Patho - Term Test III (Immunity) Flashcards
Define innate (natural or native) immunity.
defense mechanisms that are present at birth and provide the initial response to invasion and injruy
What are the first, second, and third lines of defence? What are their respective functions
1) physical, mechanical, and biochemical barriers (prevent damage from environment or infection by pathogenic microorganism)
2) inflammatory response (activated to protect body from further injury, fight infection, and promote healing - there is already tissue injury/infection at this point)
3) adaptive (acquired/specific) immunity (long term protection against specific invaders)
Define adaptive (acquired or specific) immunity.
refers to immuntiy that develops over someone’s lifetime and provides long-term protection against specific invaders
Adaptive immunity involves “memory” which serves what purpose?
allows for rapid response for future exposures to the same invader because the body already has a memory of this invader
What is the timing of defense of the following:
1) Barriers
2) Inflammatory Reponse
3) Adaptive immunity
1) constant
2) immediate response
3) there is delay between 1st exposure to antigen and max response; immediate response against 2’s exposure to the same antigen
What is the specificity of defense of the following:
1) barriers
2) inflammatory response
3) adaptive immunity
1) broadly specific
2) broadly specific
3) very specific towards target
What cells are involved with barriers?
1) epithelial cells
What cells are involved with inflammatory response?
1) mast cells
2) granulocytes (neutrophils, basophils, eosinophils)
3) monocytes/macrophages
4) NK cells
5) platelets
6) Endothelial cells
What cells are involved with adaptive immunity?
1) T lymphocytes
2) B lymphocytes
3) Macrophages
4) Dendritic cells
Memory is involved with which of the following lines of defense?
1) Barriers
2) Inflammatory response
3) adaptive immunity
4) all of the above
adaptive immunity (specific immunologic memory by T and B lymphocytes)
What molecules are active in innate barriers?
- Defensins
- Collectins
- Lactoferrin
- Bacterial toxins
What molecules are active in inflammatory response?
- Complement activation
- Clotting factors
- Kinins
- Cytokines
What molecules are active in adaptive immunity?
- antibodies
- complement
- cytokines
Innate barriers have what kind of protective functions? (3)
1) anatomical barriers (skin, mucous membranes)
2) cells and secretory molecules (lysozymes, low pH of stomach and urine)
3) ciliary activity
Inflammatory responses have what kind of protective functions? (4)
1) vascular responses
2) cellular components (mast cells, neutrophils, macrophages)
3) secretory molecules of cytokines
4) activation of plasma protein systems
Adaptive immunity has what kind of protective functions?
1) activated T and B lymphocytes
2) cytokines
3) antibodies
How does the following remove infectious microorganisms:
1) skin
2) respiratory tract
3) GI tract
4) urinary tract
1) skin: microorganisms being sloughed off with dead skin cells
2) resp tract: epithelial cells producing mucus to trap microorganisms + cilia (coughing, sneezing it out)
3) GI tract: vomiting, defecation
4) urinary tract: urination
Low temperature on skin and low pH in stomach (activate/inhibit) growth of pathogenic microorganisms.
inhibit
How do epithelial cells trap & destroy invaders?
secrete mucus, saliva, sweat, tears, and earwax & have lethal substances (ex. lyosozymes that attack cell walls of gram+ve bacteria)
How do sebaceous glands kill bacteria/fungi?
- secrete fatty acids and lactic acid
- create acidic environment (pH 3 -5 on skin)
What are antimicrobial peptides? Provide an example.
Host defense peptides that are secreted by epithelial cells and kills/inhibits growth of disease-causing microorganisms
ex. (any one of the following):
- Cathelicidins
- Defensins
- collectins
- mannose-binding lectin
What are defensins?
antimicrobial peptides produced by neutrophils and epithelial cells (disrupts bacterial membranes)
What are collectins?
soluble glycoproteins that facilitate ability of macrophages to recognize and kill pathogenic microorganism, can also activate lectin pathway of complement system
Surfactant is a type of ____________.
collectin
I am cool with manna and mustafa using my flashcards. True or false.
False (just kidding :))
How many racoons can you shove up your butthole?
almost 2
Normal microbiome has a _______ and ________ relationship with the body (parasitic/commensal/opportunistic/etc).
commensal (benefitting microorganism without affecting the body)
mutualistic (benefitting both microorganism and body)
What are 6 functions of normal microbiome?
1) produces enzymes that facilitate digestion of fatty acids and large polysaccharides
2) synthesizes essential metabolites
3) releases antibacterial substances that are toxic to invaders
4) competes with pathogens for nutrients and blocks attachment of pathogens to the epithelium
5) fosters adaptive immunity by inducing growth of gut-associated lymphoid tissue (needed for local and adaptive immunity)
6) contributes to bidirectional communication between brain and GI tract
True or False. Prolonged treatment of broad-spectrum antibiotics can decrease normal microbiome protective activity and lead to overgrowth of pathogenic microorganisms.
True (because broad-spectrum antibiotics target wide range of bacteria so it kills good and bad bacteria)
What are opportunistic pathogens?
pathogens that are part of normal microbiome that are harmless under normal conditions but then can cause disease in immunocompromised individuals who lack usual defense mechanisms
Define inflammation.
Dynamic process programmed to respond to cellular or tissue damage irrespective of location or condition of tissue; it is non-specific
What is the process of acute inflammatory response?
1) cell/tissue damage
2) release of inflammatory mediators (from mast cell degranulation, activation of plasma protein systems)
3) changes in microcirculation
4) migration of leukocytes, plasma proteins, biochemical mediators from circulation into damaged tissue
5) destroy invaders in tissue, limit tissue injury, promote healing
Which of the following is false in regards to inflammatory response?
1) process can occur in vascularized and avascularized tissues
2) activation is rapid
3) response includes cellular and chemical components
4) response is non-specific
1) process can occur in vascularized and avascularized tissues
process can only occur in vacularized tissues because a blood supply is needed for cells and chemical components to go to injury site
What are the cardinal signs of acute inflammation?
Rubor (redness, erythema)
Calor (heat)
Tumor (swelling)
Dolor (pain)
Loss of function
In inflammatory response, what sort of changes occur in the microcirculation (capillaries, venules, arterioles)?
1) hemostasis (coagulation) - clotting cascade and activates platelets (clotting slows blood flow, walls off injury, and provides a meshwork for healing)
2) vasodilation - increases blood volume delivered to injured site and slows velocity of blood flow which allows more time for fluid, cells, chemical movement into surrounding tissues which results in erythema/warmth in injury site
3) increased vascular permeability - endothelial cells contract which cause blood vessels to become porous ==> leads to exudation and edema surrounding injury site
4) WBC adhesion - adhere to inner walls of vessels where they migrate through the enlarged spaces between endothelial cells and into surrounding tissue (influx in phagocytes - neutrophils, macrophages)
Exudation vs edema
exudation - fluid leaking from vessels
edema - tissue swelling from fluid leaking
Lymphangitis vs lymphadenitis
Lymphangitis: inflammation of lymph vessels
Lymphadenitis: inflammation of lymph nodes
What are the 3 key systems for an effective inflammatory response?
1) complement system
2) clotting system
3) kinin system
True or False: Plasma protein systems have multiple proteins/enzymes that are usually inactive (proeznymes) in the blood and get activated when there is tissue damage
True
Purpose of complement system
intensifies/complements capacity of antibiotics/phagocytes to clear pathogens and damaged cells and activate inflammation (so they either destroy pathogens directly or can eradicate pathogens through enhancing activity of other components of the immune response)
Activation of C3 and C4 within the complement system lead to what molecules being produced that are critical to immune response? What are their functions?
1) C3b - serve as opsonins (coats surface of bacteria to increase their susceptibility tto phagocytosis by inflammatory cells) - getting it ready for ingestion
2) C5a - functions as chemotactic factor (stimulates movement of leukocytes and attracts them to injury site)
3) C3a, C5a - anaphylatoxins; induces rapid degranulation of mast cells to release histamine (which induces vasodilation and increased capillary permeability)
What is the membrane attack complex (MAC)?
Component of complement system that is composed of C6-C9 that lead to bacterial destruction and tissue injury by creating pores in outer membranes of cells/bacteria (water infusion occurs, leads to cell death)
What are the 3 major pathways/cascades that control complement activation?
1) classical
2) alternative
3) lectin
How is the classical pathway activated which controls complement activation?
classical pathway is activated by antibodies when they bind to antigens, which then activates complement cascade and triggers infection
How does alternative pathway get activated control complement activation?
activated directly by substances found on surfaces of infectious microorganisms –> forms a complex that then causes activation of complement cascades and triggers infection
How does lectin pathway control complement activation?
does not require antibodies for activation, activated by several plasma proteins (particularly mannose-binding lectin MBL) that bind to the bacteria and activate complement cascade
What is the purpose of the clotting/coagulation system?
A group of plasma proteins that form a blood clot when cascade is activated
What is a blood clot composed of?
meshwork of fibrin strands and platelets
How is the clotting system activated?
By a variety of substanes (collagen, enzymes, bacterial toxins) released during tissue injury/infection
Functions of Clotting/coagulation system include what?
1) plug damaged vessels to stop bleeding (hemostasis)
2) trap microorganisms (localizing them)
3) prevent spread of microorganisms to adjacent tissues
4) provide framework for future repairing and healing
What are the two converging pathways that lead to clot formation? How are these two pathways activated?
extrinsic and intrinsic pathways
Extrinsic (tissue factor) pathway activated by tissue factor/tissue thromboplastin which is released by damaged endothelial cells of blood vessels + reacts with activated factor VII
Intrinsic (contact activation) pathway activated by exposed endothelium and negatively charged substances (resulting from vessel wall damage) coming in contact with factor XII/Hageman factor
Where do the intrinsic and extrinsic pathways of the clotting system converge, and after they converge what is the end product?
They coverge at factor X and form a common pathway that leads to activation of fibrin to eventually form a fibrin clot
Fibrinogen also makes fibrinopeptides that are chemotactic and attract neutrophils and increased vascular permeability
What is the kinin system’s function?
To activate and assist inflammatory cells
How is the Kinin System activated and what is the end product?
Activated by Hageman factor (Factor XII)
End product: bradykinin
What does bradykinin do, as part of the inflammatory response?
Causes dilation of blood vessels and acts with prostaglandins to induce pain, trigger smooth muscle cell contraction (bronchoconstriction) and increase vascular permeability
All the plasma protein systems are tightly regulated and highly interactive. What are two reasons as to why this would be beneficial for the human body?
1) inflammatory process is critical for survival so interaction of these systems allows for efficient activation regardless of cause of tissue injury
2) biochemical mediators released during inflammatory response are potent and can be harmful to the person so they have to be controlled and confined to injured tissues
Which of the following do not down-regulate or inactive plasma protein systems?
1) protease inhibitors
2) Hageman factor
3) Carboxypeptidase
4) Kininase
5) Histaminase
2) Hageman factor
Formation of clots activates fibrinolytic system. What is the function of this system and how does it work?
The fibrinolytic system functions to limit clot size (works oppositely to clotting system) and degrade clot after bleeding has ceased
How it works: Thrombin (which is made in the clotting system) activates plasminogen which is converted to plasmin which then degrades fibrin polymers in clots
What types of cells/components are involved with inflammation?
1) mast cells
2) endothelial cells
3) platelets
4) phagocytes (neutrophils. macrophages)
5) lymphocytes
Which cells are the most important mediators of inflammation?
Mast cells
Precursors of macrophages are also known as:
monocytes
What lymphocytes are involved with the following?
1) innate immunity
2) adaptive immunity
1) innate: NK cells
2) adaptive: B and T lymphocytes
What are pattern recognition receptors (PRRs)?
set of receptors on cells that are involved in initiating innate immune response and recognize antigens
Where are pattern recognition receptors generally expressed on?
cells in tissues near body’s surface (skin, resp tract, GI tract, genitourinary tract) so they can monitor environment for cell damage/infectious microorganisms
What are the two types of molecular patterns that PRRs recognize?
1) pathogen-associated molecular patterns (PAMPs)
2) damage-associated molecular patterns (DAMPs)
PAMPs vs DAMPs
PAMPs: molecules expressed by infectious agents found either on surface or released as soluble molecules
DAMPs: products of cellular damage
Toll-like receptors: what do they recognize and where are they found?
Recognize PAMPs located on cell wall/surface of microorganisms
Found on outer membrane of phagocytic cells with early contact with infectious microorganisms (i.e. dendritic cells, macrophages)
C-type lectin receptors: what do they recognize and where are they found?
Recognize PAMPs (especially fungal antigens) and DAMPs
Found on outer membrane of phagocytic cells
Nucleotide-binding-like receptors (NLRs) and NOD-like receptors: what do they recognize, what is their function, and where are they found?
Recognize PAMPs and DAMPs
Function: initiate production of proinflammatory mediators and help control inflammatory response
Found in cytoplasm of innate immune cells (lymphocytes, macrophages, and dendritic cells)
Complement receptors: what do they recognize and where are they found? what is their function?
Recognize components of complement system
Found on many cells involved with immune response, platelets, epithelial cells, vascular smooth muscle
Function: result in chemotaxis and activation of innate immune cells
Scavenger receptors: what do they recognize and where are they found? What is their function?
Recognize bacterial pathogens, damaged cells, and soluble lipoproteins (HDL, LDLs, etc.)
They are found on surfaces of macrophages
Functoin: remove old RBcs and cells undergoing apoptosis
What are cytokines?
Small signaling proteins that bind to specific cell membrane receptors to regulate innate/adaptive immunity and are responsible for activating other cells; mediators of inflammation
True or false. Cytokines can be proinflammatory or anti-inflammatory
True - depends on whether they tend to induce or inhibit inflammatory response
Which of the following are not cytokines?
1) interleukins
2) lymphokines & monokines
3) chemokines
4) TNF-a
5) bradykines
6) interferon
bradykines
What are lymphokines, monokines?
cytokines that are secreted from lymphocytes and monocytes (respectively)
What are chemokines?
cytokines that are chemotactic and are typically synthesized in response to proinflammatory cytokines
What are interleukins?
cytokines that are produced primarily by WBCs (macrophages, neutrophils) in response to stimulation of PRRs/other cytokines and serve to alter behaviour of cells; can be proinflammatory or anti-inflammatory
Four functions of interleukins include what?
1) chemotaxis (attracting leukocytes)
2) regulating cell adhesion molecules (CAMs) which are proteins that facilitate binding of cells or with ECM
3) induction, proliferation, and maturation of leukocytes in bone marrow
4) general enhancement/suppression of inflammation and adaptive immune response
Which of the following is not an proinflammatory cytokine?
1) IL-1
2) TNF-a
3) IL-6
4) IL-10
IL-10
What is tumor necrosis factor-alpha (TNF-a)?
What is its role in inflammation?
A proinflammatory cytokine that is primarily secreted by macrophages in response to PAMP and toll-like receptor recognition
Function: contributes to damaging effects of chronic inflammation and causes fever, synthesis of other inflammation-related proteins (acute phase proteins), muscle wasting (cachexia), and intravascular thrombosis
What is interleukin-1 (IL-1)?
A proinflammatory cytokine mainly produced by macrophages and is an endogenous pyrogen (causing fever); also acts as a growth factor for many cells
What is interleukin-6 (IL-6)?
A proinflammatory cytokine produced by macrophages, lymphocytes, fibroblasts and other cells
Function: directly induces hepatocytes in the liver to produce acute phase proteins (proteins needed for inflammation), stimulates growth and differentiation of red blood cells in bone marrow, and growth of fibroblasts for wound healing
Proinflammatory vs anti-inflammatory
Proinflammatory: up-regulate infection with goal of eradicating pathogens (causes fever, further inflammation, tissue death)
Anti-inflammatory: diminish and control inflammatory response
Two important anti-inflammatory cytokines include:
IL-10
TGF-b (transforming growth factor-beta)
What is interleukin-10 (IL) and its function?
Anti-inflammatory cytokine primarily produced by lymphocytes
function:
- suppress activation and proliferation of other lymphoctes
- limit production of proinflammatory cytokines
- results in downregulation of inflammatory and adaptive immune responses
What is transforming growth factor-beta (TGF-b) and its function?
anti-inflammatory cytokine that is produced in response to inflammation
Function: suppress activity of lymphocytes and downregulate production of proinflammatory cytokines by macrophages
What are interferons (IFNs) and its subclasses?
cytokines that protect against viral infections
Type I interferons (IFN-a, IFN-b): produced and released by virally infected cells in response to viral dsDNA; do not kill viruses directly but induces antiviral proteins
Type II inferferons (IGN-y): produced primarily by lymphocytes and increase bactericidal activity of macrophages
List the immunoreactive cells.
1) mast cells
2) endothelial cells
3) platelets
4) neutrophils
5) eosinophils
6) basophils
7) monocytes/macrophages
8) lymphocytes and NK cells
What are mast cells?
Significant, potent activators of inflammatory response with granules containing mediators that are released in tissue injury
What are the two mechanisms in which mast cells release their mediators?
1) degranulation: release of contents of mast cell granules (histamine, chemotactic factors, cytokines)
2) synthesis: production and release of mediators in response to a stimulus
What sort of vascular changes does histamine cause?
- constriction of large blood vessels/smooth muscle and dilation of postcapillary venules (net result: increased blood flow within microcirculation)
- also causes increased vascular permeability secondary to retraction of endothelial cells
Histamine H1 vs H2 receptors?
H1 receptors: causes bronchoconstriction (smooth muscle contraction) when activated - is proinflammatory when histamine binds to it
H2 receptors: when activated, supresses leukocyte function (so function is anti-inflammatory) and induces secretion of gastric acid
Antihistamines and H2 blockers are used against histamine function. What do each of these classes of drugs do?
Antihistamines: drugs block binding of histamine to H1/H2 receptors resulting in decreased vascular effects
H2 blockers: medications that reduce gastric acidity in individuals prone to peptic ulcers/GERD
Mast cells initiate synthesis of other mediators of inflammation. These mediators include what?
1) leukotrienes
2) prostaglandins
3) platelet-activating factor
What are leukotrienes and its functions?
Leukotrienes are lipids that induce smooth muscle contraction (especially bronchoconstriction) and increase vascular permeability ; made from arachidonic acid from mast cell membranes
function: stimulate slower and more prolonged inflammatory response (similar effects to histamine in later stages of inflammatory response)
What are prostaglandins and its functions?
long-chained unsaturated fatty acids that cause increased vascular permeabiity, neutrophil chemotaxis, and pain
they are produced by the action of cyclooxygenase (COX)
What are the two forms of cyclooxygenase (COX)? If inhibited via inhibitor drugs, what will happen?
COX-1: activates platelets and protects stomach lining
- if inhibited, GI tract bleeding and ulcers (think aspirin and NSAIDs suppressing inflammation but causing GI bleeds)
COX-2: associated with inflammation
- if inhibited, increased risk of CV disease due to effects on blood vessels and clotting
What are platelet-activating factors?
- mediators that are produced by neutrophils, monocytes, endothelial cells, mast cells, and platelets
- has similar activity as leukotrienes
- causes endothelial retraction, platelet activation, mast cell activation
Where are endothelial cells found and what do they do?
They are found lining blood vessels and regulate circulation (controlling water and solute movement between blood and tissues)
What happens to endothelial cells when there is tissue injury?
endothelial cells contraction leading to increased capillary membrane permeability (allows for plasma and nutrients to move out of capillaries and into injured tissue)
Platelets have no nucleus and are formed from _______.
megakaryocytes
What do platelets do during inflammation/vascular injury?
- blood clotting
- degranulate and release mediators like serotonin that have similar effects to histamine to accelerate inflammation
- synthesizes thromboxane that vasoconstricts and induce platelet aggregation
- recognizes and kills pathogens
- release growth factors that promote wound healing
What are the three granulocytes?
neutrophils, basophils, eosinophils
The earliest phagocytes at site of inflammation are what?
neutrophils
What is the primary function of neutrophils? How are they removed?
Function: phagocytize pathogenic microbes and remove cellualr debris and dead cells from lesions
Short-lived so removed with purulent exudate (pus) through epithelium or drained through lymphatic system
What are the functions of eosinophils?
primary defence against parasites and regulate vascular mediators released from mast cells (have lysosome enzymes that degrade vasoactive substances to limit vascular effects of inflammation)
What are the functions of basophils?
- release histamine
- also has heparin (anticoagulant)
- important source of cytokines involved in adaptive immune response especially with allergies and asthma
What are monocytes?
The largest WBCs that are produced in bone marrow and migrate to site of inflammation where they transform into macrophages
What is the primary function of macrophages?
prolonged phagocytosis (can survive acidic environment of inflammatory site) so removes debris and promote healing and repair
M1 macrophages: greater bactericidal activity
M2 macrophages: primarily involved in tissue healing and repair
What do dendritic cells do?
Antigen-presenting cells: they recognize invaders via PRRs and internalize invaders, then migrate through lymphatic vessels to lymph nodes where they present the invaders to T lymphocytes
Difference between:
B lymphocytes
T lymphocyes
NK cells
B lymphocytes - produces antibodies
T lymphocytes - directly kills virus/cancer cells
NK cells: part of innate immunity; recognizes and eliminates cells infected with virus/cancerous cells
The two most important phagocytes for ingesting pathogens/damaged cells are:
neutrophils, macrophages
Margination/pavementing is defined as what?
increased adhesion of neutrophils to endothelial cell wall of capillaries and venules (adhesion molecules increase stickiness of the cells)
The emigration of cells through interendothelial junctions is known as:
diapedesis
What are the 5 stages of phagocytosis?
1) Adherence - of phagocyte to its target through PRRs and opsonization
2) engulfment - bind to surface of phagocyte and engulfed into a phagosome
3) Phagosome formation
4) Fusion with lyososomal granules = phagolysosome
5) target destruction - lysosomal enzymes kill and digest microorganisms
What are opsonins?
proteins that coat the target bacteria and act like glue tightening the affinity between phagocyte and target (makes phagocytosis more effective)
ex. the most efficienct opsonins: C3b (from complement) and antibodies
Within the phagolysosome, there are oxygen-dependent and -independent mechanisms that kill the pathogens. Describe how these mechanisms kill the pathogens.
Oxygen-dependent mechanisms: result from production of toxic oxygen species
Oxygen-independent mechanisms: acidic pH, proteins binding to and damaging target cell membrane, enzyme attack on pathogen cell wall, inhibition of bacterial growth
Phagocytes may die at inflammation sites. What occurs as a result of this?
Causes inflammation-associated tissue destruction due to releasing its enzyme contents (but this is minimized with natural inhibitors found in blood)
Define acute inflammation.
Inflammation that is rapid onset and continues only until threat to body is eliminated (self-limiting, usually lasts 8-10 days from injury onset)
Local manifestations of acute inflammation include what?
heat
swelling
redness
pain
potential loss of function
exudate
How do exudative fluids occur?
from increased vascular permeability and leakage of fluid into tissues
Exudate that is water with few plasma proteins and leukocytes (Ex. fluid in blister), and indicates early or mild inflammations is known as what?
Serous exudate
Describe fibrinous exudate and where you would find such?
thick and clotted exudate (indicates more advanced inflammation)
ex. in lungs with pneumonia
Accumulation of large number of leukocytes which occur in persistent bacterial infection (abscesses, pus) is known as what kind of exudate?
Purulent/suppurative exudate
Exudate that is filled with RBCs and indicates bleeding is known as?
hemorrhagic exudate
What are the 3 systemic manifestations of acute inflammation?
fever
leukocytosis
increased plasma protein levels
What causes fever?
endogenous and exogenous pyrogens (specific cytokines release from neutrophils and macrophages) - act directly on hypothalamus which control’s body’s thermostat
Treatment for febrile seizures?
tylenol, removing clothing “(to avoid exacerbation of problem)
What is leukocytosis?
increased in number of circulating WBCs beyond upper limit of normal (11000 ml^3 in adults)
- may also notice “left shift” (i.e. increase in ratio of immature to mature neutrophils)
What is produced by the liver during acute inflammation?
acute phase reactants/proteins
- C-reactive protein
- Fibrinogen
- Haptoglobin
- Amyloid
- Ceruloplasmin
Someone with inflammatory process going on in the body would show _______ (increased/decreased) ESR and _______ (increased/decreased) c-reactive protein.
Increased; increased
True or false. Chronic inflammation lasts at least 2 weeks and is always preceded by an unsuccessful acute inflammatory response
False.
What’s true is that it lasts at least 2 weeks
but this statement is false because chronic inflammation can follow acute inflammation that was inadequate BUT can also be a distinct process on its own
Chronic inflammation is characterized by:
- pus formation
- suppuration (purulent discharge)
- incomplete wound healing
What are granulomas?
A walled-off/isolated infected area full of macrophages (epithelioid cells and giant cells), lymphoctytes, collagen
- may calcify
Epithelioid cell formation vs Giant cell formation
Epithelioid: differentiated macrophages that specialize in taking up debris and small particles
giant cell: multinucleated active phagocytes that take up larger cells
Regeneration is the process of what?
damaged tissue is replaced with healthy tissue of the original type (occurs in wounds that are minor damage with no complications)
Define resolution/maturation in the context of wound healing
returning of injured tissue to its original structure and function (may take up to 2 years)
Resolution may not occur in what wound situations?
1) extensive damage
2) injury site is where original tissue cannot regenerate
3) areas where infection has resulted in abscesses or granuloma formation
4) where fibrin persists in the lesion
Define repair in the context of wound healing
replacement of destroyed tissue with scar tissue
What is scar tissue?
collagen that mostly fills in the lesion to restore tissue integrity and strength but has no physiologic functions of tissue
What are the 4 overlapping stages in wound healing?
1) hemostasis (coagulation)
2) inflammation
3) proliferation with new tissue formation
4) remodeling and maturation
Wounds healing by primary intention are wounds that can be described to have_______.
minimal tissue loss
Surgical incisions and paper cuts are examples of wounds that will heal by _________.
primary intention
Wounds healing by secondary intention are wounds that can be describe as__________.
needing more tissue replacement; more time and care required as well
Open wounds such as pressure ulcers and burns can be described to heal by ____________.
secondary intention
At best, repaired tissue that heals by secondary intention regains ___% of its original tensile strength
80
What are the three regions/areas of the body in which normal tissue can regenerate without scarring ? This type of healing is known as _____________.
- liver
- bones
- epithelium
- known as compensatory hyperplasia
A patient is recovering from an MI. He asks you whether or not his heart and cardiac function can return to normal. What do you say to him?
- MI heals with fibrous scar tissue rather than with cardiac muscle so cardiac function is not restored completely
Phase I of wound healing is known as _______. What happens during this phase?
Hemostasis/coagulation
- vascular injury causes immediate vasoconstriction and then vasodilation, and initiates clotting cascade and platelet activation to form a blood clot
- platelets also degranulate and release factors that cause increased permeability and promote growth factors that initiate proliferation in undamaged cells
Phase II of wound healing is known as _______. What happens during this phase?
Inflammation
- begins within minutes; macrophages and mast cells release cytokines that increase blood flow to wound and bring needed cells and proteins to injury site (neutrophils to clear wound of debris and bacteria; lymphocytes to initiate immune response)
Phase III of wound healing is known as _______. What happens during this phase?
Proliferation and New Tissue Formation
- begins 3-4 days after injury and continues up to 2 weeks
- wound is sealed and fibrin clot is replaced with normal/scar tissue (debridement)
- angiogenesis
- granulation tissue formation
- epithelization occurs: epithelial cells growing into wound (can be sped up with moist wound to prevent it from becoming a scab)
- fibroblast proliferation, collagen formation, wound contraction
What is wound contraction?
a process of wound healing where fibroblasts turn into myofibroblasts and anchor themselves to wound bed to contract their fibers and exert tension on neighbouring cells (needed for closure of all wounds, noticeable 6-12 days after injury)
Phase IV of wound healing is known as _______. What happens during this phase?
Remodeling and Maturation
- begins several weeks after injury and is normally completed within 2 years
- tissue regeneration and wound contraction continue in this phase
- cellular differentiation, scar formation/remodeling (scar tissue becomes avascular)
What factors can contribute to dysfunctional wound healing?
1) ischemia
2) excessive bleeding
3) excessive fibrin deposition
4) predisposing factors/disorders (diabetes, obesity, wound infection, inadequate nutrients, drugs, tobacco smoke)
How does ischemia cause dysfunctional wound healing?
ischemia leads to cell death and infection which prolongs inflammation/delays healing
- also reduces energy production and impairs collagen synthesis & tensile strength of regenerating tissue
How does excessive bleeding cause dysfunctional wound healing?
- delays healing because large clots increase amount of space that granulation tissue must fill
- clots also serve as mechanical barriers to oxygen diffusion
- accumulation of blood is also a great place for bacterial growth leading to infection and inflammation
How does excessive fibrin deposition cause dysfunctional wound healing?
- fibrin can eventually turn into fibrous adhesions which turn into bands that distort/impinge and strangulate organs –> leads to pain and organ dysfunction
How does diabetes cause increased risk of dysfunctional wound healing?
- persistent hyperglycemia leads to wounds being ischemic (small-vessel diseases and impaired blood flow)
- suppresses macrophage function
- hyperglycemia also increases a type of oxygen that does not allow oxygen to be readily realeased into tissues
How does obesity cause increased risk of dysfunctional wound healing?
- impaired leukocyte function predisposes wound to infection
- decrease growth factor production
- increased proinflammatory cytokines
- dysregulation of collagen synthesis
- decrease in angiogenesis
How does wound infection cause increased risk of dysfunctional wound healing?
- continued pathogen invasion into injured area means continuous need for body to fight off infection, uses nutrients, release of inflammatory mediators = delays wound healing
How does inadequate nutrients cause increased risk of dysfunctional wound healing?
- your tissues at the wound already have increased metabolic demands so lacking nutrients is no good
- vitamin A and C are requrred for collagen synthesis so lack of this leads to poorly formed connective tissue and significantly impaired healing
- others include iron, zinc, manganese, and copper
How does tobacco smoke cause increased risk of dysfunctional wound healing?
- toxic agents (CO, hydrogen cyanide) delay wound healing
- nicotine also vasoconstricts which predisposes the tissue to ischemia and infection, thus compromising wound healing
How do various drugs (antineoplastic/anticancer agents, NSAIDs, steroids) cause increased risk of dysfunctional wound healing?
- antineoplastic agents: slow cell division and inhibit angiogenesis
- NSAIDs suppress acute inflammation and inhibit prostaglandin production which delays wound healing + associated with excessive scarring
- steroids: disrupt wound healing by preventing macrophages from migrating to injruy site
Which scars are likely to recur despite surgical removal?
keloids
Which demographics have been shown to have a higher incidence of keloids with wound healing?
darker skin pigmentation
familial tendency
Define dehiscence. How does this happen and what is the treatment for it?
Complication where wound pulls apart at suture line (generally occuring 5-12 days after suturing)
Happens due to excessive strain; increase risk in obese people because adipose tissue is difficult to suture
Tx: prompt surgical attention
What is a contracture?
excessive wound contraction that leads to anatomic deformity
Where can contractures occurs and what is the management/treatment for this?
- Can occur with burns, particularly at joints
- internal contractures can occur in duodenum (from improper healing of peptic ulcers); esophagus (from chemical burns like lye ingestion); abdomen from surgery/infection/radiation
Treatment/prevention:
- proper positioning
- ROM exercises
- compression
- surgery for internal contractures
Newborn innate immunity is limited. Where do they get their immunity from?
At the beginning as their own immunity is building, their immuntiy is acquired from their mother through placenta and breast milk
Describe how the following affect/present in an infant’s innate immunity/healing ability (relative to an adult’s):
1) inflammatory response/inflammatory cytokine production
2) complement levels
3) monocyte/macrophage levels
4) Susceptibility to chemotactic defects
5) severity of sepsis and meningitis if infected
6) newborns via C-section
7) ability to fight off infection in utero
1) depressed inflammatory response, limited production of cytokine production
2) diminished complement levels
3) normal monocyte/macrophage numbers but delayed chemotaxis of monocytes
4) Predisposition to infections associated with chemotactic defects (especially cutaneous abscesses caused by Staph or Candidiasis)
5) predisposition to overwhelming sepsis and meningitis when infected by bacteria with no circulating maternal antibodies
6) reduced gut microbial diversity in newborns delivered via C-section
7) weak ability to fight off in utero infectio becaused infants have compromised oxidative and bactericidal response
Describe how the following factors affect/present in an elderly’s innate immunity/healing ability (relative to an adult’s):
1) number of cells associated with innate immunity & cell function
2) risk of chronic inflammation
3) Ability to heal and repair
4) subcutaneous fat
5) epidermal changes
6) efficacy of vaccines
1) normal number of cells associated with innate immunity, diminished cell function (decreased phagocytic activity, antibody protection, and altered cytokine synthesis)
2) increased risk
3) risk of decreased/impaired healing and increased infection associated with chronic diseases
4) less subQ fat which diminishes layers of protection against injury
5) atrophied epidermis & underlying capillaries so decreased perfusion and increased risk of hypoxia in wound beds
6) diminished effectiveness due to normal aging process
How may ASA interfere with wound healing?
ASA is an antiplatelet which prevents blood clotting so if there is excessive bleeding froma cut, it may lead to hemorrhagic stroke
What are the two effectors for adaptive immunity?
lymphocytes and antibodies
When does adaptive immunity kick in?
When external barriers have been compromised and innate immuntiy activated
