Objectives and Vocabulary for Week # 13

Question 1

Immune response to viral infection occurs in (at least) 2 stages

Answer 1

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.

Question 2

Influenza infection

Answer 2

1) Infects the epithelial cells of the respiratory tract (innate cells activated by PRR/DC induced to migrate)

Question 3

In influenza infection, by what day does IFN-b expression peak?

Answer 3

Day 4 post infection

Question 4

What cell types are responsible for PRR expression and cytokine secretion in the lung?

Answer 4

CD45 cells (Type II epithelial cells) (DCs, Macrophages)

Question 5

CD45 Cells

Answer 5

Type II epithelial cells (Macrophages, DCs, neutrophils) ; PRRs 2,3,7 and 9 upregulated during infection; cytokines released IL-6, , TNF-a and CXCL9

Question 6

CD45- cells

Answer 6

Type I epithelial cells; PRR upregulated TLR3, Rig-I; produces IFNb, IL-6, CXCL9

Question 7

CD11C+ DC

Answer 7

Specialized DCs in the lungs that migrate out of the lung early in infection. Migrate to the DLN

Question 8

CXCL9

Answer 8

Chemokine used to recruit effector T cells to sites of infection. CXCR3 is the receptor.

Question 9

By what day are CD4 and CD8 cells recruited to the lungs during influenza infection?

Answer 9

Day 8-10

Question 10

What cytokine does CD4 produce in the DLN? In the Lung?

Answer 10

IL-2 in the DLN; IFNg in the lung

Question 11

By what day do Naive T cells migrate to the lung?

Answer 11

Day 7

Question 12

Which T cell class is present at higher numbers in the lung during Influenza infection?

Answer 12

CD8 reach and persist at higher numbers that CD4 cells in the lung

Question 13

Which immunoglobulin class is used for influenza infection? What cytokine influences its derivation?

Answer 13

CD4 cells cause B cells to switch to anti-flu IgG2a antibodies (IFNg); without IFNg, cells switch to IgG1

Question 14

Highly pathogenic PR8 virus Induces higher_____ secretion in the ______

Answer 14

IFNg; Lung

Question 15

Which CD4+ subset is required for protection against influenza?

Answer 15

Th1, but not Th2 cells.

Question 16

Which type of adaBTive immunity is important in Listeria infection?

Answer 16

Cell mediated, but not humoral immunity, is important against Listeria infection.

Question 17

Which cytokine is important in extracellular Bacterial infections?

Answer 17

IL-17; produced by Th17 cells.

Question 18

CD8 cell express _______ and can lyse ______ target cells

Answer 18

GrB; peptide pulsed

Question 19

Immunological memory

Answer 19

Long lasting protection against reinfection with the same pathogen; characterized by increased frequency of cells responding to antigen

Question 20

B cell memory

Answer 20

characterized by the ability to make higher affinity Ab and higher levels of Ab on second exposure

Question 21

Naive B cells Vs. Memory B cells

Answer 21

Naive: IgM>IgG; 1:10^4-5; Low affinity; Low SHM Memory: 1:10^2-3; IgG, IgA; high affinity; High SHM

Question 22

Where are memory B cells generated?

Answer 22

Memory Cells are generated in Germinal centers by Tfh cells.

Question 23

CD8 T cell memory is ______ while CD4 T cell memory ______

Answer 23

Stable; declines

Question 24

Differences between Naive and Memory T cells

Answer 24

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);

Question 25

Linear Differentiation Model

Answer 25

Model of memory T cell generation; states that Memory cells are generated from an effector cell

Question 26

Bifurcative Differentiation

Answer 26

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.

Question 27

How is immunological memory maintained?

Answer 27

IL-7 and IL-15 signals; IL7R+ CD8 cells have shown to exhibit robust responses.

Question 28

Trm

Answer 28

T resident memory cells; are retained in tissues without recirculating (in the lung for the case of influenza)

Question 29

Tem

Answer 29

T effector memory cells; can circulate from tissues to the lymph nodes

Question 30

Tcm

Answer 30

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/

Question 31

CD44

Answer 31

Distinguishes effector and memory T cells from naive cells; naive cells do not have CD44

Question 32

What markers are on the surface of CD8+ Effector cells?

Answer 32

IL-2Ra; KLRG1

Question 33

Which surface markers are present on memory like cells?

Answer 33

IL-7R,CD44 and CXCR3

Question 34

Which transcription factors are important for CD8+ effector T cell differentiation?

Answer 34

T-bet, Blimp-1

Question 35

What transcription factor is important for CD8+ memory T cell differentiation?

Answer 35

Eomes

Question 36

In asymmetric division, which cell becomes the effector cell? memory cell?

Answer 36

Proximal daughter cell; distal daughter cell

Question 37

What cytokines are important in inducing perforin and granzymes in CD8+ effector cells?

Answer 37

IL-2; IL-12; IFNg; IL-27`

Question 38

How does the chromatin structure compare in effector cells vs. memory-like cells?

Answer 38

Chromatin is open and on in effector stages; Chromatin is closed and off in memory like cells.

Question 39

What cell type is required for CD8+ memory responses to viral infection?

Answer 39

CD4 cells are required for CD8+ memory cell responses, but the primary responses are not effected.

Question 40

What receptor is required for CD8+ memory responses?

Answer 40

IL-7R+

Question 41

What cytokines are responsible for the maintence of CD8+ memory cells?

Answer 41

IL-7 and IL-15

Question 42

How do T cells provide defense against infections?

Answer 42

CD4+ T cells Activate phagocytes through the actions of CD40L and IFNg (activation of microbes); CD8+ kill infected cells

Question 43

How do Th1 cells defend against infection?

Answer 43

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.

Question 44

What cytokines induce Th17 production? What type of pathogens do Th17 cells combat?

Answer 44

IL-6 and IL-23; combat against extracellular pathogens, fungal and bacterial

Question 45

What are the principal innate mechanisms against viruses?

Answer 45

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.

Question 46

TRM

Answer 46

Tissue Resident Memory Cells; express high levels of CD103, and GrB