Inflammation Flashcards
Given a clinical scenario be able to:
—Distinguish between acute and chronic inflammation
Acute Inflammation: early (almost immediate) response to tissue damage. Can last a few minutes –> several days
Red, Warm, Edema, Pain
Chronic:
A 23-year-old female sprained her ankle, which is now swollen, red, warm and painful. To treat the pain, she takes some ibuprofen, a non- steroidal anti-inflammatory drug (NSAID). This works for her because the ibuprofen is most likely inhibiting the formation of:
A. Chemokines B. Histamine C. Lysosomal enzymes D. Prostaglandins E. Leukotrienes
D. Prostaglandins
Match these
A. Chemokines B. Histamine C. Leukotrienes D. Prostaglandins E. TNF, IL-1
Chemotaxis Pain
Recruit and/or activate WBCs Vascular permeability
Vasodilation
A. Chemokines:
Chemotaxis
B. Histamine:
permeability
C. Leukotrienes:
permeability
D. Prostaglandins: Pain
E. TNF, IL-1: Recruit and/or activate
Match these
A. Chemokines B. Histamine C. Leukotrienes D. Prostaglandins E. TNF, IL-1
Chemotaxis Pain
Recruit and/or activate WBCs Vascular permeability
Vasodilation
A. Chemokines:
Chemotaxis
B. Histamine:
permeability
C. Leukotrienes:
permeability
D. Prostaglandins: Pain
E. TNF, IL-1: Recruit and/or activate
A 53-year-old female has a high fever and cough productive of yellowish mucus for the past day. A chest x-ray shows bilateral patchy airspace opacities (white spots that suggest that the airspaces may be filled with microorganisms and pus indicative of pneumonia). Which of the following inflammatory cells is most likely to be seen in greatly increased numbers in the coughed up mucus?
A. Plasma cells B. Macrophages C. Mast cells D. Neutrophils E. T lymphocytes
D. Neutrophils-and it is acute
Describe the role of macrophages and mast cells in starting the inflammatory process.
macrophages are first to response, mast cells cause vasodilation to allow immune cells to target the area
Compare the role of neutrophils and macrophages in acute inflammation.
a. What is the timing of each in acute inflammation?
b. Compare the function of each in acute inflammation?
c. What is the difference between a monocyte and macrophage?
d. When do you find macrophages vs neutrophils in tissue? In general, what is the lifespan of each in tissue?
e. Which immune cell is involved in tissue repair?
a. Neutrophils: leukocytes in blood that enter tissues in response to
inflammatory signals
i. first leukocytes to be recruited at the site of injury because they are
the most abundant leukocyte in blood and can respond faster
ii. major phagocytic cells, polymorphonuclear leukocytes (PMN),
iii. short lifespan! 6-24 hours
1. needs to constantly be replenished à release of mature and
less mature band neutrophils from bone marrow
iv. Activation
1. Microbes, necrotic cell products, inflammatory mediators à
bind to receptors on neutrophils à activate
a. Pathogens have damage associated molecular patterns,
so all are non-specific
2. Once activated: secrete inflammatory mediators (cytokines) to
attract other leukocytes, phagocytosis, kill bacteria and other
microbes, eliminate necrotic tissue and foreign substances
3. Bacteria binds to a receptor on neutrophil à phagocytosis à
fusion of phagocytic vacuole with lysosomes à phagolysosome
contains ROS and Lysosomal enzymes à kill and degrade the
microbe
a. Lysosomal components are also secreted to kill and
degrade extracellular microbes
b. Macrophage: tissue resident, come from monocyte (in blood)
i. Fewer than number of neutrophils, aren’t active until they act as
macrophages in the tissue. Therefore neutrophils enter first, then
monocytes take over! 24-48 hours
1. Macrophages can live for years!
ii. Macrophages always running around in tissues to look for pathogens
à attract neutrophils when activated
iii. Initiate the process of tissue repair by releasing growth factors, etc.
Morphological patterns of acute inflammation
-Serous inflammation
transudate effusion
i. transudate - watery, relatively protein poor fluid
ii. effusion: abnormal collection of fluid within a cavity
iii. Ex: blister – separation of epidermis from dermis, focal collection of
serous effusion
iv. Ex: inflammation of serous membrane that lines body cavities
(pericarditis, peritonitis, pleuritis/pleurisy)
What causes a blister, and what type of fluid does it contain, and where is the fluid located?
A result of acute inflammation!
Separation of the dermis and epidermis which is then filled with serous fluid (transudate effusion) which is..
i. transudate - watery, relatively protein poor fluid
ii. effusion: abnormal collection of fluid within a cavity
Compare the type of fluid that would be in a body cavity when there is serous inflammation, fibrinous inflammation, or purulent (suppurative) inflammation associated with either pleurititis (pleurisy), pericarditis or peritonitis.
Explain the cause and why the type of fluid is different.
Serous is transudate: waterary/protein poor
Fibrinous: from more severe injury and protein rich exudate-fibrinous
Suppurative (purulent) inflammation: full of pus. SO major cellular
component of exudate would be neutrophils
i. Often found in bacterial infections
1. Abscess: puss filled cavity.
Describe how fibrinous inflammation can lead to scarring?
Fibrinous inflammation: from more severe injury, occurs often in body
cavities
i. Releases a protein-rich exudate
- If not resolved (removed by macrophages), can turn into scar
tissue
Describe an abscess - why and where it develops and its composition.
Suppurative (purulent) inflammation:
- Abscess: puss filled cavity. Can develop with extensive acute
inflammation - Center of abscess is dead neutrophils, pus, cell debris, necrotic
tissue - Surrounding tissue is attempted repair tissue with a lot of
fibroblasts to wall it off
Describe the development of an ulcer? Where do they tend to occur?
inflammation occurring on a surface (epidermis, mucosa, etc.) à
necrotic and inflammatory tissue sloughing off
-Define chronic inflammation.
inflammation that lasts 2+ weeks, regardless of the cause.
Where both tissue injury and cell repair coexist because there is time to start the
repair process
What are the predominant immune cells in chronic inflammation?
NO NEUTOPHILS
monocytes and macrophages, plasma cells, T lymphocytes (NOT neutrophils!)
Explain the role of TH1 and M1 macrophages in chronic inflammation?
End result?
Classical macrophage activation
- M1 macrophage releases cytokines to activate Th1
- Th1 releases INF-gamma to activate M1
a. M1 phagocytoses, produces lysosomal enzymes to kill
microbes and host cells and proteases to degrade ECM
- Result: tissue destruction
Explain the role of TH2 cells and M2 type macrophages in chronic inflammation?
End result?
Alternative macrophage activation
- Th2 cell releases IL-4, IL-13 to activate M2 macrophage
- M2 releases growth factors à angiogenesis, fibroblast
proliferation and activation –> deposit collagen - Result: tissue repair with scar
What are plasma cells and explain their role in chronic inflammation?
Make antibodies…
these coat bacteria as opsonins (increase phagocytosis of macrophages)
What infiltrates acute inflammation?
What type of repair tends to occur with chronic inflammation?
Infiltration of macrophages, lymphocytes and plasma cells (instead of fluid, protein and neutrophils)
Tissue destruction induced by the products of the inflammatory cells
Repair by fibrosis (scarring) and angiogenesis
What is the main function of a granuloma?
surround and wall off the infected
macrophages
–> Macrophage walled off by Th1 cells, transforms into an
epithelioid, flat cell
–> cells fuse together to create a
multinucleated / Langerhans giant cell
What infiltrates acute inflammation?
What type of repair tends to occur with chronic inflammation?
Infiltration of macrophages, lymphocytes and plasma cells (instead of fluid, protein and neutrophils)
Tissue destruction induced by the products of the inflammatory cells
Repair by fibrosis (scarring) and angiogenesis
Compare the formation of a foreign body granuloma vs an immune granuloma (caseating and non-caseating).
caseating=necrotic
What is something that will cause an immune foreign body with a necrotic center
TB, MICROBES
Structure of a caseating granuloma (internal –> external)
Vs. non-caseating
- caseous necrosis
- Activated epithelioid macrophage
- Langerhans giant cell
- Lymphocyte
- Fibroblasts (b/c trying to repair)/Scar tissue
In non caseating you have immune cells in the middle
Explain the requirements for tissue regeneration.
i. Labile: continuously dividing tissues – will regenerate, not scar
1. Ex: surface epithelium (GI and skin epithelium), bone marrow
ii. Stable: normally quiescent, but injury can cause limited cell
proliferation – regenerate
1. Ex: many solid tissues (kidney, liver, pancreas), fibroblasts,
smooth muscle
iii. Permanent tissue: terminally differentiated and nonproliferative cells
SCAR
1. Ex: neurons, cardiac myocytes, skeletal muscle cells
Cause of non-caseating center granuloma
Non-living foreign material, such as suture material or splinter and Crohn’s disease
When does a scar form?
occurs when there are no cells left to regenerate from or too much
damage to the supporting tissue
Compare the regenerative ability of labile, stable and permanent tissues.
i. Labile: continuously dividing tissues – will regenerate, not scar
ii. Stable: normally quiescent, but injury can cause limited cell
proliferation –
iii. Permanent tissue: terminally differentiated and nonproliferative cells-SCAR
A person takes a chemotherapeutic agent which causes irreversible damage to some of the epithelial cells lining the GI tract. Which of the following will most likely happen to the damaged epithelium?
A. Develop a scar
B. Regenerate
Regenerate
Which are labile, stable or permanent tissues
i. Neurons
ii. Skeletal or cardiac muscle
iii. Epithelium of the skin or GI tract
iv. Liver, kidney
neurons-permanent
Skeletal m. and cardiac= permanent
epithelium of skin and GI (and bone marrow)= labile
Liver, kidney, pancreas and smooth muscle= stable
Describe the process of scar formation. Focus on:
What are the main cells involved and what is their role?
Tissue injury and inflammation can lead to tissue destruction or
release of growth factors from macrophages
- These growth factors can cause angiogenesis or fibroblast
migration, proliferation and activation
a. Fibroblasts: main cell of CT that produce the ECM
What stimulates angiogenesis and fibroblast migration and activation?
Tissue injury and inflammation can lead to tissue destruction or
release of growth factors from macrophages
1. These growth factors can cause angiogenesis or fibroblast
migration, proliferation and activation
What is the difference between granulation tissue and a scar. When does each occur?
Can take granulation tissue and remodel into a scar
a. Granulation tissue: red, cobblestone blood vessels,
bumpy or granular
b. Scar: few blood vessels, mostly made of collagen
What is a keloid?
excessive collagen production so that there is too much scar
tissue. Removal causes them to grow even more