13: Subversion of Immune Responses Flashcards
What are the 3 methods of evasion of host immune responses employed by pathogens?
- Antigenic variation
- Latency
- Subversion of host responses/molecular mimicry
Antigenic variation
Alteration of epitopes displayed by a pathogen that make the epitopes unrecognizable by an existing immune response
Antigenic drift
Point mutations result in minor alterations of the antigenicity of a particular protein
Antigenic shift
Reassortment of genes that results in major changes in the antigenicity of a given protein
Latency
A state in the life cycle of some viruses during which they do not replicate and remain hidden from the immune system
Superantigen
Molecules that stimulate a subset of CD4 T cells by simultaneously binding to MHC Class II and the beta chain of the TCR
T or F: Superantigen binding interactions are highly specific.
F: Not specific interactions
What are the three ways that antigenic variation can occur?
- Many infectious agents exist in a wide variety of antigenic types, so the same organism can cause disease in the same host many times (Pneumonia example)
- Antigenic drift and antigenic shift (Flu example)
- Programmed rearrangement of DNA by a pathogen (Trypanosome example)
Immunity to influenza is primarily mediated by ____________.
Neutralizing antibodies specific for its major surface proteins
T or F: In antigenic drift, symptoms associated with the new variant are typically mild. Why or why not?
T: There is usually cross-reactivity between the old variant and the new variant, so most of the population has some level of immunity.
What does antigenic shift do to the structure of the influenza virus?
Leads to major changes in the hemagglutinin protein on the surface of the virus
T or F: Antigenic shift causes a milder disease than drift. Why or why not?
F: Drift causes a milder disease because it can maintain its existing T cell response but shift can’t
What are the characteristics of the influenza virus?
- Causes seasonal epidemics: new strains arise from animal strains
- Has segmented negative sense RNA genome
- Neutralizing antibodies are probably the most important clearance mechanism for the virus
What are trypanosomes?
Insect-borne protozoa that replicate in extracellular tissue spaces in the body and cause sleeping sickness
Trypanosomes are coated with ________.
Variant-specific glycoprotein (VSG)
How do VSGs confer antigenic variation?
Trypanosomes have approximately 1000 different VSG genes that each encode a VSG protein that is antigenically distinct; One VSG can convert to another VSG, which is advantageous for the trypanosome because it takes a while to generate the antibodies for the new VSG
T or F: During latency, virally infected cells cannot be eliminated by CTLs because there are no viral antigens to flag the presence of viral infection.
T
What are good examples of viruses that enter latency phases?
Herpes simplex, varicella zoster, and Epstein-Barr virus
How can herpes infection be reactivated?
- Herpes infects epithelia and spreads to sensory neurons
- When an effective immune response controls the epithelial infection, the virus persists in a latent phase in the sensory neurons
- Herpes is reactivated and travels along the axons of sensory neurons to re-infect epithelial tissues
(Cycle can keep going)
Why do sensory neurons remain infected in herpes? (2)
- Very few viral peptides are available for presentation to CTLs
- Neurons express very low levels of MHC Class I molecules, which makes it harder for CTLs to recognize infected neurons
T or F: Reactivation of varicella zoster usually only happens once in the lifetime of an immunocompetent host.
T
What is the immune response to reactivated varicella zoster known as?
Shingles
How does mononucleosis come about?
A B cell becomes infected by EBV then proliferates, leading to the activation of T cells. The infection is controlled by CD8 effector cells that kill infected B cells.
How does EBV become latent?
By inserting its genome into host DNA
T or F: Reactivation of EBV typically causes the same disease symptoms as the initial infection.
F: It rarely causes disease symptoms in immunocompetent people
What are the pathogens most likely to subvert immune responses?
Viruses
What are 3 mechanisms by which viral pathogens can subvert various arms of the immune system?
- Capturing cellular genes for cytokines or cytokine receptors
- Synthesizing complement-regulatory proteins
- Inhibiting MHC class I molecule synthesis or assembly
By what mechanisms can viruses inhibit humoral immunity? (3)
- Virally encode Fc receptors
- Virally encode complement receptors
- Virally encode complement control proteins
By what mechanisms can viruses inhibit inflammatory response?(4)
- Virally encode chemokine receptor homologs
- Virally encode soluble cytokine receptors
- Virally inhibit adhesion molecule expression
- Protect from NFkB by mimicking TLRs
By what mechanisms can viruses block antigen processing and presentation?
- Inhibiting MHC Class I upregulation
2. Inhibiting peptide transport by TAP
By what mechanism can viruses suppress the immune response of the host?
By virally encoding the cytokine homology of IL-10
What is an example of a bacterium that can trick the immune system?
Mycobacterium tuberculosis is taken up by macrophages, but it prevents phagosome-lysosome fusion, enabling the bacterium to survive inside the phagocyte
How does Listeria monocytogenes evade immune response?
It can escape from the phagosome and replicate freely in the cytoplasm of the infected macrophage
How can listerial infection be cleared?
By antigen-specific effector CTLs
How can Toxoplasma gondii evade immune response?
It can generate its own vesicle following phagocytosis, and this vesicle isolates the parasite from the rest of the cell and prevents presentation of parasite-derived peptides (remains invisible to the immune system)
Superantigens produced by bacterial and viral pathogens induce __________.
Massive production of cytokines by CD4 cells
Cytomegaloviruses interfere with ________ and __________.
- Processing/Presentation through the MHC Class I pathway
2. NK cell functioning
What are two examples of super antigens?
Staphylococcal enterotoxins (SE) and Toxic shock syndrome toxin-1 (TSST-1)
T or F: Binding of super antigen to both MHC Class II and TCR of a T cell simultaneously primes an antigen-specific immune response.
F: Instead it causes massive production of cytokines by CD4 T cells
What is an example of a disease process that involves pathogen-induced immunosuppression?
Leprosy
What are the major forms of leprosy?
- Lepromatous leprosy
2. Tuberculoid leprosy
What are the characteristics of lepromatous leprosy?
- Cell mediated immunity is depressed and infection is not controlled
- Bacteria highly infectious and replicates freely in macrophages
- Infection goes throughout the body
- Hypergammaglobulinemia
- Low/absent T cell responsiveness
- Host ends up in anergic state
What are the characteristics of tuberculoid leprosy?
- Potent cell-mediated immunity with macrophage activation that controls but doesn’t kill infection
- Bacteria present at low/detectable levels
- Granulomas and local inflammation
- Normal levels of Igs
- Normal T cell responsiveness
What is the most likely difference between the two forms of leprosy?
A difference in the ratio of TH1 to TH2 cells, so it’s thought to be caused by cytokines
Chemokine
Small cytokines that are involved in the migration and activation of cells
Seroconversion
Phase of an immune response when antigen-specific antibody production is 1st detectable
How does reverse transcriptase help the HIV vision evade immune response?
It doesn’t have a proofreading mechanism so the virus is constantly changing (antigenic drift)
HIV is accompanied by a huge decrease in _______.
CD4 T cell numbers
How does HIV do its thing?
- HIV’s envelope protein complex binds with high affinity to CD4 molecules
- HIV then interacts with a chemokine co-receptor on the host cell to gain entry into the cell
- HIV replicates rapidly in the blood causing a marked reduction in circulating CD4 T cell numbers
When does seroconversion occur in an HIV infection?
2-6 weeks post-infection
When does the latency phase for HIV occur and how long does it typically last?
Around 2-6 weeks post-infection and it lasts around 10 years
T or F: B-cell and T-cell mediated anti-HIV responses may help the virus evolve by providing selective pressure.
T
How is AIDS clinically defined?
By very low numbers of circulating CD4 cells (<200/microliter)
Why does resistance to zidovudine (AZT) take months to develop?
Because several mutations in the reverse transcriptase gene are required to confer resistance
