Week 15 Flashcards
How are T cells activated?
T cells are activated to proliferate by binding to antigens that are presented to them by dendritic cells, professional antigen presenting cells.
T cell activation process (innate immune response)
- Pathogens enter through break in skin and are phagocytosed by dendritic cell
- Activated dendritic cell carries pathogen peptides to local lymph node
T cell activation process (adaptive immune response)
Activated dendritic cell activates specific T cells to respond to pathogen peptides bound to MHC proteins on dendritic cell surface.
An antigen must be bound to what for a T cell to bind to it?
An MHC protein.This allows T cells to recognize infection inside a cell because the dendritic cell presents the antigen on the surface.
Class I MHC proteins
MHC proteins made by dendritic cells
Functional structure of Class II MHC proteins
Composed of two proteins that form a heterodimer. The antigen binds in the peptide-binding groove.
How do MHC proteins bind peptides?
MHC proteins bind peptides promiscuously but weakly
What type of proteins do activated cytotoxic T cells bind to?
Activated cytotoxic T cells identify infected host cells by looking for antigens bound to Class I MHC proteins
In the human genome, what encodes for MHC genes?
MHC genes are encoded in the HLA complex in the human genome.
Which alleles that encode for MHC proteins are polymorphic?
Alpha and the beta chains of the MHC class II proteins and the alpha chain of the MHC class I protein are most polymorphic
Which type of cells trigger apoptosis of infected cells and cancer cells?
Cytotoxic T cells and Natural Killer cells (NK cells) trigger apoptosis of infected cells and cancer cells
Role of perforin molecules
Perforin molecules form a pore in the membrane of the host cell.
Role of granzyme B in apoptosis
Granzyme B moves through the pore and activates executioner caspases, forcing the host cell to undergo apoptosis.
Macrophages
- Long-lived
- Already present in tissue
- Survive after engaging
Neutrophils
- Short-lived (few hours)
- Recruited to site of infection from blood
- Die via apoptosis during engagement (make up majority of pus)
Two categories of viruses
- Enveloped
- Noneneloped
Packaging of nonenveloped viruses
Viral genome is packaged in a protein coat called capsid
Packaging of enveloped viruses
Viruses with a capsid coat are enclosed within a lipid bilayer
Which type of virus is SARS-CoV-2?
Enveloped
What can receptors be composed of that viruses bind to to enter cells on the host cell?
- Viruses enter cells by binding to receptors on the host cell (can be proteins, but also lipids)
- This can serve as a species barrier if there are differences in the receptor between species
Which type of viruses can sometimes enter a host cell by fusing with the plasma membrane?
Enveloped viruses. An enveloped virus will fuse with the host membrane, uncoat, and be released into the cytoplasm.
Besides fusing with the membrane, what is the alternative way an enveloped virus can enter the host cell?
Endocytosis. After endocytosis, the virus’ own lipid will fuse with the cell’s lipid and allow the genome to be released.
How do viruses leave cells? (enveloped vs nonenveloped)
Nonenveloped viruses usually leave cells by lysing it, enveloped viruses use membrane-based strategies
Which type of virus is more fragile outside the cell?
Enveloped viruses are more ‘fragile’ outside the host because of their lipid coats and hence easier to kill
What type of genetic material are viral genomes composed of?
RNA and DNA
Why don’t dsDNA viruses not need to encode their own DNA polymerase?
A viruses do not necessarily need to encode their own DNA polymerase as they can rely on the host DNA polymerase for their replication. But since DNA polymerase is only expressed during S phase, these viruses often promote the cell cycle (e.g., by inactivating Rb). Consequently, these viruses (e.g., papillomavirus) can promote cancer.
Why would a virus make the host cell enter the cell cycle?
The DNA of the host is only replicated during the cell cycle. The virus must find a way to have the host cell express DNA polymerase by forcing it to enter the cell cycle. Then the virus can use it to make more copies of its own genome.
How is -ssRNA used?
-ssRNA used as a template by RNA-dependent RNA polymerase to make +ssRNA. This +ssRNA can be used for translation, as well as a template for replication to make -ssRNA.
Why do -ssRNA viruses have to bring RNA-dependent polymerase along as part of the viral particle?
Since cells don’t have RNA-dependent RNA polymerases, -ssRNA viruses have to bring this protein along as part of the viral particle
How does +ssRNA get RNA-dependent RNA polymerase?
In contrast, +ssRNA viruses have to encode RNA-dependent RNA polymerase gene but they can make the protein once inside the host.
What additional enzyme do retroviruses have to encode?
Have to encode a reverse transcriptase in their genome.
Three reasons viruses can overcome host’s immune system
- Massive population size
- Rapid proliferation
- High mutation rates
Diversity in humans and chimpanzees vs in viruses
- Human and chimpanzee genomes differ by 1-2% after evolving separately for ~5-8 million years. Polio viruses in a single host acquire this much diversity in about 5 days.
- HIV strains can differ by as much as 30% between different isolates.
Antigenic variation
Diversity of antigens, resulting from evolution of the virus to evade host’s adaptive immune system.