Exam #1: Chronic Inflammation Flashcards
What is chronic inflammation?
Inflammation that occurs for greater than 2 weeks
What is the most common presentation of chronic inflammation?
Insidious low-grade smoldering response without signs of acute inflammation
What are the causes of chronic inflammation?
1) Persistent microbial infections
2) Immune related inflammatory disease
3) Prolonged exposure to potentially toxic agents
List the general characteristics/ morphology of chronic inflammmation.
- Infiltration with mononuclear cells (macrophages, lymphocytes, & plasma cells) vs. neutrophils
- Tissue destruction induced by persistent stimulus or by inflammatory cells
- Attempts at healing–>connective tissue replacement of damaged tissue, angiogenesis, & fibrosis
Describe the histological characteristics of chronic pancreatitis.
Remember if you see islets & ducts= pancreas
- Inflammatory cells i.e. mononuclear cells
- Fibrosis= pink substance= collagen deposition
- Residual ductal structures with fibrosis
*No acinar tissue remaining
Describe the histological characteristics of chronic lung disease.
Note that the spaces without cartilage= alveoli i.e you’re looking at the lung
- Large alveolar spaces b/c endothelial cells have been destroyed
- Fibrotic deposition (pink)
- Mononuclear cell infiltration ( looks like tons of black dots)
Describe the histological characteristics of chronic pyelonephritis.
Appearance of many black dots= mononuclear
What are the hallmark features of plasma cells? What do you assume if you see plasma cells?
- Nucleus= v. large, dense, & located on a single side
- Cell is large than the other lymphocyte
*IF you see PLASMA CELLS= CHRONIC INFLAMMATION
What are macrophages derived from?
- Circulating blood monocytes
- Once the monocyte exits the blood, it is a macrophage
*This is the key cell in chronic & granulomatous inflammation
What is the difference between monocytes & mononuclear cells?
Agranulocytes, also known as mononuclear leukocytes, are white blood cells with a one-lobed nucleus. They are characterized by the absence of granules in their cytoplasm, which distinguishes them from granulocytes.
- 2 categories:
1) Lymphocytes i.e. T, B & NK cells
2) Monocytes–>macrophages
What is a Kupffer cell?
Liver macrophages
What is an alveolar or pulmonary macrophage?
Macrophage in the lung
What is a macrophage in the bone?
Osteoclast
What is a macrophage in the brain?
Macroglia
When do monocytes emigrate to the site of injury?
Within 24-48 hours
Describe the histological features of activated macrophages. How do these differ from non-activated macrophages?
Activated=
- large i.e. increased size
- Pink
- Flat or epithelial-like or epitheloid
Non-activated=
- Small
What are the functional features of activated macrophages?
- Increased size
- increased numbers of lysosomes & lysosomal enzymes
*Activated macrophages have an increased ability to kill organisms
Describe the cell lineage of macrophages.
Stem cell
Monoblast
Monocyte= blood
Macrophage= tissue
What is the predominant cell type of inflammation after 48 hours?
Macrophages
What are the activation signals for macrophages?
- Cytokines–esp. IFN-gamma–secreted by activated T-cells & NK-cells
- Gamma interferon is the KEY player in the activation of macrophages, which is specifically secreted by Th1 cells & NK-cells
What is an exogenous sources of IFN-gamma production?
Bacterial endotoxin i.e. LPS
What causes activated macrophages to travel down a path of inflammation & tissue injury mediation vs. repair?
Inflammation & Tissue Injury= IFN-gamma
Repair= IL-4
What causes activated macrophages to persist in a chronic inflammatory state?
Continuous recruitment & local proliferation at the site of inflammation
What cytokines produced by macrophages mediate tissue injury?
IL-1
TNF-a
What are the local effects of IL-1 & TNF-a?
Vascular endothelium
Leukocytes
Fibroblasts
See figure 2-13
What are the results of chronic inflammation?
- Continued tissue damage/ destruction
- Ongoing tissue destruction can lead to CO-EXISTENCE of both acute & chronic inflammation
Why can neutrophils be seen in chronic inflammation?
Co-existence of acute and chronic inflammation
*This is referred to as “chronic active inflammation”
What are the lifestyle factors that can promote chronic inflammation?
- Smoking
- Excessive alcohol intake
- Physical & emotional stress
- Obesity
- Lack of exercise
- Diet
Aside from macrophages, what other cells can be activated in chronic inflammation?
Lymphocytes (B & T-cells) can be mobilized in response to infections and trauma
Describe the reciprocal relationship between T-cells & macrophages in chronic inflammation.
- Macrophages initially activate T-cells
- Activated lymphocytes (esp. T-cells in chronic inflammation) lead to macrophage activation
*Thus there is a reciprocal relationship between the two; activated macrophages then release cytokines
What are Th17 cells?
T-cells that secrete:
- TNF
- IL-17
- chemokines
What are Th1 cells?
T-cells that secrete IFN-gamma
What are plasma cells?
- Terminal product of B-cell activation; these are pathognomomic for chronic inflammation
- Produce antibodies against persistent antigens
What is the hallmark of chronic parasitic infections & asthma?
Eosinophils
What are eosinophils?
- Not mononuclear
- Contain granules with major basic protein (MBP)
- MBP is toxic to parasites but also contributes to tissue damage in immune reaction & allergies
*Note that these cells are “pinker” than neutrophils
What chemokine is responsible for eosinophil recruitment?
Eotaxin
What are mast cells?
- IgE arms mast cells
- Release histamine and PG
- Central role in anaphylactic reactions
- Helpful in parasitic infections
Are mast cells seen in acute or chronic inflammation?
BOTH
What are the effects of histamine?
Bronchoconstriction
Vasodilation
What are the histological features of neutrophils?
Lobular nucleus
