Chronic Inflammation Flashcards
What is chronic inflammation?
Response of prolonged duration in which inflammation, tissue injury and attempts at repair coexist in varying combinations
What are the 3 major categories for causes of chronic inflammation?
What is the disease burden of chronic inflammation (i.e. epidemiology)?
Most significant cause of death in world
3/5 people die as a result of chronic inflammatory condition
- Diabetes
- CVD
- Arthritis
- COPD
- Allergies/asthma
Compare and contrast acute and chronic inflammation with respect to:
- Causative agent
- Cellular infiltrate
- Primary mediators
- Onset
- Duration
- Outcomes
TNF
- Secreted by what cells?
- Has what actions?
- Secreted in acute or chronic inflammation?
- Macrophages, mast cells, t-cells
- Stimulate expression of endothelial cell adhesion molecules and secretion of other cytokines; systemic effects
- Acute
IL-1
- Secreted by what cells?
- What effects does this have on the body?
- Secreted in acute or chronic inflammation?
- Macrophages, endothelial cells
- Similar to TNF, greater role in prompting fever @ hypothalamus
- Acute
IL-6
- Secreted by what cells?
- What effects does it have on body?
- Secreted in acute or chronic inflammation?
- Macrophages
- Systemic effects during acute phase response
- Acute
Chemokines
- Secreted by what cells?
- What is their effect on body?
- Secreted in acute or chronic inflammation?
- Macrophages, endothelial cells, T cells, mast cells
- Recruitment of leukocytes to sites of inflammation, migration of cells in normal tissue
- Acute
IL-17
- Secreted by what cells
- What is the effect this has on the body?
- Secreted in acute or chronic inflammation?
- T-cells
- Recruitment of neutrophils and monocytes
- Acute and chronic
IL-12
- Secreted by what cells?
- Has what actions in the body?
- Secreted in acute or chronic inflammation?
- Dendritic cells, macrophages
- Increased production of INF-gamma
- Chronic
INF-gamma
- Secreted by what cells?
- What are actions in body?
- Secreted in acute or chronic inflammation?
- T-cells, NK cells
- Activation of macrophages
- Chronic
What are the morphologic features of chronic inflammation when visualized in histological staining?
Macrophages can have actions that are both beneficial to cells and detrimental to cells. Describe these different effects on cells from the actions of macrophages.
(+)
- Communicate with t-cells (APC and respond to signals from t cells)
- Secrete inflammatory mediators
- TNF
- IL-1
- Chemokines
- Ingest/eliminate microbes and dead tissue
- Initiate tissue repair process
(-)
- Cycle of elimination can be inappropriately/excessively activated leading to tissue damage beyond what is necessary to address original insult to tissue
What are the 2 types of macrophages activation?
Compare and contrast these mechanisms of activating macrophages.
Classical / M1 –> activated in acute inflammation
- Pro-inflammatory
- PAMPs and DAMPs –> PRRs (TLRs and NOD like receptors) on resident dendritic cells or invading macrophage –> consume antigen –> present to T cell –> T cell matures and secretes INF-gamma –> activate macrophages to phagocytose invading microbe / damaging substances and generate NO + ROS to degrade/inactivate/kill them
Alternative / M2 –> activated after classical
- Anti-inflammatory
- Key cytokines are IL-4 and IL-13
- Does not result in microbicidal macrophages
- Inhibits classical pathway
- Results in tissue repair
- Microbes secrete growth factors that promote:
- angiogenesis
- activation of fibroblasts
- collagen synthesis
Normally we think of lymphocytes (t cells and b cells) as having a beneficial effect on inflammation b/c they amplify the response and mediate the adaptiave arm of the immune response. When are these cells considered to actually have destructive effects?
When activated in chronic inflammation the inflammation tends to be persistent and severe so they become over stimulated and promote the persistent inflammatory response.
- Let’s say that we have a macrophage that has been classically activated by INF-gamma. What is the cycle of inflammation that it perpetuates to keep the process going?
- How is this process “turned off”?
Macrophage can
- Present antigen to t cells –> t cell becomes activated (Th1 if intracellular, Th17 if extracellular) –> T cell secretes other cytokines that lead to additional leukocyte recruitment and enhanced inflammation –> T cell could also secrete more INF-gamma to activate more macrophages
- Activated macrophage can secrete TNF and IL-1 which will promote additional leukocyte recruitment and inflammation
- Process is turned off by removal of the offending stimuli
Complete this table.
What are the 2 different kinds of chronic inflammation?
What are some examples of chronic, granulomatous inflammation that are:
- Non-caseating
- Caseating
Let’s say that a tissue is damaged from inflammation. What 2 processes does that tissue go through to repair itself?
In order for damaged tissue to regenerate, what must be true of that tissue?
It must possess labile stem cells that are capable of proliferating and differentiating to replace the damaged cells. Tissue that does not have this capacity or has a lesser degree of this capacity will undergo scar formation when damaged.
What are the 3 steps of scar formation?
Complete this table.
