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51 Cards in this Set
- Front
- Back
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How was first vaccine given?
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By scratching the skin of those who had cowpox, a virus related to smallpox. Individuals developed cross-immunity to both cowpox and smallpox.
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What are the three possible vaccine strategies(so far?)
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1) Killed virus
2) Live, attenuated virus 3) Subunit vaccines |
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What kind of viruses can be used in killed virus vaccines?
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Only those whose nucleic acid can be reliably inactivated.
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What's the principle of live, attenuated virus vaccine action?
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Virus is mutated so that it has a reduced ability to grow in human cells.
Done by growing it in cells of non-human species (sometimes they occur naturally). This is better able to elicit an immune response |
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Vaccines made by just using antigenic viral components (e.g., particular surface proteins)
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subunit vaccines
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When should attenuated vaccines not be used?
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Immunocompromised states. Sometimes the virus can back-mutate and become more virulent
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How are vaccines made against bacterial toxins?
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Since many bacterial illnesses are due to toxins the bacteria produce, vaccines are made to generate neutralizing antibodies by purifying these toxins and inactivating them.
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what groups are particularly susceptible to infection by encapsulated bacteria? why?
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Children less than 18 months don't develop good responses to polysaccharide antigens until a few years after birth.
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What are conjugate vaccines?
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Covalently couple the polysaccharide (of bacteria) to a carrier protein (eg., tetanus toxoid) which provides antigenic properties to stimulate T-cell response.
For some reason, a bacterial outer capsule of polysaccharides does not stimulate a T cell response, explaining why older people and children have a hard time responding to encapsulated bacteria. By conjugating the polysaccharide that does not elicit a T cell response with something that DOES (e.g., toxoid), T cells can stimulate B cells. |
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T/F multiple immunizations with most vaccines are recommended because they're needed to develop the memory b cells and t cells necessary for long-term protection
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T
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T/F to work effectively a vaccine must create a state of inflammationg at the site in the body where antigens are injected
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T
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What are adjuvants?
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Helpers.
they induce inflammation by antigen-indpt mechanisms. they're given with the antigen in order to induce a state of inflammation that provokes a good immune response to the antigen. May be used in future to administer cytokines that direct towards Th1 or Th2 response |
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What is Complete Freund's adjuvant?
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Oil in water emulsion with heat killed mycobacteria. Causes clumping and slow release of Ag --> induction of strong inflammatory response.
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What is MF59? alum?
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An emulsion of squalene, oil and water; alum is another used as an adjuvant in humans
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What are ISCOMS?
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Immune stimulatory complexes - lipid carriers that can load peptides or proteins into cell cytoplasm.
They allow MHC Class I responses and CD8 T cells (currently just approved for vet usage) Minimal toxicity |
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How do ISCOMs work?
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Immune stimulatory complexes are lipid micelles that hold peptide in the middle. They fuse with cell membranes, delivering peptides to the cytosol of APCs, allowing it to be transported to the ER, where it can be bound by newly synthesized MHC Class I moleculse and be delivered to cell surface as peptide: MHC Class I complexes.
Works by activating CD8 killer T cells |
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How can attenuated vaccine cause disease?
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May backmutate to develop pathogenicity. Possible solution is to give killed vaccine first which may afford some immunity, then given attenuated.
Immunocomprised can't handle the attenuated pathogen |
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Why has it been difficult to develop vaccines to pathogens causing chronic illnesses?
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-these pathogens are adept at evading immune response
-they can live for years in a host - parasites are especially hard because the immune response that is stimulated isn't helpful - difficult to study |
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Why are vaccines against parasites particularly difficult to develop?
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the immune response that is stimulated isn't helpful
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What complication is inherent to development of T cell vaccines?
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The diversity of human HLA, and the peptides they are able to present
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The success of vaccines against chronic infections will depend on their ability to steer the _____________ response in ways that are helpful.
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CD4 T cell; possibly thru manipulating the bias towards Th1 or Th2
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What is a strategy against a pathogen that expresses different (random?) proteins on the capsule in the same species?
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Do whole-genome sequencing of the pathogen. Look to see if any proteins that are expressed on surface do not mutate and are always expressed
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What are Aschoff nodules?
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Aschoff bodies are nodules found in the hearts of individuals with rheumatic fever. They result from inflammation in the heart muscle and are characteristic of rheumatic heart disease.
Types of granulomas. Their presence indicates a Th1 response being made |
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Why would the induction of factor H by a bacteria increase virulence?
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Factor H is a control protein involved in complement activation.
Overactive factor H may result in reduced complement activity on pathogenic cells - increasing susceptibility to microbial infections. Underactive factor H may result in increased complement activity on healthy host cells - resulting in autoimmune diseases. It is not surprising therefore that mutations or single nucleotide polymorphisms (SNPs) in factor H often result in pathologies. Moreover the complement inhibitory activities of factor H, and other complement regulators, are often used by pathogens to increase virulence. |
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What is factor H and how does it affect virulence?
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Overactive factor H may result in reduced complement activity on pathogenic cells - increasing susceptibility to microbial infections. Underactive factor H may result in increased complement activity on healthy host cells - resulting in autoimmune diseases. It is not surprising therefore that mutations or single nucleotide polymorphisms (SNPs) in factor H often result in pathologies. Moreover the complement inhibitory activities of factor H, and other complement regulators, are often used by pathogens to increase virulence.
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T/F Incorporation of subunits of cloned components of pathogen into adjuvant may increase the response to vaccine
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T
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Most vaccines currently elicit a (antibody, cell-mediated) response, and figuring out how to induce a (antibody, cell-mediated) may prove helpful
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antibody; cell-mediated
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What would the ideal HIV vaccine do?
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Induce neutralizing antibodies to bind tightly to the outside surface of HIV and prevent it from infecting human cells.
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What aspects of the immune system do not change much with aging?
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-Concentration of complement proteins
-Peripheral blood smear -Peripheral blood white cell and neutrophil counts -RBC count and shape - Platelet count |
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What clinically significant problems do appear with aging?
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more frequent and severe pyogenic infections; weaker response to vaccines; reactivation TB
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What are the most important inflammatory cytokines?
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IL-1, IL-6, IL-8, IL-12, TNFα
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Antigen binding to the T cell receptor (TCR) stimulates the secretion of ___, and the expression of ___ receptors. The ___/receptor interaction then stimulates the growth, differentiation and survival of antigen-selected cytotoxic T cells via the activation of the expression of specific genes.
As such, ___ is necessary for the development of T cell immunologic memory, one of the unique characteristics of the immune system, which depends upon the expansion of the number and function of antigen-selected T cell clones. |
IL-2
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What is bone marrow like of older people?
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More fat cells, fewer marrow cells, but can produce cells at same pace if stimulated.
Uncertain clinical significance. |
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How are epithelial barriers less effective in elderly?
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- Altered mucus and ciliary active
- Less physical mobility - Thinner pelvic and urethral mucosa facilitates pathogen entry - Skin thinner, less elastic, more fragile |
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What changes in cellular immunity in aging?
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T cell changes (reduced production of cytokines like IL-2)
Leads to weaker response to stimuli (less robust vaccine respopnse, less able to defend certain viruses, decreased skin test response - may lead to false negative TB test); Less able to control mycobacteria |
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What is MOST affected by aging?
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T cells.
Thymus is involuted. Less robust response to stimuli. Less production of cytokines. |
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A shift from (th1, th2) to (th1, th2) is seen in aging
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Th1 --> Th2
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What may help maintain cytokines?
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physical activity
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How do B cells change in aging?
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More memory B cells; fewer naive.
Many changes in B cells result in reduced T cell support for isotype switching. Decreased antibody response to antigen stimulation. |
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What is the significance of more auto-antibodies?
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Uncertain. Just because there are more self antibodies doesn't mean the presence of autoimmune disease
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How does neutrophil response change during aging?
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Less response to granulocyte macrophage colony stimulating factor (GM-CSF).
Less active cellular killing mechanisms such as superoxide dismutase and reduced respiratory burst. Lead to increased incidence of pyogenic infections |
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What cytokines do macrophages produces that are responsible for fever? How do these change in aging?
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Pyrogenic cytokines: <b>IL-1</b>, IL-6, TNF-α.
Decreased IL-1 production when stimulated by pathogens leads to LACK OF FEVER despite serious infection. |
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What cytokines have INCREASED production in older people? What is inflammaging?
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IL-6, IL-8, and TNFα
Inflammation is necessary to cope with damaging agents and is crucial for survival, particularly to cope with acute inflammation during our reproductive years. But chronic exposure to a variety of antigens, especially to some viruses such as cytomegalovirus, for a period much longer than that predicted by evolution, induces a chronic low-grade inflammatory status that contributes to age-associated morbidity and mortality. This condition carries the proposed name "inflammaging". |
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Why is vaccination less effective in elderly and how might this be overcome?
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Less effective because of reduced production of interferons by macrophages; Less T cell response/production of IL-2
May be overcome by giving vaccines multiple times |
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How may apoptosis play a role in aging?
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CD4 and CD8 T cells are prone to apoptosis, mediated by FAS-FASligand; TNFR and TNF
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What's importance of CD28 in aging?
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CD28 is a molecule expressed on T cells that provide co-stimulatory signals, which are required for T cell activation.
Less expression of this can mean less T cell activation. |
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People who don't make flu antibodies secrete less ________
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IL-5
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What's the role of IL-5?
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It's produced by Th2 and mast cells. Role is to stimulate B cell growth and increase Ig secretion.
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How do DCs change in elderly?
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They don't really - same reactivity, similar amounts of cytokines secreted. They're more potent than peripheral blood monocytes in stimulating T cell proliferation
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What's the role of IL-12?
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Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells[1], macrophages in response to antigenic stimulation.
Does NOT change in aging. |
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T cell proliferation can be enhanced by adding ______ cells
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Dendritic cells.
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