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280 Cards in this Set
- Front
- Back
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What are the 2 types of nonspecific responses against bacteria?
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complement
inflammation (phago cells for extracellular bacteria; nk cells for intracellular) |
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for bacteria, what type of bacteria do phagocytic cells attack?
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extracellular
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for bacteria, what type of bacteria do NK cells attack?
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intracellular
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What is the specific response against bacteria?
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Th1 mediated DTH, CTLs and ADCC for INTRAcellular
Th2 Ab responses for EXTRAcellular infxns in blood and other body fluids |
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What response takes place when the innate system fails for extracellular bacteria?
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1. APCs present microbial antigens to adaptive Th0/Bcells
2, release of early cytokines by mast cells and APCs to drive the Tcell differentiation and activation (predom Th2) 3. Humoral response against bacterial external structures and/or hydrolytic enzymes and exotoxins |
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what are the antibacterial roles of antibodies?
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1. neutralize toxins and spreading factors, hydrolytic enzymes
2. block adherence by Ab to fimbrae, lipotechoic acids and some capsules 3. opsonize to increase phagocytic removal of microbes (directly against suface Ag of organism such as M proteins and capsules) 4.immune complex formation for clearing 5. activate the classical complement pathway: Ab trigger C' mediated damage to gram negative outer lipid bilayers 6. ADCC |
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what are the 4 steps of bacteria damage that we have antibacterials against?
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attachement
proliferation/multiplication avoidance of phagocytosis damage to host via toxins and invasive hydrolytic enzymes |
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is it gram neg or gram pos bacteria that have a bilayer for MAC insertion?
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gram neg
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what is the point of Ab against toxin?
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the disease could be caused by toxin thus Ab neutralize toxin therefore no more disease even though microorg might still be present
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Why are Gram neg able to be destroyed by MAC complex and not gram pos?
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b/c gram neg have phospolipid bilayer ..disrupt outer membrane interfere with cell integrity
Gram + have a peptidoglycan cell wall..no modified bilayer therefore C' can't have MAC lysis b/c no lipid bilayer to insert into |
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What are some enzymes produced by bacteria that protect it from C' attack?
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IgA protease and C' desroying enzymes like elastase
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what are 3 bacterial structures that interfere with C' attachment?
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capsules
pili flagella |
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is Strep. pneumoniae extracellular or intracellular?
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extracellular life cycle
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what are the structural characteristics of Strep. pnuemonia?
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gram + cell wall
capsule made of mucopolysaccharides |
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what are teh 4 virulence factors of Strep. pneumoniae?
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elastase (cleaves Igs and C')
pneumolysin (pore forming toxin) mucinase (degrade/decrease visocity of mucin that coats resp. tract to move around) Neuraminidase (invasion) |
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job of elastase as virulence factor?
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cleaves Igs and C'
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job of pneumolysin as virulence factor?
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pore forming toxin
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job of mucinase as virulence factor?
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degrade/decrease viscosity of mucin that coats resp. tract to move around
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job of neurominidase as virulence factor?
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alveolar sac invasion
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how is Strep. pneumoniae spread?
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respiratory droplet spread person to person
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Strep. pnuemoniae can spread after colonization if immune response weak b/c of what causes?
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smoking, alcoholism
previous resp infxns chronic pulmonary disease |
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where does Strep. pneumoniae colonize?
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S. pneumoniae is normally found in the nasopharynx ..nasal pharyngeal tissue
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what are some features associated with Strep. pneumoniae in clinical disease?
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sinusitis, otitis media, bronchitis: movies up eustachian tubes, moves into sinue areas, may move down into bronchi
Pneumonia: movement from bronchi, aspiration |
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what happens when S. pnuemoniae is are carried into areas such as the Eustachian tube or nasal sinuses?
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cause otitis media and sinusitis
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when does pneumonia as a result of S. pnuemoniae infection?
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Pneumonia occurs if the organisms are inhaled into the lungs and not cleared (again, viral infection, or smoking-induced ciliary paralysis might be contributing factors). typical pneumonia=shortness of breath, pain on inhalation, productive sputum coughed up
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which organism is the most common bacterial cause of otitis media?
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Strep pnuemoniae
otitis media = inflammation in middle ear |
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how does strep pneumoniae cause sinusitis?
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PMN infiltrate and obstruct paranasal sinuses and stimulate inflamm response
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how does strep pnuemoniae cause otitis media?
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the tissues surrounding the Eustachian tube swell due to an upper respiratory infection, allergies, or dysfunction of the tubes. PMN's then infiltrate into middle ear further incraasing inflam. The Eustachian tube remains blocked most of the time. The air present in the middle ear is slowly absorbed into the surrounding tissues. A strong negative pressure creates a vacuum in the middle ear. The vacuum reaches a point where fluid from the surrounding tissues accumulates in the middle ear. The fluid may become infected. It has been found that dormant bacteria behind the Tympanum (eardrum) multiply when the conditions are ideal infecting the middle ear fluid.
this can lead to sharp pain and temporary loss of hearing |
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explain the features of pneumococcal pneumonia seen in association with Strep pneumoniae.
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lobar pneumonia
infxn w/n alveolar spaces leakage of RBC, PMN, mac into alveoli (pneumolysin) severe shaking chills w/ fever productive cough, thin blood tinged sputum |
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What is the hallmark of pneumococcal pneumoniae?
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pt. with cough
sputum of thin viscosity (due to mucinase) and red (leakage of RBC due to pneumolysin) |
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waht is the innate preventive response against Strep. pneumoniae?
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inflammation
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what is the adaptive response against Strep. pneumoniae?
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prevention: adherence blocking Ab due to vaccination or prior exposure-multiple capsular serotypes however)
Resolution: opsonizing Ab and neutralizating Ab against enzymes |
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What does it mean that there are multiple capsular serotypes for Strep. pneumonia?
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that can have strep. pneumonia 2x b/c you can be infected w/ different capsular strain
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Does the capsule of Strep. pnumoniae elicit an immune respnse?
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It has a polysaccharide capsule that acts as a virulence factor for the organism, however, the capsule, itself, is a poor immunogen and does not elicit an immune response
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is Clostridium botulinum intracellular or extracellular?
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extracellular
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What are the structural characteristics of Clostridium botulinum?
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gram postitive bacilli (no MAC lysis)
spore former (survival) |
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What are teh virulence factors associated with Clostridium botulinum?
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variety of hydrolytic enyzmes
Neurotoxin (botulin):8 serologically different distinct botulinum |
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What is neurotoxin and what does it do?
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virulence factor of Clostridium botulinum
-8 serologically distinct botulinum toxins AB toxin: R mediated endocytosis Targets cholinergic nn; blocks neurotransmission by preventing release of Ach -Flaccid paralysis (mm cant contract) |
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What is our bodies response against neurotoxin of Clostridium botulinum?
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mount response against B of AB to prevent binding
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where is clostridum botulinum found?
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worldwide in neutral and alkaline soils (type strains vary on soil pH and moisture levels)
*spore common, disease still uncommon in USClostridium botulinum is a soil bacterium. The spores can survive in most environments and are very hard to kill. They can survive the temperature of boiling water at sea level, thus many foods are canned with a pressurized boil that achieves an even higher temperature, sufficient to kill the spores. |
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Clostridium botulinum causes?
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Foodborne botulism..food poisoning: weak, dizzy, blurred vision, diplopia, dysphagia, constipation, abdominal pain
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What are the affects of foodborne botulinum?
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weak, dizzy, blurred vision, diplopia(double vision), dysphagia(difficulty swallowing), dry mouth, constipation, abdominal pain
-bilateral descending paralysis -no fever |
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What clinical feature is hallmark of exotoxin?
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no fever
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why do you see constipation in food poisoning?
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b/c toxin blocks contractile actions..stops peralisis
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which disease is cuased by secretion of exotoxin?
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clostridium botulinum
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why does it take months to years for complete recovery from foodborn botulinum?
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b/c toxin binds permanently therefore need to produce new synaptic jxns
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what will you see in a pt. with botulism?
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dilated fixed pupil
dry furrowed tongue |
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What is the innate response for prevention of Clostridium botulinum?
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pinocytosis for removal and inactivation of toxin
Inflammation for removal of spores/active cells |
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What is the adaptive response for prevention and resolution of Clostridium botulinum?
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prevention: nuetralizing Ab against the toxin from previous exposure (there is no vaccination)
Blocking Ab against adherence of vegetative cells Resolution: neutralizing Ab against the toxin |
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what events happen when the innate system fails for INTRAcellular pathogens?
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-APCs present microbial Ag to adaptive Th0
-Th0 become Th1 b/c cytokines -Th1 upreg mac killing and mediate DTH response -Th1 activate CTL (CD8) cells -some intracellular bacteria may be extracellular for a period of time and induce Ab response as seen for extracullar bacteria. Also ADCC therefore Th2 cells are aslo important |
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do intracellular bacteria have an extracellular phase?
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yes, b/c they have to get from 1 cell to another
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is Mycobacterium tuberculosis extracellular or intracellular?
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facultative intracellular bacteria
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is Mycobacterium tuberculosis gram +/- or acid fast? why?
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acid fast b/c lipid components inside peptidoglycan
Lipid evades INTRAcellular phago.destruction |
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What are the virulence factors associated with Mycobacterium tuberculosis?
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intracellular growth therefore can hide out
-no enzymes or toxins known |
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what is the reservoir for mycobacterium tuberculosis?
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primarily humans; other mammals may serve as sources
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how is mycobacterium tuberculosis transmitted?
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aerosol transmission
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What are the high risk populations for active disease caused by Myco. tuberculosis?
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immunocompromised, alcoholics, Intravenous drug users, homeless (poor nutrition) and incarcerated (severe depression from prison; link b/n CNS and disease)
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what are the O2 requirements for Myco tuberculosis?
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strict aerobe
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Describe the characteristics of Primary Tuberculosis caused by Myco tuberculosis
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*not contagious b/c walled off
middle to lower lung fields (site of O2 exchange therefore O2 quickly depleted) -Tubercle formation;granuloma usually in the middle to lower lungs -3-6week active replication then dormancy (replicate every 24 hrs or succomb to lack of O2) -Disease could stop here if strong Th1 if progresses to active disease due to infectoius dose and the host's immune competence |
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Describe the characteristics of secondary tuberculosis casued by Myco tuberculosis
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*highly contagous b/c coughing up organism
-break out of granuloma move to upper lung fields w/ less O2 exchange/reactivates in upper lobe -results from impaired immunity -cavitating lesions may occur (lung xray): bistandard damage w/ destruction of surrounding tissues |
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What is the innate response for prevention of myco tuberculosis?
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inflammation to wall off
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what is the adaptive response for prevention and resolution of myco tuberculosis?
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prevention: BCG vaccination for production of adherence blocking Ab (not very effective but good for certiain geo. areas where more prevalent)
Resolution: DTH response against intracellular phase Opsonizing Ab for EXTRAcellular phase of bacterium |
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explain how a tubercle is formed in primary tuberculosis.
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initiate Th1 hallmarked by DTH
upreg mac to incrase intracellular killing activities that lead to formation of granuloma: mac surrounded by T cells to wall of microbe |
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are healthy people prone to disease by fungi
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NO! disease is driven by defect in Th1 response
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what type of response is important for prevention of fungi infexns?
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non specific response
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describe the nonspecific response agaisnt fungi
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-PMNs are the most important phagocytic cells
-alveolar mac are the first line of defense against inhaled fungi; but most fungi are natrually resisitant to mac killing due to melanin or capsule--antiphagocytic -NK cells mediate direct killing of infected host (if intracellular NK play role) |
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what type of response is important for limiting fungal infxns?
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specific response..want phagocytosis!
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describe the specific response agaisnt fungi
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-Th1 mediated inflammatory actions for intracellular infxns-CTLs and ADCC
-activated mac for killing -Th2 and humoral response are counter productive once an ifxn has been established -some fungi induce hypersensitivity rxns resulting in tissue damage |
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How is a Th2 response counter productive in fighting fungi?
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Humoral down reg Th1 which you need to kill fungi..However Ab (against surface Ag) MAY protect agaisnt the initial colonization during the if the PMNs are not successful during the innate response
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what organism is responsible for the "rose growers" disease?
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Sporothrix schenickii that lives on thorny bushes
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is Sporothrix schenickii extracullar or intrac?
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extraceullar
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describe the dimorphic nature of Sporothrix schenickii
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mold in environment
yeast at body temp |
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how is Sporothrix schenickii transmitted?
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via exposure to environmental source; typically vegetation w/ thorns (subcutaneous trauma-breaks 1st barrier)
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what disease characteristics does Sporothrix schenickii cause?
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skin lesions that may progress to form necrotic or ulcerative lesion; draining lymphatics become thickened and cord-like w/ subcutaneous nodules or abscesses
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What individuals are susceptible to disease by Sporothrix schenickii?
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immunocompromised (HIV) or defective Th1 (Th2 then takes over)
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disease by which organism will you see sinus tracts: hydrolytic enzymes in lymphatics?
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Sporothrix schenickii
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what are the features of an ulcer caused by Sporothrix schenickii?
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ragged edges
clear oozing fluid can be self-limiting feel hardeneing of lymphatics |
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what is the innat response against Sporothrix schenickii?
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inflamation, PMNs are the primary phagocytic cells
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what is the adaptive response against Sporothrix schenickii for prevention?
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prevention: no known immunity established even after repeated exposure therefore mount resoltuion
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What is the adaptive response against Sporothrix schenickii for resolution?
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Resolution: Th1 and/or strong inflam response results in resolution of infxn
Th2 response and/or lttle to no inflamm response results in chronic disesae -granulomatous lesions due to DTH response |
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What does resolution mean?
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protective response agaisnt infxn trying to get rid of organism that invaded body
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Coccidiodes immitis is intracellular or extracellular?
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extracullar
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what is Coccidiodes immitis?
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dimorphic fungus w/ extracelluar yeast form that causes disease
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how is Coccidiodes immitis transmitted?
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inhalation of spores
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describe the dimorphic status of Coccidiodes immitis
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mold in environment w/ hypahe and spores
yeast in body after turning on new genes (phenotypic alteration) |
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spores in fungi are also known as?
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arthroconidia
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what type of disease does Coccidiodes immitis cause?
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influenza like disease w/ fever, cough; may progress to pnuemonia in immunocompromised
-unresolved will present w/ disseminated nodular skin lesions and arthralgias (inflammation in jts) |
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what causes the nodular skin lesions seen in unresolved Coccidiodes immitis?
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fungi that cause systemic disease have ability to enter lymphatics and get lodged around/under dermis and epidermis
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what is the innate response against Coccidiodes immitis?
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inflammation: initially alveolar mac pick up arthroconidia that are inhaled present to Th0 which develop into memory T cells. this will cause the development of wheal and flare showing that you've been exposed but not necessarily will you have Ab agaisnt organism
*effective in preventing disease in healthy |
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What is the adaptive response for prevention of Coccidiodes immitis?
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Ab are against the mold phase (repeated low level exposures will play a role in preventing the high risk populations (endemic areas))
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What is the adaptive response for resolution of Coccidiodes immitis?
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Th1 and strong CM for self-limiing disease
Th2 and strong humoral for disseminated infxns (widespread) |
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why is immunologic protection agaisnt parasites rarely long term?
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b/c difficult to develop long term immunity b/c complex life cycles therefore no good vaccins yet. they keep evading the immune response
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wht is the nonspecific response against parasites?
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C': integument of helminths that C' can attach too but limited MAC lysis; protozoans w/ PM can have MAC lysis
-phagocytic cells for smaller forms: larval and small eggs can be phagocytosed -primary innate cell to damaged helminths is EOSINOPHILS and some mast cells |
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what is the specific response agaisnt parasites?
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Th1 mediated DTH, CTLs and ADCC for INTRAcellular
Th2 Ab response for EXTRAcellular infxns in blood and other body fluids |
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protozoan antigens cuase what cell and cytokine cascade to occur?
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IL-12 from APC to activate Th1, NK and naive CD4. NK and Th1 secrete IFNg to acivate mac. Naive CD4 becomes active Th1 cell
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helminthic Ag cuase what cell and cytokine cascade to occur?
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helminthic org block secretion of IL-12 and instead IL-4.
IL-4 then activates Th2 cells to release IL-3, 4, 5, 9. IL-4 activates B cells to Ig switch to IgG against surface Ag. IL-5 activates eosiniphils to destroy integument IL3,4,9 activate mast cell to also degranulate |
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Leishmania species is what type of organism?
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flagellated protozoan
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what is the reservoir for Leishmania species ?
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dogs, cats, fox, jackels, rodents and humans
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how is Leishmania species transmitted?
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to humans by bite of sand fly (arthropod transmission: regurgitation of blood and org or through defecation)
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what are the most common clinical manifestations of Leishmania species cusing disease?
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cutaneous: ulcerating skin sores that spontaneously heal but scar b/c bistandard damage
Mucocutaneous: destruction due to IMMUNE response;start off as a reaction at the bite, and can go metastasis into the mucous membrane and become fatal. Visceral: fever, swelling of the liver and spleen, and anemia |
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is there a vaccine for Leishmania speciees?
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no
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what is happening to lead to disease by Leishamania species?
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localized at site of arthropod bite, mac will attempt to phagocytose then Leishmania will replicate w/n mac. Immune response is then Th1 to upreg more mac leading to developement of cutaneous lesions
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what is a mucocutaneous lesion caused by Leishmania species?
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destruction of carilage and skin due to IMMUNE reponse**
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what is the innate reponse against Leishmania species?
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inflammation
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what is the adaptive respone for prevention of Leishmania species?
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-memory DTH after inital exposure, prevent 2ndary infection
-opsonizing Ab if they don't override |
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What is the adaptive response for resolution of Leishmania species?
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Th1 and strong CM for self limiting disease (DTH)
Th2 and strong humoral for disseminated infxns |
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Taenia saginata is what type of organism?
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helminthic organism
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how is Taenia saginata transmitted?
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ingestion of larvae in undercooked raw beef
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Clinical disease caused by Taenia saginata ?
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primarliy infects intestines: physical presence of worm takes up space in gut and you don't get hungry
*most infxns are asymptomatic -clinical disease is anorexia (lack of appetite and loss of wt) and diarrhea |
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What is the innate response against Taenia saginata ?
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EOSINOPHILS to degranulate
inflammation |
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What is the adaptive response for prevention of Taenia saginata ?
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memory DTH?
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what is the adaptive reponse for resolution of Taenia saginata ?
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not possible..so CONTROL (best we can do is control burden of disease)
Th1 and strong CM for self limiting disease Th2 and strong humoral for disseminated infxns |
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does lysis of host cell require an extracellular phase?
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yes
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does budding have an extracellular phase?
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yes, b/c virions bud from the host
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compare lytic replication pathway with transforming pathway?
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lytic: adherence, penetration, replicatin. assembly, release
Transforming: adherence, penetration, integration |
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compare lytic replication with budding.
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lytic is for naked non enveloped
budding is for enveloped virus replication |
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ex of lytic virus that is naked?
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poliovirus
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what is the innate/nonspecific response to viral infections?
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infected cells produce IFN alpha and beta, IL-6, IL-12, chemokines to attract NK and DCs
IFNs and chemokines: soluble NK and DC: cellular -C' lysis of virions or opsonization (phagocytosis of virions) |
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what is the adaptive/specific response against viral infections?
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cell mediated: CD4 TH1 and CD8 CTL results in control of infxn and in resolution by lysis of infected cells (INTRAcellular phase)
Humoral: against viral attachment proteins-neutralization and opsonization of virus by Ab, elimination via ADCC and NK cells, and prevents spread by blocking EXTRAcellular virus particles |
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what is the antiviral state?
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presence of IFNalpha engaging uninfected cell-liimits viral spread
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which IFN is involved in innat response to virus?
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IFNalpha incresaes PKR production by host cells and RNAse L to degrade viral RNA. Both PKR and RNAase L inhibit synthesis of viral proteins
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what are the steps of adaptive response to viral infection?
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APCs phagocytose free virions
NKs and APC relesae cytokines APCs present microbial peptides to TH0 cells, TH0 differentiate into TH1 and 2, upreg mac and PMNs Bcells produce antiviral Ab that are NEUTRALIZING |
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what is the primary adaptive response to viral infection?
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IFNg (Type 2 IFN)
macs and DC as APC virus specific CD4 (Th1 and 2) and B cells for production of IgM, IgG and IgA (virus extracelllular phase *) virus specific CD8 for intracellular phase of virus* |
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What is the memory or secondary response to viral infections?
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circulating Ab (IgG, M, A) and virus sepcific memory B and T cells
**Secretory IgA against re-infection through mucosal routes |
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what are some of the host early nonspecific responses against viruses?
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fever to stop virus replication
phagocytosis inflammation to stop virus replication NK cell activtiy IFN |
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What effect does IFNg have in the adaptive antiviral response?
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activation of NK cells that leads to enhanced killing of infected cells by NK
enchanced MHC expression by host cells that leads to enhanced killing of cells by CTLs |
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cytokines and NK cells combine to provide ____defense against virus infexns
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early defense whle T and B cells provide resolution
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in the late stage of viral infxn, what is happeneing with viral titer?
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decreasing b/c T cell killing is increasing and antibody production is increasing to prevent spread of extracellular phase
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does the innate system kill a virus?
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NO..keeps it under control until differention of adaptive cells
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what are the 2 ways to kill via CTLs?
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1 perforin and granzymes
pore in target cell, caspase cascade leading to apoptosis 2. FAS on target, FAS L induced on effector T cell leading to apoptosis |
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what is the purpose of antibody mediated antiviral response?
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antiviral Ab made against surface Ag, enzymes and core components *they act to neutralize, mediate C' destruction of infected host cell or mediate ADCC via NK
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what is an example of a neutralizing viral Ab made against?
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Ab to glycoprotein spike to block R binding thefore neutralizing **best kind
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which type of viruses can have MAC lysis?
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only enveloped viruses that bud. naked viruses have to be opsonized then phagocytosed
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what are the antiviral effects of Ab alone?
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blocks binding to cell
blocks entry into cell blocks uncoating of virus |
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job of IFN alpha and beta in terms of antiviral
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protection of non-infected cells by blocking viral replication
activation of NK cells |
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jobs of NK cells in terms of antiviral?
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direct killing of virus infected cells
activation of macs via IFNg |
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jobs of macs in terms of antiviral?
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presentation of viral Ag to CD4 Th cells
phagocytosis of opsonized virions filtration of virions from blood in liver |
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jobs of T cells in terms of antiviral?
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-cytolytic Th1 response more impt than Th2 response in resolving nonlytic and enveloped viral infxns
-destruction of virus infected cells by CTLs |
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jobs of secreted Ab in terms of antiviral?
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resolution of lytic viral infxns
-neutralization of extracellular virions by Ab binding to viral attachement proteins -inhibiting viral spread -protection of mucosal surfaces (IgA) -opsonization -ADCC |
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what are 5 viral evasion strategies used ?
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1. antigenic variation
2. Down reg of MHC I (T cells need MHC I to recog Ag) 3. Down reg of accesory molecules involved in immune recognition 4. infxn of immuno-priveleged sites 5. Direct infxn of the cells of the immune system itself |
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why is antigenic variation a good viral evasion strategy?
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b/c many viruses have many different serotypes therefore if devleop neutralizing Ab to one serotype, don't have Ab against other-get same cold over and over again
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is it the innate system or adaptive that keeps replication in check?
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innate..doesn't clear virus but keeps replication of virus under control via IFN alpha and beta
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where does poxvirus replicate?
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cytoplasm
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what are viroceptors?
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viral homologues to R's that block effect of cytokines
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what are virokines?
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viral homologues to cytokines that make IL-10 to downreg Th1 for example
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structure of HPV?
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ds circular DNA, non-enveloped
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how is HPV transmitted?
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direct or indirect inoculuation of skin or mucosa, STD
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clinical disease caused by HPV?
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warts (cutaneous or mucosal), carcinoma of cervix, anus and rectum
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HPV infection stimulates waht?
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cell growth
-replication in nucleus -viral proteins bind to and inactivate p53 and p105Rb promoting cell growth |
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How does HPV promote cell growth?
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inactivate p53 and p105RB
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what is diagnostic of HPV?
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inclusion bodies in nucleus
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How are HPV virions released?
|
in dead keratinocytes that are sloughed, virions are released
|
|
|
innate reponse agaisnt HPV?
|
IFN alpha and beta
NK cells C' opsonization b/c naked!! |
|
|
Adaptive response against HPV?
|
prevention: blocking Ab
resolution: opsonizing Ab, *CTLs |
|
|
Structure of influenza virus?
|
ss - sense RNA, enveloped, segemented genome
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|
|
where is the envelope of influenza from?
|
PM
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|
|
what does influenza virus have on its surface?
|
Peplomers H and N
H= hemagglutinin (HA)-attachment N= neuraminidase (NA)-release |
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|
what is teh fxn of hemagglutinin pepomer found on influenza?
|
attachement of host cell and allow entry
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what is the fxn of neuraminidase peplomer found on influenza
|
release
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what structural components of influenza are antiviral targets?
|
hemagglutinin and neuraminidase peplomers
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|
|
what are the 2 immune evasion tactics used by influenza?
|
antigenic drift: slowly changing with individual aa mutations
antigenic shift: suddenly changing due to reassortments |
|
|
are epidemic or pandemic strains related to antigenic shift?
|
shift causes pandemic strains: worldwide outbreak w/ same strain due to reassortments
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|
|
are epidemic or pandemic strains related to antigenic drift?
|
epidemic: varios strains evolve thefore get sick to new flu every year
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|
how is influenza spread?
|
repiratory droplet spread person-person
|
|
|
what are the reservoirs for influenza?
|
humans, birds, pigs
|
|
|
what is the clinical disease associated with influenza?
|
**fever, chills, headache,myalgias, cough
|
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|
a pandemic is due to ?
|
reassortments of same strain
|
|
|
what is the innate prevention of influenza?
|
IFN alpha and beta
NK C' opsonization AND MAC lysis b/c enveloped |
|
|
what is the adaptive response aginast influenza?
|
prevention: blocking Ab
resolution: CTLs, opsonizing Ab |
|
|
structure of herpes simplex virus?
|
ds linear DNA, enveloped
|
|
|
what is the reservoir for herpes simplex?
|
man
|
|
|
how is herpes simplx transmitted?
|
direct or indirect contact with skin and mucosa, STD, transplacental
|
|
|
what does the herpes virus cause?
|
direct cytopathologic effects such as latency, reactivationg by stress, and formation of intranuclear inclusion bodies
|
|
|
what are the 3 cytopathologic effects of herpes virus?
|
1.latency in neurons: doesnt make proteins therefore not loaded on MHC or recog by T
2. reactivation by stress or immune suppression 3. form intranuclear inclusion bodies |
|
|
HSV I is latent in what neurons?
|
trigeminal root ganglion (oral)
|
|
|
HSV II is latent in what neurons?
|
sacral nerve ganglia (genital)
|
|
|
what is the clinical disease associated with herpes virus?
|
cold sores, genital herpes
fever, malaise followed by vesicular lesions in infected area |
|
|
explain the latency and reactivation of herpes virus.
|
productive in epithelial cells
retrograde travels to nuclus of neuron to hide out stress releases virus that travel antegrade down neuron to re-infect epithelial cells and by symptomatic or asymptomatic (shed or cause skin lesions) |
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|
innate preventions of herpes virus?
|
IFN alpha and beta
NK C' opsonization of extracellular phase |
|
|
adaptive response to herpes virus?
|
resolution: opsonizing Ab
CTLs...doesn't clear virus virus always will be latent until reactivated |
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|
what indicates a vaccination?
|
presence of Ab that is specific to a single organism (B and T cells with immunity)
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|
|
What is active immunity?
|
protection produced by the person's own immune system in response to infectious agent
*usually permanent |
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|
what is passive immunity?
|
protection transferred from another person or animal
*temporary protection that wanes with time *transfer of Ab..can't transfer T cells b/c they need MHC to recognize |
|
|
what are the 2 most effective ways to prevent disease?
|
1 prevent transmission
2. prevent infexn or disease |
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|
How do you prevent transmission?
|
sanitation
vector control (eradicating mosquitos) |
|
|
How do you prevent infexn or disease?
|
Immunization when possible *acitvely immunize
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|
what is a vaccine?
|
preperation of a weakened or killed pathogen such as bacterium or virus, or of portion of the pathogen's structure that upon administration stimulates Ab production or cellular immunity against the pathogen
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|
What is immunization/vaccination?
|
act of inoculating an individual with a vaccine (active) or providing protective Ab (passive)
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|
|
what are the 2 types of active immunity?
|
natural and artificial
natural = direct exposure to an infectious agent (get sick from pathogen via transmission) artificial= intentional exposure to microbes or their Ag in vaccine preparations |
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|
what is the this type of immuity: immune response is stimulated in response to challenge w/ an immunogen?
|
active immunity
|
|
|
what is natural active immunuity?
|
a form of active immunity in which you are directly exposed to infectious agent via transmission
|
|
|
what is artificial active immunity?
|
a form of active immunity in which your are intentionally exposed to microbes or their Ag in vaccine preparations
|
|
|
What is natural passive immunity?
|
transplacental maternal Ab to fetus or Ab in breast milk to neonate
|
|
|
what is artificial passive immunity?
|
injection of purified Ab, antibody containing serum or sensitized cells from individual with highly specific ab
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|
|
which type of immunity is transient?
|
passive..used mostly for treatment
|
|
|
what is active immunization?
|
the pt's own body produces humoral and/or CMI responses and memory to protect the body from infxn or disease
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|
|
waht is passive immunization?
|
transfer of Ab from a source other than the pt to provide rapid, transient protection from disease
|
|
|
what is artificial passive immunization?
|
transfer of Ab produced by one human or other animal to another
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|
|
What is natural passive immunity?
|
transplacental/colostrum -most important source in infancy
IgA in colostrum IgM used to diagnose neonatal infxns |
|
|
what Ig is used to diagnose neonatal infxns?
|
IgM
|
|
|
why do neonates have fewer infxns in the first few months after birth?
|
high levels of maternal IgG until 5-6 months old
|
|
|
when do children w/ immunodef become ill?
|
after 5-6 months old when maternal IgG becomes low
|
|
|
pre and post exposure prophylaxis are indications for use of what?
|
passive immunotherapy
|
|
|
why do you preexpose someone passively?
|
when you might need a vaccine when traveling to area where disease is endemic and are leaving in less than 1 week need to get passive immunity to prevent disease from occuring
|
|
|
how long does post-exposure from passive immunity last?
|
short lived about a week
Ex: Hep A, measles |
|
|
what are the 3 indications of use for passive immunity?
|
1. pre and post exposure prophylaxis
2. reduce symptoms in ongoing diseases 3. protection in immunosuppressed (active wont work b/c no T cells) |
|
|
how does passive immunity reduce symptoms in ongoing disease?
|
assists INNATE immune response
neutralize/block action of toxins (ex botulism-antitoxin will stop further toxins from binding) |
|
|
what are the sources of passive immunity?
|
1. pooled sera from blood donors (Ig)
2. pooled plasma from seropos humans to provide protection against SPECIFIC pathogens (hyperimmune) 3. monoclonal Ab 4. Heterologous hyperimmune serum (antitoxin from animal source) |
|
|
what does pooled sera from blood donors provide?
|
protection against major pathogens
|
|
|
waht does pooled plasma from seropostive humans provide?
|
protection against SPECIFIC pathogens such as when pt. was intentionally immunized to particular pathogen take those Ab and immunize someone else with them
|
|
|
why use monoclonal ab for passive immunity?
|
b/c developed in mouse that was immunized to pathogen then B cells make particular Ig and that Ig is further engineered to work in humans by making the constant region look like human so we don't respond against it
|
|
|
What are the 4 immunization risks to patients?
|
1. allergic rxns or anaphylactic rxns against contaminants in vaccine solns
2. serum sickness 3. transmission of blood borne pathogens 4. immunosuppression |
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|
serum sickness is what type of HSR?
|
type III HSR
|
|
|
how can a pt develop serum sickness from immunization?
|
immune reponse against antigenic determinants of the foreign Ab when from a nonhuman source. then immune complexes form and activate C'
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|
|
how is transmission of blood borne pathogens an immunization risk?
|
b/c could be contaminated blood from donors that escaped screening at time of donation (advantagious pathogen: weren't screenign for that pathogen at that time)
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|
why is immunosuppression a risk to immunized pts.?
|
blocks progression to an active adaptive response by blocking/neutralizing
*Ab could block virus by binding and no acive response devlops |
|
|
what immune globulins are available for pooled sera?
|
hepatitis A - IG
Measles - IG |
|
|
What immune globulins are available from hyperimmune sera?
|
Hep B
Rabies Chickenpox Cytomegalovirus Vaccinia |
|
|
what immune globulins are available as antitoxins (from animal source)?
|
tetanus
botulism diptheria |
|
|
what immune globulins are available as M Ab?
|
respiratory syncytial virus -"humanized" mouse
*severe disase in infants *don't get lifetime immunity *no vaccine therefore passive immunity with M Ab |
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|
active immunity is produced by ____
|
vaccine
|
|
|
how is a vaccine immunogenic [5 things]?
|
blocks adherence to prevent colonization
neutralization of toxins promote opsonophagocytic killing promote Th1 response induce memory |
|
|
which type of T cells need live virus to be processed and presented to it?
|
CD8
|
|
|
Which T cells can be presented dead virus that comes from the outside?
|
CD4
|
|
|
what is the main characteristic of a vaccine?
|
it induces memory
|
|
|
what are the 3 antigenic targets of bacteria?
|
toxins
capsular polysaccharides surface Ag/proteins |
|
|
What are the 2 antigenic targets of bacteria?
|
capsid coat protein
internal core Ag |
|
|
Humoral arm targets what?
|
surface Ag or toxins
|
|
|
Cellular arm targets whhat?
|
any microbial component that can be processed and presented by APCs to appropriate T cells
|
|
|
what are the 5 types of artificial active immunizations?
|
1. inactivated whole cell (bacteria or virus)
2. live attenuated 3. toxoids 4. subunits (capsular or surface proteins, cell free extracts) 5. DNA vaccines 5. DNA vaccines |
|
|
what is an inactivated virus?
|
Inactivated, or 'killed,' viral vaccines consist of viruses treated so that they are unable to replicate. Live-attenuated viral vaccines are generally far more potent, perhaps because they elicit a greater number of relevant effector mechanisms, including cytotoxic CD8 T cells: inactivated viruses cannot produce proteins in the cytosol, so peptides from the viral antigens cannot be presented by MHC class I molecules and thus cytotoxic CD8 T cells are not generated by these vaccines.
|
|
|
why do we use attenuated strains?
|
Because these attenuated strains replicate poorly in human hosts, they induce immunity but not disease when given to people.
|
|
|
does it make sense to give a live attenuated HIV virus?
|
no b/c it will integrate but dead virus won't work either b/c it won't be recognized by Ab therefore DNA vaccines could work
|
|
|
of the pre-1990 vaccines, what disease had the lowest percent decrease in morbidity (disease)?
|
pertussis
remains refractory agent for whooping cough |
|
|
what was the most efficacious post-1990 vaccine?
|
Hib (invasive): In infants and young children, H. influenzae type B (HIB) causes bacteremia, and acute bacterial meningitis. Due to routine use of the HIB conjugate vaccine in the U.S. since 1990, the incidence of invasive HIB disease has decreased to 1.3/100,000 children
|
|
|
what are the phases of the vaccination trials?
|
phase 1: safe, no further harm
phase 2: efficacy phase 3: combine protocols from other trials to recommend to specific group |
|
|
what is the approximate vaccination national coverage?
|
81%
|
|
|
how do you prepare an inactivated vaccine?
|
formalin or heat inactivation of whole bacteria or viruses
|
|
|
when would you use inactivated vaccines?
|
microbes which cannot be attenuated (can't grow in tissue culture therefore inactivate them)
microbes w/ potential oncogenic potential (can integrate therfore inactivate them) |
|
|
examples of inactivated vaccines?
|
polio, influenza, cholera, plague
|
|
|
disadvantages of inactivated vaccines?
|
not as effective as live
lack lifelong immunity need large doses (3-5 doses) mostly humoral responses Ab titer may diminish w/ time therefore boosters needed (b/c it isn't allowed to replicate) can cause anaphylaxis |
|
|
why is the immune response to inactivated vaccines mostly humoral?
|
hard to get CD8 elicited
|
|
|
why is the humoral response the main response to inactivated vaccines?
|
b/c your CTL's need to recognize an intracellular bug and inactived vaccines aren't replicating
|
|
|
what are some viral inactivated vaccines?
|
polio
hep A rabies influenza |
|
|
what are some bacterial inactivatd vaccines?
|
pertussis
typhoid cholera (b/c has recombined protein-B subunit so can't bind anymore) plague |
|
|
what type of vaccine must replicate to be effective?
|
live attenuated vaccine: mimics natural infxn
|
|
|
how do your prepare a live attenuated vaccine?
|
virulence is eliminated or reduced but it is alive with same antigenicity then when you admister the vaccine it will multiply and boost immune stimulation
*can create genetic mutant (weakend form of "wild" virus or bacterium) *can genetically engineer to delete dangerous part of pathogen |
|
|
why would you use a live attenuated vaccine?
|
protection requring T cell (CD8, CTLs)immune response and/or a secreted IgA reponse
|
|
|
advantages of live attenuated vaccine?
|
mimics natural infxn
**low doses effective (like natural infxn) celluar AND humoral response |
|
|
disadvantages of live attenuated vaccines?
|
severe rxns possible
dangerous to immunesuppressed or pregnant **reversion to virulent form *fragile |
|
|
ex of live attenuated viruses?
|
MMR
Varicella yellow fever rotavirus intranasal influenza vaccinia |
|
|
ex of live attenuated bacteria?
|
BCG
oral typhoid |
|
|
w/n how many days do you see an increase in serum IgM to live and killed polio virus?
|
rapid peak until 16 days then rapidly falls at day 16 and gradually decrases from day 16-64
|
|
|
what is the reponse of secretory IgA to live and dead polioviruses?
|
dead: no secretory IgA
live: increases in first few days then levels out at high titer from day 64-96 |
|
|
what is the response of serum IgG to live and killed polio viruses?
|
they both cause continuous increase
|
|
|
what is the diff in IgA in live and dead polioviruses?
|
secretory nasal IgA: only get with live virus
serum IgA: see increase after few days from both types of viruses |
|
|
what is a subunit vaccine?
|
take components of pathogens that could elicit adverse effects but not antigenic effects and remove them (B subunit of AB toxins) then give vaccine of Ag portions to elict protective properties ex: surfce structures, flagella
|
|
|
what is recombinant antigen vaccine?
|
Vaccinia virus genomic DNA is cut with an endonuclease. A specific sequence of DNA (with appropriate regulatory sequences) coding for a protein (e.g., cholera toxin) to be used as an immunogen is ligated into the vaccinia virus genome, making a recombinant vaccinia virus. The DNA will be transcribed and the immunogen will be produced along with vaccinia virus proteins in infected cells following vaccination. The immunogen will then elicit antibody production by the host, providing protective immunity.
*good b/c they self-assemble into particles, no genome just protein |
|
|
what do you clone in recombinant antigen vaccine?
|
clone gene for antigenic portion that will be used to stimulate neutralizing Ab
|
|
|
What are virus like particles? ex?
|
recombinant antigen vaccines of surface Ag that look like viruses but don't have viral genome Ex: Hep B
|
|
|
when would you use subunit vaccines or toxiod vaccines?
|
w/ microbes that cannot be attenuated
|
|
|
a polysaccharie vaccine will elicit what type of response?
|
IgM (T independent response)
|
|
|
disadvantages of subunit vaccines?
|
lack of lifelong immunity
require boosters larger doses humoral response only b/c not live anaphylaxis *acts like inactivated vaccine |
|
|
subunit vaccine ex?
|
hep B
acellular pertussis HPV anthrax |
|
|
are pure polysach vaccines consistenly immunogenic?
|
no, not in children younger than 2 years old b/c they are immature in development of T immunity
|
|
|
do you have a booster response w/ pure poly vaccines?
|
no
|
|
|
why do we want polysaccharide vaccines?
|
Many bacteria, including Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), and Haemophilus species, have an outer capsule composed of polysaccharides that are species- and typespecific for particular strains of the bacterium. The most effective defense against these microorganisms is opsonization of the polysaccharide coat with antibody. The aim of vaccination is therefore to elicit antibodies against the polysaccharide capsules of the bacteria.
B/c capsules are T-independent antigens, they can be used on their own |
|
|
what is an effective way of overcoming this problem: However, young children under the age of 2 years cannot make good T-cell independent antibody responses and cannot be vaccinated effectively with polysaccharide vaccines.
|
chemically conjugate bacterial polysaccharides to protein carriers, which provide peptides that can be recognized by antigen-specific T cells, thus converting a T-cell independent response into a T-cell dependent anti-polysaccharide antibody response. By using this approach, various conjugate vaccines have been developed against Haemophilus influenzae, an important cause of serious childhood chest infections and meningitis
|
|
|
besides Hib, what is another conjugate polysacchardie?
|
pneumococcal heptavalent conjugated with diptheria toxin CRM197 *most efficacoius form
|
|
|
what 2 diseases are treated w/ conjugate polysach viruses?
|
meningitis and sepsis caused by Hib and Meningococcal(DPT)
pnuemonia caused by pneumococcal *most susceptible population is elderly and babies |
|
|
what does the tuberculosis vaccine composed of?
|
live attenuated BCG
|
|
|
waht are the 3 viral vaccines we need to know that consist of live attenuated virus?
|
MMR
|
|
|
what is the original antigenic sin?
|
the body tends to preferentially use immunologic memory and after primary infxn make memory B cells. however when new strain enters, B cell response makes old Ab against new strain that nuetralize the bug. that new Ag was then never allowed to stimulate the immune response and no new memory was created.
|
|
|
what is a synthetic peptide vaccine?
|
Know Ag epitope therefore you make synthetic peptides of Ag regions
need B and T cell epitopes for Ab response problem: need lots of peptides for T cell epitope b/c peptide is MHC depedent |
|
|
does recombinant vector vaccines involve replication?
|
yes
|
|
|
what are recombinant vector vaccines?
|
Genes encoding protective antigens from several different organisms could be placed in a single vaccine strain. This approach makes it possible to immunize individuals against several different pathogens at once, but such a vaccine could not be used twice because the vaccinia vector itself generates long-lasting immunity that would neutralize its effectiveness on a second administration; this is an example of the phenomenon called 'original antigenic sin'
|
|
|
purpose of reverse vaccinology?
|
'Reverse' immunogenetics can be used to identify protective T-cell epitopes against infectious diseases
|
|
|
what is the new DNA vaccine method?
|
DNA coated onto minute metal projectiles can be administered by 'biolistic' (biological ballistic) gun, so that several metal particles penetrate the skin and enter the muscle beneath.
|
|
|
why vaccine adjuvants?
|
Adjuvants trick the immune system into responding as though there were an active infection, They increase immunogenicity in NONspecific way
*involve TLR's ex: LPS uses TLR4 |
|
|
what are virosomes?
|
new vaccine delivery method
spherical, unilamellar lipid bilayer w/ purified influenza HA and NA inserted |
