Lecture 15: Polio sIgA, Sec immune system & Virus neutralization Flashcards
Explain how Ag at one mucosal site results in Ab protection at all mucosal sites?
- Specialized Ag- presenting cells (APC) (M-cells) within sites, present these antigens and unique T and B cells specific for this Ag then react and clone. This results in IgA producing B cell clones specific to that antigen.
- These multiplying daughter B cells migrate to other mucosal sites and start secreting the IgA dimers.
What is the role of IgA?
- Involved in surface immunity
- Major Ab at mucosal surfaces and secretion within and outside the body.
Following release of these “emigrant” B cells the dimeric Ig-A molecules are picked up by what?
Poly-Ig Fc receptors that are on the tissue-side surface (inside-or baslolateral-surface) of submucosal epithelium
The Ig A is bound by the ____________, then taken up by the epithelial cells and extruded through the other side of the cell onto the mucosal surface ( other, or lumen surface).
Fc receptor
While in the cell the Fc receptor is cleaved by a _____________ but a portion is left clinging to the Ig A, and is still there after the IgA is released in to the lumen.
protease
What is the clinging part of the Fc receptor called?
The secretory component
What does the secretory component help do?
Helps protect secretory IgA (sIgA) dimers from proteases at the mucosal surfaces.
How does IgA pass to neonates in milk?
Through passive immunity from mom at the GI lumen.
Does the sIgA pass through the lumen into the baby’s vasculature or tissues?
No; IgA passive immunity protects the oral and gut mucosa of babies.
What offers protection for the tissues/blood for babies?
Ig G passive immunity from placental transfer
Where is the one surface site where IgA is not the major antibody involved in protection?
The cervical space between teeth and gingiva
What are some functions of SIgA?
Dimeric sIgA functions to
1) neutralize toxins and viruses at mucosal surfaces and block colonization of bad organisms.
2) Decreases unwanted immune rxn to FOOD.
sIgA is sticky and binds to what? And what does this prevent?
Binds to mucous preventing its rapid loss by the flushing action of saliva.
***It is also insensitive to acids and proteolytic enzymes!
True or False SIgA is a poor activator of complement and an inconsistent opsonizer?
True
True or False. Some medically important bacteria (N. gonorrhoeae, N. meningitides, S. pneumonieae, and H. influenzae have a virulence factor that produces proteases that degrade SIgA?
True
What system is partially Invovled in preventing any destructive immune reactions to our food?
IgA system mechanisms (Oral tolerance) are and they also serve to protect us from GI pathogens.
What is anergy?
immune unresponsiveness
What does high dose Ag feeding result in?
the induction of anergy (immune unresponsiveness)
What does feeding of multiple low doses of Ag induce?
Induces regulatory T cells that secrete the inhibitory cytokine TGF-Beta.
Note: ***Lack of Inflammation to food may also play a role.
(Inflammation may be required for initial Th cell responses)
What are the secondary lymphoid tissues?
Peyer’s patches, MALT ( mammary associated lymphoid tissues), BALT (bronchial associated lymphoid tissues), GALT (gut associated lymphoid tissues)
* More than all other immune tissues combined
What are M- cells?
M-cells process and present external Ags on class II HLA molecules. Specialized Th cells respond to the Ags and help local Ag specific B cells respond and clone.
What sticks to mucins and is resistant to proteases?
sIgA
Poliovirus is a member of what virus family?
Picornavirus that is (+) ssRNA enterovirus.
- Small
- Non-envelope (naked virus)
Where does the Poliovirus specifically bind and replicate ?
in the oropharynx and the GI mucosa
How is the Poliovirus (Picornavirus) spread?
Mainly spread by fecal contamination of food and water.
***Virus is extremely stable due to lack of envelope.
What are the signs/symptoms of the Poliovirus?
- It actually is usually asymptomatic (BIG ICEBERG EFFECT)
- However, since it is neurotropic it can cause CNS infection and paralysis if “viremia” occurs and it becomes systemic.
What antibody can prevent the initial establishment of infection?
What antibody prevents viremia spread to the target tissue (CNS), and therefore disease ?
SIgA and IgG respectively.
What is the Salk vaccine?
-Non infectious and inactivated
-Injected
-induces great “IgG” protection, which neutralizes systemic viruses.
(good systemic bc of IgG and poor surface Ab response bc of little IgA)
What is the Sabin vaccine?
- infectious, & live (attenuated vaccine)
- induces great “SIgA” protection, which neutralizes the virus before it even can start an infection at the primary mucosal infection sites.
- Ingested orally
- Good surface response (sIgA ) and good IgG response since it infects gut epithelial cells.
Which vaccine is considered a “bystander” immunization of family?
Sabin (Attenuated)
Which vaccine does a good job at protecting us from getting polio in blood stream?
Salk and Sabin because both have good IgG reponse (blood and tissues)
Which vaccine induces a very good mucosal sIgA response?
Sabin (Attenuated)
Note: India uses this vaccine provides whole immune response.
Benefit: This will neutralize any polivirus ingested, thus stopping an infection from ever getting started.
What is poliomyelitis?
A viral disease that can affect nerves and can lead to partial or full paralysis.
- Entry into mouth
- Replication in pharynx, GI tract, local lymphatics
- Blood viremia- spread to lymphatics and CNS
- Viral spread along nerve fibers
- Destruction of motor neurons in spinal cord
- First described by Michael Underwood in 1789
- 21,000 cases in the US in 1952
What are some characteristics of Poliovirus?
- Enterovirus- Picornaviridae +ssRNA
- Non- Enveloped
- Three serotypes: 1,2,3
- Spread by fecal-oral route
- Rapidly inactivated by heat, formaldehyde, chloride, UV light
What are outcomes of poliovirus infection:
Asymptomatic: 95%
Minor non-CNS illness: 4%
Non paralytic aspectic meningitis: 1%
Paralytic: 0.5%
What is the reservoir for poliovirus?
Only infects humans
Transmission of Poliovirus?
Fecal-oral and oral-oral possible
