Chapter 6: Innate Immunity: Inflammation Flashcards
First Line of Defense: biochemical barriers
Synthesized and secreted saliva, tears, earwax, sweat, and sebum
Antimicrobial peptides: cathelicidines, defensins(alpha defensins in neutrophil granules), and collectins(lungs), normal bacterial flora; vaginal:lactobacillus, intestinal:produce ammonia, phenols, indoles, etc. that inhibit colonization by pathogens
First Line of Defense: physical and mechanical barriers
Skin
Linings of gastrointestinal, genitourinary, and respiratory tracts: sloughing off if cells, coughing and sneezing, vomiting, mucus and cilia
Second line of defense: inflammatory response
Causes: infection, mechanical damage, ischemia, nutrient deprivation, temperature extremes, radiation, etc.
COMPONENTS
Vascular response: blood vessel dilation, increased vascular permeability and leakage, WBC adherence to the inner walls of the vessels and migrations through the vessels
Second line of defense: goals
Limit and control the inflammatory process
Prevent and limit infection and further damage
Control bleeding
Interact with components of the adaptive immune system
Prepare the area of injury for healing
Plasma Protein Systems
Complement system
Coagulation system
Kinin system
Involve a series of proteolytic cleavages to produce active proteins for each function
Complement system
Can destroy pathogens directly
Activates or collaborates with every other component of the inflammatory response
Activated through following pathways: classical, lectin, alternative, leads to generation of a membrane attack complex that inserts into a bacterium to cause lysis
Coagulation (clotting) system
Forms a fibrinous meshwork at an injured or inflamed site
Prevents spread of infection
Keeps microorganisms and foreign bodies at the site of greatest inflammatory cell activity
Forms a clot that stops bleeding
Provides a framework for repair and healing
Main substance is an insoluble protein called fibrin
Kinin system
Functions to activate and assist inflammatory cells
Primary kinin is bradykinin
Causes dilation of blood vessel, pain, smooth muscle contraction, vascular permeability and leukocyte chemotaxis
Cellular mediators of inflammation
Cellular components: granulocytes, platelets, monocytes and lymphocytes
Basic process: infectious particles activate cell surface receptors that recognize microbial molecular patterns, receptor activation leads to cellular activations that results in degranulation and/or phagocytosis
Pattern recognition receptors (PRRs)
Recognize molecular “patterns” on infectious agents or their products(pathogen-associated molecular patterns, or PAMPs), or products of cellular damage(necrosis or apoptosis)
Toll like receptors (TLRs)
Expressed on the surface of many cells that have direct and early contact with potential pathogenic microorganisms
Complement receptors
Found on many cells of the innate and acquired immune responses
Scavenger receptors
Primarily expressed on macrophages and facilitate recognition and phagocytosis of bacterial pathogens as well as damaged cells and altered soluble lipoproteins associated with vascular damage
Mast cells
Cellular bags of granules located in loose connective tissues close to blood vessels
-skin, digestive lining, respiratory tract
Activation
-physical injury, chemical agents, immunologic processes
-activation of mast cells result in degranulation and secretion of long term mediators
Degranulation
Results in release of histamine, cytokines, and chemotactic factors that cause vasodilation and recruitment of other immune cells to affected area
Long term mediators: include prostaglandins, leukotrienes, platelet activating factor and growth factors
Phagocytes
Process of phagocytosis:
- Opsonization: recognition, and adherence to the target for phagocytosis
- Engulfment: endocytosis and formation of the phagosome
- Fusion with lysosomes inside the phagocytosis cell to produce a lysophagosome
- Destruction of the target by enzymatic degradation
Margination(pavementing)
Process by which leukocytes adhere better to endothelial cells of the capillary walls and venues by the reciprocal change in adhesion molecules on leukocytes
Diapedesis
Emigration of the cells through the endothelial junctions that have retracted response to the same mediators
Neutrophils
First responders–arrive at inflammatory site within 6-12 hours
Ingest bacteria, dead cells and cellular debris
Cells are short lived and become a component of the purulent exudate
Monocytes and macrophages
Monocytes produced in bone marrow, enter circulation and migrate to the inflammatory site where they develop into macrophages
Macrophages typically arrive at inflammatory site 3-7 days after neutrophils
Macrophages are activated by cytokines, activation results in increased size, plasma membrane area, glucose metabolism, number of lysosomes, and secretory products. Activated macrophages secrete factors that help promote healing
Eosinophils
Mildly phagocytic
Fight against parasites and are activated by mast cells
Basophils
Become active in allergic reactions
Release cytokine IL-4 (interleukin 4) so help to limit inflammation since IL-4 is an anti-inflammatory cytokine
Natural killer (NK) cells
Function: recognize and eliminate cells infected with viruses and some function in eliminating cancer cells. More efficient with infected cells in circulatory system vs in tissues
Platelets
Activation results in degranulation and interaction with components of the coagulation system to stop bleeding
Acute inflammation
2 weeks or less
Local responses: heat, redness, swelling, pain
Systemic responses: fever, leukocytosis, increased levels in circulating plasma proteins
Chronic inflammation
More than 2 weeks
Causes: often related to an unsuccessful acute inflammatory response, high lipid and wax content of microorganism ability to survive inside the macrophage toxins, chemicals, particulate matter, or physical irritants
Chronic inflammation characteristics
Dense infiltration of lymphocytes and macrophages, granuloma formation, epithelioid cell formation, giant cell formation
Wound healing
Regeneration: return of wound to normal structure and function
Resolution: in adults, returning injured tissue to the near normal structure and function
Repair: replacement of destroyed tissue with scar tissue
Processes of healing
Filling in the wound
Sealing the wound (epithelialization)
Shrinking the wound (contraction)
Primary intention healing
Wounds that heal under conditions of minimal tissue loss
Secondary intention healing
Wounds the require a great deal more tissue replacement: open wound
Phases of resolution and repair
Reconstructive phase: Begins 3-4 days after initial injury Fibroblast proliferation Collagen synthesis Epithelialization Contraction of the wound by myofibriblast Maturation phase: Begins several weeks after the injury Cellular differentiation Scar formation
