Viral Infections

Front 1

How does viruses infect cells?

Back 1

Virus must enter cells in order to replicate
-To enter the cell, virus must first bind to a receptor on the surface of cell
-Many viruses take over the cells metabolic resources and use the machinery in order to make copies of themselves
-Progeny viruses are released from the first infected cell and then bind and infect a neighbouring cell and the cycle is repeated

Front 2

How does the immune system response to viral infections?

Back 2

Some of the virus particles that enter the body of a host will bind to and infect cells and begin to replicate
-APC cells may phagocytose other virus particles
-B cells that have mIg that recognize epitopes on viral proteins may bind to the virus particles that have entered the lymph node or spleen
-Immune response that develops following a viral infection includes both cell-mediated immunity involving cytotoxic T cells and humoral (antibody) immunity

Front 3

How does cell mediated immunity fight off viruses?

Back 3

-Antibodies can neutralize viruses and prevent them from infecting cells
-Antibodies are very effective against viruses that spend a signficiant amount of time outside of cells
-For exmaple, poliovirus which must migrate through the blood from its initial target cells in the gut to its final target cells in the central nervous system
-However they are not very effective against viruses that quickly infect cells and then remain in that cell for long periods of time (herpes virus)
-In this case cytotoxic T cells are more important
-CTLs kill the viral infected cell and help to eliminate the virus by disrupting its replication cycle

Front 4

In dealing with viruses, when are cytotoxic cells more effective?

Back 4

When dealing with viruses that quickly infect cells and remain in that cell for long periods of time

Front 5

In dealing with viruses when are antibodies most effective?

Back 5

When the virus spends a significant amount of time outside the cell because antibodies are too large to diffuse into cells

Front 6

After a virus has infected a host cell, viral proteins are made in cytoplasm of the host cell as part of the virus replication cycle. What happens next?

Back 6

Some of these proteins are broken down by the proteasome into peptides in the cytoplasm
-The peptides are transported into the ER by the TAP transporter proteins
-In lumen of the ER peptides bind to MHC class I proteins
-Peptide/MHC class I complex is transported to cell surface
-Antigen presneting cells would phagocytose some viruses
-After processing, viral peptides are displayed on MHC class II proteins on the cell surface

Front 7

Then what?

Back 7

T helper cells are activated when TCR binds to viral peptide-MHC II complex of the APC and CD28 binds to the B7 costimulatory molecule
-In early stages of a viral infection, some of the CD4 T cells receieve cytokines from the APCs (IL-12 and IFN-gamma) that direct the T helper cell to differentiate into a Th1 cell
-Th1 cells are important in the activation of CTLs by providing a cytokine called IL-2

Front 8

Then what?

Back 8

CTL-precursors CTL-P are incapable of killing target cells because they do not synthesize granules containing perforin and granzymes
-Perforin forms pores in the membrane of the target cell
-Granzymes are a set of enzymes that initiate apoptosis (programmed cell death) in target cell
-Activation of CTL-P into a functional CTL with cytotoxic activity requires at least three sequential signals
1) Signal transmitted by TCR/CD3 complex after recognition of peptide MHC class I complex on an APC
2) Co sitmulatory signal transmitted by the interaction of CD38 and B7.
3) Il-2 produced by the CTL by activated CTL-P or by activated TH1 cells drive proliferation
Often the amount of IL-2 produced by CTL is not enough to allow for much proliferation. More IL-2 can be provided by the T helper cell

Front 9

Then what?

Back 9

Some of progeny of the CTL-P cells become memory cells
-Others become activated cytotoxic T cells
-activated CTL are ready to kill their targets and require only one signal provided by the recognition of the viral peptide presetned by MHC class I on any infected cell
-The TCR of activated CTL cells bind to cells displaying the same peptide/MHC class I complex sending a signal to the inside of the CTL
-This signal causes the CTL to make both secreted and cell surface proteins that kill the infected cell
-Killing requires cell to cell contact

Front 10

What happens after the killing of an infected cell?

Back 10

THe CTL can release this dead cell and kill other infected cells displaying the same viral petide-MHC clss I complex
-Non infected cells are not killed because they do not have this viral peptide bound to MHC class I protein on their surface
-Killing is antigen specific