Evasion of Immune Responses Flashcards
What 3 methods do pathogens use to evade host immune responses?
Antigenic variation, latency, and subversion of host responses/molecular mimicry.
What is antigenic variation?
Pathogens display new antigens that are not recognized by immune responses formed in response to previous infection.
That type of immune response does antigenic variation allow pathogens to evade?
Pre-formed memory immune responses.
How does Streptococcus pneumoniae utilize antigenic variation?
Changes its capsular polysaccharide.
How many distinct serotypes does S. pneumoniae have?
84.
What is antigenic drift?
Viral genome mutates and changes its particular antigen expression thus not recognized by patient first infected with the non-mutated form.
What is antigenic shift?
Two or more different strains of a virus combine to form a new recombinant virus. Upon infection, the patient does not recognize the new recombinant form of the virus.
Which is more serious: antigenic drift or shift? Why?
Antigenic shift b/c there are no memory T cells that can recognize the new combination of antigens displayed by the recombinant virus. Note: genetic drift variant causes milder disease b/c of the existing memory T cell responses formed form previous infection.
How do trypanosomes utilize antigenic variation?
Trypanosomes possess a cassette gene system of VSGs (variant-specific glycoproteins) containing over 1,000 different glycoprotein genes the organism can express. When the immune system forms a response to one gp, trypanosomes change gp expression resulting in cyclic infections. Termed programmed rearrangement.
What is latency?
A state adopted by some viruses in which they have entered cells but do not replicate.
In latency, what usually happens to the viral genome?
The viral genome is usually integrated into the host cell DNA.
What 2 viruses are prime examples of latency?
Herpes virus and varicella zoster virus.
During the latency phase, where does the herpes virus hide?
In nerves (particularly in the trigeminal ganglion?).
What triggers reactivation of the herpes virus leading to a recurrent infection?
Stress –> usually herpes blister on lips.
Primary infection of varicella zoster virus causes what?
Chickenpox.
Reactivation and recurrent infection of varicella zoster virus causes what?
Shingles.
What is unique about the recurrent infection of varicella zoster virus?
It occurs only on one side of the body and usually follows nerve pattern.
What virus is a primary example of antigenic shift and antigenic drift?
Influenza virus: new strains every year.
What are 2 mechanisms by which CMV subverts immune response?
- Interrupts loading of MHC Class I molecules
2. Inhibits NK cell recognition of infected cells
How do superantigens initiate massive production of cytokines?
Superantigens simultaneously bind to MHC Class II molecules and TCR, thus bypassing antigen-specific T cell recognition and activation.
The massive cytokine production elicited by superantigens results in what?
Systemic toxicity and/or suppression of immune response.
What are 2 examples of superantigens?
SE and TSST-1.
Are there antigen-specific responses in the case of a superantigen?
No: that’s the whole point of a superantigen.
Superantigens bind to which chain of MHC Class II molecules?
Alpha.
Superantigens bind to which chain of the TCR?
Beta.
What are 2 enzymes found in the HIV virion?
Integrase and reverse transcriptase.
Why is HIV prone to undergoing antigenic drift?
Reverse transcriptase is sloppy and highly error prone.
How does HIV take advantage of human behavior?
Sexually transmitted and shared needles.
What does the HIV virion bind to?
Binds to CD4 and co-receptor on T cell.
How does the HIV viral genome enter host cells?
Viral envelope fuses with host cell membrane allowing HIV virion to spill its viral genome into the cell.
Reverse transcriptase copies viral RNA genome into what and what does that do?
Into double-stranded cDNA which enters nucleus and integrates into host DNA.
T cell activation induces what of the HIV provirus?
Some transcription of the provirus.
HIV RNA transcripts are spliced to allow synthesis of what HIV proteins?
The early proteins: Tat and Rev.
What does Tat do?
Tat amplifies transcription of viral RNA.
What does Rev do?
Rev increases transport of viral RNA to the cytoplasm of the host cell.
Gag, pol, and env HIV proteins are made and assembled into what which does what?
Packaged into virions which bud from the host cell.
What is the ultimate outcome of HIV infection?
Depletes CD4+ T cells.
Which cells mediate the patient’s anti-HIV immune response?
Potent B and T cell mediated responses.
How does the patient’s immune response actually help the virus?
Immune response provides selective pressure for the HIV virus to evolve.
What are the 4 phases of HIV infection?
- Initial infection
- Asymptomatic Phase (latency period)
- Symptomatic Phase
- Full Blown AIDS (death)
What viremia levels are observed in the asymptomatic phase?
After initial infection, viremia levels are controlled by host immune response so viremia levels remain low and are variable.
What are 3 immune responses the patient forms to control HIV infection?
- Ab’s against HIV envelope protein
- HIV-specific cytotoxic T cells
- Ab’s against HIV core protein
2-6 weeks post HIV infection, why does the patient present with flu-like symptoms?
Due to an initial rapid drop in CD4+ T cells.
T or F. Once a patient is infected with HIV, CD4+ T cell levels begin to decline until they are eventually depleted?
F: after the rapid drop in CD4+ T cells, levels go back up in the asymptomatic phase then slowly decline until symptomatic phase and full blown AIDS develops.
What is the average length of the asymptomatic phase?
10 years.
What qualifies a patient as a full blown AIDS patient?
CD4+ T cell count <200 cell/microliter.
What is the eventual cause of death in a terminal AIDS patient?
Death by infection due to CD4+ T cells being completely depleted.
What does HIV-induced immunodeficiency allow?
Opportunistic infections including many species of parasites, bacteria, fungi, and viruses.
What malignancies can occur in HIV infected patients?
- Kaposi’s sarcoma caused by herpesvirus 8
- Non-Hodgkin’s lymphoma (including EBV-positive Burkitt’s lymphoma)
- Primary lymphoma of the brain
What 4 mechanisms does HIV employ to evade immune response?
- Antigenic drift
- Latency
- Molecular mimicry
- Induction of acquired immunodeficiency (CD4+ T cell depletion leads to death)
