Chronic inflammation Flashcards
What is chronic inflammation
Prolonged inflammation (weeks to years)
+- acute inflammation
Why is it prolonged?
Acute inflammatory response fails to eliminate stimulus
Resistance to phagocytosis or enzymatic breakdown
Autoimmune reactions
What effector cells are involved in chronic inflammation?
Macrophages
Adaptive immune cells
- lymphocytes
- plasma cells
Fibroblasts
What is the function of macrophages
Phagocytosis
Antigen presentation
Facilitate repair
Action depends on environment
Describe the classic activation of macrophages (M1)
Activated by microbes, interferon-y
M1 macrophages are pro-inflammatory & microbiocidal
produce:
- reactive O2 species (ROS), nitric oxide, proteases, cytokines
Describe alternative activation of macrophages (M2)
Activated by IL-4 (& others) produced by T-lymphocytes
M2 macrophages are pro-fibrosis & cause wound repair
produce:
- growth factors (e.g. TGT-b), anti-inflammatory cytokines
Describe the function of lymphocytes in inflammation
Amplification & modulation of immune response
Eliminate virus-infected or neoplastic cells
Formation of long-lived, specific memory cells
What are the type of T lymphocytes & their function?
CD4+ T cells
- propagate & 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 the macrophage-lymphocyte interactions in chronic inflammation
Activated T-cells produce cytokines that recruit macrophages (TNF, IL-17, chemokines) & others that activate macrophages (IFN-y)
Activated macrophages in turn stimulate T cells by presenting antigens & via cytokines such as IL-12
How are fibroblasts activated?
by cytokines & growth factors
Mediated by macrophage signalling
What is the function of fibroblasts
Produce collagen
- fibroblasts + collagen = fibrous tissue
- replaces destroyed tissue
- walls of microbes from rest of body
Angiogenesis
- formation of new blood supply
- immature fibroplasia + angiogenesis = granulation tissue
What causes granulomas?
Nodular granulomas are typical pathologic response to specific stimuli
- Mycobacterium tuberculosis complex bacteria
- deep fungal infections
- foreign material
- parasites
TH1 response
What is the structure of granulomas
Central accumulation of activated macrophages, multinucleated giant cells +- necrosis
Peripheral rim of lymphocytes, plasma cells & fibroblasts
What are the possible outcomes of chronic inflammation?
Resolution by eliminating stimulus or walling it off with fibrosis
Dysfunction of original tissue due to destruction/displacement of normal cell population
- e.g. inflammatory bowel disease –> impaired absorption leading to weightloss
Outcome depends on location & extent of tissue involvement
What are the morphologic patterns of chronic inflammation?
Lymphoplasmacytic
Abscesses
Granulomas
Granulomatous inflammation
Pyogranulomatous inflammation
Granulation tissue
Fibrosis and repair
Describe lymphoplasmacytic inflammation
Main cells present: lymphocytes & plasma cells
Very common (not specific for any one aetiology)
Lymphocytes & plasma cells almost always present to some degree in early stages of chronic inflammation
Common type of inflammation at mucosal surfaces:
- chronic gingivitis, rhinitis, enteritis
What are the clinical signs of chronic dermatitis?
Diffusely firm & thickened skin
Multifocal crusting
Multifocal alopecia
What are abscesses?
Discrete, dense collection of neutrophils surrounded by rim of connective tissue (fibroblasts, small blood vessels & collagen), nodular
Why do abscesses occur?
When acute inflammatory response fails
Attempt to wall of exudate & agent
Can be sterile or septic
Pyrogenic bacteria can often be cause
Why can abscesses be a problem?
Antibiotics sometimes cant permeate
Can require drainage to eliminate
Describe the gross appearance of granulomas
Discrete, well demarcated nodules, round/oval
Tan, grey or white
Firm/hard
Caseating granulomas have central core of yellowish pasty necrotic material, can have gritty areas of mineralisation
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 T-helper cell & 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
If lesions are discrete & nodular = pyogranuloma
Can occur in areas transitioning from acute to chronic inflammation or in response to specific stimuli
Give examples of some infectious aetiologies of pyogranulomatous inflammation
Fungi
- Blastomyces dermatitidis
Bacteria
- Bartonella spp., Actinomyces spp., Rhodococcus equi
Protozoa
- Leishmania spp., Toxoplasma spp.
Viruses
- Feline infectious peritonitis virus
Give an example of a sterile cause of pyogranulomatous inflammation
e.g., Pyogranulomatous dermatitis and panniculitis
Can be treated with corticosteroids
Sterile is a diagnosis of exclusion
What is the gross appearance of granulation tissue
Red and granular
Can be edematous; newly formed blood vessels can be leaky
(Granulation tissue consists of fibrovascular tissue that is formed during wound repair)
What is the best gross indicator of chronic inflammation?
Fibrosis results in contracture of organ parenchyma => irregular, undulating appearance to capsular surface
Liver can additionally respond to loss of parenchyma with regeneration, which grossly look like nodules
