Chronic inflammation Flashcards
What is chronic inflammation?
Chronic inflammation is prolonged inflammation ( >3 months), where tissue injury & attempts at repair coexist, in varying combinations
What causes chronic inflammation?
- Persistent infections - by microorganisms that are difficult to eradicate e.g. mycobacteria, some viruses, fungi & parasites.
- Hypersensitivity diseases - Autoimmune diseases or Allergic diseases.
- Foreign material e.g. thorn, hair…
- Carcinoma - the immune system reacts to abnormal proteins found in tumour cells.
What are the morphologic features of chronic inflammation?
- Infiltration by mononuclear cells e.g. macrophages, lymphocytes & plasma cells.
- Tissue destruction
- Attempts at healing - by angiogenesis & fibrosis.
What are the cells involved in inflammation?
Macrophages
Lymphocytes
Plasma cells
What is the role of macrophages in chronic inflammation?
Dominant cell in most chronic inflammatory reactions.
- Become dominant 2 days after infection or injury.
Role
- They secrete cytokines & growth factors
- Destroy foreign invaders & tissues
- Activate other cells e.g. T-lymphocytes.
Where are macrophages derived from?
Derived from haematopoietic stem cells in bone marrow.
Circulate as monocytes before activation.
Where are macrophages found inn the body?
-Connective tissue
- CNS (Microglia)
- Liver (Kuppfer cells)
- Lymph nodes (Sinus histiocytes)
- Lungs (Alveolar macrophages)
- Spleen (Sinus histiocytes)
Explain the function of the 2 different macrophage subtypes & what activates them?
- M1 - activated by bacteria or interferon gamma (INF-𝛄) from T-cells. M1 macrophages will:
- Present antigens
- Produce NO and ROS
- Upregulate lysomal enzymes.
- Secrete cytokines that stimulate inflammation e.g. IL-1, TNF-⍺, IL-6 & IL-12. Interleukin-12 causes T-helper cells to differentiate into TH1 cells.
- CLASSICAL MACROPHAGE ACTIVATION - M2 - activated by IL-4 or IL-13 from T-cells. M2 will:
- Secrete growth factors e.g. IL-10, TGF-β
- Stimulate angiogenesis
- Stimulate collagen synthesis
- ALTERNATIVE MACROPHAGE ACTIVATION
Name the lymphocytes seen in chronic inflammation
- T lymphocytes
- B lymphocytes
What is granulomatous inflammation? What is a granuloma?
A form of chronic inflammation which the body uses to get rid of pathogens which are difficult to eliminate
A granuloma- collection of activated macrophages also called epithelioid histiocytes.
- Epithelioid= resembling epithelial cells but there are no actual epithelial cells, just macrophages.
How can granulomas be classified?
Either caseating or non-caseating.
Caseating:
central region of necrosis
- appear cheese-like
- Usually in lungs
Non-caseating:
- no central region of necrosis
- occur more commonly
Give an example of each classification
Caseating granulomas- seen in:
-mycobacterium tuberculosis infection (TB)
- Fungal infection
- Syphilis - Treponema pallidum infection.
- Mycobacterium leprae - cause of leprosy.
Non-caseating granulomas seen in:
- Foreign bodies
- Sarcoidosis - involves the lung & lymph nodes.
- Crohns’ disease - form of inflammatory bowl disease.
- Cat scratch disease - Bartonella henselae infection (bacterial)
How do Granulomas form?
- Macrophages present antigen on their surfaces with MHC II molecules to helper T-cells
- Macrophages then secrete IL-12 which causes helper T cells to differentiate into TH1 cells
- TH1 cells secrete interferon gamma (IN-Y) & IL-2
- Interferon gamma then converts macrophages into granulomas & giant cells- I.e. macrophage activation
- Macrophages & T-cells secrete TNF alpha
- Increased accumulation of inflammatory cells
NOTE: interferon gamma production can be detected clinically to help make a diagnosis of tuberculosis.
When does process of wound healing occur?
Healing begins when inflammation begins.
What does wound healing involve?
Tissue regeneration & repair.
This is dependent on the regenerative capacity of the tissue.
What are the 3 types of tissue based on regenerative capacity?
- Labile - contain stem cells e.g. skin, bowel lining & bone marrow.
- Stable - quiescent (dormant) but can regenerate in the need arises e.g. liver (hyperplasia).
- Permanent - lack significant regenerative potential e.g. myocardium, skeletal muscle & neurons.
Explain the 4 phases of wound healing
Coagulation Phase:
- Damage to blood vessels brings Hageman factor into contact w/ collagen, which starts clotting cascade.
- Thrombus is formed.
Inflammatory Phase:
- Platelets:
- Platelets contribute to clot formation (coagulation).
- fibrin mesh of the blood clot acts as a scaffold for the immune cells.
- Platelets degranulate & release growth factors e.g. PDGF. Stimulates proliferation by mitosis of undamaged cells. - Neutrophils:
- Clear* wound of debris & bacteria. - Macrophages:
- Replace neutrophils to continue removing debris & bacteria.
- They release wound healing mediators e.g. IL-10.
- Release growth factors that recruit fibroblasts & help promote the formation of new blood supply (angiogenesis).
- NOTE: angiogenesis occurs in the proliferative phase of wound healing.
Proliferative/ granulation tissue phase;
- Starts 3 days after injury.
- Granulation tissue forms - this is a proliferation of new capillaries & fibroblasts.
- Fibroblasts deposit type 3 collagen.
Remodelling phase:
- 1-2 weeks after injury
- Myofibroblasts remodel the extracellular matrix.
- Remodelling followed by apoptosis & aceullular scar formation.
Name the growth factors in healing & their effect
- Transforming Growth Factor alpha (TGF-α) - epithelial & fibroblast growth.
- Transforming Growth Factor beta (TGF-β) - fibroblast growth & inhibits inflammation.
- Platelet Derived Growth Factor (PDGF) - growth of endothelium, smooth muscle & fibroblasts.
- Fibroblast Growth Factor (FGF) - Angiogenesis & fibroblast proliferation.
-Vascular Endothelial Growth Factor(VEGF) - angiogenesis
What are the 2 types of surgical wound healing?
Primary Intention - wound edges brought together = minimal scarring.
Secondary Intention - edges not brought together.
- Occurs when there is lots of tissue loss or there is a need to delay wound closure e.g. infection.
- Granulation tissue fills the gap, then myofibroblasts contract the wound = scar forms.
What are the 2 types of excess scar formation?
Hypertrophic scar
- excess production of scar tissue that is localised to the would.
Keloid Scar
- Scar overgrows the wound edges.
Due to an excess of Type III collagen
- More common in black people.
What can delay wound healing?
Infection - continued production of PAMPs = more acute inflammation.
Ischaemia - cells can’t get to site if blood flow is impaired.
Foreign bodies - act as a ‘nidus’ (nest) for infection.
Diabetes- pathogens love sugar. Diabetes narrows blood vessels & impair growth factor production.
Malnutrition - Vit C is needed for collagen cross linking; Zinc is a co-factor for collengenase (which replaces type III collagen from graulation tissue w/ stronger type I).
Name one vitamin & two minerals which are important for wound healing. How do these contribute to the wound healing process?
Vitamin C, copper & zinc.
Deficiencies of vitamin C and copper will delay healing as both are involved in the formation of collagen crosslinks.
Zinc deficiency - zinc is a co-factor for collagenase which is required to replace type 3 collagen with type 1 collagen.
