Chronic inflammation

Question 1

What does the stimulus do, that causes chronic inflammation to begin?

Answer 1

Prolonged inflammation (weeks-months) due to persistence of the stimulus

Question 2

What are the 3 main cell types involved in chronic inflammation?

Answer 2

Macrophages

Lymphocytes

Plasma cells

Question 3

Why is chronic inflammation more specific than acute inflammation?

Answer 3

Involves adaptive immune system

Question 4

What are the 5 most common causes of chronic inflammation?

Answer 4

Excessive allergic reaction

Autoimmune disease

Persistent infection that is hard to eradicate

Foreign material eg. blocks hair follicle and causes hair to grow in foreign compartment

Carcinoma

Question 5

Why can carcinoma cause chronic inflammation?

Answer 5

Immune response due to abnormal proteins in tumour cells

Question 6

What is the main and most dominant cell type, that regulates chronic inflammation?

Answer 6

Macrophage

Question 7

Give 6 body areas where macrophages reside?

Answer 7

Connective tissue

Kupffer cells: liver resident macrophages

Spleen

Sinus histiocytes: lymph nodes resident macrophages

Microglia: CNS resident macrophages

Alveolar macrophages: lung resident macrophages

Question 8

What are the 3 characteristic microscopic findings of macrophages?

Answer 8

Lots of cytoplasm

Foreign material granules

Phagocytic vacuoles

Question 9

In chronic inflammation, which macrophage subtype stimulates inflammation?

Answer 9

M1

Question 10

In chronic inflammation, which macrophage subtype stimulates repair/healing?

Answer 10

M2

Question 11

What 2 substances stimulate M1 macrophages to cause chronic inflammation?

Answer 11

Bacteria

Interferon gamma produced by T cells

Question 12

When M1 macrophages have be recruited in chronic inflammation, what is their primary and initial role?

Answer 12

To present antigens

Question 13

What 2 substances stimulate M2 macrophages to cause repair after chronic inflammation?

Answer 13

IL-13

IL-14

Both are produced by T cells

Question 14

When M2 macrophages have be recruited in chronic inflammation, what is their primary and initial role?

Answer 14

To build ECM

Question 15

Apart from chronic inflammation, lymphocytes are the dominant population in which 2 types of conditions?

Answer 15

Autoimmune diseases

Hypersensitivity diseases

Question 16

What is the difference between T and B lymphocytes, in terms of where they mature?

Answer 16

T-cells mature in thymus, B-cells mature in bone marrow

Question 17

In the thymus, what 2 cell subtypes do progenitor T lymphocytes mature into?

Answer 17

CD4+ helper T-cells

CD8+ cytotoxic T-cells

Question 18

How is the T-receptor complex formed, what is its main role and how is it activated?

Answer 18

Combination of CD3 antigen and T-receptor

Used by T cells to recognises antigen-bound MHC molecules (the first signal)

Needs second signal to be activated

Question 19

What is the first signal to activate CD4+ T helper cells, in chronic inflammation?

Answer 19

Foreign materials processed, fragments bound to MHC II, complex is presented on outside of APC cell membrane

Question 20

What is the second and final signal to activate CD4+ T helper cells?

Answer 20

T-cell receptor complex binds to presented antigen on MHC II, CD28 from T-cell binds to B7 from APC

This provides second signal

Question 21

When CD4+ TH-1 cells are activated, what is their main role?

Answer 21

Secrete interferon gamma to stimulate M1 macrophages

Question 22

When CD4+ TH-2 cells are activated, what is their main role?

Answer 22

Recruit eosinophils so that B-cells are stimulated to produce IgE (eg. in allergy)

Question 23

What is the first signal to activate CD8+ T cytotoxic cells, in chronic inflammation?

Answer 23

Intracellular antigens processed, fragments bound to MHC I, complex is presented on APC cell membrane

Question 24

What cell types express MHC I?

Answer 24

All nucleated cells and platelets

Question 25

How does the CD8+ cytotoxic T cell bind to the APC?

Answer 25

Cytotoxic T-cell receptor with CD8 co-receptor binds to antigen-MHC I complex

Question 26

What is the second and final signal to activate CD8+ T cytotoxic cells?

Answer 26

TH-1 CD4+ cells produce IL-2, which provides second activation signal

Question 27

What are the 2 killing methods of CD8+ cytotoxic T cells?

Answer 27

Perforin and granzyme secretion: Perforin creates pores for granzymes to enter target cell Binding of FAS ligand to FAS on target cell: Apoptosis of target cell

Question 28

How do B lymphocytes become naive B cells in chronic inflammation?

Answer 28

Undergo immunoglobulin gene arrangement to become naive B-cells which express IgD and IgM

Question 29

What triggers the conversion of naive B cells into mature plasma cells, in chronic inflammation?

Answer 29

Antigen binds to IgD or IgM (which are both expressed by naive B cells) Triggers maturation of naive B-cell into IgD or IgM-secreting plasma cell

Question 30

How is the plasma cell activated by T helper cells in chronic inflammation, to start secreting antibodies?

Answer 30

CD40 receptor on B-cell binds to CD40 ligand on helper T-cell

Question 31

What determines whether a mature plasma cell will secrete IgM or IgD antibodies, in chronic inflammation?

Answer 31

Cytokines which are present determine the class of immunoglobulin which the B-cell will produce

Question 32

What form of chronic inflammation is used for pathogens that are hard to eradicate?

Answer 32

Granulomatous inflammation

Question 33

What cell type makes up a granuloma?

Answer 33

Epithelioid histiocytes (resembles epithelial cells but there are actually no epithelial cells, just plump macrophages)

Question 34

Are granulomas caseating or noncaseating?

Answer 34

Can be either

Question 35

Give 5 examples of conditions that can activate granulomatous inflammation?

Answer 35

Sarcoidosis, Crohn’s disease, Cat scratch disease, mycobacterial infection, fungal infection

Question 36

If the granulomatous inflammation occurs due to a foreign material, is the granuloma more likely to be caseous or noncaseous?

Answer 36

Noncaseous

Question 37

What is the role of interferon gamma in formation of caseating granulomas, and where does the interferon gamma come from?

Answer 37

TH-1 CD4+ cells secrete interferon gamma interferon gamma converts macrophages into epithelioid histiocytes and giant cells

Question 38

Do all types of tissue have the same ability to repair and heal wounds?

Answer 38

No, each tissue has different regenerative capacity Ability of tissue to repair depends on type of tissue that is damaged

Question 39

What is the regenerative capacity of labile tissue, and give 3 examples of labile tissue?

Answer 39

Contains stem cells so can heal eg. Skin, bowel lining, bone marrow

Question 40

What is the regenerative capacity of stable tissue, and give an example of stable tissue?

Answer 40

Normally quiescent but can regenerate if the need arises eg. Liver

Question 41

What is the regenerative capacity of permanent tissue, and give 3 examples of permanent tissue?

Answer 41

Lack significant regenerative potential so needs to be repaired if damaged eg. myocardium, skeletal muscle and neurons

Question 42

What are the 4 phases of wound healing?

Answer 42

Coagulation phase Inflammatory phase Proliferative phase Remodeling phase

Question 43

What is the main regulatory system that initiates the coagulation phase of wound healing, and what is it activated by?

Answer 43

Clotting system activated by hageman factor

Question 44

In the inflammatory phase of wound healing, what do platelets do?

Answer 44

Platelets congregate and degranulate, release platelet derived growth factor

Question 45

In the inflammatory phase of wound healing, what 2 cell types regulate inflammation?

Answer 45

Neutrophils: Acute Macrophages: Chronic

Question 46

In the proliferative phase of wound healing, which 3 cell types produce growth factors and what is their purpose?

Answer 46

Damaged epithelial cells, platelets, macrophages Growth factors cause new vessels to grow into wound

Question 47

In the proliferative phase of wound healing, what 2 new tissues form?

Answer 47

Granulation tissue Scar tissue

Question 48

In granulation tissue during the proliferative phase of wound healing, what cells does it contain apart from new blood vessels and what are their roles?

Answer 48

Fibroblasts: deposits type III collagen (stretchy, pliable) Myofibroblasts: causes wound contraction as they have actin in cytoplasm

Question 49

In scar tissue during the proliferative phase of wound healing, what 2 layers does it have?

Answer 49

Top: Granulation tissue layer Bottom: Predominantly fibroblast layer with type I collagen

Question 50

In scar tissue during the proliferative phase of wound healing, what type of collagen is in the fibroblast layer and how is it formed?

Answer 50

Type I collagen Breakdown of type III collagen by collagenase with zinc cofactor produces type I collagen

Question 51

In the remodeling phase of wound healing, what 2 steps lead to the formation of an acellular scar?

Answer 51

1. myofibroblasts begin to remodel the extracellular matrix 2. myofibroblasts undergo apoptosis leading to the formation of an acellular scar

Question 52

What is the importance of platelet derived growth factor in wound healing?

Answer 52

Causes new vessels to grow and help scars to form

Question 53

What is the importance of TGF-beta in wound healing, and what cell type secretes it?

Answer 53

Secreted by macrophages Stops inflammation and causes fibroblasts to proliferate

Question 54

Why can lack of vitamin C cause delayed wound healing?

Answer 54

Vitamin C is needed for collagen cross-linking

Question 55

Why can lack of copper cause delayed wound healing?

Answer 55

Copper is needed for collagen cross-linking

Question 56

Why can lack of zinc cause delayed wound healing?

Answer 56

Zinc is a cofactor for the enzyme collagenase, which replaces the type III collagen of granulation tissue with stronger type I collagen

Question 57

Why can diabetes delay wound healing?

Answer 57

Diabetes can impair growth factor production

Question 58

What are the 2 types of scars that can form as a result of excess scar tissue?

Answer 58

Hypertrophic: confined to area of the wound Keloid: overgrown wound, not confined to area

Question 59

Where are keloid scars most likely to form, after wound healing?

Answer 59

Head and neck, ear lobes, shoulder and chest

Question 60

Which 2 growth factors specifically promote scar formation and vessel growth, in wound healing and repair?

Answer 60

Fibroblast growth factor Vascular endothelial growth factor

Question 61

What is meant by surgical wound healing by primary intention, and what kind of scar does this leave?

Answer 61

Wound edges are brought together (suturing) Minimum scarring

Question 62

What is meant by surgical wound healing by secondary intention, and what kind of scar does this leave?

Answer 62

Edges not brought together, so granulation tissue forms in between Forms scar

Question 63

What is meant by surgical wound healing by tertiary intention?

Answer 63

Wound closing is delayed

Question 64

Why is surgical wound healing by tertiary intention used to close infected tissue?

Answer 64

Infected tissue needs to be treated with antibiotics first Once infection has resolved, wound is closed

Question 65

What type of collagen is present in excess in keloid scars?

Answer 65

Type III collagen