Objectives and Vocabulary for Week # 13 Flashcards
Immune response to viral infection occurs in (at least) 2 stages
1) Innate Immune response (PRR activation, innate cytokine secretion, DC mobilization) 2) Adaptive immune response (priming (activation) in the draining LN (naive T cells and B cells) Effector responses at the site of infection.
Influenza infection
1) Infects the epithelial cells of the respiratory tract (innate cells activated by PRR/DC induced to migrate)
In influenza infection, by what day does IFN-b expression peak?
Day 4 post infection
What cell types are responsible for PRR expression and cytokine secretion in the lung?
CD45 cells (Type II epithelial cells) (DCs, Macrophages)
CD45 Cells
Type II epithelial cells (Macrophages, DCs, neutrophils) ; PRRs 2,3,7 and 9 upregulated during infection; cytokines released IL-6, , TNF-a and CXCL9
CD45- cells
Type I epithelial cells; PRR upregulated TLR3, Rig-I; produces IFNb, IL-6, CXCL9
CD11C+ DC
Specialized DCs in the lungs that migrate out of the lung early in infection. Migrate to the DLN
CXCL9
Chemokine used to recruit effector T cells to sites of infection. CXCR3 is the receptor.
By what day are CD4 and CD8 cells recruited to the lungs during influenza infection?
Day 8-10
What cytokine does CD4 produce in the DLN? In the Lung?
IL-2 in the DLN; IFNg in the lung
By what day do Naive T cells migrate to the lung?
Day 7
Which T cell class is present at higher numbers in the lung during Influenza infection?
CD8 reach and persist at higher numbers that CD4 cells in the lung
Which immunoglobulin class is used for influenza infection? What cytokine influences its derivation?
CD4 cells cause B cells to switch to anti-flu IgG2a antibodies (IFNg); without IFNg, cells switch to IgG1
Highly pathogenic PR8 virus Induces higher_____ secretion in the ______
IFNg; Lung
Which CD4+ subset is required for protection against influenza?
Th1, but not Th2 cells.
Which type of adaBTive immunity is important in Listeria infection?
Cell mediated, but not humoral immunity, is important against Listeria infection.
Which cytokine is important in extracellular Bacterial infections?
IL-17; produced by Th17 cells.
CD8 cell express _______ and can lyse ______ target cells
GrB; peptide pulsed
Immunological memory
Long lasting protection against reinfection with the same pathogen; characterized by increased frequency of cells responding to antigen
B cell memory
characterized by the ability to make higher affinity Ab and higher levels of Ab on second exposure
Naive B cells Vs. Memory B cells
Naive: IgM>IgG; 1:10^4-5; Low affinity; Low SHM Memory: 1:10^2-3; IgG, IgA; high affinity; High SHM
Where are memory B cells generated?
Memory Cells are generated in Germinal centers by Tfh cells.
CD8 T cell memory is ______ while CD4 T cell memory ______
Stable; declines
Differences between Naive and Memory T cells
Memory T cells have different cell surface phenotypes; are less stringent on activation requirements; less dependent on costimulatory signals; express effector cytokines more rapidly; higher volume of adhesion molecules; can be activated by a wider array of APCs (not just DCs);
Linear Differentiation Model
Model of memory T cell generation; states that Memory cells are generated from an effector cell
Bifurcative Differentiation
Model of memory T cell generation; Asymmetrical cell division upon interaction between the DC and T lymphocyte in the DL; Progenitor cell has two pathways 1) Becomes a TCM cell 2) Becomes either an Effector T cell or a TEM cell.
How is immunological memory maintained?
IL-7 and IL-15 signals; IL7R+ CD8 cells have shown to exhibit robust responses.
Trm
T resident memory cells; are retained in tissues without recirculating (in the lung for the case of influenza)
Tem
T effector memory cells; can circulate from tissues to the lymph nodes
Tcm
T central memory cells; reside in the lymphoid organs, but they have differing surface receptor population; naive and Tcm use CD62L and CCR7 to enter and stay in lymph node, but Tcm have high levels of CD44/
CD44
Distinguishes effector and memory T cells from naive cells; naive cells do not have CD44
What markers are on the surface of CD8+ Effector cells?
IL-2Ra; KLRG1
Which surface markers are present on memory like cells?
IL-7R,CD44 and CXCR3
Which transcription factors are important for CD8+ effector T cell differentiation?
T-bet, Blimp-1
What transcription factor is important for CD8+ memory T cell differentiation?
Eomes
In asymmetric division, which cell becomes the effector cell? memory cell?
Proximal daughter cell; distal daughter cell
What cytokines are important in inducing perforin and granzymes in CD8+ effector cells?
IL-2; IL-12; IFNg; IL-27`
How does the chromatin structure compare in effector cells vs. memory-like cells?
Chromatin is open and on in effector stages; Chromatin is closed and off in memory like cells.
What cell type is required for CD8+ memory responses to viral infection?
CD4 cells are required for CD8+ memory cell responses, but the primary responses are not effected.
What receptor is required for CD8+ memory responses?
IL-7R+
What cytokines are responsible for the maintence of CD8+ memory cells?
IL-7 and IL-15
How do T cells provide defense against infections?
CD4+ T cells Activate phagocytes through the actions of CD40L and IFNg (activation of microbes); CD8+ kill infected cells
How do Th1 cells defend against infection?
Th1 cells differentiate into such, by interaction with IL-12 and IFNg; They then express CD40L and secrete IFNg, which helps macrophages produces ROS, NO and lysosomal enzymes.
What cytokines induce Th17 production? What type of pathogens do Th17 cells combat?
IL-6 and IL-23; combat against extracellular pathogens, fungal and bacterial
What are the principal innate mechanisms against viruses?
Inhibition of infection by Type I interferons and NK cell mediated killing of infected cells; recall interferons block viral replication, and NK cells notice abnormalities in MHC I molecules, thus activating them.
TRM
Tissue Resident Memory Cells; express high levels of CD103, and GrB
