Chronic inflammation + wound healing

Question 1

What is chronic inflammation?

Answer 1

• prolonged inflammation (weeks/months) due to persistence of stimulus
• characterised by macrophages, lymphocytes + plasma cells in tissue
• delayed response but more specific (adaptive immunity)

Question 2

Causes of chronic inflammation

Answer 2

• persistent infection
• infection with viruses, mycobacteria, parasites + fungi
• autoimmune disease
• foreign material
• carcinoma (immune system reacts to abnormal proteins in tumour cells)

Question 3

Describe macrophages

Answer 3

• tissue macrophage lifespan = months/years
• dominant around 2 days post-insult

M1:
- activated by bacteria of interferon gamma from T-cells
- stimulate inflammation
(If T-cells produce interferon gamma, M1 macrophages are recruited + these present antigens promoting inflammation)

M2:
- activated by IL-4 or IL-13 from T-cells
- stimulate repair
(If T-cells produce IL-4 or IL-13 then M2 macrophages are recruited + these build extracellular matrix, stimulating repair)

Question 4

What is a granuloma?

Answer 4

collection of activated macrophages/epitheliad histiocytes

- can be caseating (eg caused by TB) or non-caseating (eg caused by foreign bodies)

Question 5

How do granulomas form?

Answer 5

• macrophages process + present antigen on surface in association with MHC 2 molecules to CD4+ helper T-cells
• macrophages secrete IL-12 - causes CD4+ helper T-cells to differentiate into TH1 subtype
• TH1 cells secrete interferon gamma - converts macrophages into epitheliod histiocytes + giant cells

Question 6

Describe CD4+ helper T-cell activation

Answer 6

• foreign proteins processed by antigen-presenting cell + presented in association with MHC 2 on cell surface + B7 on APC membrane is molecule which provides 2nd activation signal for T-helper cells
• T-cell receptor complex (TCR + CD3) binds to antigen on MHC 2 and CD28 binds to B7, providing 2nd signal
• 2 types T-helper cells (Th1 + Th2)

Question 7

Th1 cells function

Answer 7

secrete interferon gamma to recruit macrophages

Question 8

Th2 cells function

Answer 8

involved in allergy
recruit eosinophils
cause B-lymphocytes to produce IgE

Question 9

Describe CD8+ T-cell activation

Answer 9

• cytotoxic T-cells needed to deal with intracellular antigens
• proteins processed + presented on MHC 1 molecules (expressed by all nucleated cells + platelets)
• cytotoxic T-cell receptor with CD8 co-receptor binds to complex (antigen + MHC 1) + IL-2 produced by CD4+ T-helper cells provides 2nd activation signal
• cytotoxic T-cells activated for killing

Question 10

2 killing methods of cytotoxic T-cells

Answer 10

• secretion of perforin + granzyme (perforin creates pores so granzyme can enter + destroy target cell)
• binding of FAS ligand to FAS on target cell (end result = apoptosis)

Question 11

Describe B-cell activation

Answer 11

• occurs via antigen binding by surface IgM or IgD
• results in maturation to IgM- or IgD-secreting plasma cells
• CD40 receptor on B-cell then binds CD40 ligand on helper T-cells, providing 2nd activation signal
• cytokines which are present determine class of immunoglobulin B-cell will produce
• hypermutation in antibody variable region (arms of Y-shape) determines affinity of antibody for antigen

Question 12

Wound healing platelet function

Answer 12

contribute to clot formation:

- degranulate + release growth factors that begin proliferation of undamaged cells

Question 13

Wound healing neutrophil function

Answer 13

clear wound of debris + bacteria

later replaced by macrophages

Question 14

Wound healing macrophage function

Answer 14

vacuum cleaners

release wound healing mediators + growth factors that recruit fibroblasts

Question 15

Wound healing fibroblast function

Answer 15

promote formation of new blood supply (angiogenesis) during wound healing proliferative phase

Question 16

3 types of tissue (by regenerative capacity)

Answer 16

labile = have stem cells (eg bone marrow, bowel lining, skin)
stable = normally quiescent but can regenerate if needed (eg liver)
permanent = lack significant regenerative potential (eg myocardium, skeletal muscles, neurones)

Question 17

What is repair?

Answer 17

damaged tissue replaced by fibrous scar

needed if stem cells lost or damaged tissue = permanent tissue

Question 18

List the 4 wound healing stages

Answer 18

Coagulation phase
Inflammatory phase
Proliferative phase
Remodelling phase

Question 19

Describe coagulation phase

Answer 19

damage to blood vessels brings Hageman factor in contact with collagen
coagulation cascade occurs
thrombosis

Question 20

Describe inflammatory phase

Answer 20

platelets congregate + degranulate
neutrophils arrive + later macrophages
cells from blood provide scaffold + provide growth factors needed to recruit epithelial cells + connective tissue into wound bed

Question 21

Describe proliferative phase

Answer 21

~3 days post-injury
granulation tissue formation
damaged epithelial cells, platelets + macrophages produce growth factors
new vessels grow into wound

Question 22

Describe remodelling phase

Answer 22

1-2 weeks post-injury
myofibroblasts remodel extracellular matrix
followed by apoptosis
acellular scar

Question 23

Transforming growth factor (TGF) alpha

Answer 23

epithelial + fibroblast growth

Question 24

Transforming growth factor (TGF) beta

Answer 24

secreted by macrophages
fibroblast growth (fibroblasts secrete collagen)
inflammation inhibition

Question 25

Platelet derived growth factor (PDGF)

Answer 25

released when platelets degranulate

growth of endothelium, smooth muscle + fibroblasts

Question 26

Fibroblast growth factor (FGF)

Answer 26

angiogenesis

fibroblast proliferation

Question 27

Vascular endothelial growth factor (VEGF)

Answer 27

angiogenesis

Question 28

What is primary intention?

Answer 28

wound edges brought together (eg suturing)

minimal scarring

Question 29

What is secondary intention?

Answer 29

edges not brought together
granulation tissue fills gap
myofibroblasts contract wound
scar forms

Question 30

What is tertiary intention?

Answer 30

occurs when need to delay wound closure

Question 31

Name 2 types of excess scar tissue

Answer 31

hypertrophic scar

keloid scar

Question 32

Describe hypertrophic scar

Answer 32

excess production of scar tissue

localised to wound

Question 33

Describe keloid scar

Answer 33

production of scar tissue out of proportion to wound size
excess type 3 collagen
more common in black people
very thick pink collagen bundles under microscope

Question 34

Causes of delayed wound healing

Answer 34

DID NOT HEAL

D = diabetes 
I = Infection/ischaemia
D = drugs (eg steroids, chemotherapy)

N = nutritional deficiencies
O = object (foreign material)
T = tissue necrosis

H = hypoxia
E = excess tension on wound
A = another wound
L = low temperature