Chronic inflammation and wound healing - Pathology Flashcards
What are the 3 factors in chronic inflammation
Prolonged inflammation from persistence of injury causing agent,
Presence of lymphocytes and plasma cells in tissue
Delayed specific (adaptive) response
What are the 4 things that can cause chronic inflammation
Persistent infection of difficult onganisms (viruses, mycobacteria, parasites and fungi)
Autoimmune disease
FOreign material
Carcinoma
What role do macrophages play in chronic inflammation
Dominant role, become so within 48 hours of onset
How are macrophages activated via the classical pathway
Bacterial products engage TLRs, or by interferon gamma. M1 macrophages produce NO, ROS and upregulate lysosomal enzymes killinf ingested organisms.
Cytokines secreted, inflammation stimulated
Describe how macrophages are stimulated via the alternative pathway
Induced by cytokines other than interferon gamma. M2 macrophages secrete growth factors promoting angiogenesis, fibroblast activation and collagen synthesis. These focus on tissue repair
What is angiogenesis
The process where new blood vessels form from existing ones
Where are T-lymphocytes produced and where do they develop
Produced as progenitor cells in bone marrow, develop further in the thymus.
What two types of cell can progenitor T cells develop into
CD4+ T helper cells, or CD8+ cytotoxic T-cells
What do T-cells use for antigen surveillance?
TCR complex (TCR and CD3). THis recognises antigens on MHC molecules. T cells activated with a second signal
What is the second ligand that activated T helper cells apart from MHC II
B7 on antigen binding to CD28 on the T helper cell provides the necessary second activation signal
WHAT do T h 1 cells do
Secrete interferon Gamma, Promotes B-cells to class switch from IgM to IgG, Activates macrophages by classical path Promotes Th1 cells and inhibits Th2 cells.
Involved against viruses and bacteria
What do Th2 cells do?
Secrete IL4, 5, and 13. IL4 stimulates B cells to class switch to IgE, IL5 stimulates eosinophil (so does IL13) chemotaxis/activatin, and class switching to IgA
Involved against parasites or allergic reactions
How are cytotoxic t cells activated?
MHC I molecules present intracellular antigens, meet with TCR and CD8 co-receptor on cytotoxic t cell.
IL-2 from a CD4 T helper cell provides a second activation signal
Another cytotoxic t cell binds to oringinal cell via FAS ligand, activating apoptosis
What do naive B cells express to meet with antigens before maturation to plasma cells
IgM or IgD.
What happens once an antigen binds to a B cell
The antigen complex is preented to CD4+ helper T cells, along with MHC II. CD40 is a coreceptor, T helper cell secretes IL4 and IL5 to cause B cell to mature to plasma cell
What are the two types of granuloma
immune granuloma or foreign body granuloma
When do foreign body granulomas form?
Forms when the inciting agent cannot be readily eliminated,
When do foreign body granulomas form
In response to relatively inert foreign bodies in the absence of T-cell mediated immune responses
How do granulomas form
Macrophages present ingected antigen to CD4+ th cells. Macrophages release Il12 to form TH1 cells which secrete interferon gamma, converting macrophages into epithelioid histiocytes and giant cells
What are the two basic principles of wound healing
regeneration and repair
What is a labile tissue
One that possesses stem cells that continuously cycle to regenerate tissue
What is a stable tissue
Cells that can re-enter the cell cycle to regenerate tissue when necessary
What is a permanent tissue?
There is no significant regenerative potential
What is replacement in a healing sense
Replacement of a damaged tissue with natice tissue
What is repair in a healing sense
Replacement of damaged tissue with a fibrous scar
when does the repair stage occur
When regenrative stem cells are lost or tissue lacks regenerative capacity
What is the initial phase of repair?
Granulation tissue
What makes up granulation tissue
Proliferated capillaries (nutrients), fibroblasts (III collagen) and myofibroblasts (wound closure)
How does collagen change in scar formation
From type III (pliable) to type I (high tensile strength
How are tissue regeneration and repair mediated?
Paracrine signalling as macrophages secrete growth factors targeting fibroblasts.
these result in gene expression and cellular growth
What does transforming growth factor (TGF) alpha do
Promotes epithelial and fibroblast growth
What does TGF beta do
Promotes fibroblast growth anf inhibition of inflammation
What does Platelet derived growth factor (PDGF) do?
Encourages growth of endothelium, smooth muscle and fibroblasts
What does fibroblast growth factor do
Promotes angiogenesis and skeletal development
What does vascular endothelial growth factor do?
Promotes angiogenesis
What are the four stages of wound healing
Coagulation
Inflammatory
Proliferative/granulation
Remodelling
What is healing by primary intention?
Wound edges brought together (suturing) leading to minimal scarring
What is healing by secondary intention
Edges not brought together, granulation tissue fills the gap, myofibroblasts contract the wound. Scar forms
What is a hypertrophic scar
Excess production of scar tissue, localised around the wound
What is a keloid scar
Exuberant production of scar tissue disporportionate of wound size.
How does vitamin C deficiency play a role in delayed healing?
Disrupted collagen cross-linking
How does copper deficiency play a role in delayed healing?
Disrupted collagen cross-linking
How does zinc deficiency play a role in delayed healing?
Replaces type III with type I
What is autoimmunity
Failure of self tolerance
What is hypersensitivity
Excess immune reaction
What are the four types of hypersensitivity reaction
Tyoe I (anaphylaxis, allergy, asthma)
Type II (Antibody mediated, haemolytic anaemia)
Type III (Immune complex related, SLE, glomerulonephritis)
Type IV (T-cell mediated, RA, Psoriasis)
How do regulatory T-cells suppress autoimmunity?
Blocking T-cell activation and producing anti-inflammatory cytokines
