Acute inflammation Flashcards
What is the definition of inflammation?
A protective response that brings cells and molecules of host defense from circulation to the sites where they are needed in order to rid the host of injury and the consequences of that injury.
Compare and contrast acute vs. chronic inflammation with regards to:
- Onset
- Duration
- Cells involved in response
- Tissue injury extent
- Local and systemic signs
- Immune branches involved
What are the 3 major components of acute inflammation?
What are some causes of inflammation?
What are the 5Rs of the inflammatory reaction sequence?
- Recognition
- Recruitment
- Removal
- Regulation
- Repair
Describe what happpens in an inflammation reaction (5Rs) starting with a microbe presenting in the body.
- Recognition: Microbes (PAMPs) or products of cellular damage (DAMPs) bind to receptors on resident macrophages, mast cells or dendritic cells.
- Recruitment: resident cells release cytokines and amines (i.e. vasoactive amines –> histamine from mast cells) to do several things. They will circulate in the blood and have systemic affects, including recruitment of more leukocytes from the bone marrow and causing local vasodilation and increasing vascular permeability, but they will also lead to local recruitment of leukocytes circulating in the blood to enter the tissue.
- Removal: leukocytes enter the ECM and phagocytose or break down microbes and dead tissue
- Regulation: plasma proteins act as mediators of the inflammatory response to ensure that it doesn’t continue unchecked
- Repair: rebuilding of ECM and scar formatoin
What are the signs of inflammation?
Describe the sequence of vascular events that occur in inflammation.
Describe the sequence of cellular events that occur in inflammation.
- Margination - vasodilation pushes neutrophils from center of blood vessel to periphery
- Rolling - binding between neutrophils and transient low-affinity selectins on endothelial cells causing neutrophils to slow down
- Adhesion - slowed neutrophils are able to bind with high affinity to integrins on endothelial cells causing them to stop moving
- Transmigration - neutrophils move between endothelial cells with help of PECAM-1
- Chemotaxis - neutrophils follow the chemical gradient of chemokines secreted by resident cell to the site of injury
- Phagocytosis - opsonization by neutrophil, ingestion into phagolysosome, killing via ROS and NO
What triggers vasodilation in inflammation?
Histamine released from resident mast cells
How are selectins and integrins upregulated in endothelial cells during neutrophil entry into ECM?
IL-1 and TNF secreted by resident macrophages causes the endothelial cells to upregulte expression of these proteins
Which substances are able to initiate and regulate inflammatory reactions?
- Histamine –> cell derived
- Serotonin –> cell derived
- Cytokines –> de novo synthesis in response to stimuli
- Lipid products (prostaglandins, leukotrienes) –> de novo synthesis in response to stimuli
- Products of complement (C3a and C5a) –> plasma derived mediator
Histamine binds to the […] receptor on endothelial cells
H1
Prostaglandins and leukotrienes are produced from […], found in the cell […], by the actions of […] and […].
Arachadonic acid
membrane
cyclooxygenase; lipoxygenase
Review the pathway of formation of prostaglandins and leukotrienes starting with a cell membrane phospholipid.
What are the systemic effects, both protective and pathological, that result from the release of cytokines IL-1, IL-6 and TNF from resident macrophages during inflammation?
What are the ultimate outcomes of activation of the complement cascade?
What are the 3 ways in which complement cascade can be initiated?
- Classic - IgG or IgM combines with antigen and triggers complement via binding of C3b
- Alternative - microbial surface molecules bind with circulating C3b and trigger complement
- Lectin - Mannose binding lectin binds to microbial surface carbohydrates, binds to C3b, triggers complement
What are the 4 morphologic patterns of acute inflammation?
What type of inflammation is this?
What type of inflammation is this?
Fibrinous
What type of inflammation is this?
Purulent
What type of inflammation is this?
Ulceration
What signals the termination of acute inflammation?
What are the possible outcomes of acute inflammation?
