Chronic inflammation Flashcards
What is chronic inflammation?
Chronic inflammation is referred to as slow, long-term inflammation lasting for prolonged periods of several months to years.
Histological features of chronic inflammation
Hard (indurated), red (erythematous) swelling
Mononuclear cell infiltrate
Little oedema
Angiogenesis (neovascularisation)
Collagen deposition (with time)
How is chronic inflammation sustained/ caused?
WBC in tissue produce inflammatory cytokines, growth factors, enzymes and hence contributing to the progression of tissue damage
Secondary repair including fibrosis and granuloma formation.
Give examples of one infectious and one non-infectious cause of chronic inflammation.
Infectious: Tuberculosis
Non-infectious: Gout/silicosis
What is the nature of the giant cells?
Langhans cells (in TB) are formed from the fusion of macrophages infected with TB
What is the most likely cause for the formation of the granuloma (TB)?
Immune system was overcome by the TB infection - could not eliminate infection and so granuloma was formed to contain the infection
Macrophages are the major source of the cytokine TNF alpha
True
Neutrophil recruitment is a key feature of chronic inflammation
False, (probably) composition of the white blood cells changes and macrophages and lymphocytes begin to replace short-lived neutrophils.
(TNF alpha contributes to the weight loss (cachexia) seen in chronic infection
True
Role of cytokines in chronic inflammation
Induce the injury-site-endothelial cells to release Selectins and Integrins which stimulate chemotaxis and diapedesis of the circulating leukocytes.
Role of neutrophils in the early stages of inflammation
Contain granules rich with lysozyme, matrix metalloproteinases, myeloperoxidase which are released on the foreign or self-antigen leading to its destruction.
Role of macrophages and DCs in chronic inflammation
Release cytokines such as IL-1 and TNF-α
Clear the antigen by phagocytosis and serve as antigen-presenting-cells to lymphocytes.
Role of platelets in chronic inflammation
Platelet aggregation, thrombus formation and degranulation releasing chemokines and inflammatory mediators.
Chronic osteomyelitis is associated with infection with…
Chronic inflammatory process of the bone secondary to infection with pyogenic organisms: Staphylococcus aureus and occasionally Enterobacter or Streptococcus species
Silicosis is caused by
Simple chronic silicosis results from long-term exposure (more than 20 years) to low amounts of silica dust. Nodules of chronic inflammation and scarring provoked by the silica dust form in the lungs and chest lymph nodes.
What is the response to inhaled silica particles
Particles phagocytosed by alveolar macrophages and induce breakdown of lysosomes - activates NALP3 inflammasome - macrophages die and release cytokines (IL1Beta, TNF) - further macrophage recruitment and fibroblast proliferation - collagen deposits and fibrosis around the silica particles - nodules of inflammation and scarring form in lung and chest lymph nodules.
Describe a silicosis nodule
Nodules characterised by concentric onion skin arrangement with collagen fibres, central hyalinization and cellular peripheral zone.
When does TB primary infection often occur?
Childhood
What is a Ghon focus?
Infection develops in periphery of lung, primary lesion seen on an x-ray
What is a primary complex?
Ghon focus and lymph node involvement
What are the two main sequelae of primary TB infection?
Most infections heal without clinical disease
Small proportion of infected individuals cannot contain infection, this leads to widespread dissemination (primary disease)
Why may lead to secondary TB?
Re-activation of Tb infection is seen in drug addicts and alcoholics, HIV-infected individuals, patients treated with anti TNF-alpha drugs
What does HIV positive individuals being at a higher secondary infection risk tell us about granuloma?
Importance of CD4+ T cells in contain Tb within granulomata
What does risk of anti-TNF alpha in TB patients tell us about TNF alphas role in TB?
TNF-alpha important in host suppression of Tb infection
