(2) Acute vs. Chronic Inflammation, Apoptosis vs. Necrosis

secreted proteins that function as mediators of immune and inflammatory reactions

cytokines

What secretes cytokines? (4)

macrophages, NK cells, T cells, endothelial cells

2 examples of cytokines

TNF, ILs

family of low molecular weight cytokines that stimulate leukocyte movement and regulate migration of leukocytes from blood to tissues

chemokines

severe immune reaction in which the body releases too many cytokines into the blood too quickly

occurs as a result of an infection, autoimmune condition, or other disease; includes fever, inflammation, fatigue, and nausea, and it may be severe or life-threatening and lead to multiple organ failure

cytokine storm

Which leukocytes are responsible for the initial response in acute inflammation?

neutrophils

Is it more common for acute inflammation to be resolved or progress to chronic inflammation?

resolved

True or false: If acute inflammation doesn't result in resolution and regeneration, then it undergoes repair, which forms a scar.

true

What is the most common outcome of acute inflammation?

resolution

What is the most common outcome of chronic inflammation?

scarring

What are 3 effects of acute inflammation? (Hint: pertains to blood vessels, leukocytes present, and other chemicals present)

vascular changes, neutrophil recruitment, mediators

What are 3 effects of chronic inflammation? (Hint: pertains to blood vessels, leukocytes present, and histologic consequences)

angiogenesis, fibrosis, mononuclear cell infiltrate (along with B & T cells)

What are two possible outcomes of chronic inflammation?

scarring, regeneration

Which outcome of chronic inflammation is more common: scarring or regeneration?

scarring

(results in dense fibrosis & loss of function)

What are two examples of tissues that can undergo regeneration back to normal after chronic inflammation?

liver, GI epithelium

How long does acute inflammation last?

few minutes to few days

How long does chronic inflammation last?

few days to years

What is the first thing that happens in the inflammatory response?

edema

When do neutrophils peak in the inflammatory response?

24 hours

When do monocytes/macrophages peak in the inflammatory response?

2 days

(but they can stay elevated for a while after that)

What are the 2 main vascular changes that occur in acute inflammation?

vasodilation, increased capillary permeability

What are the 3 main cellular events that occur in acute inflammation?

leukocyte extravasation, accumulation, activation

What happens in the initial inflammatory response: vasodilation or vasoconstriction?

vasodilation

(to bring plasma proteins and leukocytes to the area)

Why does edema occur first thing in inflammation?

increased capillary permeability results in extravasation of fluid and plasma proteins

fluid that accumulates in a wound; may contain serum, cellular debris, bacteria, and white blood cells

exudate

refers to acute inflammation that involves increased fluid accumulation; basically is a skin blister with fluid edema directly beneath the epidermis

serous inflammation

refers to acute inflammation that involves fibrin leaking out of vessels, which occurs in body cavity linings and tissues

fibrinous inflammation

refers to acute inflammation that involves abscesses forming and the accumulation of pus

suppurative inflammation

What makes up pus? (3)

neutrophils, edema, necrotic cell debris

refers to an inflammatory response that is so destructive it destroys tissue in that area, causing that necrotic issue to shed

ulceration

Upon injury, before vasodilation occurs to start the inflammatory response, there is actually a transient vasoconstriction response that happens first. Why?

don't want excess blood leaking out

(which would lead to a hemorrhage)

Upon injury, does blood flow to the area get faster or slower?

slower

(due to increased vascular permeability - more fluid flowing out of capillaries, so more blood is leaving than flowing through the vessels)

refers to leukocytes starting to gather near the affected area upon injury that will eventually result in extravasation

leukocyte margination

Does capillary hydrostatic pressure increase or decrease during inflammation?

increase

(due to vasodilation, resulting in more blood flow to capillaries)

Does capillary osmotic pressure increase or decrease during inflammation?

decrease

(due to more plasma proteins leaking out into interstitial fluid as a result of increased permeability)

Typically, acute inflammation is resolved. When this resolution occurs, where does the excess fluid (edema) drain into?

lymphatic vessels

Typically, acute inflammation is resolved. When this resolution occurs, what happens to neutrophils and debris?

phagocytosed by macrophages

Typically, acute inflammation is resolved. When this resolution occurs, what do macrophages release? What is the result?

growth factors, new blood vessels and increased fibroblasts

(both aid in the repair process)

What are three histologic characteristics of chronic inflammation?

monocyte infiltration, tissue destruction, fibrosis/repair

When infiltration occurs in chronic inflammation, this mostly includes what two types of leukocytes?

macrophages, lymphocytes

True or false: Both acute and chronic inflammation can result in scar formation.

true

Does angiogenesis occur in acute or chronic inflammation or both?

chronic

What triggers angiogenesis, or neovascularization?

VEGF, FGF-2

Why is angiogenesis (neovascularization) important?

delivers cells and nutrients to site of repair

Why can angiogenesis (neovascularization) be detrimental?

**as seen in retinopathies, AMD, and cancer

new vessels have incomplete basement membranes, so they are very leaky

In blood vessels, do we have monocytes or macrophages?

monocytes

At what point do monocytes become macrophages?

when they migrate into tissues

Monocytes differentiate into macrophages when they enter tissues from the blood. However, these macrophages are not yet activated because they have to be activated by what? (3)

microbes, dead cells in the area, cytokines released by nearby T cells

Activated macrophages can go on to play roles in what 2 processes?

inflammation, fibrosis

If activated macrophages go on to be involved in tissue injury and inflammation, then what 4 things can be released to also contribute to this process?

ROS, proteases, cytokines, coagulation factors

If activated macrophages go on to be involved in fibrosis, then what 3 things can be released to also contribute to this process?

growth factors, fibrogenic cytokines, angiogenesis factors

What is the relationship between macrophages and T lymphocytes in regards to stimulation?

they constantly activate each other

cytokine released by activated macrophages that activates T cells

IL-12

cytokine released by activated T cells that activates macrophages

IFN-y

What is the first phase of wound healing?

inflammation

(so we do need inflammation to occur in order for wounds to heal properly!)

3 examples of acute inflammatory disorders

acute transplant rejection, asthma, glomerulonephritis

5 examples of chronic inflammatory disorders

arthritis, asthma, atherosclerosis, chronic transplant rejection, pulmonary fibrosis

If we have more neutrophils, are we in chronic or acute inflammation?

acute

If we have more macrophages, are we in chronic or acute inflammation?

chronic

What are 4 ways that cells can adapt to injury?

atrophy, hypertrophy, hyperplasia, metaplasia

refers to decrease in cell size

atrophy

refers to increase in cell size

hypertrophy

refers to increase in amount of cells

hyperplasia

refers to conversion of cells of one type to cells of another type

metaplasia

Does loss of ATP result in reversible or irreversible cell injury?

reversible

What is the main consequence of loss of ATP in reversible cell injury?

cell swelling

Does increased glycolysis result in reversible or irreversible cell injury?

reversible

What is the main consequence of increased glycolysis in reversible cell injury?

decreased pH (due to buildup of lactic acid)

Does decreased protein production result in reversible or irreversible cell injury?

reversible

Does plasma membrane damage result in reversible or irreversible cell injury?

irreversible

Do damaged mitochondria result in reversible or irreversible cell injury?

irreversible

Do damaged lysosomes result in reversible or irreversible cell injury?

irreversible

What happens to chromatin in necrosis?

clumping

What happens to organelles in necrosis?

swelling

When membranes are damaged in necrosis, why is this so detrimental?

lysosomal enzymes may escape and damage nearby structures

What happens to chromatin in apoptosis?

condensation and fragmentation

What happens to the cytoplasm in apoptosis?

budding

(these apoptotic bodies are then phagocytosed by nearby cells)

What is the difference between apoptosis and necrosis?

apoptosis is cell suicide, necrosis is cell homicide

How does cell size change in necrosis vs. apoptosis?

enlarged in necrosis, reduced in apoptosis

How does the nucleus change in necrosis vs. apoptosis?

shrinks and then lyses in necrosis, fragments in apoptosis

How does the plasma membrane change in necrosis vs. apoptosis?

disrupted in necrosis, intact but with altered structure in apoptosis

How do the cellular contents change in necrosis vs. apoptosis?

digested by enzymes in necrosis, intact in apoptosis

Which apoptosis pathway is known as the mitochondrial pathway?

intrinsic

Which apoptosis pathway is known as the death receptor pathway?

extrinsic

6 steps of the intrinsic pathway (only) of apoptosis:

1. Cell injury triggers [these molecules]

2. Those trigger [these molecules]

3. Those cause the mitochondria to release [this protein]

4. That protein activates [these enzymes]

5. That protein also releases [these other proteins]

6. Those other proteins activate [these enzymes]

Bcl-2 family sensors, Bcl-2 family effectors, cytochrome c, initiator caspases, pro-apoptotic proteins, executioner caspases

4 steps of the extrinsic pathway (only) of apoptosis:

1. [this ligand] binds with [this receptor]

2. [these proteins] are activated

3. Those proteins activate [these enzymes]

4. Those enzymes activate [these other enzymes]

Fas, TNF receptor, adaptor proteins, initiator caspases, executioner caspases

What do the intrinsic and extrinsic pathways in apoptosis have in common? (i.e. What is the fundamental event that ensures that apoptosis will occur?)

both activate executioner caspases to activate endonuclease and proteinases and break down cytoskeleton

Which of the following is most likely to convert reversible cell injury to irreversible cell injury?

A. plasma membrane damage

B. protein degradation

C. cell swelling

A

The primary purpose of the vascular changes in an invaded or injured area is to...

A. produce swelling, redness, heat, and pain.

B. bring to the affected area phagocytes and plasma proteins that defend against the offending agent.

C. produce pus

D. exert an anti-inflammatory effect to protect against damage by potentially over-reactive defense mechanisms

E. trigger specific immune responses

B