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21 Cards in this Set
- Front
- Back
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Why is the administration and measurement of mucosal immune responses difficult?
(Like with a mucosal vaccine) |
The DOSE of mucosal vaccine that enters the body can't be measured because antibodies in mucosal secretions can't really be captured or quantitated
Injection vaccines, however, deliver a KNOWN QUANTITY into the body and the generation of specific antibodies by lymphoid cells CAN BE QUANTITATED EASILY by serum samples |
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List the currently available mucosal vaccines approved for human use
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Oral vaccines:
o Polio virus o Salmonella typhi o V. cholera o Rotovirus Nasal vaccine: influenza virus |
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List a few of the innate defenses at mucosal surfaces
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Epithelial Cells Secrete:
-Mucins -antimicrobial proteins Also present: -Lymph Tissue -APCs |
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How do epithelial cells participate in mucosal defense?
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Fxn as sensors that detect dangerous microbial components via TLRs
↓ Respond by sending cytokine and chemokine signals to underlying mucosal cells (DC's and Macrophages) ↓ triggers innate nonspecific defenses and promotes adaptive immune responses |
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Explain why injected (ex. intramuscular) vaccines do not produce robust mucosal immune responses
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mucosal tissues = in a constant state of alert, but they are adapted to the presence of foreign microorganisms and their products
So, when a vaccine is injected, mucosal cells will most likely IGNORE it... |
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List a few of the adaptive immune defenses at mucosal surfaces
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- Dimeric or multimeric immunoglobulin A (IgA) antibodies
- IgG - Cytotoxic T Lymphocytes |
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Describe the role of secretory IgA (sIgA) in mucosal defense
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**Secretory IgA (sIgA)**
- posesses protease resistance "Immune exclusion” Promotes entrapment of antigens or micro-organisms in mucus, preventing direct contact of pathogens with the mucosal surface -Sterically hindersand blocks microbial surface molecules that mediate epithelial attachment |
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Explain "Immune Exclusion" carried out by secretory IgA
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"Immune exclusion”
Promotes entrapment of antigens or micro-organisms in mucus, preventing direct contact of pathogens with the mucosal surface |
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List the mucosal sites of the body where IgG antibodies may play a protective role
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Female genital tract - blocks STDs
Human Intestines- prevent systemic spread -Airways |
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Briefly describe how sIgA and IgG are transported onto mucosal surfaces
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**IgG**
- Specific Fc receptor is expressed by epithelial cells in intestine and airways - Can mediate IgG transport in both directions across epithelial barriers **IgA** - Specific receptor IDed on apical surfaces of microfold cells (M cells) - Can mediate uptake of luminal IgA into Peyer’s patches |
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Explain why the gut is a major reservoir of HIV infection regardless of the site of initial viral entry
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Intestinal tract = an immunologically active mucosal tissue
**Contains abundant CD4+ T cells—targets for HIV** Thus, the intestinal mucosa becomes a reservoir of HIV infection regardless of the site of initial viral entry |
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Describe the sites and mechanisms by which antigens are sampled at mucosal surfaces
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- **Peyer’s patches**
in the distal ileum and abundant isolated follicles are present in the appendix, colon and rectum - **M cells** form intraepithelial pockets which give lymphocytes samples of foreign material from intestinal lumen -**Dendritic Cells** • Means of antigens and pathogens sampling on mucosal surfaces in the absence of organized mucosal lymphoid tissues • DCs migrate into narrow spaces between epithelial cells and to the outer limit of epithelium—can obtain samples of foreign material directly from luminal compartments |
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Where are DCs most immunologically important
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female genital tract
where there are no organized lymphoid follicles and the epithelium lacks M cells |
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what is meant by the ‘common mucosal immune system’?
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- Activated B and T cells upregulate expression of tissue specific adhesion molecules and chemokine receptors that function as “homing receptors”
- These guide lymphocytes back to mucosa via recognition of endothelial counter-Receptots of mucosal vasculature **Broad recognition system *** mucosal immunization at one site can result in the secretion of specific IgA antibodies in other mucosal or glandular tissues—this is known as common mucosal immune system***** |
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Explain why systemic immunization is generally ineffective for the induction of mucosal IgA antibody responses
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Expression of CCR10, α4β1-integrin and other mucosal homing receptors is NOT INDUCED on B cells that are activated in the peripheral lymph nodes
- CD8+ T cells that are activated in response to mucosal antigen might initially have a fairly unrestricted migration pattern, but long term show preference for tissue in which antigen was originally encountered |
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List a few of the challenges faced by mucosal vaccines given orally or deposited on mucosal surfaces
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- Diluted in mucosal secretions
- Captured in mucus gels - Attacked by proteases and nucleases and excluded by epithelial barriers - Thus, relatively large doses are required and is impossible to determine exact dose that crosses |
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Briefly describe why live vaccines are effective as mucosal vaccines
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**Effectiveness is d/t:**
- Adaptation to survive in luminal environments - Efficient invasion of organized mucosal lymphoid tissues -Ability to activate multiple innate responses |
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Describe the role of adjuvant in mucosal vaccines and list a few of the molecules that have been explored as adjuvants
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-Substance added to make vaccine "stand out" and initiate an innate immune response
-Best-known mucosal adjuvants: • Cholera toxin • E. coli heat-labile enterotoxin |
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Describe the ways in which HIV is transmitted
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- Occurs mainly through exposure of mucosal surfaces to HIV and HIV infected cells
Epithelial cells serve as a gateway for delivery of infectious HIV parasites to antigen presenting DCs and macrophages ↓ Cells interact with local CD4 T cells (HIV's Target!) |
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List the type of immune responses an effective HIV vaccine would elicit
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First--Interrupt mucosal transmission at its earliest stages—before virus has crossed the epithelial barrier and infected its first target cell
Secondly—prevent establishment of viral reservoirs in mucosal tissues The vaccine would need to: -Produce HIV specific envelope antibodies in mucosal secretions -Induce CTLs to reduce plasma viral loads in mucosa - induce Neutralizing HIV envelope specific antibodies in the mucosa and circulation |
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List the mucosal sites where IgA antibody is induced following nasal vaccination
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Nasal vaccinations have induced IgA antibody responses in the rectum and vagina
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