- neutrophils

____________ are activated to form ____________ that will encircle the offending organism - then ____________ will fuse with intracellular lysosome to form ____________ which will release its enzymes and oxygen radicals to attack

neutrophils

pseudopods

phagocyte

phagolysosome

Phagocytosis Review

The process begins with ____________ - the slowing and adherance of leukocytes to endothelial wall

Margination

____________ ____________ - the plasma membrane of the phagocyte extends into finger like projections through the gaps between the endothelial cells and leaves the blood vessel by digesting the ____________ ____________

Pseudopod Formation

Basement membrane

Phagocyte migrates to target - which is opsonized by ____________ or antibodies - Phagocyte uses fingers to engulf target - now it is called a ____________

C3b

Phagosome

Phagosome + Lysosome fuse to = ____________ and then the target is digested

Phagolysosome

Diapedesis is the movement of the leukocytes through the widened junction between endothelial cells into tissue

____________

1. Margination

2. Pseudopod formation

3. Diapedesis

4. Migration

5. Opsonization

6. Engulfment

7. Fusion

8. DESTRUCTION

Phagocytosis

Phagocytes die and become ____________ - phagocyte products exit via the ____________

pus

lymphatics

When phagocytes die their lysosomal contents are released

- increasing ____________

- ____________ of monocytes

- connective tissue ____________

- activation of the ____________ protein systems

permeability

chemotaxis

breakdown

plasma

To avoid toxicity alpha 1 _____________ - a plasma protein from the liver is released and INHIBITS destructive effects

antitrypsin

Heat and redness are caused by increased ____________ and movement of ____________ to injury site

vasodilation

blood

Edema is caused by

-

- increased movement of ____________ to site of injury

- increased capillary ____________

- leakage of ____________ and cells out of endothelial wall taking ____________ with it

vasodilation

blood

permeability

proteins

water

Pain is caused by increased ____________ in tissues + ____________ act on nerve endings

fluid

prostaglandins

Loss of Function

- Pain and edema

after a ______ ____________ period the inflammatory process is now considered chronic

two weeks

some organisms have _______ cell walls and are not easily ______________ - so it persist

Others like leprosy, syphilis and bricellosis can live in ____________

some release ____________ upon death

waxy

phagocytized

macrophages

toxins

Granulomatous inflammation - characterized by infiltration of lymphocytes and macrophages - the body ____________ the site and walls it off

isolates

____________ is encapsulated by fibrous deposits and can become calcified

Granuloma

Acute inflammation is the ____________ phase of wound healing - before the ____________ response becomes established - aims at ____________ the injury causing agent and limit tissue damage

first

immune

removing

____________ are composed of serous fluid, RBCs, fibrinogen or tissue debris, and white blood cell breakdown products.

Mediators can be derived from the _______ or the _________

exudate

plasma

cells

One of the first mediators is cell derived _____________ - in high concentrations in mast cells in connective tissues + basophils and platlets

Histamine

Histamine is released in response to a variety of stimuli and causes dilation and increased permeability of caps

The THREE major plasma derived factors are located in the plasma as PRECURSOR forms that myst be activated

- the ____________ increase cap permeability and stimulate pain receptors

- the ____________ system traps exudates, microorganisms and foreign bodies

- the ____________ cascade causes vasodilation, promotes chemotaxis and augment phagocytosis

kinin

clotting

compliment

High LDL - LDL moves into Tunic ____________ - Endothelial cells release _______ --> Oxidized ________ causes expression of adhesion molecules for ____________ cells on endothelial cells

Intima

ROS and Metaloproteases

LDL

Immune

If LDL is oxidized it CANNOT LEAVE the Tunica Intima

Adhesion of ____________ to activated endothelial cells --> allows ____________ and ____________ cells to move into Tunica Intima - ____________ become macrophages when they move in, and will take up the ____________ ____________ - they become ____________ cells

Leukocytes

Monocytes

T Helper

monocytes

oxidized LDL

foam

Foam cells will release ____________ to attract more macrophages

Can release ____________ (which is a growth factor) will cause smooth muscle cells to ____________ and ____________

Chemokines

IgF1

Migrate

Proliferate in tunica intima

Foam cells promote migration of ____________ ____________ cells into the tunica Intima from tunica media + ____________ ____________ cell proliferation

smooth muscle

smooth muscle

Increase in smooth muscle cells = increased synthesis of ____________ which leads to ____________ of the plaque

collagen

hardening

Foam cells die, and release ____________ content - which drives GROWTH of the plaque - it can then ____________

lipid

rupture

Foam cells when they die release ____________ material -- which attracts ____________

Foam cells can also release ____________ cytokines and ROS

Together these with neutrophils will increase _____________ in the plaque

DNA

Neutrophils

Proinflammatory

Inflammation

There is an increase in blood supply to the ____________ ____________ layer of the vessel - vasa vasorum

tunica intima

_____ cells, bind and move into tunica intima - they enter the plaque and can be activated by ____________

They release ____________ -- which promotes inflammation and activated endothelial cells to attract more white blood cells

T (killer)

Macrophages

Interferon Gamma

Phagocytes (macrophages) release arachidonic acid like compounds or ____________ or ____________ - which change the surrounding tissue

They also release protein mediators ____________ which interact with local tissue and are pro or anti inflamatory

prostaglandins

leuotrienes

cytokines

The role of the adaptive immune system is unclear - it may promote or decrease atherogenesis

Cytokines from activated T cells such as interferon gamma and TNF-alpha promote ____________

Cytokines such as IL-10 and transforming growth factor beta from regulatory T cells may serve a ____________ role

inflammation

protectve

T and B cells may recognize autoantibodies and INCREASe atherogenisis

Pro atherogenic autoantigens include

- ____________

- oxidized ____________

- Apolipoprotein B - the core protein of ____________

LDL

LDL

LDL

There is communication between the innate and adapative immune cells - but adaptive role is unclear

Smooth muscle proliferation makes the endothelial layer pouch out, and makes the lumen of the vessel ____________

smaller

Formation of a hard ____________ core --> Formation of Protective fibrous ____________ --> Lymphocytes signal to smooth muscle to stop ____________ formation --> Enzymes are synthesized to eat away at the ____________ --> Atherosclerotic plaques are now considered ____________ or vulnerable as they can rupture and cause thrombus - if the rupture there are signals for formation of ____________ mediators - ____________ adhere to the lesion + procoagulent factors and they form a ____________ - occludes blood vessel - pain, angina, MI

lipid

cap

collagen

cap

unstable

prothrombogenic

platelets

thrombus

Major complications of athersclerosis

- ____________ heart disease

- ____________ vascular accidents

- ____________

- ____________ vascular disease

Ischemic

Cerebral

Stroke

Peripheral

two main types of stroke

-

-

Ischemic

Hemorhagic

____________ stroke

- 80%

- Due to cerebral vascular obstruction caused by thrombus or emboli

- Neuro deficits depend on cerebral artery impacted

Ischemic

____________ stroke

- less common

- brain bleeding

- blood vessel rupture caused by HTN, aneurysm, arteriovenous malformation, head injury

- more fatal

Hemorrhagic

Peripheral vascular disease

- poor perfusion of the extremities

- may result in ischemia, pain, impaired function, infarction, necrosis

30% of deaths in Canada due to complications therefor identifying risk factors is key