Test 1: 08-09 Chronic Inflammation

Question 1

1. What extends chronic inflammation?

Answer 1

Causative stimuli persistence

Question 2

2. What are 3 morphological features of chronic inflammation

Answer 2

i. Infiltration of mononuclear cells
ii. Tissue destruction
iii. attempts at healing by CT tissue replacement, angiogenesis, and fibrosis

Question 3

3. How does chronic inflammation begin?

Answer 3

Low grade, smoldering response without signs of acute inflammation

Question 4

4. Chronic inflammation may be the result of?

Answer 4

i. Persistent infections by certain microbes
ii. Immune-mediated inflammatory diseases
iii. Prolonged exposure to toxic exogenous (silica) or endogenous (atherosclerosis) agents

Question 5

5. Persistent infections by certain microbes can be difficult to erase. What do they have in common?

Answer 5

i. Low toxicity
ii. Evoke delayed hypersensitivity response
iii. Pattern called “granulomatous reaction”

Question 6

6. What are causes immune-mediated inflammatory diseases and give an example of each? Pattern?

Answer 6

a. Three causes
i. Autoimmune diseases i.e. rheumatoid arthritis, multiple sclerosis
ii. Unregulated immune responses i.e. inflammatory bowel diseases
iii. Allergic response i.e. bronchial asthma
b. Pattern: mixed acute and chronic inflammation, fibrosis may occur

Question 7

7. What do macrophages formed from and migrate to? Origin?

Answer 7

a. From circulating blood monocytes and migrate out of bloodstream into tissue
b. Bone marrow

Question 8

8. What are organs/tissues are macrophages especially concentrated in and what are their names?

Answer 8

i. Liver (Kupffer cells)
ii. Spleen and lymph nodes (sinus histiocytosis)
iii. Lungs (alveolar/pulmonary macrophages)
iv. CNS microglia

Question 9

9. Macrophages serve as? What is this system called?

Answer 9

a) Filter for matter, microbes, senescent (old) cells

b) The mononucleated phagocyte system

Question 10

10. Activation signals for macrophages include cytokines, what are these secreted by? Give two more activation signals

Answer 10

Sensitized T & NK cells, bacterial endotoxin, other chemical mediators

Question 11

11. After activation, macrophages secrete many biologically active proteins whose roles are?

Answer 11

Keep pathogens in check, can also cause host injury and fibrosis if inappropriately activated

Question 12

12. Give six products secreted by macrophages and a brief description if any

Answer 12

i. Acid and neutral proteases (toxic to ECM)
ii. Complement components and coagulation factors
iii. Reactive oxygen species and nitrogen species (toxic to microbes and host cells)
iv. AA metabolites (eicosandoids)
v. Cytokines, (IL-1 & TNF) and chemotactic factors (cause influx of other cells)
vi. Growth factors (cause collagen deposition and angiogenesis)

Question 13

13. In chronic inflammation, what happens to macrophages? What mediates one of these processes?

Answer 13

a. Macrophages persistently accumulate and proliferate
b. Accumulation mediated by
i. Recruitment of monocytes from circulation
ii. Local proliferation after emigration from bloodstream
iii. Immobilization of macrophages

Question 14

14. Tissue damage in chronic inflammation may also be caused by what four things?

Answer 14

i. Necrotic tissue
ii. Leukocyte mediators
iii. Liberation of substances from dying tissue
iv. Killing by T lymphocytes

Question 15

15. What mobilizes lymphocytes? What relationship do T-lymphocytes and macrophages have?

Answer 15

a. Any immune stimulus/non-immune inflammation

b. Reciprocal (bidirectional) relationship

Question 16

16. What initially activates T-lymphocytes? What do these activated ones produce? What do these activated ones release?

Answer 16

a. Antigen-presenting macrophages
b. Cytokines that recruit monocytes including IFN-y(major activator of macrophages)
c. Cytokines, including IL-4 and TNF further activating lymphocytes/other cell types

Question 17

a. Antigen-presenting macrophages
b. Cytokines that recruit monocytes including IFN-y(major activator of macrophages)
c. Cytokines, including IL-4 and TNF further activating lymphocytes/other cell types

Answer 17

a. B-cell activation
b. Antibodies against persistent antigens
c. Patterns of organogenesis, resembling lymphoid organs

Question 18

18. Eosinophils are seen? One of the most powerful chemokines recruiting eosinophils is? What eosinophils contain and what does this cause?

Answer 18

a. Parasitic infections or immune reactions mediated with IgE (allergies)
b. Eotaxin
c. Granules with major basic protein (MBP), cationic protein toxic to paratsites but also causes epithelial cell lysis

Question 19

19. Mast cells participate in? “Armed” with? Releases? 3 roles?

Answer 19

a. Both acute and chronic inflammation
b. IgE to certain antigens
c. Histamines and prostaglandins
d. Roles
i. Anaphylactic shock
ii. Infections
iii. Elaborating cytokines (TNF) contributes to fibrosis

Question 20

20. Neutrophils appear where? Also called?

Answer 20

a. Both acute and chronic inflammation

b. Acute chronic inflammation or chronic active inflammation

Question 21

21. What is granulomatous inflammation? Mechanism dealing with? Activator of? Activation of which leads to?

Answer 21

fill in

Question 22

22. What is responsible for persistent macrophage activation in granulomatous inflammation? What is a granuloma and what are the types?

Answer 22

a. T-cell derived cytokines
b. Granuloma: focus of chronic inflammation of macrophage aggregation turned into epithelium like cells surrounded by mononuclear leukocytes (mainly lymphocytes and sometimes plasma cells)
c. Foreign body granuloma and immune granuloma

Question 23

23. Foreign body granulomas form as a response to? Form when? What forms as a result? In the end usually granulomas function as?

Answer 23

a. Response to usually inert foreign bodies
b. When foreign material is too large for a single macrophage and does not incite inflammation/immune response
c. Epithelioid cells and giant cells
d. Walls off offending object so may be defense

Question 24

24. Immune granulomas are caused by a variety of agents capable of? Usually occurs when? Process? Give four settings in which granulomas may form

Answer 24

a. Cell-mediated response
b. Insoluble particles
c. Macrophages take in and present to appropriate T-lymphocytes leading to T-lymph activation
d. Persistent T-cell responses to certain microbes such as:
i. Treponema pallidum (syphilitic gumma)
ii. Certain fungi
iii. Mycobacterium tuberculosis

Question 25

25. Morphologically how do macrophages in granulomas appear in H&E sections? When it ages what do granulomas form and how is it formed?

Answer 25

a. Activated macrophages in granulomas have pink, granular cytoplasm and indistinct boundaries b. Rim of fibroblasts and CT due to cytokines secreted by activated macrophages

Question 26

26. Sometimes multinucleated giant cells appear; what are they derived from? How are these they arranged?

Answer 26

a. Fusion of macrophages | b. Peripherally (Langhans-type giant cells) or haphazardly (foreign body-type giant cells)

Question 27

27. In some infections (TB) there may be a central zone of necrosis in the granuloma, what is this caused by? How does it appear grossly? What is the name for this appearance? What is needed for granulomas to form?

Answer 27

a. Hypoxia and free radical injury b. Cheesy, granular appearance c. Caseous necrosis d. Poorly digestible irritants/T-cell mediated immunity

Question 28

28. Lymphatics provide defense by? Purpose of lymph flow in inflammation? Significance of valves? Drainage may transport the offending agent and lymphatics may become?

Answer 28

a. Filtering and policing extravascular fluid b. Drainage from extravascular space c. Lymph flow only proximally d. Lymphatics inflamed (lymphangitis), lymph nodes (lymphadenitis)

Question 29

29. If the secondary barriers of inflammation defense are overwhelmed, what may this lead to? What is the next line of defense? What may form when the pathogens enter the heart vavles, meninges, kidneys, and joints?

Answer 29

a. Pathogen access to circulation leading to bacteremia (sepsis) b. Phagocytic cells of liver, spleen, and bone marrow c. Organs and massive infection names: i. Heart valves: endocarditis ii. Meninges: meningitis iii. Kidneys: renal abscesses iv. Joints: septic arthritis

Question 30

30. Sepsis causes activation of? Inflammation symptoms attributed to? Most prominent systemic manifestation of inflammation and process?

Answer 30

a. Mediator systems in plasma and inflammatory cells b. Cytokines c. Hypothalamic-pituitary-adrenal axis, leukocytes/acute phase response, fever and shock

Question 31

31. Systemic effects of inflammation are called?

Answer 31

Acute-phase response or systemic inflammatory response syndrome (SIRS)

Question 32

32. What is the acute-phase response characterized by (5)? Give the cause and its stimulation?

Answer 32

a. Symptoms i. Fever ii. Leukocytosis iii. Decreased appetite iv. Altered sleep patterns v. Changes of plasma in acute phase proteins b. Cytokines whose production stimulated by bacterial products like LPS etc.

Question 33

33. Fever is produced in response to? Give examples

Answer 33

Exogenous pyrogens (bacteria LPS) or endogenous pyrogens (cytokines such as IL-1 and TNF)

Question 34

34. What do cytokines stimulate in the hypothalamic thermoregulatory centers that increase fever? This in turn, has production stimulated by? What inhibits the fever response and how?

Answer 34

a. Cytokines stimulate prostaglandin synthesis b. IL-1 and TNF increase the enzymes (cyclooxygenase) that convert AA into prostaglandins c. Inhibitors of cyclooxygenase (i.e. aspirin) by inhibiting prostaglandin synthesis in the hypothalamus

Question 35

35. Acute-phase proteins are plasma proteins that are mostly synthesized in? What changes the plasma levels of this?

Answer 35

a. Liver | b. IL-1, IL-6, and TNF-α

Question 36

36. Give three famous acute phase proteins. Role? Markers/indicators for what test(s)?

Answer 36

a. Acute phase proteins: i. C-reactive protein (CRP) ii. Fibrinogen iii. Serum amyloid A protein (cause 2° amyloidosis) b. Bind to microbial cell walls acting as opsonins and fix complements c. Indicators i. Elevated CRP: risk of myocardial infarction ii. Rise in fibrinogen levels (makes RBCs stick and form stacks called rouleaux) is basis of test called Erythrocyte Sedimentation Rate (ESR) = presence of systemic inflammatory response

Question 37

37. Leukocytosis is common in inflammatory reactions. What are three characteristics of it?

Answer 37

i. Neutrophilia: increase of neutrophils ii. Lymphocytosis: increase of lymphocytes iii. Eosinophila

Question 38

38. In neutrophilia, what are high WBC counts called?

Answer 38

Leukemoid reactions

Question 39

39. Why does leukocytosis occur?

Answer 39

An accelerated release of cells from bone marrow and rise of immature neutrophils in blood

Question 40

40. Lymphocytosis is an? Seen in?

Answer 40

Increase number of lymphocytes seen in infectious mononucleosis, mumps, and German measles

Question 41

41. When does eosinophilia occur?

Answer 41

Bronchial asthma, hay fever, and parasitic infections

Question 42

42. Leukopenia is?

Answer 42

Decrease in number of white cells

Question 43

43. What are two other manifestations of leukopenia?

Answer 43

i. Autonomic: increase pulse and blood pressure, decreased sweating, redirect blood flow from shallow to deep beds ii. Behavioral: shivering, chills, anorexia, somnolence, and malaise

Question 44

44. In severe bacterial infections (sepsis), large quantities of what is produced? High levels of these change what?

Answer 44

a. Cytokines b. Host response changes: i. Disseminated intravascular coagulation (DIC) ii. Thrombosis iii. Liver injury iv. Overproduction of NO

Question 45

45. What does overproduction of NO do?

Answer 45

Leads to heart failure, drop in blood pressure (hemodynamic shock)

Question 46

46. Septic shock is a triad of?

Answer 46

i. DIC ii. Hypoglycemia iii. Cardiovascular failure

Question 47

what are two consequences of defective(3)/excessive inflammation(2)?

Answer 47

a. Defective i. Increase susceptibility of infections ii. Delayed healing of wounds iii. Tissue damage b. Excessive i. Basis of many diseases ii. Non primary immune disorders (e.g. cancer, atherosclerosis, ischemic heart disease, and some neurodegenerative diseases, chronic infectious metabolic and other diseases)