Chapter 6 Notes - Innate Immunity: Inflammation and Wound Healing PDF

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Innate Immunity: Inflammation and Wound Healing...

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Chapter 6 Notes: Innate Immunity: Inflammation and Wound Healing Immunity: 

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FIRST LINE OF DEFENSE; INNATE IMMUNITY o Physical barriers  Skin  Linings of the ________________, ____________________, and _________________ ___________  Sloughing off of cells when _____________ cells get replaced  _______________ and __________________- upper respiratory tracts’ way to keep out organisms  Flushing of organisms out of the _______________ tract  Vomiting flushes out the_______________; when needed  Mucus and cilia: ___________ traps while _____________ remove unwanted organisms from respiratory tract  Epithelial cell-derived chemical barriers:  Synthesized and secreted ___________, _____________, ______ ________, ____________, and __________________  _________________ peptides  Normal ______________ ___________________ _____________ ______________: nonpathogenic microorganisms that live on the body’s surfaces (skin, mucus membranes of eyes, respiratory tract, linings of the gut, urethra, and vaginal vulva.)  Prevent growth of pathogenic organisms, thus preventing _________________  Prolonged use of ___________________ may destroy these normal flora and cause infections to develop. Example: is yeast infection of the mouth, gut, urinary tract or vagina after prolonged use of antibiotics. As nurses we need to be aware of this and assess frequently for. We may have to give meds that will kill the yeast. (Explain swish and swallow medications.) SECOND LINE OF DEFENSE o ______________________ response  Caused by basically anything that causes damage to the cells  Infection, Mechanical damage, Ischemia, Nutrient deprivation, Temperature extremes, Radiation  Local manifestations  __________________, ___________, _______________, ____________, _______ _____ ______________  Vascular responses  Blood vessel dilation, Increased permeability and leakage, WBC adherence to the inner walls of the vessels and migration through the vessels.  GOALS FOR INFLAMMATION:  Limit and control the ______________________ process  Prevent and limit ______________________ and further __________________  Initiate ______________________ ______________________ response  Initiate ______________________

Plasma Protein Systems 

PROTEIN SYSTEMS: ______________________ system, ______________________ system, _______________ system

All contain _______________ enzymes (proenzymes); sequentially activated process. o Complement System  Can ______________________ pathogens directly (bug eater)  Activates or collabs with every other component of the ______________________ response  The complement system’s major job is to send out ______________________ that destroy the ______________________  Attacks the bacteria by activating ______________________ and ______________________ o Coagulation (clotting) system  Forms a _________________ _________________ at an injured or inflamed site  Prevents the spread of ______________________  Keeps microorganisms and foreign bodies at the site of ______________________ inflammatory cell activity  Forms a _______ that stops bleeding  Provides framework for __________ and ______________  Main substance is an insoluble protein called ___________  Pathways  Extrinsic pathway  Intrinsic pathway o Kinin System  Functions to activate and assist inflammatory _________  PRIMARY KININ IS ______________________  Causes __________________ of blood vessels, smooth muscle ______________________, increased ________________ _________________, and acts with ____________________ to produce pain  Inflammatory Response is so critical for survival that activation of one cascade will automatically activate the other two  The biochemical mediators generated during these processes are so potent that they must be strictly controlled.  Histaminase degrades ______________________ and ____________  Plasmin degrades fibrin polymers in the clots thus breaking down the clot

CELLULAR MEDIATORS OF INFLAMMATION o Erythrocytes (RBC) o Platelets o Leukocytes (WBC)  Monocytes (precursors of ___________________)  Lymphocytes (Innate and acquired immune response)  Granulocytes (basophils, eosinophils, and neutrophils) BEN o Cell surface receptors; when activated, initiate an immune response o Cellular products  Cytokines; Responsible for ___________________ other cells and regulating ______________________ response  Chemokines  synthesized by many cells (macrophages, fibroblasts, endothelial cells) in response to ______________________ cytokines.  Induced chemotaxis to promote ______________________ and wound healing

Examples:

monocytes/macrophages chemotactic proteins Macrophage inflammatory proteins Neutrophils

Interleukins (IL)  Produced primarily by ______________________ and ______________________ in response to a pathogen or stimulation by other products of inflammation.  Many types;  examples: IL-1 is a ______________________ cytokine IL-2 is an anti-______-_______________ cytokine  Major effects of interleukins: 1. Attraction of _________________ to the site of inflammation 2. Induction of the ________________ and __________________of leukocytes in the bone marrow 3. General ____________________ or suppression of inflammation 4. Stimulates the production of other _____________ to come to the area of inflammation.  Interferons (IFN)  Protect against ___________ infections  Produced and released by virally infected host cells in response to viral double stranded _________ 1. IFN-alpha and IFN-beta  Induce production of antiviral proteins 2. IFN-gamma  Increases microbiocidal activity of macrophages  Tumor necrosis factor-alpha - Secreted by ________________  Induces _____________ by acting as an endogenous pyrogen  Increased synthesis of inflammatory ____________ proteins  Causes muscle wasting (cachexia) and intravascular __________  Mast Cells and Basophils - ________________ are found in blood and probably function in the same way as mast cells - Cellular bags of ________________ located in the loose connective tissue close to blood vessels  Skin, digestive lining, and respiratory tract - Contain ________________ and ________________ factors  Activation: Physical injury, chemical agents, immunologic processes, and toll-like receptors  Chemical release in 2 ways 1. _____________________; the release of the content of mast cell granules 2. ________________; the new production and release of mediators in response to a stimulus 

MAST CELL DEGRANULATION

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Vasoactive amine that causes temporary, rapid constriction of the large blood vessels and the dilation of the postcapillary venules Retraction of the endothelial cells lining the capillaries causing increased permeability of the capillary walls. Receptors; H1 receptor (proinflammatory) & H2 receptor (anti-inflammatory)

Mast cell Degranulation o HISTAMINE H1 receptor ____________________ Present in ________________ muscle cells of the ____________ In the ___________  H2 receptor - ______-___________________ (reduces activity of the lymphocytes, eosinophils, neutrophils, and mast cells) - Present on partial cells of the ________________ mucosa ~ increases the secretion of ________________ acid

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o Chemotactic factors:  Neutrophils chemotactic factor - Attracts ________________  Eosinophil chemotactic factor of anaphylaxis (ECF-A) - Attracts ________________ o Mast Cell Synthesis of Mediators  Leukotrienes - Product of arachidonic acid from mast cell membranes - Similar effects of ___________________ in later stages (smooth muscle contractions and increased vascular permeability) - Active in the later stages of _____________________  Prostaglandins - Similar effects of leukotrienes; they also induce _________ - Aspirin and some other nonsteroidal anti-inflammatory drugs (___________) block the synthesis of _____________________, thereby inhibiting inflammation  Platelet-activating factor - Similar effect to leukotrienes and platelet activation Example: If you have ever taken singular, you have taken a leukotriene inhibitor. Given to patients with asthma to reduce inflammation of the airways to relax the smooth muscle of the airways. Explain allergy testing:

Endothelium of Vessel Walls o Endothelial cells adhere to underlying connective tissue matrix - Basically… lines the vessel wall and regulates the circulating components of the _____________ response  Interact with ________________ cells, ________________, ________________ ________________

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Regulate circulating _____________________ components Damage to these initiates platelet adherence

o Platelets  Activated by tissue ____________________ and inflammation  Activation leads to interaction with ________________ cascades - Assists with clotting at the site of the injury - Low dose aspirin prohibits platelet ________________. Aspirin is given to cardiac patients to prevent platelet aggregation and reduce clot formation.

Phagocytes ________________________: process by which a cell ingests and disposes of foreign material. - 2 most important are neutrophils and macrophages STEPS:

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1. Adherence 2. Engulfment 3. Phagosome formation (capsule that surrounds the bacteria) 4. Fusion with lysosomal granules 5. Destruction of the target  Neutrophils (polymorphonuclear neutrophils (PMNs)) - ________________ in early inflammatory responses - Ingest bacteria, dead cells, and cellular debris - Cells are short lived and arrive at site within ___-___hours after injury.  mature cells that __________ divide once they get to the area of inflammation  Sensitive to the __________environment (these are the cells that engulf (eat) and destroy invading organisms) Eosinophils  _____________ phagocytic  Defense against parasites and regulation of ________________ mediators Basophils  Least ________________ granulocytes  Primary role is ________________  Thought to do the same things as mast cells but in the blood stream Monocytes and macrophages  Monocytes are produced in the ________ ____________, enter the circulation, and migrate to the ___________________ site, where they develop into ________________  Macrophages typically arrive at the inflammatory site ____ hours or later after neutrophils  They can multiply in the tissues.  This is what starts the wound healing by cleaning up the site ________________ cells  In the peripheral organs and skin  Migrate through lymph vessels to lymph tissue and interact with T lymphocytes to generate an acquired immune response

o T lymphocytes  Active during wound healing

Natural Killer Cells   

________________ and __________________ cells infected with viruses Inhibitory and activating receptors to allow ___________________ between normal and abnormal cells Binds to target cell releasing ________________ and ________________ molecules

Acute inflammation 

ACUTE - _______-________________ (usually last __-__ days) - Local manifestations-result from vascular changes and corresponding leakage of circulating components into the tissue  ______, ____________, ____________, _________  Exudative fluids o Exudative Fluids; exudate is fluids or cells that have leaked from the blood vessel into the interstitial tissues. Usually associated to the inflammatory response. - Serous Exudate  Watery exudate: indicates ___________ inflammation  Fluid in a _____________ - Fibrous exudate  _________, clotted exudate indicates more advanced inflammation (pneumonia) - Purulent exudate (suppurative)  ______: indicates a ________________ infection  Characteristics of walls of lesions like cysts and abscesses - Hemorrhage exudate  Exudate contains _____________: indicated bleeding

Systemic manifestations of acute inflammation o ________________  Caused by exogenous and endogenous pyrogens  Act directly on the hypothalamus (temp regulating part of the brain) o Leukocytosis  Increased number of circulating _____________________  Normal WBC _______-_______

Chronic inflammation 

CHRONIC - Inflammation lasting __ weeks or longer - Often related to an ______________acute inflammatory response  Characterized by pus formation, suppuration, and ______________would healing - Other causes of chronic inflammation  High lipid and wax content of a microorganism  Ability to survive inside the macrophage  Toxins

Chemicals, particulate matter, or physical irritants may remain in the wound causing chronic, prolonged inflammation Characteristics  Defense infiltration of ______________ and ______________  ______________ formation: body’s attempt to wall off and isolate organisms - Common granuloma is one that walls off TB and prevents the spread of TB through the body.  Cells that clean up and remove large debris: Epithelioid cells & Giant cells - These 2 cells form during ______________ inflammation 

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Wound Healing o Regeneration (may take up to __ years) o Resolution  Returning ______________ tissue to the original structure and function o Repair  Replacement of destroyed tissue with scar tissue  Scar Tissue - Composed primarily of ______________ to restore the tensile strength of the tissue but cannot carry out the same functions as the original tissue. o Debridement  Cleaning up the dissolved clots, microorganisms, erythrocytes, and dead tissue cells o Healing  ______________ in the wound  Sealing the wound (_____________________)  Shrinking the wound (_____________________)  PRIMARY INTENTION - Wounds that heal under conditions of minimal tissue loss  SECONDARY INTENTION - Wounds that require a great deal more tissue replacement (_______ wound) heal from the bottom, up. o Healing process 1. Inflammation phase - Begins ______________ after injury - Coagulation - Infiltration of wound-healing cells - _____________________ (formation of new blood supply) 2. Proliferative phase - Begins 3-4 days after the injury and continues as long as 2 weeks - Granulation - Epithelialization - Requires ______________ proliferation, ______________ formation, _______ contraction - New tissue grows _______ the clot or scab 3. Remodeling and maturation phase - Starts _______ _______ after the injury and is complete within __ years - Continuation of cellular _____________________ - _______ _______ formation - Scar ______________

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For wounds that heal by scarring, scar tissue is remodeled, and ______________ disappear, leaving the scar ______________ Within 2-3 weeks after maturation has begun the scar tissue has gained __/__of its eventual strength The scar tissue regains ______________ of the initial tissue but does not ______________like the original tissue

Dysfunctional Wound Healing o May occur during _______ phase of wound healing  _______ _______ (reduced O2 and nutrients)  _______ bleeding; large clot and increased amount of space for granulation tissue must fill  Excess _______ deposition  Predisposing disorders - Diabetes - Obesity: causes impaired leukocyte function and predisposition to infection. Obesity is a _____________________ - Wound infection - Inadequate ______________ - Numerous __________ (medications): many cancer medications, NSAIDS, and steroids may delay healing - ______________ smoke o Dysfunction during the reconstruction phase  Dysfunctional collagen synthesis - _______ scar - ______________ scar  Wound disruption - Dehiscence (increases risk of infection) frequently seen after abdominal surgery  Impaired Contraction - Contracture seen in burns

Pediatrics o o o o o

Neonates have transiently depressed ______________ and ______________function Neutrophils are not capable of efficient ______________ Neonates express and complement deficiency Deficient oxidative and bacterial responses Develop overwhelming _______

Older Adults o Impaired function of ______________ immunity cells (phagocytes) o Impaired inflammation is likely a result of _______ illness - Diabetes, cardiovascular disease, etc. o Chronic medication intake ______________ the inflammatory response o Healing response is ______________ because of skin loss of regenerative ability o _________________ and ___________ inflammation are more common in older adults...