Inflammation and Tissue Healing - Physiology Flashcards
Inflammation Basic Definition
Non-specific defense and healing mechanism of the body to tissue damage and infection.
Causes of Cell Injury
- Ischemia (lack of blood supply)
- Infectious agents
- Immune reactions
- Genetic factors
- Nutritional factors
- Physical factors
- Chemical factors
Necrosis vs Apoptosis
Necrosis: causes inflammation, invariably pathologic (culmination of irreversible cell injury).
Apoptosis: no inflammation, physiologic )eliminating unwanted cells).
Phases of Inflammatory Reaction
- Recognition (tissue damage or infection)
- Recruitment (additional immune cells)
- Removal (what caused the problem e.g. pathogen)
- Resolution/repair (remove inflammation)
Operational Characteristics (Signs) of Inflammatory Response
Redness, pain, swelling, heat at the site of infection.
Recognition - PAMPs
Innate immunity uses limited nr of pattern recognition receptors (PRRs) to spot pathogens.
Pathogen-associated molecular patterns (PAMPs): structural features expressed by microbes but not by host. Recognized by PRRs.
→ Synthesis and secretion of pro-inflammatory cytokines.
Recognition - DAMPs
Innate immunity uses a limited number of pattern recognition receptors (PRRs) to spot damaged cells.
Danger-associated molecular patterns: Exposure of molecules from injured tissue, such as nuclear or cytosolic protein. If cell explodes, receptor is exposed.
Scavenger Receptors
Few receptors, either release pro-inflammatory cytokines or eat the cell (phagocytosis of host cells undergoing apoptosis).
Recruitment
Phagocytotic macrophages often not enough to remove all pathogens → start an inflammatory response → recruitment of additional immune cells.
What are the effect of acute inflammation on surrounding blood vessels?
- Vasodilation increases local blood flow (heat & redness)
- Activation of endothelial cells.
- Increased vascular permeability(space between cells becomes bigger): exit of fluid and proteins from the blood (swelling and pain).
Order of Recruitment of Cells
1st: Neutrophils
2nd: Monocytes (in blood), differentiate into Macrophages (in tissue).
3rd: Lymphocytes
Chemotactic Agents
Cause cells to move into a particular direction.
Chemotaxis tells cells to go to site of infection.
IL-8 chemotactic for neutrophils.
IL-12 chemotactic for NK cells
Removal - Protection Against Viral Infections
Soluble molecules for protection from viral infections.
Interferons induce both virally infected and noninfected cells to activate numerous antiviral defenses.
Removal - Compliment System
Enzymes and proteins providing protection against pathogens. Series of Plasma Proteins.
- Opsonization: Facilitate phagocytosis.
- Anaphylatoxins: Chemoattractant effect. Increase inflammation - Pro inflammatory mediators.
- Lytic death: Creates holes in cell membrane and induces death.
Phagocytosis Definition
Engulfment and degradation of microbes and cellular debris - pathogens (bacteria, viruses), apoptotic bodies.
Removal - Phagocytosis
PRR binds to PAMP or DAMP, or binding of
complement receptor or antibody receptor to an opsonized microbe → Engulfment → bacteria trapped within phagosomes → broken down by digestive enzymes through fusion of lysosomes.
Removal - Macrophages
Able to phagocyte dead cells and tissue debris. Responsible for cleaning up damaged tissue.
Resolution
An active process that suppresses the inflammatory reactions once the main objective is attained.
It ensures tissue repair and regain of physiological
function.
Resolution - Stop Recruitment
Termination of neutrophil influx: prerequisite for resolution of inflammation.
Clearance of neutrophils: undergo apoptosis. Secrete annexin A1 → inhibit recruitment, promote apoptosis and clearance. Find me signals, eat me signals.
Resolution - Efferocytosis
Apoptotic neutrophils cleared by macrophages via efferocytosis → causes a switch in macrophages to a anti-inflammatory pro healing cell (from M-1 like cells to M-2 like cells).
Resolution - M1-like cells, M-2 like cells
Macrophages
M1-like cells: pro-inflammatory mediator, early phase of repair → phagocytosis of neutrophils.
M2-like cells: Express anti-inflammatory mediator and produce of growth factors. Later stage of repair.
Resolution - Reestablishment of Tissue Functionality
Macrophages, stem cells and connective tissue cells prevent fibrosis.
M2-like cells orchestrate reparative processes:
- Proliferation of progenitor cells
- Influence ECM composition
- Angiogenesis
4 Phases of Tissue Healing
- Hemostasis & degeneration
- Inflammation
- Proliferation & migration
- Remodeling & maturation
Hemostasis and Degeneration
Hemostasis: stop the bleeding - Formation of a platelet clot - Activation of coagulation cascade - Formation of a blood clot Degeneration: - Formation of a hematoma - Necrosis of cells => inflammation
