Term
| How do epithelial tissues provide resistance to microbial invasion? |
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Definition
| A physical/mechanical barrier that organizes as a tight monolayer; it is constitutive and non-specific |
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Term
| How do innate immune systems recognize infectious agents and infected cells as distinct from self? |
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Definition
| microbes has angtigen and innate immunity picks up microbe-derived signals; the body also determines ICAM-1 and LFA to be non-self and indicators of and immune response as well as cytokines and chemokines released from macrophages that are attacking a foreign object. |
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Term
| Under what circumstances is acute inflammation induced? In what ways it is essential for host defense? |
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Definition
induced = rapid, inducible, localized activation and mobilization of secretory and cellular defense after primary barriers are breached
- local efectors and secretory products and macrophage action as well as local cells such as mast cells, keratinocytes, fibroblasts, and epithelial cells
It is essential to limit multiplication and dissemination of invading microbes to eliminate it and its bioactive microbial products |
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Term
| UNder what circumstances can acute inflammation be harmful? |
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Definition
| If the host defenses are not able to eliminate invading microbes and/or the immune-stimulating products, sensitive responses to more products produce a greater inflammatory response; life threatening immunopathology - sepsis |
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Term
| How are the duration and sites of acute inflammation controlled? |
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Definition
Response is local and reversible:
- resting local signaling cells like macrophages produce little or no cytokines
- induction of expression of cytokines is linked to detection of molecules signaling infection.injury
- cytokines are produced in small amounts and cytokine mRNA and proteins have a short life near the site and time of expression
- resolution of the infection and elimination of infectious products ends cytokine expression and repairs inflammatory changes to endothelium |
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Term
| What are the stages of innate immune function? (4) |
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Definition
1. primary barriers to invasion (constitutive and non-specific)
2. acute inflammation
3. acute phase response/reactants
4. antigen - adaptive immunity |
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Term
|
Definition
rapidly inducible (min-hr)
- localized activation and mobilization of secretory and cellular defenses after primary barriers are breached |
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Term
| acute phase response/reactants |
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Definition
up to 24 hr after initial invasion
- induced systemic changes (reprogramming of hepatocyte gene expression in liver) for changes in plasma protein composition
- localized changes in permeability of endothelium and increased proteins |
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Term
| antigen - how does it initiate adaptive immunitu |
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Definition
| present in the intact microbe or remnants of microbes- picked up through the lymph and presented to naive T and B cells to intiate induction of adaptive immunity |
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Term
| What are the primary barriers to microbial invasion? (5) |
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Definition
1. physical/mechanical (epithelial and flow)
2. biochemical products (secretory)
3. microbiological (normal flora)
4. immunologic (secretory)
5. chemical (anti-septic) |
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Term
| flow barriers to invasion |
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Definition
| ciliated cells, cough reflex, peristalsis, urine (constitutive and non-specific) |
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Term
biochemical products as barriers to invasion
- secretory |
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Definition
consistutive and or inducible
broad spectrum
secretory antimicrobial peptides/proteins (secreted in lumen) |
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Term
| microbiological barriers to invasion |
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Definition
acquired
specific
normal flora - competes with more pathogenic (exogenous) microbes - probiotics |
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Term
| immunologic barriers to invasion |
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Definition
acquired
specifc
secretory adaptive mucosal immunity |
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Term
| chemical barriers to invasion |
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Definition
constitutive
non-specific
anti-septic - low pH, free FA's, detergent compounds |
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Term
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Definition
| normal residents of microbial flora with no pathogenic effects in its normal place; beneficial effects |
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Term
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Definition
| normally avirulent with low V, but can act as a pathogen when normal, innate host defenses are compromised (low R) |
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Term
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Definition
| more likely to cause disease even in a host with normal innate immunity (higher V) |
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Term
Bacteria as pathogens
- where do they replicate |
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Definition
| replicated extraceullularly or intracellularly in a compartment or in the cytosol |
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Term
Fungi as pathogens
-where do they replicate |
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Definition
| replicate extracellularly or intracellularly in a compartment or the cytosol |
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Term
Viruses as pathogens
- where do they replicate |
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Definition
obligate intracellular parasites that require host machinery
- may be in the cytosol or an intracellular compartment
- dissemination occurs extracellularly |
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Term
protozoa as pathogens
-where do they replicate? |
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Definition
| replicate in or out of host cells |
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Term
| what is the goal of acute inflammation? |
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Definition
| limit multiplication and dissemination of invading microbes, eliminate invading microbes and bioactive microbial products |
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Term
| what are local effectors (examples) |
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Definition
secretory products of mucosal epithelia and subepithelia
phagocytic macrophages (resident) |
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Term
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Definition
| macrophages, mast cells, keratinocytes, fibroblasts, epithelia |
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Term
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Definition
attractive force that brings in more defense cells leading to redness, heat, swelling, and pain
- large superfamily that regulates selective trafficking through receptor-mediated and complex actions
- neccessary for iniation and control of innate and adaptive immunity and is regulated by infectious products
- form of altered self |
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Term
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Definition
alter local cells and the endothelium to increase its permeability at sites of infection
- structurally diverse with greater than 100 identified
- highly inducible expression, receptor-mediated actions, physiology is complex with a short half life for its mRNA and protein to limite action
- necessary for intiation and control of many innate and adaptive immunity; form of altered self |
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Term
| what can lead to immunopathology? |
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Definition
| excess production of cytokines or chemokines for an excess immune response |
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Term
| what is the first recruited innate immune effector (cytotoxic) cell at a site of infection? |
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Definition
| neutrophils (induced more greatly by bacteria than fungi) |
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Term
| what cells can monocytes differentiate into? |
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Definition
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Term
| What are three recruited innate immune effector cells? |
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Definition
| neutrophils, monocytes, natural killer cells |
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Term
| what are some changes in the local endothelium during acute inflammation? |
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Definition
1. increased vascular permeability
2. altered endothelial (lumenal) surface properties with adherence proteins and penetration of blood cells (neutrophils more than monocytes or NK cells)
3. platelet activation |
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Term
| How does neutrophil diapedesis occur> |
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Definition
1. induced expression of adherence molecules on endothelium (ICAM-1)
2. incudeced expression of adherence molecules on neutrophils (LFA-1)
3. local increase in chemotactic factors (IL-8 or CXCL8 from host cells, fMLP from bacteria) to induce migrating cells expressing these receptors to go towards site of infection |
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Term
| what are three ways in which cytokines can be released in the body? |
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Definition
1. autocrine (at the site)
2. paracrine (to neighboring areas)\
3. endocrine (system with big consequences) |
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Term
| What is the order of induction of cytokines from macrophages? |
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Definition
1. TNF-alpha, CXCL8
2. IL-1 Beta
3. IL-6
4. IL-12 |
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Term
| What occurs if the infection is not resolved quickly? |
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Definition
1. increase in recruitment of inflammatory cells including monocytes that become macrphages - becomes chronic inflammation
2. increase flow/migration of infectious material via lymphatics to induce an adaptive immune response
3. increase IL-6 to bloodstream and induce the acute phase response in the liver
4. systemic infection.cytokines results in systemic inflammation increasing the risk of pathology |
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Term
| what are 2 types of altered self cells that the body recognizes to determine if an immune response is needed? |
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Definition
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Term
| what are 4 mechanisms to constrain acute inflammation? |
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Definition
1. resting local signals such as resident macrophages will make little or no cytokines
2. inducing cytokines is linked to detecting molecules for signaling infection/injury - danger signals or alarms
3. cytokines are made in small amounts and have a short half life for its mRNA - act near site and and time of stimulation
4. when there is resolution and no more cytokines, reversal and reair of endothelium occurs |
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Term
| What are the benefits? and disadvantages? to a sensitive innate detection and response? |
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Definition
benefit: early, robust mobilization/activation of host defenses before the microbe disemminates or multiplies
danger: if it cannot be eliminated, the response will be greater leading to greater inflammatory response and more damage; can lead to sepsis |
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Term
| How do signaling cells of innate immunity sense invading microbes? |
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Definition
| Microbes contain MAMP's/PAMP's (microbe or pathogen associated molecular patterns) which are recognized by our germ-line encoded PRR's (pattern-recognition receptors) |
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Term
Which PAMP's are found on each of the following microbial envelope?
1. Gram negative bacteria
2. gram positive bacteria
3. bacteria
4. bacteria
5. bacteria
6. bacteria
7. fungi |
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Definition
1. LPS
2. glycolipids
3. mannose-containg polymers
4. peptidoglycan (PGN)
5. lipopeptides
6. flagellin
7. glucans |
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Term
| What are some soluble molecules/metabolites that are secreted by microbes and recognized by PRR's? |
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Definition
formyl-met-leu-phe (bacteria)
PGN metabolites (bacteria)
dsRNA (RNA viruses)
CpG DNA (bacteria) |
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Term
| WHere is LPS found? WHat is it made of? |
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Definition
| on the outer leaflet of gram negative bacteria; contains an O-antigen repeat, outer core of hexoses and and inner core of heptoses and KDO, and Lipid A |
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Term
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Definition
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Term
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Definition
| faciliates host defense against large numbers of bacteria |
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Term
| Describe the selectivity of the TLR's? |
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Definition
1. respond to conserved, unique microbes
2. location in the intracellular compoartment (endosomes) where there is microbe derived nucleic acids but NOT host nucleic acids |
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Term
What does each TLR recognize?
1. TLR2/TLR1
2. TLR4
3. TLR5
4. TLR3, 7, 8, 9 |
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Definition
1. peptidoglycans, lipopeptides, glycoproteins, glucans
2. LPS
3. flagellin
4. dsRNA, ssRNA, CpG DNA |
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Term
| Where are NLR (nod-like receptor) found? and what is their function? |
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Definition
found in the host cell cytosol
function: confer ability to recognize and respond (inflammation and cell death) to cues of microbial invasion and/or altered host in host cell cytosol |
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Term
| Describe the domains of the TLR? |
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Definition
1. extracellular domain (ligand recognition) and low homology
2. cytosolic domain (signal transduction) with high homology
- similar to Mammalian IL-1 receptor |
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