Chronic inflammation Flashcards
What does the stimulus do, that causes chronic inflammation to begin?
Prolonged inflammation (weeks-months) due to persistence of the stimulus
What are the 3 main cell types involved in chronic inflammation?
Macrophages
Lymphocytes
Plasma cells
Why is chronic inflammation more specific than acute inflammation?
Involves adaptive immune system
What are the 5 most common causes of chronic inflammation?
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
Why can carcinoma cause chronic inflammation?
Immune response due to abnormal proteins in tumour cells
What is the main and most dominant cell type, that regulates chronic inflammation?
Macrophage
Give 6 body areas where macrophages reside?
Connective tissue
Kupffer cells: liver resident macrophages
Spleen
Sinus histiocytes: lymph nodes resident macrophages
Microglia: CNS resident macrophages
Alveolar macrophages: lung resident macrophages
What are the 3 characteristic microscopic findings of macrophages?
Lots of cytoplasm
Foreign material granules
Phagocytic vacuoles
In chronic inflammation, which macrophage subtype stimulates inflammation?
M1
In chronic inflammation, which macrophage subtype stimulates repair/healing?
M2
What 2 substances stimulate M1 macrophages to cause chronic inflammation?
Bacteria
Interferon gamma produced by T cells
When M1 macrophages have be recruited in chronic inflammation, what is their primary and initial role?
To present antigens
What 2 substances stimulate M2 macrophages to cause repair after chronic inflammation?
IL-13
IL-14
Both are produced by T cells
When M2 macrophages have be recruited in chronic inflammation, what is their primary and initial role?
To build ECM
Apart from chronic inflammation, lymphocytes are the dominant population in which 2 types of conditions?
Autoimmune diseases
Hypersensitivity diseases
What is the difference between T and B lymphocytes, in terms of where they mature?
T-cells mature in thymus, B-cells mature in bone marrow
In the thymus, what 2 cell subtypes do progenitor T lymphocytes mature into?
CD4+ helper T-cells
CD8+ cytotoxic T-cells
How is the T-receptor complex formed, what is its main role and how is it activated?
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
What is the first signal to activate CD4+ T helper cells, in chronic inflammation?
Foreign materials processed, fragments bound to MHC II, complex is presented on outside of APC cell membrane
What is the second and final signal to activate CD4+ T helper cells?
T-cell receptor complex binds to presented antigen on MHC II, CD28 from T-cell binds to B7 from APC
This provides second signal
When CD4+ TH-1 cells are activated, what is their main role?
Secrete interferon gamma to stimulate M1 macrophages
When CD4+ TH-2 cells are activated, what is their main role?
Recruit eosinophils so that B-cells are stimulated to produce IgE (eg. in allergy)
What is the first signal to activate CD8+ T cytotoxic cells, in chronic inflammation?
Intracellular antigens processed, fragments bound to MHC I, complex is presented on APC cell membrane
What cell types express MHC I?
All nucleated cells and platelets
How does the CD8+ cytotoxic T cell bind to the APC?
Cytotoxic T-cell receptor with CD8 co-receptor binds to antigen-MHC I complex
What is the second and final signal to activate CD8+ T cytotoxic cells?
TH-1 CD4+ cells produce IL-2, which provides second activation signal
What are the 2 killing methods of CD8+ cytotoxic T cells?
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
How do B lymphocytes become naive B cells in chronic inflammation?
Undergo immunoglobulin gene arrangement to become naive B-cells which express IgD and IgM
What triggers the conversion of naive B cells into mature plasma cells, in chronic inflammation?
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
How is the plasma cell activated by T helper cells in chronic inflammation, to start secreting antibodies?
CD40 receptor on B-cell binds to CD40 ligand on helper T-cell
What determines whether a mature plasma cell will secrete IgM or IgD antibodies, in chronic inflammation?
Cytokines which are present determine the class of immunoglobulin which the B-cell will produce
What form of chronic inflammation is used for pathogens that are hard to eradicate?
Granulomatous inflammation
What cell type makes up a granuloma?
Epithelioid histiocytes (resembles epithelial cells but there are actually no epithelial cells, just plump macrophages)
Are granulomas caseating or noncaseating?
Can be either
Give 5 examples of conditions that can activate granulomatous inflammation?
Sarcoidosis,
Crohn’s disease,
Cat scratch disease,
mycobacterial infection,
fungal infection
If the granulomatous inflammation occurs due to a foreign material, is the granuloma more likely to be caseous or noncaseous?
Noncaseous
What is the role of interferon gamma in formation of caseating granulomas, and where does the interferon gamma come from?
TH-1 CD4+ cells secrete interferon gamma
interferon gamma converts macrophages into epithelioid histiocytes and giant cells
Do all types of tissue have the same ability to repair and heal wounds?
No, each tissue has different regenerative capacity
Ability of tissue to repair depends on type of tissue that is damaged
What is the regenerative capacity of labile tissue, and give 3 examples of labile tissue?
Contains stem cells so can heal
eg. Skin, bowel lining, bone marrow
What is the regenerative capacity of stable tissue, and give an example of stable tissue?
Normally quiescent but can regenerate if the need arises
eg. Liver
What is the regenerative capacity of permanent tissue, and give 3 examples of permanent tissue?
Lack significant regenerative potential so needs to be repaired if damaged
eg. myocardium, skeletal muscle and neurons
What are the 4 phases of wound healing?
Coagulation phase
Inflammatory phase
Proliferative phase
Remodeling phase
What is the main regulatory system that initiates the coagulation phase of wound healing, and what is it activated by?
Clotting system activated by hageman factor
In the inflammatory phase of wound healing, what do platelets do?
Platelets congregate and degranulate, release platelet derived growth factor
In the inflammatory phase of wound healing, what 2 cell types regulate inflammation?
Neutrophils: Acute
Macrophages: Chronic
In the proliferative phase of wound healing, which 3 cell types produce growth factors and what is their purpose?
Damaged epithelial cells, platelets, macrophages
Growth factors cause new vessels to grow into wound
In the proliferative phase of wound healing, what 2 new tissues form?
Granulation tissue
Scar tissue
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?
Fibroblasts: deposits type III collagen (stretchy, pliable)
Myofibroblasts: causes wound contraction as they have actin in cytoplasm
In scar tissue during the proliferative phase of wound healing, what 2 layers does it have?
Top: Granulation tissue layer
Bottom: Predominantly fibroblast layer with type I collagen
In scar tissue during the proliferative phase of wound healing, what type of collagen is in the fibroblast layer and how is it formed?
Type I collagen
Breakdown of type III collagen by collagenase with zinc cofactor produces type I collagen
In the remodeling phase of wound healing, what 2 steps lead to the formation of an acellular scar?
- myofibroblasts begin to remodel the extracellular matrix
- myofibroblasts undergo apoptosis leading to the formation of an acellular scar
What is the importance of platelet derived growth factor in wound healing?
Causes new vessels to grow and help scars to form
What is the importance of TGF-beta in wound healing, and what cell type secretes it?
Secreted by macrophages
Stops inflammation and causes fibroblasts to proliferate
Why can lack of vitamin C cause delayed wound healing?
Vitamin C is needed for collagen cross-linking
Why can lack of copper cause delayed wound healing?
Copper is needed for collagen cross-linking
Why can lack of zinc cause delayed wound healing?
Zinc is a cofactor for the enzyme collagenase, which replaces the type III collagen of granulation tissue with stronger type I collagen
Why can diabetes delay wound healing?
Diabetes can impair growth factor production
What are the 2 types of scars that can form as a result of excess scar tissue?
Hypertrophic: confined to area of the wound
Keloid: overgrown wound, not confined to area
Where are keloid scars most likely to form, after wound healing?
Head and neck, ear lobes, shoulder and chest
Which 2 growth factors specifically promote scar formation and vessel growth, in wound healing and repair?
Fibroblast growth factor
Vascular endothelial growth factor
What is meant by surgical wound healing by primary intention, and what kind of scar does this leave?
Wound edges are brought together (suturing)
Minimum scarring
What is meant by surgical wound healing by secondary intention, and what kind of scar does this leave?
Edges not brought together, so granulation tissue forms in between
Forms scar
What is meant by surgical wound healing by tertiary intention?
Wound closing is delayed
Why is surgical wound healing by tertiary intention used to close infected tissue?
Infected tissue needs to be treated with antibiotics first
Once infection has resolved, wound is closed
What type of collagen is present in excess in keloid scars?
Type III collagen
