I13 Flashcards
What is antigenic variation?
display of new antigens by a pathogen that are not recognized by immune responses formed in response to previous infectionenables the pathogen to evade pre-formed memory immune responses
What kind of antigenic variation does Strep. pneumo use?
capsular variationStreptococcus pneumonia uses an antigenic variation mechanism that is fairly standard in the microbe world. There are 84 distinct serotypes of S. pneumo which all differ in the structure of their capsular polysaccharides.When one serotype of S. pneumo infects a host, the host will produce a capsular polysaccharide-specific antibody response that will clear the infection and leave the host immune to that serotype.However, the host is not resistant to any of the other 83 serotypes of S. pneumo. Upon infection with any of the other serotypes, the preformed immune response to the 1st serotype cannot mediate clearance, and the host has to produce a new immune response to the different serotype of capsular polysaccharide.Therefore, S. pneumo can cause 84 distinct infections in the same host that will result in acute infection and a chance for transmission before the host can produce an acquired B cell response.
Influenza virus uses two different forms of antigenic variation. What is one?
ANTIGENIC DRIFT (introduction of point mutations that result in minor alterations of the antigenicity of a particular protein). Influenza virus makes two surface proteins (neuraminadase and hemagglutinin) that are the primary targets of antibody responses that can protect the host from this virus (once the immune response is produced). The antibodies neutralize the virus by binding to these surface proteins and interfering with their ability to bind to their host cell receptors.During the replicative cycle of flu in another person, or in a non-human host such as a pig or fowl, the hemagglutinin and/or neuraminadase accrue point mutations that alter the determinants that were recognized by protective antibody responses in human hosts.Upon infection of another person that had already experienced the flu, this new virus that has undergone antigenic variation (drift) can evade that person’s pre-formed anti-flu antibodies and cause a symptomatic infection that will allow transmission of the virus to other hosts.Typically, this type of antigenic variation in influenza results in a new pandemic that is not terribly serious, probably because many of the determinants recognized by flu-specific T cells in previously infected/immune patients have not been altered, so generating a new B cell response is very efficient and happens relatively quickly.
What is the second form of antigenic variation employed by Influenza virus?
ANTIGENIC SHIFTInfluenza virus has a segmented genome that has either 7 or 8 segments of ssRNA. During co-infection of a non-human host (pig or fowl, typically), two different viruses can undergo their replicative cycle simultaneously in the same cell.As two flu viruses replicate simultaneously inside the same cell, it is possible for the resulting virions to be packaged with a shuffled version of the genome segments.The resulting virus now may express a completely different version of either the hemagglutinin or neuraminidase surface proteins. This more completely nullifies any previous immune response a person has made to a previous strain of influenza because not only are the B cell determinants different, so are many or even most of the T cell determinants.Therefore, the resulting antigenically shifted virus can cause a new pandemic that causes much more severe disease than a viral strain that arose via antigenic drift.
How do Trypanasomes (insect-borne protozoa that replicate in extracellular tissue spaces in the body; they cause sleeping sickness) employ antigenic variation?
These pathogens have genes that encode over 1000 distinct “variant-specific glycoproteins” using a sort of cassette system. During any trypanosome infection, most of the newly generated trypanosomes will express the predominant VSG (in this example, VSGa).Once the host has begun to make immune responses directed at VSGa……some of the daughter trypanosomes begin to express a different VSG protein (in this case, VSGb). Now, the new VSG-bearing trypanosomes are able to escape the pre- formed immune response of the host, and their numbers increase in the host until the host makes a new VSGb-specific immune response.Now the trypanosome switches VSG expression again, allowing the bug to escape the preformed immune response, and the whole cycle repeats again.This is why African sleeping sickness is a chronic episodic condition. Ultimately, the inflammation caused by the recurrent immune responses and immune complex formation/clearance causes damage to host tissues, including neural tissue, and ultimately results in coma.
What is latency?
a non-replicative state that some viruses can achieve in host cells. The viral genome integrates into host cell DNA (either chromosomal or episomal DNA). While in this state, there is no way for the immune system to recognize infected host cells.usually, viral infections are characterized by rapid production of viral proteins (for replication); some of these proteins are processed, and fragments of them are displayed on the surface bound to MHC class I molecules of the infected cell, where they can be recognized by antigen-specific effector CTLs (the cell is killed)• during latency, the virally-infected cells cannot be eliminated by CTLs because there are no viral antigens (peptides) to flag the presence of viral infection
What causes oral herpes lesions?
This is caused by herpes virus replication along the sensory neurons that serve the mouth. The virus initially infects the epithelium, but is travels up the nerve and integrates into host episomal DNA in nerve cells in the trigeminal ganglion.During the primary infection, viral replication causes a lesion near the mouth as it travels up the nerve serving that tissue, and it enters a latency stage in the trigeminal ganglion.During the latency phase, the viral genome remains integrated into episomal DNA in the trigeminal ganglion, and because there are very few virus-derived peptides, the immune system (CTLs) has no method of identification of these infected cells. (Also, neurons express very low levels of MHC class I molecules, which makes it harder for CTLs to recognize infected neurons. This is an important feature of neurons; since they cannot be regenerated, the lack of MHC class I molecules helps to prevent unnecessary killing of the vital cells. Lack of MHC class I makes neurons extremely susceptible to persistent infections)Eventually some stressor (sunlight, mental stress, etc.) causes reactivation of the viral replicative cycle. The virus replicates and travels down the sensory nerve into the overlying epithelium, and immune responses again control the infection by killing the infected epithelial cells (leaving cold sores).This cycle can happen over and over for the rest of the patient’s life. The immune system likely never clears these types of infections.
What is another latent viral infection type?
Latent chickenpox (varicella-Zoster virus) that has been reactivated, a condition known as the shingles.
Where does VZ remain latent after an initial chicken pox infection?
VZ remains latent after chickenpox infection in the dorsal root ganglia that serve one side of the trunk or one side of the face. THIS IS WHY when reactivation occurs, the lesions are typically confined to that side of the trunk or face, often from front midline to back midline.
Can people have shingles more than once?
It has been thought for some time that only one reactivation of this latent virus was possible, but there is mounting evidence that one person can have the shingles more than once. The experience is quite painful.
How does the herpes simplex subvert the immune system? Which part of the immune system?
Humoral: It has virally encoded Fc receptors that block effector functions of antibodies bound to infected cells It also has virally encoded complement receptors that block complement-mediated effector pathways Blocking of antigen processing and presentation: Inhibition of MHC class I up regulation by IFN-y and inhibition of peptide transfer by TAP
How does cytomegalovirus subvert the immune system? Which part of the immune system?
Humoral: It has virally encoded Fc receptors that block effector functions of antibodies bound to infected cells Inhibition of inflammatory response: It encodes a chemokine receptor homolog that sensitizes infected cells to effects of some cheekiness (advantage to virus unknown)Blocking of antigen processing and presentation: Inhibition of MHC class I up regulation by IFN-y
How does vaccinia subvert the immune system? Which part of the immune system?
Humoral: virally encoded complement control protein hat inhibits complement activation fo infected cells Inhibition of inflammatory response: Virally encoded cytokines receptors (e.g. IL-1, TNF-a receptor homologs) that block the effects of cytokines by inhibiting their interaction with host receptors AND protection from NFkB activation by short sequences that mimc TLRs that block the inflammatory responses elicited by IL-1 or bacterial pathogens
How does Epstein-Barr virus subvert the immune system? Which part of the immune system?
Inhibition of inflammatory response: viral inhibition of adhesion molecule expression (e.g. LFA-3, ICAM-1) that blocks adhesion of lymphocytes to infected cells Immunosuppression of host: virally encoded cytokines homolog of IL-10 that inhibits TH2 production
How does the surface protein US2 of human cytomegalovirus cause subversive effects on the immune response?
Targets HLA class I molecules to the proteasome by transporting them to the cytosol
How does the surface protein US3 of human cytomegalovirus cause subversive effects on the immune response?
Retains HLA class I in the ER by blocking tapasin function
How does the surface protein US6 of human cytomegalovirus cause subversive effects on the immune response?
Inhibits TAP ATPase activity and function
How does the surface protein US10 of human cytomegalovirus cause subversive effects on the immune response?
Binds HLA class I and delays its departure from the ER to the cell surface
