Breakout Session #6 Flashcards
What are three strategies employed by which pathogens change how they look so they can evade the immune system?
1) Gene Arrangements
2) Point Mutations
3) Genome Shuffling
Which pathogen utilize gene rearrangements?
African trypanosomes
True or False: The African Trypanosomes can undergo DNA rearrangement to change the glycoprotein expressed on the surface to evade the immune response
True
During the lifecycle of trypanosome, only ___ surface glycoprotein is transcribed from the active “expression site”
one
In response to ______, the trypanosome can undergo DNA rearrangement in order to bring a gene that encodes a different surface glycoprotein into the active expression site and behind an active promoter sequence
selective pressure
True or False: Point mutations (due to errors via DNAP/RNAP) can be introduced into the genome during replication, leading to changes in translated protein. These changes in protein can change the epitope.
True
_____: A process by which pathogens with segmented genomes are able to mix genomes with species to develop a novel species of pathogen
Genome shuffling
Which virus is most closely associated with Genome Shuffling
A. E. coli
B. Trypanosomes
C. Influenza
C. Influenza
The genetic shuffling causes a major change in the ____ of the virus and is called ______
antigenicity; antigenic shift
Why is the immune response absent in the case of genome shuffling?
Body has not seen the new proteins on the surface before
True or False: Influenza cannot undergo point mutations
False - they can!
When point mutations are introduced into the genome and makes small changes to it, it is called ____
Antigenic Drift
In response to antigenic drift, the immune response may be ____ due to a change in the affinity for the antigen or protective antibodies may not work any longer
decreased
What are the three major outcomes of the complement pathway?
1) C3b acts as an opsonin
2) Increase in phagocytosis of pathogens that are bound by complement proteins
3) Formation of MAC complex by terminal pathway of complement - critical for pathogen lysis
True or False: Pathogens have found ways to block the classical, alternative, and terminal pathways of complement in order to avoid complement-mediated destruction
True
What are the three major ways that pathogens have evolved to avoid complement?
1) Recruitment of negative regulators/producing homologs of negative regulators
2) Inactivation of complement cascade via: enzymatic degradation
3) Modulation or direct inhibition of complement proteins by direct interaction
Pathogens have evolved to encode homologs of negative regulators, such as ____, which dissociates C3 convertase
Decay Activating Factor (DAF)
How have pathogens evolved their own enzymes that can inhibit the complement cascade?
Which pathogen almost exclusively uses this strategy?
By cleaving active components involved in the pathway
Bacteria
What are two examples of targets of degradation?
C1a and Immunoglobulins
Some pathogens will degrade ___ into non-functional components, so that the activation of both the ___ and ___ pathway are diminished
C3; classical; alternative
How do pathogens eliminate the ability of immunoglobulins to activate C1?
Pathogens produce Fc receptors that bind immunoglobulins in the vicinity of the bacteria at the Fc portion, which effectively eliminates the ability of these immunoglobulins to activate C1
There are multiple homologs that have similar activity to CD59 that inhibit the polymerization of ___ and, thus, the formation of the MAC.
What is the result of blocking the formation of MAC?
C9;
you will have less complement-mediated lysis of pathogen
Pathogens have evolved to modulate the cytokine environment to promote a less-effective immune response. They primarily do this through which two mechanisms?
1) Production of cytokine homologs
2) Production of cytokine receptor homologs
Which pathogen has evolved to encode cytokines that will dampen a pro-inflammatory response and promote less-effective antibody production?
A. Influenza
B. Vaccina Virus
C. Epstein-Barr Virus
D. Streptococcus Pneumoniae
C. Epstein-Barr Virus
Epstein-Barr Virus encodes a homolog to the cytokine ___
IL-10
What is the normal function of IL-10?
It acts as an anti-inflammatory cytokine that inhibits CD8+ T cells (critical in fighting EBV) and promotes the survival of its target cell (B cell)
What is an example of a pathogen that makes a soluble form of a cytokine receptor, which then binds cytokines in this microenvironment and neutralizes their activity?
A. Influenza
B. Vaccina Virus
C. Epstein-Barr Virus
D. Streptococcus Pneumoniae
B. Vaccina Virus
Vaccina Virus encodes for a soluble ____ receptor
IFN-gamma
What is IFN-gamma critical for?
1) Activating macrophages to increase phagocytosis
2) Macrophage-mediated killing
3) Activating CD8+ T cells
True or False: By producing a soluble IFN-gamma receptor, the Vaccina Virus neutralizes the effects of IFN gamma in an effort to minimize macrophage involvement
True
True or False: Pathogens can hide from the immune system by infecting immunoprivileged sites, transforming into latency, or blocking antigen presentation
True
Which organs are considered to be immunoprivileged?
Eyes, Brain, and Testes
- They are considered to be immunoprivileged because non-activated lymphocytes do no circulate through these organs
___ is a pathogen strategy that aids pathogens in evading the immune response and promotes life long infections
Latency
True or False: By switching from active infection to latency, the pathogen can be maintained in the host indefinitely, in many cases co-existing with the host for the rest of their life
True
What is a hallmark of latent pathogens?
They maintain the ability to transition back to a replicative state to produce more infectious pathogens
True or False: Pathogens have evolved to downregulate both HLA Class 1/2 expression to avoid CD8+ T cells or CD4+ T cell recognition to avoid recognition by immune system
True
How does EBV stop EBV-peptides from being loaded onto HLA-1 for presentation?
EBNA-1 contains internal amino acids that block proteosome degradation of peptides
How does EBV block binding of peptides to TAP 1 and 2?
BNFL2a
In EBV, ____ targets HLA Class 1 for internalization and degradation
BILF-1
In EBV, ___ sterically inhibits HLA II from interacting with the T cell receptor
gp42
