Lecture 16 Flashcards
What is meant by the term chronic inflammation?
Refers to inflammation of a prolonged duration in which active inflammation and tissue destruction occurs while attempts at repair occur simultaneously
When does chronic inflammation occur?
- AI fails
- Repeat AI episodes
- Due to unique characteristics of inciting stimulus
Can chronic inflammation arise without a prior discernible AI phase?
yes
What are the biological mechanisms under which AI occurs?
- Persistence/Resistance (occurs with certain infections)
- Isolation (microbial agents have developed mechanisms to hide from the pathogens
- Unresponsiveness - inert yet an irritant (e.g. when certain foreign materials are indestructible- e.g grass seed)
- Autoimmunity, hypersensitivity and leukocyte defects (genetic dysfunction of oxidative killing in leukocytes or in adaptive immune responses)
- Unidentified mechanisms - unusual diseases e.g Alzheimer’s
What are the classical cellular features that will always be observed
- Cellular infiltrate (Macrophages = granulomatous inflammation, lymphocytes (+NK), plasma cells, multi nucleated giant cells, +/- eosinophils/mast cells, +/- neutrophils
- Tissue destruction and replacement by inflammatory infiltrate
- Attempts at healing by connective tissue (replacement of damaged tissue, proliferation, angiogenesis and organ architecture morphologically altered)
Explain what happens in the process of sequestration:
Two concurrently occurring processes are occurring:
1) Cellular infiltration
2) Fibroplasia
If these processes fail the lesion eventually becomes completely walled off by collagen from the fibroblasts encapsulating the lesion and it’s agents functionally placing them outside the body.
What do the macrophages come from?
They are derived from blood monocytes and they and migrate into areas of tissue injury.
Differentiate between the M1 and the M2 macrophages:
M1 (Classical) = exposed to antigens, activated by endotoxin + TLR, then release ROS, NO, IL-1, IL-12 to promote inflammation and destruction of microbial pathogens.
M2 (alternative) = activated by IL-4, IL-13 to stimulate tissue repair
What are the factors that are responsible for the conversion of monocytes to dendritic cells?
IL-4, GM-CSF
What are the surface receptors that are expressed on dendritic cells?
TLR, lectins, +/- Fc, C3b
What is the function of the dendritic cells?
They present the antigen to the T-lymphocytes resulting in the acquired/adaptive immune response
What are the cytokines and growth factors that are produced by the dendritic cells?
Pro-inflammatory cytokines: IL-1, TNF-a, IL-12 (pro-inflammatory cytokines)
Anti-inflammatory: IL-10
Growth factors for fibrosis: FGF, TGF-B
What is the name of the B lymphocytes that produce specific antibodies and appear morphologically different?
plasma cells
Would lymphocytes be present in autoimmune and delayed type hypersensitivity responses?
yes
Are lymphocytes present in granulomatous inflammation?
It is dependent on lymphocyte responses and bi-directional interaction between lymphocytes and macrophages
What is the main type of cell that is found within connective tissue?
fibroblasts
What is the role of fibroblasts?
- They proliferate and synthesize ECM components providing structural integrity and tensile strength to wounds
- They are a rich source of growth factors including keratinocyte GF and IGF-1
What is chronic inflammation with macrophages classified as?
histiocytic
What is chronic inflammation based on epithelioid macrophages and MNGC classified as?
granulomatous
What is chronic inflammation based on lymphocytes and plasma cells called?
lymphoplasmacytic
What is chronic inflammation based neutrophils and epithelioid macrophages called?
pyogranulomatous
Briefly describe the gross pathology you would expect to observe as a consequence of chronic inflammation:
- Areas of swelling/thickening/nodularity
- Fibrosis - areas will appear pale and firm
- Cellular infiltration & proliferation - areas appear pale (cell type) and of variable texture (could be harder or softer)
- Concurrent tissue loss - the organ has an irregular surface +/- shrunken tissue loss
What are the key features seen in a microbial abscess?
- Persistent inciting agent (bacteria/fungi)
- Acute inflammatory response (neutrophils) fails to kill the microorganism
- Central lytic core of necrotic debris (purulent exudate) surrounded by a zone of macrophages/lymphocytes/plasma cells and encapsulated by fibrous tissue (walled off)
What is the problem with chronic pulmonary abscesses?
They may also provide an environment suitable for micro-organism survival and low pH and O2 concentration means impaired neutrophil function
What are some possible sequelae to abscess rupture?
External rupture: the cavity fills with granulation tissue and heals by second intention –> replacement by a fibrous connective tissue scar
Internal rupture: Spreads along fascial planes –> widespread fasciitis/cellulitis –> ruptures into a blood vessel or airway –> bacteraemia and septicaemia
What are the complications of osteomyelitis?
Sequestrum: necrotic bone acts as a foreign body
Involucrum: subperiosteal new bone covers the sequestrum
