T Cell Immunity

Question 1

Kinetics of a T cell response

Answer 1

• clonal expansion
• Effector response
• Decline (homeostasis)
• memory

Question 2

T cell homeostasis

Answer 2

-needs MHC and IL7 to survive

Question 3

T cell life

Answer 3

• enter lymph nodes across high endothelial venules in cortex
• monitor antigen presented by macrophages and dendritic cells
• if don’t see antigen leave lymph node
• if see antigen-proliferate and differentiate to effector cells

Question 4

T cell accessory molecules

Answer 4

• control routes of T cell migration-selectins, integrins, and chemokine receptors control migration of naive t cells in and out of nodes and of effector and memory t cells to sites of infection
• strengthen adhesion with APCs-integrins, affinity of ingetrins increased by cytokines produced during IF and Ag recognition
• signal transduction-CD4 and CD8 coreceptors recognize MHC, CD28, CD40L are receptors for costimulators expressed on APCs

Question 5

LFA-1 and ICAM-1

Answer 5

• lymphocyte function associated antigen 1
• Intercellular Adhesion molecule 1
• T cells binds APC via LFA1 and ICAM1 interactions
• starts out low affinity, then TCR binds, then increase in affinity by conformational change

Question 6

T cell activation

Answer 6

-needs 2 signals- TCR and costimulation

Question 7

signal 1

Answer 7

• antigen recognition

- ensures that the response is antigen specific

Question 8

-signal 2

Answer 8

• microbes or substances released during innate response to microbes
• ensures that the immune system responds to microbes and not to harmless antigenic substances
• activated APCs express molecules which in turn bind to their respective ligands on T cells to deliver a co stim signal
• needs to be bacteria to activate-which can then show non bacterial protein

Question 9

CD28

Answer 9

-needs to bind to B7 for co stimulation

Question 10

CD28 ligands

Answer 10

B7-1 and B7-2

• in general induction of B7-2 expression follows faster kinetics and usually reaches higher expression levels than the induction of B7-1
• B7-2 is the major initial ligand for CD28, while B7-1 is expressed later and sustains T cell activation

Question 11

B7-1

Answer 11

• CD80

- absent from unstimulated cells (macrophages)

Question 12

B7-2

Answer 12

• CD86

- constitutively expressed at low levels on unstimulated DCs and blood monocytes

Question 13

CD28 isn’t everything

Answer 13

• some T cell responses, from CD8 or deltagamma T cells are CD28 independent
• high avidity responses to certain viruses are CD28 independent
• in the presence of a strong signal 1, CD28 mediated co stimulation is not required
• other costimulatory pathways are possible

Question 14

TH1 cells

Answer 14

• give macrophages 007 and induces B cells to produce opsonizing antibody
• TH1 cell makes IFN gamma, TNFa, CD40 ligand (to bind with CD40 on macrophage), Fas ligand, CM-CSF, IL3, TNFb, CCL2
• bacteria are in macrophage vesicles
• recognizes peptide/MHC class II
• activates infected macrophages
• cell mediated immunity

Question 15

TH2 cells

Answer 15

• respond to B cells with antigens on their antibodies
• tell B cells to turn into plasma cells
• makes IL4,5, CD40 ligand (to bind with CD40 on B cell), GM-CSF, IL3, IL10, TGFb
• pathogens are in extracellular fluid
• peptide/MHC class II on B cell
• humoral immunity-uses TH1 cells as well

Question 16

CTL

Answer 16

• cell mediated immunity
• pathogens in cytosol
• recognizes peptide/MHC class I
• kills cell

Question 17

Stages of CD4 T cell activation

Answer 17

• naive CD4 T cell
• proliferating T cell
• immature effector T cell (TH0)
• differentiates into TH1 or TH2

Question 18

TH1 and TH2

Answer 18

• both need additional help other than CD28
• CD40 is used to tell cells to do their jobs too
• induce a lot of cytokines-see slides

Question 19

killer T cell

Answer 19

• makes Fas ligand to bind with Fas on infected cell

- makes perforin, granzymes, granulysin, IFN gamma, TNF a and b

Question 20

IFN gamma and CD 40 ligand

Answer 20

-activates macrophage to destroy engulfed bacteria

Question 21

Fas ligand for TNFb

Answer 21

-kills chronically infected cells, releasing bacteria to be destroyed by fresh macrophages

Question 22

IL2

Answer 22

-induces T cell proliferation, increasing numbers of effector cells

Question 23

IL# and GM-CSF

Answer 23

-induces macrophage differentiation in the bone marrow

Question 24

TNF a and b

Answer 24

-activates endothelium to induce macrophage binding and exit from blood vessel at site of infection

Question 25

CCL2

Answer 25

causes macrophages to accumulate at site of infection

Question 26

Priming a CTL

Answer 26

• CTL precursors-low frequency, no lytic granules, non-dividing
• naive T cell and APC interactions
• results in:
• proliferation, synthesis of granzymes and perforin
• cytokine production (INF gamma, TNF, Fas L, IL2)
• primary CD8 cells may or may not require CD4 cell help

Question 27

killing mechanisms

Answer 27

• granule exocytosis-predominant pathway (FAST killing)-granzymes and perforin
• expression of cell surface TNF family effector molecules (slow killing)-membrane TNF, lymphotoxin, Fas ligand, Trail
• secretion of soluble toxic cytokines (slow killing) TNF and interferon gamma

Question 28

granule exocytosis

Answer 28

• activation induced re-orientation of granules to site of interaction in T cell
• release of perforin and granzymes
• granzyme B cleaves pro caspases
• induces apoptosis in target cell
• caspase-DNA fragmentation
• mito damage-cyto c release

Question 29

released lytic granules

Answer 29

• dont kill CTL because surface cathespin B protects it

- proteinase inhibitor 9-serpin that inhibits granzyme B expressed by CTL, DCs, endo cells, some tumors

Question 30

shut down of T cell response

Answer 30

• activated T cells express CTLA-4
• leads to functional inactivation
• some cells apoptose
• some cells stay for memory

Question 31

CTLA-4

Answer 31

• binds B7 (on macrophage) instead of CD28 and has higher affinity than CD28
• delivers inhibitory signals to activated T cells

Question 32

other factors for T cell shut down

Answer 32

• elimination of Ag
• elimination of other stimuli
• IL2/IL2R signaling (T regulatory cells grow by IL2 but inhibit it to stop other T cells growing too much)
• killing by immunoregulatory cells (Fas/FasL)