Chronic inflammation Flashcards
Definition of chronic inflammation?
Inflammation of prolonged duration (weeks/months/years)
When does chronic inflammation occur?
-The acute inflammation
response fails to remove the stimulus
- Repeated episodes of acute inflammation
- The stimulus or microbe has unique biochemical characteristics or virulence factors which incite chronic inflammation
Mechanisms of chronic inflammation?
- Persistent or resistant infections
- Isolation
- Unresponsiveness to phagocytosis or enzymatic breakdown (e.g. plant material, asbestos)
- Autoimmunity (response to self antigens promote chronic inflammation) or defects in leukocyte function
- Idiopathic
What is the chronic inflammation response maintained by?
- Cytokines
- Chemokines
- Other inflammation mediators
What incites chronic inflammation?
- Ongoing inflammation mediated by infiltration and activation of lymphocytes, macrophages, plasma cells and multinucleate giant cells
- Tissue destruction
- Proliferation of fibroblasts and deposition of collagen
- Angiogenesis and neovascularisation (granulation tissue formation)
- Initiation of wound healing (reepitheliasation and tissue repair)
Beneficial aspects of chronic inflammation?
-‘Walling off’ the inciting agent or substance
Harmful aspects of chronic inflammation?
- Space occupying lesions (focal, multifocal, diffuse) can be formed resulting in:
- Displacement, replacement or obliteration of original tissue
- Loss of function
- Clinical significance determined by the size, tissue and position
-Dysplasia and malignant transformation of chronically inflamed tissue
What do birds and reptile lack?
-Myeloperoxidase (in neutrophils)- so unable to liquefy neutrophils into pus
What is Granulomatous inflammation?
- Distinct type of chronic inflammation
- Dominated by cells of the monocyte-macrophage system
- take the form of macrophages, epithelioid macrophages, multinucleated giant cells (MCGs)
- These cells may be :
- dispersed as sheets at random within tissue (diffuse or lepromatous granulomas)
- arranged in descrete masses or nodules (nodular or tuberculoid granulomas)
What are Nodular (tuberculoid) granulomas?
-Develop with a T helper lymphocyte Type 1 response
- May or may not have a central core of necrotic debris, which can mineralise
- with necrotic core = caseating
- without= noncaseating - Microscopic appearance:
- Round to oval
- Numerous macrophages with variable number of epithelioid macrophages, MCGs
- Peripheral zone of fibroblasts, lymphocytes and plasma cells
- may have fibrous capsule
Causes of Nodular granulomas?
- Mycobacterium bovis/ Tuberculosis
- Deep fungal infections
What are Diffuse (lepromatous) granulomas?
- Develop with a T Helper Lymphocte Type 2 response
- Poorly delineated, forming sheets within tissue
- Composed of numerous macrophages and few lymphocytes and plasma cells
Causes of Diffuse (lepromatous) granulomas?
- Mycobacterium avian subsp. paratuberculosis (Johne’s disease)
- Mycobacterium lapraemurium (Feline leprosy)
What is Eosinophilic granulomas?
-Characterised by dense infiltration of eosinophils, macrophages and varying numbers of lymphocytes and plasma cells
What do all species have?
- Eosinophilic (TH2) granuloma secondary to parasitic infections
What do cats have?
- Eosinophilic plaque
- Eosinophilic granuloma
- Eosinophilic dermatitis
What do dogs have?
-Eosinophilic granuloma of oral cavity of huskies and other breeds
What do horses have?
- Equine collagenolytic granuloma
- Axillary nodular necrosis
- Unilateral papular dermatosis
What is Pyogranulomatous inflammation?
- A pyogranuloma = nodular granuloma with a central area of neutrophils
- same cellular constituents as granulomatous inflammation
- Also contains neutrophils, plasma proteins and fibrin (acute inflammation response)
- Occurs when the inciting stimulus continues to elicit and acute inflammatory response
What is lymphoplasmacytic inflammation?
- also called chronic inflammation (often seen in the early stages)
- composed of lymphocytes and plasma cells (lymphoplasmacytic)
- sometimes lymphocytes and macrophages predominate over plasma cells (=lymphohistiocytic)
- seen in response to specific microbes e.g. viruses
What is chronic-active inflammation?
- occurs when inciting cause has not been removed from the exudate of a chronic inflammatory response
- Cellular components of chronic inflammation (lymphocytes, plasma cells, macrophages)
- Also constituents of acute inflammation (neutrophils, fibrin, plasma proteins)
Neutrophils
- first type of leukocyte recruited into acute inflammation response
- Kill microbes
- Kill tumour cells
- eliminate foreign material
- Phagocytosis and secretion/release of contents of granules
- allow time for adaptive immune response to act
Eosinophils
- Recruited by eosinophil chemoattractants present in allergic and parasitic diseases
- enter at transition between acute and chronic inflammation
- prominent granules that release basic protein
- when activated- produce cytokines, chemokines, proteases, oxidative radical
- contribute to damage in many diseases
- when activated- produce cytokines, chemokines, proteases, oxidative radical
NK cells
- enter regions of acute inflammation hour to days after onset
- Lyse tumour cells and virus infected cells without prior encounter
- Release perforin from cytoplasmic granules
Monocytes and macrophages
- enter acute inflammation 12-48 hours after onset
- circulating monocytes mature to macrophages in this environment due to cytokines, antigens
- Tissues have resident macrophages e.g. alveolar, Kupffer. microglial
- set stage for chronic inflammation
- main trigger for adaptive immune response
Lymphocytes
- enter sites of acute inflammation 12-48 hours after onset
- recruited by chemokines, cytokines
- part of adaptive immune response
- contribute to chronic inflammetion, autoimmune disease, and diseases with persistent antigen
- plasma cells differentiate to B lymphocytes- secrete immunoglobulin
Mott cells?
- lymphocytes
- ‘constipated’ plasma cells
Mast cells
- Normally distributed in connective tissue adjacent to blood and lymphatic vessels of skin and mucous membranes
- allows rapid response to antigens (mainly in acute inflammation, but is found in chronic)
Other cells contributing to inflammation:
- Endothelial
- Fibroblasts
- Dendritic
- Epithelium
