Chronic inflammation + wound healing Flashcards
What is chronic inflammation?
- prolonged inflammation (weeks/months) due to persistence of stimulus
- characterised by macrophages, lymphocytes + plasma cells in tissue
- delayed response but more specific (adaptive immunity)
Causes of chronic inflammation
- persistent infection
- infection with viruses, mycobacteria, parasites + fungi
- autoimmune disease
- foreign material
- carcinoma (immune system reacts to abnormal proteins in tumour cells)
Describe macrophages
- 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)
What is a granuloma?
collection of activated macrophages/epitheliad histiocytes
- can be caseating (eg caused by TB) or non-caseating (eg caused by foreign bodies)
How do granulomas form?
- 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
Describe CD4+ helper T-cell activation
- 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)
Th1 cells function
secrete interferon gamma to recruit macrophages
Th2 cells function
involved in allergy
recruit eosinophils
cause B-lymphocytes to produce IgE
Describe CD8+ T-cell activation
- 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
2 killing methods of cytotoxic T-cells
- 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)
Describe B-cell activation
- 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
Wound healing platelet function
contribute to clot formation:
- degranulate + release growth factors that begin proliferation of undamaged cells
Wound healing neutrophil function
clear wound of debris + bacteria
later replaced by macrophages
Wound healing macrophage function
vacuum cleaners
release wound healing mediators + growth factors that recruit fibroblasts
Wound healing fibroblast function
promote formation of new blood supply (angiogenesis) during wound healing proliferative phase
3 types of tissue (by regenerative capacity)
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)
What is repair?
damaged tissue replaced by fibrous scar
needed if stem cells lost or damaged tissue = permanent tissue
List the 4 wound healing stages
Coagulation phase
Inflammatory phase
Proliferative phase
Remodelling phase
Describe coagulation phase
damage to blood vessels brings Hageman factor in contact with collagen
coagulation cascade occurs
thrombosis
Describe inflammatory phase
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
Describe proliferative phase
~3 days post-injury
granulation tissue formation
damaged epithelial cells, platelets + macrophages produce growth factors
new vessels grow into wound
Describe remodelling phase
1-2 weeks post-injury
myofibroblasts remodel extracellular matrix
followed by apoptosis
acellular scar
Transforming growth factor (TGF) alpha
epithelial + fibroblast growth
Transforming growth factor (TGF) beta
secreted by macrophages
fibroblast growth (fibroblasts secrete collagen)
inflammation inhibition
