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279 Cards in this Set
- Front
- Back
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What are the four outcomes of viral infection?
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1. Productive infection (release of progeny)
2. Persistent infection (virus doesn't kill cell, low level of progeny shed from cell) 3. Abortive infection (viral multiplication arrested, no progeny) 4. Latent infection w/reactivation (virus goes through cycles of latency and reactivation) |
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In general, what are the six stages in the (productive) viral life cycle?
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1. Attachment
2. Penetration 3. Uncoating 4. Replication 5. Assembly 6. Egress |
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What is a one-step growth curve and how is it obtained for a particular virus?
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one step growth curve is a curve showing the rate of viral replication at different stages in time after the infection. The infection must be synchronized: therefore all viruses must be at the same point of the life cycle.
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Why is there a latent period shortly after infection onset?
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The latent period is due to the virus uncoating. During this time it is inactive.
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Where would you find the viral attachment proteins?
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on the capsid (naked virus) or on the envelope (enveloped virus)
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In treating viral infections, why can't we just knock out the viral receptors on the host cells?
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these receptors often perform important cell functions. to knock them out would mean death of the host.
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Define:
1. tropism 2. host range |
1. tropism is specificity for a certain tissue (ie. hepatotoxic viruses)
3. host range is the range of different types of hosts that the virus can infect. (ie. rabies in both humans and other mammals) |
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How do enveloped viruses penetrate the host cell membrane?
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via membrane fusion
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How do naked viruses penetrate the host cell membrane? (2)
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1. creating a pore-like structure in the membrane
2. receptor mediated endocytosis, then lysing the internal cellular membrane (ie. endosomal membrane) |
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What is viropexis?
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viropexis is another word for receptor mediated endocytosis
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What happens to the viral envelope during membrane fusion and why is this an important drawback?
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The viral envelope is incorporated into the host cell membrane. This leaves an external marker that is easily recognizable by the immune system.
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How does a naked virus penetrate via pore formation?
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The capsid proteins of the virus insert into the cell membrane creating a pore, then RNA is released through the pore into the cytoplasm.
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What occurs in uncoating?
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Uncoating releases the viral genome into the host cell cytoplasm
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What are the 3 mechanisms of uncoating?
What is the main mechanism? |
1. conformational changes in capsid subunit
2. host or viral protease 3. acidification of endosome acidification of endosome |
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How does acidification of the endosome occur?
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there are proton pumps in membrane of the endosome - they pump H+ out of the cytoplasm into the endosome (plasma membrane H+ pumps also pump out of the cytoplasm). The endosome becomes very acidic due to the increased [H+].
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1. Where do most RNA viruses replicate?
2. Where do all DNA viruses replicate? |
1. in the cytoplasm
2. in the nucleus |
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1. How are DNA viruses targeted to the nucleus?
2. How are DNA viruses transported to the nucleus? |
1. DNA viruses are targeted to the nucleus via "nuclear localization signals" found on viral protiens.
2. the DNA viruses are transported using cytoskeleton and cellular motor protiens (dynein). |
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What are the 3 ways a DNA virus enters the nucleus?
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1. passage of virus through nuclear pores (small viruses)
2. release of DNA through nuclear pores (virus is too big to fit through pore) 3. Transient Rupture of the nuclear membrane |
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mRNA production during viral gene expression is mediated by what general type of protien?
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RNA polymerase
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Which type of RNA polymerase do:
1. DNA Viruses use? 2. RNA Viruses use? |
1. DNA viruses use DNA-dependent RNA polymerase that is usually of host origin.
2. RNA viruses use RNA-dependent RNA polymerase, it is always of viral origin |
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In regards to RNA viruses: what determines if the RNA transcriptase is virion associated?
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the polarity of the RNA determines whether there will be virion association or not.(+)ssRNA is the only RNA virus that is not virion associated.
**+ssRNA can be read by the host directly as mRNA, the other RNA virus types can't and therefore need their own "virion associated" RNA transcriptase** |
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What does virion associated mean?
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The RNA transcriptase enters the cell with the virion to allow expression of the uncoated viral genome.
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Which RNA polarities are virion associated? (2)
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1. (-)ssRNA
2. dsRNA |
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What are the three mechanisms in which RNA viruses can undergo gene expression?
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1. Expression of segmented genomes
2. Start-Stop expression 3. Polyprotein expression |
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What is the mechanism behind polyprotien expession of RNA viruses?
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translation of mRNA produces a polyprotien. The polyprotien is cleaved by proteases into the proper separate protiens.
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How does a dsDNA virus replicate?
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dsDNA--> dsDNA (DNA polymerase is used)
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How does a (+)ssRNA Virus replicate?
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(+)ssRNA->(-)ssRNA->(+)ssRNA (ssRNA viruses have their antigenome as an intermediate in replication)
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How does a (-)ssRNA Virus replicate?
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(-)ssRNA -> (+)ssRNA -> (-)ssRNA
The antigenome intermediate once again... |
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Assembly of progeny virions: where is the site of assembly for:
1. DNA viruses 2. RNA viruses |
1. nucleus
2. cytoplasm |
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What is the mechanism for capsid assembly?
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capsids self assemble
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When is nucleic acid incorporated into the virus?
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it is incorporated during assembly or after empty capsid is complete
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What type of capsid processing is sometimes required for infectivity?
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proteolytic processing
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Where is the site of envelope acquisition for enveloped viruses (the progeny)?
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envelope acquisition usually occurs at the outer cell membrane.
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1. How do naked capsules usually escape the cell?
2. How do enveloped viruses usually escape the cell? |
1. lysis
2. budding |
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what is a major difference between lysing and budding that allows a virus to be more virulent?
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lysing kills the cell. A host cell can survive budding; this results in the release of thousands of progeny before it dies.
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1. What is the significance behind viruses that have a high mutation rate?
2. Which class of virus has the highest mutation rate? |
1. a high mutation rate leads to rapid adaptations (ie. drug resistance).
2. RNA viruses are known for their "sloppiness," they lack a proofreading function |
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1. Viruses can undergo genetic reassortment. What could this lead to?
2. Which type of virus undergoes genetic reassortment? |
1. genetic reassortment could lead to an antigenic shift
2. viruses with segmented genomes undergo genetic reassortment. (ie. influenza A) |
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Viral transformation that is associated with continued expression is known to induce?
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oncogenesis
(EBV, HPV) |
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Which class of viruses are most often seen in viral induced oncogenicity?
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DNA viruses (oncogenicity induced by RNA viruses is not so common)
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How is size related to viral dependancy on their host?
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The smaller the virus the more dependent they are on their host.
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What are the 3 major functions of the viral capsid?
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1. Protect nucleic acid from degradation
2. Provide attachment site for host cell (naked viruses) 3. provide antigens that are recognized by the host immune system (naked and enveloped) |
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What are the two major capsid types?
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1. Helical
2. Icosahedral |
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Define monopartite in regards to the viral RNA genome.
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monopartite refers to a single RNA molecule as the genome (vs. segmented which refers to multiple RNA molecules)
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what difference do the (+) and (-) ssRNA genomes have in regards to translation?
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the (+)ssRNA can be directly translated because it is the same polarity (sense) as mRNA. (-)ssRNA is antisense to mRNA and must be converted to (+)ssRNA before translation can occur.
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in dsDNA or (+)ssRNA: What happens if the viral genome is separated from the capsid and injected into a host cell?
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the genome alone can initiate a complete replication cycle and produce progeny viruses.
**dsDNA and (+)ssRNA are considered infectious, whereas (-)ssRNA is not. |
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Which enzyme is required for conversion of (-)ssRNA to (+)ssRNA?
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Virion-associated RNA polymerase
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the viral envelope is acquired via budding through which type of membrane?
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the membrane can be cytoplasmic, nuclear, rough ER or Golgi membranes
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in regards to the viral envelope: where are glycoprotiens found and what is their function?
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glycoprotiens are visualized as spikes on the viral surface. They function in receptor binding and membrane fusion.
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In some viruses a matrix protien lines the inner side of the envelope. Function?
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the matrix protien plays an important role in viral maturation
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compare naked and enveloped virions in the following aspects:
1. stability in the environment |
1. naked - environmentally stable (can pass thru GI tract)
Enveloped - environmentally labile (succumb to acids, detergents, heat) |
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compare naked and enveloped virions in the following aspects:
infectivity in regards to drying |
naked - retain infectivity after drying
enveloped - lose infectivity after drying |
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compare naked and enveloped virions in the following aspects:
route of egress |
naked - escape via lysis
enveloped - escape via budding or lysis |
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compare naked and enveloped virions in the following aspects:
how easily they are spread |
naked: spread easily by dust, small droplets, fomites
enveloped: spread in droplets, secretions, blood |
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which class of virus is resistant to detergents?
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naked viruses
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Which class of virus...
1. causes host pathogenesis due to hypersensitivity and inflammation? 2. What causes the hypersensitivity and inflammation? |
1. enveloped viruses
2. cell mediated immunity is responsible for the pathogenesis |
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Do naked virions elicit cell mediated immunity?
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NO, they only elicit a protective antibody response
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What are the chemical criteria used for viral classification (3)?
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1. nucleic acid composition and sequence
2. genome polarity 3. structure |
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What are the morphological criteria used for viral classification (2)?
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1. capsoid shape
2. presence or absence of an envelope |
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after a wound occurs a thrombus is formed. What is it formed by and what is its function?
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plasma fibrin and fibronectin form the thrombus. The thrombus is a two-way barrier: it stops things from entering and exiting the wound.
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1. what is the name of the molecule that crosslinks fibronectin?
2. benefit of crosslinked fibronectin? |
1. transglutaminases crosslink fibronectin
2. crosslinked fibronectin provides tensile strength and maintains closure. |
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what is the source of early growth factors at the wound site?
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platelets
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what happens to the thrombus late in wound healing?
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the thrombus undergoes proteolysis, then it is penetrated by regenerating epithelium.
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in what sequence does repair and regeneration occur in regards to wound healing?
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repair and regeneration occurs after the inflammatory response
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1. which type of acute inflammation will leave a scar?
2. what is the molecule that lays down the scar? |
1. progressive acute inflammation (macrophage predominant inflammation)
2. collagen |
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what is the main function of neutrophils in a wound?
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neutrophils liquefy and remove necrotic tissue
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fibronectin and cellular debris release chemotactic factors to attract which two cell types?
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macrophages
fibroblasts |
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what officially begins when macrophages appear at the site of injury?
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the repair process
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what types of things do macrophages secrete?
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1. collagenase (assists with further liquefaction)
2. growth factors for: - fibroblast proliferation - collagen secretion - neovascularization |
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what is the provisional matrix eventually replaced by?
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granulation tissue replaces the provisional matrix
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which cell type actively coordinates the development of granulation tissue? How does it do this?
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macrophages
they release cytokines and growth factors |
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in the formation of granulation tissue, what cells are myofibroblasts and fibroblasts derived from?
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mesenchymal stem cells
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in the formation of granulation tissue, what cells do capillaries form from?
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capillaries form from the division of existing vessel endothelial cells
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what are some reasons as to why granulation tissue is so highly resistant to bacterial infection?
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granulation tissue is fluid-laden. It is highly vascularized and can therefore supply antibacterial antibodies.
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what are the three main ingredients found in the early matrix of granulation tissue?
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1. proteoglycans
2. glycoproteins 3. type III collagen |
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what change do fibroblasts undergo once activated and what do they do?
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fibroblasts change from round to bipolar upon activation.
Fibroblasts form collagen and other matrix proteins (such as fibronectin). |
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what is the difference between type I and type III collagen in relation to wound healing?
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Type III collagen is formed first and is weaker.
Type I collagen is formed later and has greater tensile strength. |
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what is the difference between angiogenesis and vasculogenesis?
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angiogenesis - sprouting of endothelial cells from pre-existing capillary venules.
vasculogenesis - blood vessels form de novo from angioblasts. |
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What are BFGF (B for Beta) and VFGF and what do they do?
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BFGF and VFGF are potent angiogenic growth factors. They associate with heparan sulfate - this is a crucial feature of angiogenesis.
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how (and in which layer) does the epidermis renew itself?
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how - mitosis
where - at the basal layer |
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what is the primary source of regenerating epithelium?
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the hair follicle
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in repair and regeneration, what is the main way that the cell surface is reepithelialized?
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cellular migration is the predominant means of reepithelialization
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which specialized cell is wound contraction dependant on and where is this cell found?
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wound contraction is dependant on the myofibroblast - it is found in granulation tissue
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what is the timeframe for myofibroblast appearance at the wound site?
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myofibroblasts are first seen around day 3 of wound healing. they dissappear as repair progresses and wound has contracted.
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how do myofibroblasts exert their contractile effects?
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by forming tight junctions between myofibroblasts, this binds the cells together in a unit.
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what is the difference between the structure of myofibroblasts and fibroblasts?
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myofibroblasts bind together in a unit, fibroblasts are solitary cells
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what cell types can myofibroblasts be derived from? (3)
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1. pericyte
2. fibroblast 3. stem cell |
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what is the decrease in the size of a wound dependant on?
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the presence of myofibroblasts
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healed wounds have what percentage of the strength of the original unwounded site?
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75%
takes about 1 yr to gain this much function. |
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approximately what percentage of the original strength is present in a 2 week old wound?
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20%
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what do platelets release when they are activated and what does this molecule facilitate?
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platelets release PDGF, which facilitates adhesion, coagulation, vasoconstriction, repair and clot reabsorption.
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What is the cell?
arrives at wound site early and migrates rapidly using small focal adhesions... |
leukocyte
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What is the cell?
is rapidly recruited from the bone marrow and invades the wound site within the 1st day... |
neutrophil
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What is the cell?
invades wound site within 1st day, releases granule contents resulting in degradation and destruction of non-viable tissue |
neutrophil
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arrive shortly after neutrophils but persist longer.
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macrophage
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What are the two main macrophage actions:
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1. phagocytose debris
2. orchestrate developing granulation tissue by release of cytokines and chemoattractants |
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when do the fibroblasts, myofibroblasts, pericytes and smooth muscle cells arrive on the scene?
what recruits these cells? |
day 3 to 4.
recruited by growth factors and matrix degradation products. |
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what is:
1. lamellipodia 2. where are these seen 3. function? |
1. broad, wavelike membrane extensions
2. leukocytes 3. locomotion for migrating leukocytes |
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what are:
1. filopodia 2. where seen |
1. narrower and slower than lamellipodia, fingerlike extensions.
2. fibroblasts, smooth muscle cells |
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during cell movement the leading edge of the cell interacts with what molecule?
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integrin
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what are the 4 components of the ECM?
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1. collagen fibers
2. elastin fibers 3. ground substance 4. fibronectin |
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what is important about fibronectin?
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it can associate with the integrin receptor on the surface of the cell.
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define: basement membrane
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thin, well-defined layers of specialized ECM that separate the cells that synthesize it from the connective tissue.
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what cell types produce basement membranes?
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1. epithelium
2. endothelium 3. adipocytes 4. muscle cells 5. Schwann cells |
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which type of collagen is found in the basement membrane?
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collagen type IV
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besides collagen, what is the other predominant ECM molecule that is found in the basement membrane?
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laminin
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what happens when:
1. the equilibrium between collagen deposition and degradation has been restored 2. capillary formation is complete 3. inflammatory cells are diminished |
remodeling begins
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what is the class of main digestive enzymes during remodeling?
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metalloproteinases (MMP)- function in matrix degradation during remodeling
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what is the reason for digesting matrix proteins during remodeling?
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degradation allows cellular migration through the stroma
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MMPs are synthesized as zymogens. what activates them?
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already activated MMPs or serine proteases
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what regulates MMP activity?
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MMP activity is regulated by TIMPs. (a series of endogenous tissue inhibitors of metalloproteinases)
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the reaction of vascularized living tissue to local injury is known as________?
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inflammation
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why is inflammation considered a protective process?
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inflammation:
neutralizes the cause of injury rids the body of necrotic tissue |
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acute inflammation is characterized by ______________ and lasts how long?
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neutrophils, lasts minutes to a few days
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chronic inflammation is characterized by which cell types and lasts how long?
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characterized by macrophages and lymphocytes, lasts days to years
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Regarding morphology of inflammation: One type of inflammation is generally more variable and the other is generally more uniform. Which is which?
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acute - uniform
chronic - varied |
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what are the four cardinal signs of inflammation as described by Celcus?
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1. Rubor (redness)
2. Tumor (swelling) 3. Calor (heat) 4. Dolor (pain) |
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what is the additional cardinal sign of inflammation that was added later by Virchow?
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Functio laesa (loss of function)
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in inflammation what does the following effect have:
1. vasodilation 2. structural changes in microvasculature |
1. increased blood flow
2. allows plasma cells and leukocytes to leave the capillary. |
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when inflammation first begins, what do the blood vessels do (only for a short while)
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vasoconstrict
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Why is there slowing and stasis in the microvasculature during inflammation?
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because of the increased vascular permeability
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1. what is exudate?
2. what does it commonly cause? |
1. protein rich fluid that leaks out of vascular system during inflammation
2. swelling is often due to exudate |
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1. what is transudate?
2. what are the normal components of transudate? |
1. fluid with low protein content (this fluid leaks out of vascular system on a regular basis). it is non-inflammatory.
2. transudate consists of mainly H2O and albumin |
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1. define edema
2. define pus |
1. excess fluid in interstitial tissue or serous cavity (can be transudate or exudate)
2. exudate rich in neutrophils |
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what forms the gaps in the microvasculature?
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contraction of endothelial cells
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where do these gaps in microvasculature most commonly occur?
(which type of vessel) |
venules
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1. describe leukocyte dependent injury of the vasculature.
2. what is the timeframe for this injury in regards to inflammation? |
1. leukocytes have a toxic effect when they adhere to the vascular wall, this damages the vessel.
2. it is a late inflammatory response |
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what are the three main cytokines that leak via gaps in the vasculature?
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IL-1
TNF IFN-gamma |
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which cell type can intervene in allergic reactions and can kill parasites?
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eosinophils
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a macrophage precursor is called a ___________.
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monocyte
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what are the two main functions of macrophages?
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1. phagocytosis
2. synthesis of chemical mediators |
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which cell types (2) produce histamine and play a key role in anaphylaxis?
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mast cells
basophils |
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what three things make up the sequence a leukocyte goes through before it can undergo diapedesis?
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1. margination
2. rolling 3. adhesion (pavementing) |
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what two things does the leukocyte do in order to increase the avidity of binding in adhesion?
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1. redistributes adhesion molecules to cell surface
2. induces adhesion molecules on endothelium |
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what is chemotaxis?
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migration along a chemical gradient
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what type of chemotactic agent would bacterial products be?
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exogenous agent
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give an example of 3 endogenous chemotactic agents
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C5a
LTB4 cytokines |
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leukocytes move via which structure?
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pseudopods (lamellapodia)
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IgG Fc, C3b and collectins are all examples of?
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opsonins
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what happens to the newly engulfed toxic agent?
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killing or degradation via fusion of the phagosome with the lysosome
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what most commonly mediates oxygen dependant degradation?
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ROS (HOCl)
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how do lysozymes mediate oxygen independent microbial killing?
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by hydrolyzing the coating of bacteria
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where is MBP found and what does it do?
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MBP is found in eosinophils, it is cytotoxic to parasites
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what are the three functions a leukocyte can have a defect in?
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1. defect in adhesion
2. defect in phagocytosis 3. defect in microbiocidal activity |
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what would be observed in a defect of leukocyte adhesion? (2)
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1. recurrent bacterial infections
2. impaired wound healing |
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Chediak-Higashi syndrome is a defect in which leukocyte function?
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defect in phagocytosis (degranulation and killing)
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chronic granulomous disease (CGD) is a result of a defect in which leukocyte function?
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defect in microbiocidal activity
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1. what is "frustrated" or "surface" phagocytosis?
2. why is this important? |
1. when a leukocyte cannot phagocytose a microbe (most often due to its large size).
2. This can cause additional damage because lysozyme is released into the tissue. |
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give an example of chronic inflammation caused by:
1. organisms producing delayed hypersensitivity 2. prolonged exposure to toxic agents 3. autoimmunity |
1. TB
2. silica, asbestos 3. SLE, RA |
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what are the three types of mononuclear cells?
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1. macrophages
2. lymphocytes 3. plasma cells |
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what is characteristically seen in chronic inflammation that is attempting to heal?
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damaged tissue (from acute inflammation) is replaced by connective tissue
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chronic granulomatous inflammation is caused by a granuloma. What is a granuloma and what surrounds it?
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a granuloma is a nodular collection of epitheliod cells (specialized macrophages). These epithelial cells are surrounded by lymphocytes.
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what are the two major causes of chronic granulomatous inflammation (general)
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1. T-cell mediated immunity (TB-a delayed hypersensitivity rxn)
2. poorly digestible irritants, foreign body rxn (sutures, sliver) |
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There are six morphologic patterns of inflammation. Describe serous inflammation
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effusion, an outpouring of thin fluid derived from serum
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There are six morphologic patterns of inflammation.
Describe fibrinous inflammation |
exudate rich in fibrin
organization is seen |
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There are six morphologic patterns of inflammation.
Describe Suppurative (purulent) inflammation |
mainly neutrophils present
lots of necrotic cells edema |
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There are six morphologic patterns of inflammation.
Describe an ulcer and what produces it. |
a local defect or excavation of the surface of an organ, produced by sloughing of inflammatory necrotic tissue
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There are six morphologic patterns of inflammation.
Describe an abscess |
a localized collection of neutrophils with liquified necrotic tissue in the center
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There are six morphologic patterns of inflammation.
Describe membranous inflammation |
exudate seen on the surface
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describe non-oxygen dependent bacterial killing by defensins
(what releases them, what do they kill) |
defensins are released by PMNs and some lysozomes - they kill tons of things (gram + and - bacteria, fungi, some enveloped viruses)
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describe non-oxygen dependent bacterial killing by lactoferrin
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lactoferrin competes with bacteria for iron (lactoferrin is an iron chelator)
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what is responsible for the Rubor seen in inflammation?
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Rubor=redness: caused by dilation of blood vessels
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what is responsible for the Calor seen in inflammation?
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Calor=heat: caused by increased blood flow to area of injury
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what is responsible for the Dolor seen in inflammation?
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Dolor=pain: caused by:
1. increased pressure (accumulated interstitial fluid) 2. mediators such as bradykinin |
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what is responsible for the Tumor seen in inflammation?
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Tumor=swelling: caused by an extravascular accumulation of fluid
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define:
1. lymphokine 2. monokines |
1. soluble factors released from lymphocytes, are involved in the immune system
2. soluble factors released by monocytes and macrophages, are involved in the immune system |
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lymphokines and monokines are collectively known as?
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cytokines
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what are chemokines?
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chemokines are a subset of cytokines involved in chemotaxis
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besides regulating the immune response what are the other functions of chemokines? (2)
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1. cell growth and differentiation
2. tissue repair and remodeling |
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what do I mean when I say that cytokines are pleiotropic?
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they act upon many different cell types
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What are the three families of cytokines/receptors?
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1. TNF related
2. Chemokines 3. Hematopoietins (Type I) |
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What are two examples of TNF related cytokines?
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TNF
Fas |
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what are the two main functions of TNF receptors?
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1. activation of gene expression
-or- 2. influence cell death via death domain |
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What is the difference between a Type I and a Type II TNF receptor?
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TNF Type I receptor - functions in activation of gene expression
TNF Type II Receptor - contains death domain |
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What are 5 examples of Hematopoietins (Type I) cytokines?
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IL-2,3,4,5,6
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describe the structure of the hematopoietin receptors
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1. made up of 2 or more subunits
2. lots of redundancy because sub-units are shared by several members |
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Which cytokine receptors share a common beta chain?
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IL 3,4,5,13
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Which cytokine receptors share a common gamma chain?
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IL 2,4,7,9,15
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In general, describe the Jak-Stat paradigm
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IL-R associates with Jak
Jak binds to Stat results in modulation of gene expression |
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describe the structure of chemokine receptors
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7 transmembrane helices
interacts with G proteins |
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what are 3 examples of chemokines?
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IL-8, MIP, MCP
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in regards to chemokines:
1. what does its function of chemokinesis mean? 2. what does its function of chemotaxis mean? |
1. stimulation of leukocyte motility
2. direction of leukocyte movement |
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what are the two classes of cytokines?
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CXC
CC |
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What is the difference between CXC and CC?
(which cell types does each attract) |
CXC - predominately atract neutrophils
CC - predominately attract macrophages and monocytes |
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what are 3 early pro-inflammatory cytokines?
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IL-1
IL-6 TNF-alpha |
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which cytokine is known as the bridge cytokine because it bridges innate and acquired immunity
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IL-12
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in relation to a viral infection, put the following in chronological order:
NK cell mediated killing of infected cells T-cell mediated killing of infected cells production of IFN-alpha and beta, TNF-alpha, IL-12 |
1. production of IFN-alpha and beta, TNF-alpha, IL-12
2. NK mediated killing 3. T cell mediated killing |
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what are the pro-inflammatory cytokines we need to know? (5)
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1. IFN-alpha and beta
2. IL-1 3. IL-6 4. IL-12 5. TNF-alpha |
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what are the four effects of IFN-alpha and beta?
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1. inhibit viral replication
2. increase NK cells lytic ability 3. increase MHC class I expression 4. decrease MHC class II expression |
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what is the source of IFN-alpha vs. the source of IFN-beta?
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IFN-alpha: macrophages
IFN-beta: fibroblasts |
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what is the stimulus for both IFN-alpha and beta?
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viral infection
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1. what is the source of TNF-alpha?
2. what two cells are the target of TNF-a? 3. what is the stimulus for TNF-a? |
1. early - macrophages
later - TH1 cells 2. macrophages and neutrophils 3. LPS |
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what does TNF-alpha accomplish by targeting and stimulating macrophages?
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chemotaxis
production of TNF-a, IL-1, IL-6, NO. |
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what does TNF-alpha accomplish by targeting and stimulating neutrophils?
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bacterial lysis
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functionally, which two cytokines is TNF-alpha equivalent to?
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IL-1 and IL-6 (IL-6 has a lesser effect on neutrophils)
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1. what molecule triggers most of the cytokine production?
2. what other molecule can induce cytokine production? |
1. NFKB
2. LPS |
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regarding IL-12:
1. what is the source? 2. what is the target? 3. what effect does it have on NK cells? 4. what effect does it have on T cells? |
1. macrophages and dendritic cells
2. NK cells and T cells 3. production of IFN-gamma and cytolysis 4. CD4+ T cell differentiation |
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Regarding TNF-alpha:
1. cell of origin? 2. target cell? 3. effector function? |
1. macrophages (early) and T cells (later)
2. macrophages and neutrophils 3. induce adhesion molecule expression, facilitate chemotaxis, cell lysis via neutrophils |
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Regarding IL-2:
1. cell of origin? 2. target cell? 3. effector function? |
1. activated T cells only (TH0, TH1, CTL)
2. principle T cell growth factor 3. mainly T cell proliferation (also B cell growth, NK cell growth) |
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Is the manner in which IL-2 activates T cells autocrine or paracrine?
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both autocrine and paracrine
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In an activated T cell:
1. what is the result of adding an alpha chain to the IL-2 receptor (making it IL-2R.alpha.beta.gamma) 2. what is the result of having only an IL-2R alpha chain? |
1. upregulation of IL-2 (receptor has increased affinity)
2. IL-2 downregulation (receptor has decreased affinity) |
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what would a deficiency in IL-2 result in?
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decreased T cell function
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what is unique about the interferon (IFN) gamma receptor?
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it must be a dimer to be biologically active
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regarding IFN-gamma:
1. cell of origin? 2. target cells? |
1. TH1, CTL and NK cells
2. T cells, B cells, macrophages, other leukocytes |
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what effect does IFN-gamma have on T cells? (2)
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1. correlates with IL-12 to induce a TH1 response
2. Inhibits IL-4 induced TH2 responses |
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what effect does IFN-gamma have on B cells?
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stimulates differentiation
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what effect does IFN-gamma have on macrophages?
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1. activation
2. upregulation of MHC class I and II responses |
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what would a deficiency in IFN-gamma result in?
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an increased susceptibility to mycobacterial infections
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Regarding IL-4:
1. cell of origin? 2. target cell? 3. effector function? |
1. activated T cells
2. B and T cells 3. primary growth factor for B cells. Enhances synthesis of IgE. Responsible for TH2 response, Inhibits IL-2, IL-12, IFN-gamma TH1 type responses |
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what effect does IL-4 have on B cells? (3)
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1. activation and growth
2. upregulation of MHC class II 3. Stimulation of IgG and IgE synthesis |
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what effect does IL-4 have on macrophages and mast cells?
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inhibits activation of macrophages, stimulates mast cell growth
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what would a deficiency of IL-4 result in?
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and absent TH2 type response
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regarding IL-10:
1. cell of origin? 2. target cell? 3. effector function? |
1. TH2, B cells, macrophages, keratinocytes
2. TH1 cytokines (IL-2,3,12, IFN-gamma, TNF-alpha) 3. Indirectly favor TH2 functions (via suppressing IL-12 and IFN-gamma). |
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IL-10 is STRUCTURALLY similar to which cytokine?
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IFN-gamma (function is opposite: IFN-gamma favors TH1 response, IL-10 favors TH2 response)
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What effect does IL-10 have on:
1. B cells 2. macrophages 3. mast cells |
1. upregulation of MHC class II
2. inhibits cytokine release 3. stimulates mast cell growth |
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What would a deficiency in IL-10 result in?
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an alteration of the TH1:TH2 balance (in favor of the TH1 response)
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regarding TGF-beta:
1. produced by? 2. general function? |
1. virtually all cells of the immune system
2. general suppressive function |
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why are TGF-beta levels elevated late in an immune response?
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TFG-beta downregulates the immune response
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TH1 cells produce which cytokines (2)?
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1. INF-gamma
2. IL-2 |
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TH2 cells produce which cytokines (2)?
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1. IL-4
2. IL-5 |
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What happens in a TH1 response?
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CELL MEDIATED IMMUNITY.
macrophages are activated CD8 cells are formed |
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What happens in a TH2 response?
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ANTIBODY MEDIATED IMMUNITY.
B cells make antibody (B is 2nd letter of the alphabet) |
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1. when a TH1 cell produces IFN-gamma the result is...
2. when a TH1 cell produces IL-2 the result is... |
1. an activated macrophage
2. CD8 (cytotoxic) cell |
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a TH-o (naive helper T cell)would have to be exposed to which cytokines in order to become a TH1 cell?
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IL-12
IFN-gamma |
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a TH-o (naive helper T cell) would have to be exposed to which cytokine in order to become a TH2 cell?
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IL-4
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Which type of infection would induce a TH1 response?
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intracellular viral or bacterial (these induce dendritic cells to be the APCs)
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Which type of infection would induce a TH2 response?
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pathogens not inducing dendritic cells (ie. parasites)
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what is the role of the Ag binding affinity in the TH1/TH2 decision?
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Binds strongly --> TH1
Binds weakly --> TH2 |
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TH1 cytokines have what role on TH2 activation and growth?
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they inhibit
likewise, TH2 cytokines inhibit TH1 activation and growth |
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which type of response is this?
graft and tumor rejection host defense against bacterial, viral or fungal infection? |
TH1 (T cell mediated/ cell mediated immunity)
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which type of response is this?
host defense against infection by opsonization autoimmunity |
TH2 (B cell mediated/ Antibody mediated immunity)
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which immune response mediates chronic inflammation of the airways (as in asthma or hayfever)
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TH2
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which immune response mediates an acute allergy?
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TH1
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define SCID
molecular cause? |
(severe combined immunodeficiency disease)
mutation in IL-2 and Jak receptors, result=can't make T cells. |
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define 5q minus syndrome
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deletion in long arm of chromosome 5: result is error in development of hematopoietic stem cells,
lack of IL development |
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a patient that presents with increased susceptibility to mycobacterium infections and is also more prone to allergic reactions may have what kind of deficiency?
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IL-12 deficiency
(could also be an IFN-gamma receptor deficiency but less likely) |
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which disorder is a virtually complete immunodeficiency?
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SCID
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Elevated levels of IL-4 are commonly seen in which disorders?
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Hodgkin's lymphoma
chronic lymphocytic leukemia |
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after a parasitic infection a patient would have high levels of which cytokines?
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IL-10, IL-3, IL-4 (mastocytosis)
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in general what happens to cytokine levels in autoimmune diseases?
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they increase significantly
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what are the 5 portals of entry for viral infection?
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1. skin
2. conjunctiva 3. respiratory tract 4. alimentary tract 5. urogenital tract |
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what is the innate defense present in the skin? (3)
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outer layer is dead cells
constant shedding dry |
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what is the innate defense present in the conjunctiva? (2)
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tear flow
lid wiping |
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what is the innate defense present in the respiratory tract? (4)
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mucoid proteins
turibinate baffles cause virus to get trapped in mucus mucociliary cells alveolar macrophages |
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what is the innate defense present in the alimentary tract? (4)
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mucoid proteins
acid bile proteases |
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what is the innate defense present in the urogenital tract? (4)
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mucus
phagocytic cells mechanical flushing by urine acid environment (vagina) |
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how is virulence of a virus measured?
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LD50 (the number of viruses required to kill 50% of the animals following viral infection)
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what is changes in viral virulence usually associated with?
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alterations/mutations in viral proteins (ie. 1918 flu pandemic)
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How do viruses inhibit cell function? (3)
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inhibit:
1. protein synthesis 2. DNA synthesis 3. RNA synthesis |
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how do viruses destroy cellular integrity? (5)
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1. syncitia (giant cells)
2. inclusion bodies (viral factories) 3. vacuolation 4. chromosome condensation 5. apoptosis |
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what is the difference between a local infection and a disseminated infection?
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local - confined, short incubation period
disseminated - spread, prolonged incubation period |
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give an example of a local infection
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influenza, rhinoviruses
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give an example of a disseminated infection
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measles, rabies
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what are the three routes of viral spread?
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1. neural
2. lymphatic 3. hematogenous |
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describe the mechanism behind neural viral dissemination.
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viral entry at nerve endings
transported up axons to soma moves from peripheral nerves to CNS (or vice versa) |
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describe the mechanism behind lymphatic viral dissemination.
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entry via lymphatic capillaries, transported to nodes. some viruses replicate in lymph nodes.
spread by lymph to blood infected macrophages or lymphocytes disseminate infection |
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describe the mechanism behind hematogenous dissemination
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virus entry via lymphatics or direct injury (needle, bite).
can move to secondary sites of replication can establish primary/secondary/persistent viremia |
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in hematogenous dissemination how is the virus distributed?
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free particles or cell associated
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anatomical, physical and chemical barriers are considered which type of immunity?
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innate
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give some examples of molecules that mediate innate immunity (5)
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TLR, interferon, cytokines
macrophages, NK cells |
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in general, how do TLRs function in innate immunity?
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they bind to pathogen associated molecules (PAMPs) and thereby induce expression of effector molecules (such as cytokines and IFN)
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why is IFN-alpha and beta known as the "Paul Revere" of the immune system?
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viral infected cells release IFN-alpha and beta: these bind to uninfected cells to "warn" them of the virus: this blocks viral replication
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why is IFN-alpha and beta very effective?
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they act early and limit the infection to the original cell
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molecularly: how does IFN-alpha and beta block viral replication in uninfected cells?
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they bind to cell and:
degrade mRNA inhibit protein synthesis |
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what part of viruses can serve as antigens? (2)
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1. surface proteins (capsid or envelope proteins)
2. Internal proteins |
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where in a virus would you look to distinguish between different viral groups (ie. to find group specific antigens)?
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look at the internal proteins (not the surface ones)
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what is the earliest antibody to show up in the immune response?
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IgM
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When does IgM peak?
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2-3 weeks post infection
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which antibody peaks a little later than IgM and correlates with resistance to a future infection?
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IgG
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Which antibody is a secretory antibody and correlates with local resistance at portals of entry?
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IgA
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antibodies are most important against viruses characterized by _________?
examples? |
viremia (ie. yellow fever, polio)
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how do macrophages participate in cell mediated immunity? (3)
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1. produce TNF-alpha and compliment factors
2. phagocytose viral aggregates 3. process and present antigens to CD4+ T cells |
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how do CD4+ cytokines participate in cell mediated immunity?
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1. recognize antigens bound to APCs
2. secrete cytokines 3. activate macrophages, NK cells, B cells and CTLs |
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what does the immune system resort to when a virus suppresses MHC I expression?
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NK cells take care of it (CD8+ cells are MHC dependent)
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what is an immune complex and what is it responsible for?
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an aggregate of antibodies and antigens deposited in blood vessels. Activates compliment and induces vasoactive cytokine release -this causes increased vascular permeability and hemorrhage (ie. dengue fever)
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what is a live vaccine composed of?
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an attenuated strain of the virus (has reduced virulence)
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what are the advantages of live vaccines? (3)
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1. viral multiplication occurs which increases viral load
2. local response is usually caused 3. enhanced Ab and cell-mediated immune response |
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what are the disadvantages of live vaccines? (3)
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1. possible reversion to virulent strain
2. possibility of dissemination 3. live preparation - has stricter care requirements (ie. must keep cold etc.) |
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what are the advantages of a killed vaccine? (2)
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1. stable
2. no potential for reversion |
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what are the disadvantages of a killed vaccine? (3)
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1. requires high concentrations of Antigen
2. injection only 3. lower cell mediated immunity |
