Lec 18: Dynamics of Adaptive Immunity part 2

Question 1

B cell memory half life is _____ than T cell memory

Answer 1

more robust - no significant decline vs 8-15 years

Question 2

As pathogen starts to clear, antibodies with ______ will continue to capture antigen and interact with effector TH cells, dominating ______ response

Answer 2

the highest affinity;
secondary and tertiary

Question 3

Original Antigenic Sin

Answer 3

whatever antigens you respond to the first time are the antigens you will respond to the next time you get the virus, even if it has mutated. Your immune system will ignore other epitopes based on the success it had in clearing the pathogen the first time around

Question 4

Recall response to pathogens is based on your _____ infection

Answer 4

first

Question 5

What happens when memory response ineffectively targets the pathogen?

Answer 5

cytokine storm, antibody dependent enhancement

Question 6

Which boosts immunity better - virus first or vaccine first?

Answer 6

Virus first - broader range of epitopes for cross reactive immunity and the subsequent times being exposed to the virus

Question 7

Antibody escape concept

Answer 7

High antibody binding of pathogen does not mean high neutralization of the pathogen

Question 8

How was efficacy of bivalent vaccine?

Answer 8

poor, many breakthrough infections of Omicron because it boosted immunity to original strain but due to original antigenic sin, it ignored Omicron epitopes

Question 9

IL-12p70 is made up of _____ subunits

Answer 9

p35 and p40

Question 10

IL-12 and IL-23 share ____ subunit and their receptors share _____

Answer 10

p40;
IL-12Rbeta1

Question 11

IL-23 is made up of ____ and _____ subunits

Answer 11

p19 and p40

Question 12

IL-12p70 leads to ____ expression and ___ differentiation

Answer 12

STAT4;
TH1

Question 13

IL-23 leads to ____ expression and ____ differentiation

Answer 13

STAT1,3,5;
TH17

Question 14

IL12p70 is critical for __ and ___. Continuous IL12p70 is critical for ____

Answer 14

NK and CTL;
TH1

Question 15

transfer of TH1 memory cells into RAG- and p40- mice leads to protection for ___ mice because they can continue to produce ______

Answer 15

RAG-;
IL-12p70

Question 16

When WT mice and mice that lack MHC class II are infected with ovalbumin antigen, CTL response is ____ in both after 7 days. After 70 days CTL response is only high in ____ mice. Suggesting ____ is required for long term CD8+ function

Answer 16

high;
WT;
CD4 help

Question 17

Expression of ___ determines CD8+ T cell memory response

Answer 17

IL7R

Question 18

transgenic mice with transfer of ILR7___ CD8+ T cells had robust expansion of antigen specific CD8+ T cells

Answer 18

high

Question 19

Establishment of CD8+ memory is dependent on _______. About ____% of cells present at peak persist as memory cells

Answer 19

initial burst;
5%

Question 20

What are important components for long term CTL immunity

Answer 20

• IL7R expression/availability
• antigen expression on MHC I and II
• IL12p70 production and maintenance
• CD4+ help through CD40L
• big burst during primary induction
• removing shutdown mechanisms

Question 21

Tregs produce ___, ____, and ____ which participate in signal 3

Answer 21

TGFbeta, IL2, IL10

Question 22

___ produced by TH2 and ____ produced by Treg inhibit Th1

Answer 22

IL10 and TGFbeta

Question 23

___ produced by TH1 inhibit TH2

Answer 23

IFN-gamma

Question 24

One immune checkpoint is Fas. FasL binds to and ___ Fas. Clustering of __ allows Fas to recruits FADD. Clustered ___ of FADD recruit pro-caspase 8 to initiate apoptosis

Answer 24

trimerizes;
DD (death domains);
DED (death effector domains

Question 25

Immune checkpoint examples

Answer 25

Fas (FasL)
CTLA4 (B.7)
PD-1 (PD-L1)
LAG3 (MHC II)
TIGIT (CD155:PVR)
TIM3 (Galectin-9/HMGB1

KIRs
NKG2A/CD94

Question 26

NKG2A is expressed by ___ cells and is _____ by MHC

Answer 26

NK; inhibited

Question 27

_____ binds to CD80/86, stopping CD28 from binding so T cells don’t get signal 2 and die. antibodies can block this brake so T cells can live longer. Exact mechanism is _____

Answer 27

CTLA-4
unknown

Question 28

____ is a marker of activation in T cells. ITIMS recruit _____ and ______ which are phosphatases for PI3K and ZAP70 (screw up signal 2)

Answer 28

PD-1
SHP1 and SHP2

Question 29

____ is produced by DCs in response to CD4+ help (CD40L)

Answer 29

IL-12

Question 30

____ are effective inducers of primary CTL responses. Basically when pathogen is gone, the only antigen left will be ____

Answer 30

alphaDC1
on DC

Question 31

When HIV viral load spikes, _____ is made responding to first epitopes. With mutations/new epitopes, there is _____ (don’t make new CTL response)

Answer 31

T cell memory;
cross-reaction

Question 32

______ CTL are cross-reactive to natural variants

Answer 32

DC1-primed

Question 33

_____ is priming epitope that make IFNgamma and IL2, which downregulate ___ - shut off mechanism. Variant epitope ____ does not do this

Answer 33

TLN9;
CD8
PLN9

Question 34

Priming peptide TLN9 has CTL ______ DC. Variant peptide PLN9 has CTL______ DC. This initiates cytokine production, but you can’t generate a new ___ response because ____ cells get in the way leading to chronic inflammation

Answer 34

killed
activated
CTL
memory

Question 35

Cross reactive CTL leads to

Answer 35

activation and differentiation of pro inflammatory DC

Question 36

DC based vaccine therapies: take ____ monocytes and stimulate with IL4/GMCSF to generate ___. Add antigen to mature along with TNFalpha, IFNgamma, etc and administer ______ DC

Answer 36

CD14+;
CD14- immature DC;
mature, programmed DC

Question 37

alpha DC1 have been shown to be useful in treatments for ___ and ____

Answer 37

gliomas and melanomas