Flashcards in Lecture 15 - Polio Deck (41):
*The IgA immune system is uniquely involved in what type of immunity?
Surface immunity. It does not enter a babies vasculature or tissue. It protects our surfaces.
IgA is the major antibody active at what types of surfaces?
Active at mucosal surfaces and secretions within and outside the body.
Explain the method by which IgA's are made and released
-The antigens that stimulate IgA are taken up in cell and specialized AG-presenting cells (APC) within these sites present these antigens.
- Unique T cells and B cells, specific for this Ag, react and clone resulting in IgA-producing B cell clones specific to that antigen.
- Multiplying daughter B cells migrate to other mucosal sites and start secreting the IgA dimers
What action will result in antibody protection at all mucosal sites?
Antigen at one mucosal site results in antibody protection at ALL mucosal sites
After the IgA dimers are secreted in response to an Ag, what occurs?
The dimeric-IgA molecules are picked up by poly-Ig Fc receptors on the tissue-side surface of submucosal epithelium, the IgA is bound by the Fc receptor, taken up by the epithelial cell and extruded through the other side of the cell onto the mucosal surface.
What is the secretory component of IgA?
-While IgA is in the cell, the Fc receptor is cleaved by a protease but a portion is left clinging to the IgA, and is still there after the IgA is released into the lumen.
General role of secretory component of IgA
Helps protect secretory IgA (sIgA) dimers from proteases at the mucosal surface.
*Does sIgA from maternal milk pass into the baby's vasculature or tissues?
No, it protects the oral and gut mucosa of babies and compliments the tissue/blood protection offered by the IgG passive immunity from placental transfer.
Where is the one surface site where IgA is not the major antibody involved in protection?
Cervicular space between teeth and gingiva
Some animals are born without any maternal-derived antibodies. How do they receive their passive immunity?
Passive transfer of maternal IgG as well as IgA is accomplished within the first couple of hours after birth. Maternal colostrum milk containing a sampling of all her antibodies are given orally to the baby. The neonatal gut is somewhat porous and allows for absorption into tissues and vasculature. The gut epithelium closes at about 12 hrs after birth. It is crucial they receive this colostrum milk as soon as possible after birth.
Name 4 specific functions of sIgA
1. Neutralize toxins and viruses at mucosal surfaces
2. Block colonization by undesirable organisms
3. May decrease unwanted immune reactions to food
4. Binds to mucus (IgA is sticky) preventing rapid loss by flushing action of saliva.
T or F, IgA does not survive well on our gut mucosal surfaces because it is very sensitive to acids and proteolytic enzymes
False. sIgA is INSENSITIVE to acids and proteolytic enzymes which allows it to be the antibody protecting our mucosal surfaces.
Is sIgA a good activator of complement?
No it is a poor activator of complement and an inconsistent opsonizer
Is IgA found in the body or just on the mucosal surfaces?
To a much lesser extent, IgA is found inside the body. It is typically monomeric and functions similarly to IgG and IgM. It is still a poor complement activator.
4 bacteria we have talked about in class have a virulence factor called IgA protease to degrade sIgA. What are they?
1. N. gonorrhoeae
2. N. meningitides
3. S. pneumoniae
4. H. influenzae
Regarding oral tolerance, high dose Ag feeding results in what?
In the induction of anergy (immune unresponsiveness)
What is anergy?
Feeding of multiple low doses of Ag induces what?
Regulatory T cells that secrete the inhibitory cytokine TGF-B.
Other than feeding doses of Ag, what else may play a role in the oral cavity being able to determine between food Ags and pathogenic microbial Ags
Lack of inflammation to food may also play a role. Inflammation may be required for initial Th cell responses.
*Describe the process by which the IgA immune system works when an antigen is present on the mucosal surface.
1-Specialized APC cells, called M-cells, are found in the mucosa. They process and present external Ags on class II HLA molecules.
2. Specialized Th cells respond to the AGs and help local Ag-specific B cells respond and clone.
3. The stimulated B cells then enter blood stream and seed other parts of mucsoal/secretory system.
4. B cells secrete dimeric IgA which quickly bind to Fc receptors on mucosal epithelial cells
5. Mucosal epithelial cells endocytose the bound IgA and transfer it out to the mucosal surface.
6. During transit through cell, Fc receptor is cleaved but some is left on IgA (sIgA) to protect it from proteases as well as other functions.
Poliovirus is a member of what family?
What is an enterovirus? Does this apply to Polio
An enterovirus primarily infects via gut mucosa. Yes Poliovirus is a small positive-stranded RNA enterovirus
Describe the following characteristics of Poliovirus:
1-Envelope or No envelope
2-Type of genetic information
3-Place of action in body
4-How it is spread
2. + ssRNA
3. Replicates in pharynx, GI tract and Local lymphatics.
Acts on CNS and paralysis can occur if becomes systemic
4. Spread by fecal contamination of food and water
Poliovirus is considered neurotropic and has a Poliomyelitis Pathogenesis. Describe this relationship
Being neurotropic it can cause CNS infection and paralysis if and when viremia occurs and it becomes systemic. It enters the mouth by fecal-oral route, replicates in pharynx, Gi tract, local lymphatics and spreads to CNS through blood. The virus spreads along nerve fibers and motor neurons are destroyed in spinal cord.
*Is poliovirus stable or very sensitive and why?
It is extremely stable due to the lack of an envelope.
How does the iceberg effect relate to Poliovirus
When the virus binds and replicates in the oropharynx and GI mucosa it does so usually asymptomatically.
What percentage of people infected are asymptomatic?
Is poliovirus contagious?
Highly contagious through fecal-oral route. Oral-Oral is possible as well.
What is the reservoir for Poliovirus?
It only infects humans
What is the major protective immune mechanism against poliovirus?
Antibody - specifically sIgA and IgG
Explain how sIgA and IgG work together to protect the body against poliovirus
sIgA can prevent the initial establishment of infection and serum IgG prevents viremia spread to the target tissues in CNS and therefore disease.
*What are the two vaccines used to battle poliovirus
*Explain the Salk vaccine and what it does
-Non-infectious and inactivated
-Induces great IgG protection, which neutralizes systemic viruses.
*Explain the Sabin vaccine and what it does
-Infectious, attenuated and live
-Induces great sIgA protection, which neutralizes the virus before it even can start an infection at the primary mucosal infection sites
-Also induces a good IgG response
T or F, Sabin vaccine only induces a strong sIgA protection
False, it also induces a good IgG response
The Salk vaccine works differently by activating only one antibody compared to Sabin that activates two. What is the different outcome in the Salk vaccine because of this difference.
The Salk vaccine induces a good systemic (blood and tissues) IgG response. The anti-polio IgG will protect NOT AGAINST INFECTION, but against polio viremia than can cause CNS infection and paralysis. Sabin protects from an infection from even getting started.
The U.S. has a recommendation of exclusive use of what vaccine since 2000?
The inactivated polio vaccine (Salk vaccine)
When should Oral polio vaccine be used?
Only in special circumstances (Sabin)
When was the last case of Polio in the U.S.
Is polio eradicated globally?
Not yet but is in progress