Robbins 7th ed - Chapter 2 - Acute and Chronic Inflammation (1)

Question 1

What are the four classic clinical signs of inflammation?

Answer 1

Heat (calor), Redness (rubor), Oedema (tumor), Pain (dolor)

Question 2

What is the difference between exudate and transudate?

Answer 2

Exudate is an inflammatory extravascular fluid that has a high protein concentration and cellular debris; specific gravity above 1.020. **Transudate **is an extravascular fluid with low protein content and specific gravity below 1.012; essentially an ultrafiltrate of blood plasma resulting from elevated fluid pressures or diminished osmotic forces in the plasma.

Question 3

Name four categories of events that can trigger an inflammatory reaction.

Answer 3

Infections.

Tissue necrosis (ischaemia, trauma, burns, etc).

Foreign bodies (splinter, suture, etc).

Immune hypersensitivity (autoimmune, allergy, etc).

Question 4

What is the major force that normally keeps fluid inside blood vessels? What is the major force that normally promotes fluid movement out of blood vessels?

Answer 4

Plasma colloid oncotic pressure. Hydrostatic pressure.

Question 5

During inflammation, what is the most common mechanism underlying increased vascular permeability?

Answer 5

Formation of venule intercellular endothelial gaps.

Question 6

What are the three steps in leukocyte migration through blood vessels?

Answer 6

1. Margination, Rolling, Adhesion.
2. Transmigration across the endothelium (diapedesis)
3. Migration in interstitial tissues toward a chemotactic stimulus (towards the site of the insult).

Question 7

What are selectins and integrins? How do they work?

Answer 7

Selectins are proteins that are expressed on the endothelial cell surface, and bind to leukocytes’ receptors, in order to adhere leukocytes loosely during their “rolling” process.

**Integrins **are proteins that are expressed on the leukocyte cell membrane. They become activated during the “rolling” process, and then bind to integrin ligands on the endothelial surface, in order to adhere leukocytes firmly.

Question 8

Name the three selectins. Give an example of an integrin ligand that binds integrins.

Answer 8

Selectin-E, Selectin-P, Selectin-L. ICAM-1 (intercellular adhesion molecule 1) binds integrin from leukocytes.

Question 9

At what stage of the inflammatory response do neutrophils act, and when do monocytes act?

Answer 9

Neutrophils are more numerous in blood than monocytes. Neutrophils predominate during the first 6-24 hours, and then are replaced by monocytes after 24-48 hours: at this stage, neutrophils undergo apoptosis.

Question 10

What kind of cell signalling process is used in chemotaxis? Explain, giving examples of some chemotactic agents.

Answer 10

Chemotactic agents (such as complement fragments, arachidonic acid metabolites, chemokines, and exogenous bacterial products) bind to G-protein coupled receptors on the leukocyte surface –> activation of phospholipase C, etc.

Question 11

What are the three steps in phagocytosis?

Answer 11

1. Recognition (microbes bind to phagocyte receptors).
2. Engulfment (phagocyte membrane zips up around microbe).
3. Degradation (ingested material is now in a phagosome, which fuses with a lysosome, where enzymes, ROS and NO degrade the material)

Question 12

What do all these have in common? Lysozyme, collagenase, gelatinase, lactoferrin, plasminogen activator, histaminase, and alkaline phosphatase.

Answer 12

They are all contained in neutrophil lysosomal granules.

Question 13

What are the two ways that neutrophil lysosomal granules can make use of their contents?

Answer 13

1. They can fuse with phagosomes, and digest the contents.
2. They can be released into the extracellular space, to act there. (ROS can also be released into the extracellular environment, so you can imagine how this can be damaging to nearby tissue)

Question 14

Under what circumstances can leukocytes damage normal cells? What mechanisms do leukocytes use to damage normal cells?

Answer 14

1. Infections that are difficult to eradicate, causing a chronic inflammatory response.
2. Autoimmune diseases.
3. Allergy.

In all these situations, the mechanisms by which leukocytes damage normal tissues are the same as the mechanisms involved in antimicrobial defense, because once the leukocytes are activated, their effector mechanisms do not distinguish between offender and host.

Question 15

Describe the two major processes that act to terminate the inflammatory process.

Answer 15

1. Inflammatory mediators have short half-lives, and degrade quickly after their release, whilst neutrophils undergo apoptosis hours after leaving the blood.
2. The inflammatory process involves production of “stop” signals, including various anti-inflammatory cytokines.

Question 16

Complement System 1

What are the names of the various complement proteins, and where are they found when inactive?

Answer 16

Complement proteins are present as inactive plasma forms numbered C1 through C9.

Question 17

Complement System 2

What is the critical step in complement activation? What are the three different pathways that can activate the complement system?

Answer 17

Cleavage of C3.

1. Alternative pathway (C3b opsonizes microbes)
2. Classical pathway (antigen-antibody complexes)
3. Lectin pathway (Mannose-binding lectin)

Question 18

What is an opsonin? Give three examples.

Answer 18

An opsonin is something that binds to an antigen, marking it for phagocytosis.

1. Antibodies
2. Complement proteins
3. Mannose-binding lectin

Other examples include CRP and Serum Amyloid A

Question 19

What are the two major vasoactive amines, and where are they stored?

Answer 19

Histamine and serotonin. They are stored as preformed molecules in cells (e.g. histamine in mast cells and serotonin in neuroendocrine cells, and both in platelets) and are therefore among the first mediators to be released during inflammation. (Other vasoactive amines need to be newly synthesized or activated first).

Question 20

Complement System 3

What is MAC? What does it do?

Answer 20

Membrane Attack Complex, composed of multiple C9 molecules. It causes lysis of the microbe.

Question 21

Complement System 4

Apart from MAC, what are some other ways that the complement system can combat microbes?

Answer 21

C3b opsonizes microbes for phagocytosis. C5a and C3a stimulate histamine release and additional inflammation, and leukocyte chemoattraction.

Question 22

What are the two major categories of arachidonic acid metabolites?

Answer 22

Prostaglandins and Leukotrienes.

Question 23

What is the major difference between COX-1 and COX-2 ?

Answer 23

They are both induced by inflammatory stimuli, but COX-1 is also consitutively expressed in most normal tissues, whilst COX-2 is only involved in inflammatory responses.

Question 24

What specific process do steroids inhibit?

Answer 24

Steroids inhibit phospholipases. Phospholipases convert cell membrane phospholipids into arachidonic acid.

Question 25

What is an important function of thromboxane A2 (TxA 2) ? Which drug inhibits its production, and how?

Answer 25

It is an important mediator of platelet aggregation and vasoconstriction. Aspirin is a COX-inhibitor, thereby inhibiting production of TXA2.

Question 26

Cyclooxygenases produces prostaglandins and TXA2. What produces leukotrienes?

Answer 26

Lipoxygenases.

Question 27

Apart from lymphocytes, macrophages and dendritic cells, what other cells can release cytokines?

Answer 27

Endothelial, epithelial, and connective tissue cells.

Question 28

Name two important cytokines that come from macrophages and are important activators of leukocyte recruitment.

Answer 28

TNF and IL-1.

Question 29

Apart from cytokines, chemokines and complement proteins, name a few other mediators of inflammation.

Answer 29

Kinins (e.g. bradykinin), PAF (platelet activating factor), Neuropeptides (e.g. substance P)

Question 30

What causes purulent inflammation? (Also called suppurative inflammation)

Answer 30

Bacterial infection causing liquefactive tissue necrosis –> pus. e.g. staphylococci.

Question 31

Name three possible final outcomes of acute inflammation in tissue.

Answer 31

1. Complete resolution.
2. Scarring, fibrosis.
3. Progression to chronic inflammation.

Question 32

How are macrophages produced?

Answer 32

Maturation of monocytes.

Question 33

What is granulomatous inflammation?

Answer 33

Granulomatous inflammation is a form of chronic inflammation characterized by collections of activated macrophages, often with T lymphocytes, and sometimes associated with central necrosis. Granuloma formation is a cellular attempt to contain an offending agent that is difficult to eradicate.

Question 34

In granulomatous inflammation, what is a giant cell?

Answer 34

A giant cell is formed when multiple macrophages fuse together, forming a multinucleated giant cell.

Question 35

When granulomatous inflammation involves central necrosis, what kind of necrosis is it usually?

Answer 35

Caseous necrosis.

Question 36

Give some examples of diseases involving granulomatous inflammation.

Answer 36

Tuberculosis. Leprosy. Syphilis. Cat-scratch disease. Sarcoidosis. Crohn’s disease.

Question 37

Give some examples of acute phase proteins. Where are they produced? What do they do in inflammation?

Answer 37

CRP, fibrinogen, serum amyloid A. Produced in the liver. CRP and SAA can act as opsonins. Fibrinogen causes RBCs to stack into rouleaux.

Question 38

*Reversed Card*

They are all contained in neutrophil lysosomal granules.

Answer 38

What do all these have in common? Lysozyme, collagenase, gelatinase, lactoferrin, plasminogen activator, histaminase, and alkaline phosphatase.