Chronic inflammation Flashcards
Why can inflammation be prolonged?
Acute inflammatory response fails to eliminate stimulus
Resistance to phagocytosis or enzymatic breakdown
Autoimmune reactions
What are the effector cells involved in chronic inflammation?
Macrophages
Adaptive immune cells (lymphocytes, plasma cells)
Fibroblasts
What is the function of macrophages?
Phagocytosis
Antigen presentation
Facilitate repair
Describe the classic activation of macrophages (M1 macrophages)
Activated by microbes, cytokines (e.g., interferon-γ)
M1 microphages are Proinflammatory, microbiocidal
Produce: reactive O2 species (ROS), Nitric Oxide (NO), proteases, cytokines
Describe the alternative activation of macrophages (M2 macrophages)
Activated by IL-4 (+ others) produced by T-lymphocytes
M2 macrophages are Pro-fibrosis and cause wound repair
Produce: growth factors (e.g. TGF-β), anti-inflammatory cytokines
Describe the function of lymphocytes in inflammation
Amplification and modulation of immune response
Eliminate virus-infected or neoplastic cells
Formation of long-lived, specific memory cells
What are the different types of T-lymphocytes and their functions?
CD4+ T cells:
- Propagate and modulate inflammation
- T helper cells, T regulatory cells
CD8+ T cells:
- Cytotoxic killing
- Cytotoxic T cells
What is the function of plasma cells in inflammation?
Produce antibodies
Describe macrophage-lymphocyte interaction in chronic inflammation
Activated T-cells produce cytokines that recruit macrophages (TNF, IL-17, chemokines) and other that activate macrophages (IFN-y)
Activated macrophages in turn stimulate T cells by presenting antigens and via cytokines such as IL-12
How are fibroblasts activated?
Activated by cytokines and growth factors (e.g., TGF-B)
What is the function of fibroblasts?
Produce collagen => fibrous tissue to replace destroyed tissue and wall off microbes from the rest of the body
Also stimulate angiogenesis
How can granulation tissue be produced in chronic inflammation?
Immature fibroplasia + angiogenesis = granulation tissue
Describe the structure of granulomas
Central accumulation of activated macrophages, multinucleated giant cells +/- necrosis
Peripheral rim of lymphocytes, plasma cells, fibroblasts
What causes granulomas?
Nodular granulomas are a typical pathologic response to specific stimuli:
- Mycobacterium tuberculosis complex bacteria (M. bovis +)
- Deep fungal infections
- Foreign material (e.g. suture)
- Parasites
T helper 1 cell response
How can chronic inflammation result in resolution?
eliminating the stimulus or walling off the stimulus with fibrosis
How can chronic inflammation cause dysfunction?
due to destruction/ displacement of the normal cell population
e.g., Inflammatory bowl disease→ impaired absorption leading to weight loss.
Inflammatory brain disease→ destruction of neurons/glia, increased intracranial pressure, obstruction of CSF outflow
What are the morphological patterns of chronic inflammation?
Lymphoplasmacytic
Abscesses
Granulomas
Granulomatous inflammation
Pyogranulomatous inflammation
Granulation tissue
Fibrosis and repair
What are the main cells present in lymphoplasmacytic inflammation?
lymphocytes
plasma cells
Where is lymphoplasmacytic inflammation most common?
Mucosal surfaces
e.g., chronic gingivitis, rhinitis, enteritis
What are the clinical signs of chronic dermatitis?
Diffusely firm and thickened skin
Multifocal crusting - hyperkeratosis
Multifocal alopecia
What is an abscess?
Discrete, dense collection of neutrophils surrounded by a rim of connective tissue (fibroblasts, small blood vessels and collagen
Why do abscesses occur?
Failed acute inflammatory response
Attempt to wall off exudate and agent
Can be sterile or septic
Often caused by pyogenic bacteria
Why can abscesses be difficult to solve?
Antibiotics sometimes cannot permeate
Can require drainage to eliminate
Describe the gross appearance of granulomas
Discrete, well demarcated masses/ nodules; round to oval
Tan, grey, or white
Firm to hard
Caseating granulomas have a central core of grey-white-yellow pasty necrotic material; can have gritty areas of mineralization
Can be VERY small
Label the granuloma
What cells are present in granulomatous inflammation?
Macrophages; typically activated (epithelioid) +/- multinucleated giant cells (MNGCs)
Lymphocytes, plasma cells also often present
What does the development of granulomatous inflammation require?
Stimulus that is either poorly degradable or provides persistent antigens
Incites a T-helper cell and macrophage response
Describe the gross appearance of granulomatous inflammation
Poorly demarcated areas of thickened tissue
Grey, tan, or white
Firm
Give examples of causes of granulomatous inflammation
T helper 2 response
Mycobacterium avium subsp. paratuberculosis (Johne’s disease)
Granulomatous colitis/ Histiocytic ulcerative colitis in dogs
Invasive E. coli
Migrating parasites (Helminth larvae)
What are histiocytes?
macrophages in tissues
What is pyogranulomatous inflammation?
Granulomatous inflammation + neutrophils
Discrete and nodular lesions (neutrophils in center)
Describe the gross appearance of granulation tissue
Red and granular
Can be edematous; newly formed blood vessels can be leaky
What is the best gross indicator of chronic inflammation?
Fibrosis results in contracture of the organ parenchyma => irregular, undulating appearance to the capsular surface.
