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Compare adaptive (acquired) immunity with innate immunity.
- innate - born with this, initial response, nonspecific defense
- adaptive - develops throughout life, antigen-specific defenses
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Compare immediate innate immunity with early induced innate immunity.
- immediate - 0 to 4 hours after exposure, antimcrobial molecules
- early induced - 4 to 96 hours after exposure, use of defense cells in response to PAMPs
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Define pathogen-associated molecular patterns (PAMPs)
molecules shared by groups of related microbes that are essential for the survival of those organisms and are not found associated with mammalian cells
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Define pattern-recognition receptors (PRRs)
recognize/bind to PAMPs to induce innate immunity
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Define antigen
a substance that reacts with antibody molecules and antigen receptors on lymphocytes
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Define immunogen
an antigen that is recognized by the body as nonself and stimulates an adaptive immune response
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Define epitope
The actual portions or fragments of an antigen that react with antibodies and lymphocyte receptors
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What does CBC determine
determines the total number of both leukocytes and erythrocytes per ml of blood
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What does leukocyte differential count determine
the number of each type of leukocyte calculated as a percentage of the total number of leukocytes
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What is the significance of an elevated white blood cell count
it is seen in infection, inflammation, leukemia, and parasitic infestations
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What is the significance of a shift to the left (elevated bands)
indicates an active infection, bc people are generally producing large numbers of new neutrophils and therefore will have a higher percentage of the immature band forms
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Describe and state the major functions of the following leukocytes: neutrophils
- abundance - 54-75% of WBCs in the blood
- short life span, few hours to days
- functions - phagocytes, release enzymes that promote inflammation
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Describe and state the major functions of the following leukocytes: basophils
- abundance - 0-1% of WBCs in the blood
- short life span, a few hours to days
- stain purplish blue
- not important in phagocytosis
- function - release histamine, leukotrienes, and prostaglandins -> promote inflammation by causing vasodilation
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Describe and state the major functions of the following leukocytes: eosinophils
- abundance - 1-4% of WBCs in the blood
- life span of 8-12 days
- stain red
- functions - phagocytes, secrete chemicals that promote inflammation, granules contain agents to kill fungi/protozoa/parasitic worms
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Describe and state the major functions of the following leukocytes: monocytes
- abundance - 2-8% of WBCs in the blood
- life span of months
- functions - phagocytes, antigen-presenting cells during adaptive immune responses
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Describe and state the major functions of the following leukocytes: B-lymphocytes
- function - mediate humoral immunity, the production of antibody molecules against a specific antigen
- have B-cell receptors (BCR) on their surface for antigen recognition
- differentiate into antibody-secreting plasma cells
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Describe and state the major functions of the following leukocytes: T4-lymphocytes
- differentiate into effector T4-lymphocytes
- function - regulate the adaptive immune responses through cytokine production
- have CD4 molecules and T-cell receptors (TCR) on their surface for protein antigen recognition
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Describe and state the major functions of the following leukocytes: T8-lymphocytes
- differentiate into cytotoxic T-lymphocytes (CTLs)
- function - mediate cell-mediated immunity, the production of cytotoxic T-lymphocytes (CTLs), activated macrophages, activated NK cells, and cytokines against a specific antigen
- have CD8 molecules and TCRs on their surface for protein antigen recognition
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Describe and state the major functions of the following leukocytes: NK cells
- kill human cells lacking MHC-I molecules on their surface
- lack B-cell receptors and T-cell receptors
- function - kill cells to which antibody molecules have attached through a process called antibody-dependent cellular cytotoxicity (ADCC)
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State what type of cell monocytes differentiate into when they enter tissue.
macrophages and dendritic cells
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State 2 functions of platelets.
- promote clotting by sticking together after becoming activated and forming platelet plugs to close up damaged capillaries
- secrete cytokines and chemokines to promote inflammation
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State 3 different functions of macrophages in body defense.
- kill microbes, infected cells, and tumor cells by phagocytosis
- process antigens so they can be recognized by effector T-lymphocytes (which activate macrophages) during the adaptive immune response
- produce cytokines
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State the primary function of dendritic cells in body defense
to capture and present protein antigens to naive T-lymphocytes
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Name the cells in the tissue whose primary function is to present antigen to naive T-lymphocytes.
myeloid dendritic cells
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Name the cells in the tissue whose primary function is to present antigen to effector T-lymphocytes.
macrophages (aka antigen-presenting cells/ APCs)
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State the primary function of mast cells in body defense.
- promote inflammation
- attract phagocytes to infected side
- activate platelets
- increase mucus production
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State how long it takes for immediate innate immunity to become activated and what it involves.
- beings 0-4 hours after exposure
- involves the action of soluble preformed antimicrobial molecules that circulate in the blood, are found in extracellular tissue fluids, and are secreted by epithelial cells
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State the function of the following antimicrobial enzymes/peptides: lysozyme
- breaks down peptidoglycan in bacteria, causing osmotic lysis
- breaks bond between NAG and NAM molecules
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State the function of the following antimicrobial enzymes/peptides: phospholipase A2
hydrolizes the phospholipids in bacterial cytoplasmic membrane
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State the function of the following antimicrobial enzymes/peptides: defensins
- disrupts the cytoplasmic membrane, causing leakage of cellular needs
- also activate cells for inflammatory response
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State the function of the following antimicrobial enzymes/peptides: cathelicidins
- produces peptides that are toxic to a variety of microorganisms
- can also reduce inflammation by neutralizing LPS in gram-neg cell wall
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State the function of the following antimicrobial enzymes/peptides: lactotransferrin and transferrin
trap iron for use by human cells while preventing its use by microorganisms
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Briefly describe how the classical complement pathway is activated
- Fab of IgG/IgM binds to epitopes of an antigen
- this activates C1 enzyme
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Briefly describe the beneficial effects of the following complement pathway products: C5a
- triggers inflammation - delivers WBCs and defense chemicals to infection site
- it is a chemoattractant for phagocytes
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Briefly describe the beneficial effects of the following complement pathway products: C3a
- triggers inflammation
- delivers WBCs to infection site
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Briefly describe the beneficial effects of the following complement pathway products: C3b
binds to antigen as an opsonin = enhanced attachment of antigen to phagocytes
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Briefly describe the beneficial effects of the following complement pathway products: C4b
binds to antigen as an opsonin = enhanced attachment of antigen to phagocytes
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Briefly describe the beneficial effects of the following complement pathway products: C3d
binds to receptors on B-lymphocytes and activates them
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Briefly describe the beneficial effects of the following complement pathway products: C5b6789n (MAC)
cause lysis of gram-negative bacteria and human cells displaying foreign epitopes
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Briefly describe how the lectin pathway is activated.
by the interaction of microbial carbohydrates (lectins) with mannose-binding lectin (MBL) found in the plasma + tissue fluids
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Briefly describe how the alternative complement pathway is activated
by C3b binding to microbial surfaces and to antibody molecules
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Describe what is meant by anatomical barriers to infection.
- tough, intact barriers that prevent the entry and colonization of many microbes
- ex- skin, mucous membranes, bony encasements
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List 4 ways in which the body can physically remove microorganisms or their products.
- mucus and cilia - cilia propel mucus and trapped microbes upwards towards the throat where it is swallowed and killed in the stomach
- cough and sneeze reflex - removes mucus and trapped microbes
- vomitting and diarrhea - remove pathogens and toxins in the GI tract
- physical flushing action of body fluids - urine, tears, saliva, perspiration
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Briefly describe how intraepithelial T-lymphocytes and B-1 cells play a role in innate immunity.
recognize microbes common to the epidermis + mucous membranes and start immediate adaptive immune responses against these commonly encountered microbes
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Describe how bacterial antagonism by normal microbiota acts as a non-specific body defense mechanism and name 2 opportunistic microbes that may cause superinfection upon destruction of the normal microbiota
- normal body microbiota keep harmful pathogens in check
- also inhibits the growth or colonization of opportunistic pathogens
- ex of microbes that cause superinfection - Candida, Clostridium difficile
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Briefly describe the process involved in the development of antibiotic-associated colitis
- Clostridium difficile survives the exposure to the antibiotic by sporulation
- after the antibiotic is no longer in the body, the endospores germinate and C. difficile secretes toxins into the colon
- the colon becomes infected following destruction of the microbiota
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State how long it takes for early induced innate immunity to become activated and what it involves.
- beings 4-96 hours after exposure to infectious agent
- involves recruitment of defense cells as a result of PAMPs binding to PRRs
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State what is meant by pathogen-associated molecular patterns (PAMPs), and the role PAMPs play in inducing innate immunity
- PAMPs are molecules that are not normally found on mammalian cells
- they trigger inflammation by binding to PRRs
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Name at least 5 PAMPS associated with bacteria.
- LPS
- peptidoglycan
- mannose
- lipoteichoic acids
- mycolic acids
- bacterial flagellin
- porins
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Name at least 2 PAMPS associated with viruses.
- double-stranded viral RNA
- single-stranded viral RNA
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Define DAMPs and give two examples.
- danger-associated molecular patterns
- they are unique molecules displayed on stressed, injured, infected, or transformed human cells
- ex - heat shock proteins, altered membrane phospholipids, things normally found inside cell that spill out of damaged cells (ATP, DNA, RNA)
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State the function of the following as they relate to innate immunity - pattern recognition receptors (PRRs)
- recognize and bind to PAMPs
- most are located on the surface of cells, some are located inside phagolysosomes where they interact with PAMPs located within microbes that have been phagocytosed
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State the function of the following as they relate to innate immunity - endocytic pattern recognition receptors
- found on the surface of phagocytes
- promote attachment of microorganisms to phagocytes
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State the function of the following as they relate to innate immunity - signaling pattern recognition receptors
- bind microbial PAMPs and promote production of:
- inflammatory cytokines
- type-1 interferons
- chemokines
- antimicrobial peptides (denfensins + cathelicidins)
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State the function of the following as they relate to innate immunity - danger recognition receptors
- recognize DAMPs in the cytosol
- this triggers activation of inflammasomes, release of inflammatory cytokines, and pyroptosis
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State the function of the following as they relate to innate immunity - inflammasome
- multiprotein complex that forms in macrophages as a result of PAMPs/DAMPs binding to PRRs/DRRs
- leads to inflammatory response + production of cytokines
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State the function of the following as they relate to innate immunity - pyroptosis
programmed cell suicide induced as a result of PAMPs binding to PRRs
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Name 2 endocytic PRRs.
- mannose receptors
- dectin-1
- opsonin receptors
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Name 2 signaling PRRs found on host cell surfaces.
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Name 2 signaling PRRs found in the endosomes of phagocytic cells.
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Name 2 signaling PRRs found on the host cell cytoplasm.
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Briefly describe the major difference between the effect of the cytokines produced in response to PAMPs that bind to cell surface signaling PRRs and endosomal PRRs
- PAMPS that bind to cell surfaces - trigger inflammation, fever, phagocytosis to provide immediate response
- PAMPs that bind to endosomal PRRs - produce interferons that block viral replication in infected host cells + inflammatory cytokines
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Describe the following: cytokines
- low, molecular weight soluble proteins
- produced in response to an antigen
- function as chemical messengers for regulating the innate + adaptive immune responses
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Describe the following: chemokines
enable migration of leukocytes from the blood to the tissues at the site of inflammation
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Describe the following: interferons
modulate the activity of every component of the immune system
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State what is meant by the phrase "Cytokines are pleiotropic, redundant, and multifunctional."
- pleiotropic - a particular cytokine can act on a number of different types of cells rather than a single cell type
- redundant - ability of a number of different cytokines to carry out the same function
- multifunctional - the same cytokine is able to regulate a number of different functions
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Name the two cytokines that are most important in stimulating acute inflammation.
- Tumor necrosis factor-alpha (TNF-alpha)
- Interleukin-1 (IL-1)
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Describe specifically how type I interferons are able to block viral replication within an infected host cell.
- they induce uninfeted cells to produce an enzyme capable of degrading viral mRNA
- the enzymes become activated and begin to degrade viral mRNA
- which also blocks viral protein synthesis
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Describe how an overactive TLR-4 receptor can increase the risk of SIRS in a person if Gram-negative bacteria enter the bloodstream.
if the TLR-4 encounters even a little bit of LPS it will overreact and induce excessive inflammation, which can lead to SIRS
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Briefly describe two specific examples of how an improper functioning PRR can lead to an increased risk of a specific infection or disease
- underactive PRRs or deficient PRR immune signaling pathways - increased risk of infection by specific pathogens due to decreased innate immune responses
- overactive PRRs or deficient PRR immune signaling pathways - increased risk of inflammatory damage by lower numbers of specific pathogens
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Briefly describe the role of the following as they relate to phagocytosis: inflammation
allows phagocytes to enter the tissue and go to the site of infection
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Briefly describe the role of the following as they relate to phagocytosis: lymph nodules
- unencapsulated masses of lymphoid tissue containing fixed macrophages and ever-changing populations of B/T-lymphocytes
- located in respiratory and GI tracts
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Briefly describe the role of the following as they relate to phagocytosis: lymph nodes
- tissue fluid picks up microbes, enters lymph vessels as lymph and enters this area
- here the antigens are exposed to populations of B/T-lymphocytes to be phagocytosed
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Briefly describe the role of the following as they relate to phagocytosis: spleen
blood carries microorganisms to the spleen where they are filtered out and phagocytosed by the fixed macrophages and dendritic cells + presented to B/T-lymphocytes to initiate adaptive immune responses
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Describe the following steps in phagocytosis: activation
- activated by inflammatory mediators (PAMPs, cytokines, complement proteins)
- activated phagocytes start producing surface glycoprotein receptors that allow them to adhere to inner capillary walls
- they also produce endocytic PRRs to recognize PAMPs
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Describe the following steps in phagocytosis: chemotaxis
- Movement of phagocytes towards increasing concentration of some attractant
- ex. LPS, peptidoglycan, complement proteins
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Describe the following steps in phagocytosis: attachment (both unenhanced and enhanced)
- Unenhanced -- binding of PAMPs to endocytic PRRs
- Enhanced -- opsonizing antibodies (ex. IgG, C3b, C4b) attach microbes to phagocytes (more specific and efficent)
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Describe the following steps in phagocytosis: ingestion
Polymerization and depolymerization of actin filaments sends pseudopods out to engulf the microbe and place it in an endocytic vesicle called a phagosome
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Describe the following steps in phagocytosis: destruction
- Electron pump brings protons into the phagosome, which lowers the pH inside enough for acidification
- Lysosomes fuse with the phagosome inside the phagocyte and destroy the microbe
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State what happens when either phagocytes are overwhelmed with microbes or they adhere to cells to large to be phagocytosed.
they empty the contents of its lysosomes in order to kill the microorganism extracelullarly
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Describe what causes most of the tissue destruction seen during microbial infections.
- when the phagocyte empties the contents of its lysosomes in order to kill the microorganisms extracellularly
- this ends up killing surrounding host cells and tissue
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Compare the oxygen-dependent and oxygen-independent killing systems of neutrophils and macrophages.
- oxygen-dependent: oxidase pumps protons into the phagosome to lower the pH so it is good for when lysosome fuses, neutrophils also release chemicals to kill extracellularly
- oxygen-independent: use of defensins, peptides, lysozymes, lactoferring, elastase, etc
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Briefly describe the role of autophagy in removing intracellular microbes
this is when microbes that have invaded host cells are engulfed and delivered to lysosomes for degradation
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Describe how NK cells are able to recognize and kill infected cells and cancer cells lacking MHC-I molecules.
- use a dual receptor system
- the first receptor (killer-activating receptor) binds to cells that exhibit MICA and MICB and lack MHC-I molecules
- activates release of perforins + granzymes, which lyse the cell
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State two factors that can result in a nucleated human cell not producing MHC-I molecules
- viruses
- stress
- malignant transformation
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Describe the 4 processes that make up the inflammatory mechanism.
- Smooth muscles around larger blood vessels contract to slow the flow of blood through the capillary beds at the infected/injured site --> which gives leukocytes more time to adhere to the walls of the capillary
- Endothelial cells that make up the wall of the smaller blood vessels contract --> this increases the space between the edothelial cells, resulting in increased capillary permeability = vasodilation
- Selectins can bind to corresponding selectin glycoprotein receptors on inner wall of venule --> enables leukocytes to roll along the inner wall of the venule and activate adhesion molecules on surface of endothelial cells on inner wall of capillaries. Integrins attach to these adhession molecules --> allows leukocytes to flatten and squeeze through the spaces between the spaces between the endothelial cells = diapedesis
- Activation of the coagulation pathway causes fibrin clots to physically trap the infection microbes and prevent entry into the bloodstream -> this also triggers blood clotting in small blood vessels to stop bleeding + preventing microbes from spreading into bloodstream
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Briefly describe the various beneficial effects of inflammation that are associated with plasma leakage and with diapedesis
- plasma enters the tissue delivering antibodies, clotting factors, lysozymes, complement proteins
- diapedesis leads to increased phagocytosis, more vasodilation, CTLs/NK cells/effector T4-lymphocytes enter the tissue
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Briefly describe the process of diapedesis, indicating the role of P-selectins, integrins, and adhesion molecules.
- infection triggers release of inflammatory mediators -> leads to vasodilation
- mast cells in connective tissue release vasodilators (histamine, leukotrienes, kinins)
- histamine binds to histamine receptors on endothelial cells -> upregulation of P-selectins & PAF
- P-selectins bind to their receptor and allow leukocytes to roll along inner wall of venule
- PAF binds to its receptor and upregulates expression of integrin (LFA-1)
- integrins on the surface of leukocytes bind to adhesion molecules on inner surface of endothelial cells -> leukocytes flatten out and squeeze between endothelial cells to leave the blood vessels = diapedesis
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Briefly describe the healing stage of inflammation.
- macrophages + inflammatory cytokinesproduce fibroblast growth factor + angiogenic factors for tissue remodeling
- fibroblast lays down collagen, which forms connective scar tissue
- endothelial cells restore circulation by forming new capillaries
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Briefly describe the problems that arise from chronic inflammation
- tissue damage and scarring
- hypotension
- ARDS (acute respiratory distress syndrome)
- DIC (disseminated intravascular coagulation)
- hypovolemia
- SIRS
- heart disease, diabetes, cancer, alzheimer's
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Describe at least 4 ways the body deprives microorganisms of iron
- decreased intestinal absorption of iron from the diet
- decrease of iron in the plasma, increased storage as ferritin
- increased synthesis of iron chelators that trap iron for use by human cells, making it unavailable to microbes
- decreased ability of bacteria to make their own iron chelators = siderophores
- stationing of human iron chelators at common sites of microbial invasion
- entry of transferrin (human iron chelator) into tissue during inflammation
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Describe the mechanism behind fever induction
- cytokines stimulate the anterior hypothalamus of the brain
- this produces prostaglandin E2, which leads to an increase bodily heat production + increased vasoconstriction
- this decreases loss of heat from the skin and increases body temp
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What are some possible benefits of a fever in immunity
- increases temp to one that is above optimum growth temp for many microbes
- leads to production of heat shock proteins that are recognized by intraepithelial T-lymphocytes, which produce more cytokines
- increases rate of enzyme reactions, which speeds up metabolism in the body (helps with inflammatory response + repair)
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Define hyperpyrexia
a fever with an extreme elevation of body temp greater than or equal to 106.7F/41.5C
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Briefly describe the mechanism behind the acute phase response
- PAMPs bind to PRRs and trigger release of cytokines
- cytokines travel through blood and stimulate heopatocytes in the liver to synthesize/secrete acute phase proteins
- this provides early defense before full activation of immune response
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State the functions of the following acute phase proteins: C-reactive protein
- functions as an opsonin, binds to membrane phospholipids and sticks the microorganism to phagocytes
- activates the classical complement pathway
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State the functions of the following acute phase proteins: mannose-binding lectin
- functions as an opsonin, binds to mannose-rich glycans and sticks the microorganism to phagocytes
- activates the lectin pathway
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