5. Inflammation Flashcards
What is the main function of inflammation?
To remove infected or damaged tissue to restore homeostasis
- crucial to maintaining the health and integrity of an organism
- soluble mediators (humoral) and cellular components work together in a systematic fashion
- tightly regulated response
- traditionally divided into acute and chronic responses
What is acute inflammation?
The rapid, short-lived (minutes to days), relatively uniform response to acute injury, characterized by accumulation of fluid, plasma proteins, and leukocytes (WBC)
What is paramount in acute inflammation? What happens if one does not occur?
Both the effective induction and resolution of inflammation are paramount
- timing, location , absolute levels and duration are important
- sustained induction or improper control contributes to chronic inflammation
What are the 4 main features of the physiologic changes accompanying acute inflammation?
- Vasodilation
- Vascular permeability
- Recruitment
- Fever
What are 4 cardinal clinical signs of inflammation?
- Rubor (redness)
- Dolor (pain)
- Calor (heat)
- Tumor (swelling)
Vasodilation
One of the earliest physical responses to acute tissue injury
- arterioles are the first to be involved, followed by the capillary beds, resulting in a net increase in blood flow
- increase blood flow = characteristic heat and redness (calor and rubor) associated with foci of acute inflammation
- increased transport of: O2, nutrients, glucose, leukocytes
- decreased blood pressure
- removal of cellular waste products
Vascular permeability
- Under normal conditions, the vascular endothelial cells fxn as a semipermeable membrane, restricting the plasma proteins to the intravascular space
- In response to inflammatory stimuli, endothelial cells lining the venules contract, widening the intercellular jxns to produce gaps, permitting passage of plasma proteins (tumor) and facilitating leukocyte extravasation. More severe injury is associated with endothelial cell necrosis.
- Leukocyte recruitment
Process recruits leukocytes from bloodstream and ultimately involves the bone marrow to focus on inflammatory activity
- these leukocytes migrate through the enlarged endothelial cell jxns and the basement membrane
- leukocytes released due to signals from soluble mediators (hormones, cytokines)
Fever
Agents producing fever (pyrogens) are released from leukocytes in response to specific stimuli, such as bacterial endotoxin
- a number of soluble pro-inflammatory mediators have been implicated in this process (IL-1, TNF-a, IL-6) and prostaglandins
- contributions from immune and neuronal systems
- fever remains the most poorly understood of the acute inflammatory responses
Initiation of inflammation - Recognition
- Innate immune recognition triggers an inflammatory response that focuses the immune system on the site of infection; recognition by mast cell or macrophage releases cytokines (pyrogens), chemokines, and lipid mediators
- Inflammation requires the coordinated response from resident cells, blood vessels, circulating leukocytes and hematopoietic compartment
3 Self and non-self triggers of inflammation
- Pathogens
- activation of the plasma protease systems by interaction with degradation products of the bacterial cell walls
- secretion of toxins - Injured cells
- release degradation products that initiate one or more of the plasma protease cascades
- upregulate expression of soluble molecules (ex. pro-inflammatory cytokines) - Foreign bodies from exogenous (ex. asbestos) or endogenous (ex. immune complexes) sources, physical injury (ex. burns), chemical agents (ex. caustic)
The toll-like receptors (TLRs) initiate many pro-inflammatory responses:
- First line of defense against incoming pathogens
- “Danger” hypothesis
- This family of receptors detects pathogens including bacteria, viruses, and fungi - Well conserved across evolution
- Conserved bc of its importance to early pathogen recognition - Remember that they work together with several other types of recognition receptors (ex resident macrophages, epithelial cells)
TLR signaling pathways
- TLRs
- MyD88 dependent or independent pathways
- Transcription factors
- Gene expression
- Functional protein
- Cellular response
3 inflammatory mediators
- Cytokines
- polypeptide signaling molecule that participates in immune responses
- often act locally (in an autocrine or paracrine manner) but can act systemically
- most are secreted molecules but membrane-bound versions often occur - Chemokines
- family of closely related small basic cytokines
- main fxn is as chemoattractants
- name in a contraction of a chemotactic cytokine - Hormones
- biomolecules synthesized in small amounts by ductless (endocrine) glands: polypeptide, amide, or steroid
- travel from site of synthesis to distant target tissues
- mediate regulatory effects by binding to specific cell surface receptors- intracellular receptors in case of steroid hormones
4 main actions of inflammatory regulators
- Induce vascular permeability to allow the influx of soluble immune components from the blood
- Change the adhesive properties of the endothelium to attract more phagocytes to the site of infection
- Activate the incoming leukocytes to promote their microbicidal action
- Induce production of complementary cytokines
- early: positive feedback to amplify pro-inflammatory repsonse
- later: negative feedback to induce anti-inflammatory responses
