Well uh I'd assume that uh we have a 2nd MST

Question 1

what is the purpose of immune therapy

Answer 1

reprogram immune system to recognise and kill disease

Question 2

what is the purpose of cancer vaccines

Answer 2

increase immunogeniciy of cancer in host

Question 3

what are prophylactic vaccines

Answer 3

block infection of oncotic viruses
examples is hpv

Question 4

what are theraputic vaccines

Answer 4

stimulate response against tumour and disease
examples are inactivated tb for bladder cancer

Question 5

what is adoptive cell therapy and what are the types

Answer 5

isolating t cells from tumour or blood samples, then activated, proliferated EX-VIVO, and delivered into patient
TIL therapy, tcr t cell therapy, car-t therapy,

Question 6

what is til therapy

Answer 6

tumour infiltrating lymphocyte
lymphocytes (B, NK, Cd4 and 8), taken out, and proliferated using Il-2
no genetic engineering

Question 7

what is tcr t therapy

Answer 7

engineered to recognise tumour ag ex vivo
yes genetic engineering

Question 8

what is car-t therapy

Answer 8

t cells from blood, synthetic chimeric ag receptors (with single chain variable fragment, receptors contain extracellular ag recognition domain) added to t cells ex vivo
yes genetic engineering
can cause cytokine release (il-6)

Question 9

what can monoclonal ab do?

Answer 9

opsonise tumor cell ag, allow nk recognition and death by nk or adct
bind to tumour with toxins, causes their death (can cause off target toxicity if tumour ag is on healthy cells)
inhibit function of signalling receptors

Question 11

How do b and T cells come into contact in the ln

Answer 11

B cells stay in follicle by expressing cxcr5 (attracted to cxcl13), after activation express ccr7 to move to paracortex (ccl19/21)
T cells after activation and differentiation by dcs into tfh express cxcr5

Question 12

How are b cell responses optimised

Answer 12

Affinity maturation and isotope switching In germinal centre to produce more specific abs and better suited abs

Question 13

Describe affinity maturation

Answer 13

Somatic hypermutation
Aid/ activation induced cytidine deaminase expressed on b cells cuts c… ring and deaminates it into uridine
Point mutation has downstream effects and alters b cell affinity
B cells with high affinity for ag presents ag to tfh, cd40/40l interaction to promote survival

Question 14

Describe isotype switching

Answer 14

Aid/ activation induced cytidine deaminase expressed on b cells allows vh exon to be expressed with diff ch genes, also regulated by dna switch regions upstream of constant regions
Aid forms rosettes, splices them out, leaving the m,g,e,d, or a switch regions Aid forms

Question 15

How do cytokines released by tfh influence isotype switch

Answer 15

Il-4 gets you Ige and IgG
Ifn-y gets you 2 forms of IgG

Question 16

What are the direct secretory ig effector functions

Answer 16

Neutralisation, iga and and g bind to antigen through fab

Question 17

how do soluble ig move

Answer 17

Polymeric ig receptor binds to fc region of dimeric iga and some igm, transports it to epithelial barrier from basal to muscosal layers/surfaces
Neonatal fc receptor carries IgG across placenta into fetal circulation and prevents IgG excretion from body

Question 18

How are immunoglobulins transported

Answer 18

Polymeric ig recep

Question 19

How is IgD developed

Answer 19

RNA splicing according to the notes

Question 20

What happens if there is no rna splicing in b cell development

Answer 20

PAs/Poly A tail sequence remains, means it is likely secretory igg

Question 21

What happens if there is rna splicing in b cell development

Answer 21

PAs removed pAm (membrane anchor) remains, becomes membrane IgG

Question 22

Immunological memory forms predominantly from CD4 or CD8 T cells?

Answer 22

CD8, they said CD4 is understudied and as keit like to always say “i don’t know”

Question 23

What do activated CD8 T cells release in response to recognising tumour antigens?

Answer 23

release TFNy: ↓tumour proliferation ↑MHC on tumour cells ↑T cell proliferation

TNFa: ↑ inflammation to recruit more immune cells + induce apoptosis

Question 24

Explain the 2 possible initial differentiation pathways of CD8 T cells

Answer 24

depending on the amount of inflammation in the environment

CD8 T cells will either become:

effector T cells (high inflammation ie. IL12 which down regulates IL7R and upregulates T-bet)

OR

memory T cells (low inflammation ie. IL12 which upregulates IL7R and Eomes), this pathway requires IL15!

NOTE: THE TBET AND EOMES!

Question 25

Explain the 3 possible memory T cell differentiation pathways

Answer 25

CIRCULATING: Tem (effector memory) - provides immediate effector function upon restimulation Tcm (central memory) - provides long-lived recall response IN TISSUE: Trm (tissue-resident memory) - provides long-lived and immediate effector function within tissue - very important for inducing long term cancer dormancy

Question 26

what are the 3 possible 'postcodes' following activation which we have been taught?

Answer 26

inflammation = T cell upregulates CXCR3 and is drawn to CXCL9/10/11 at inflamation site skin = vitamin D presented to T cells via DCs, causes increased CCR10, CR4, P&E selectin drawing them to skin gut - vitamin A presented to T cells via DCs, causes increased a4b7 and CCR9 drawing them to the gut

Question 27

What are the key interactions between T and B cells at the border which kickstarts the 'better' B cell response?

Answer 27

T/B cells interact at the border of LN/spleen via 3 key signals: TCR/MHC2+antigen: confirms specificity between T/B cell CD40L/CD40: co-stimulation (notice how this differs to T cells which use CD28/CD80/86) ICOS/ICOSL: supports B cell activation by upregulating Bcl-6 in B cells !!!

Question 28

explain how B cell memory is generated

Answer 28

these interactions at the T/B border stimulate the B cells to differantiate into a few cells and form the primary foci: (predominantly) plasmablasts - shorted lived IgM only, plasma cells (travel to BM and are long lived), and memory B cells as the primary foci becomes the germinal centre, the plasma and memory B cells will become more prominant rather than plasmablasts (ie. more memory) At any point following the T/B interactions, B cells can become memory B cells of varying specificity.

Question 29

describe what happens in the mantle zone and germinal zone of the germinal centre

Answer 29

mantle zone = Tfh and B cell interaction germinal zone has 2 sections: light zone = centrocytes, less proliferation more surface Ig, mutations made in dark zone are tested via CD40/40L on FDCs, class switching initiated by AID enzyme dark zone = centroblasts, lots of proliferation, somatic hypermutation facilitated by AID enzyme

Question 30

What do TH1, 2, and 17 secrete? what pathogens are they particularly good against?

Answer 30

TH1: IL2, TNFa, IFNy via T-Bet - intracelluar bacteria/virus TH2: IL4, IL5, IL13 via GATA3 - parasites TH17: IL17, IL22 via RORyt - extracellular bacteria/fungi

Question 31

what are the consequences of constant immune pressure on a genetically unstable tumour?

Answer 31

Ideally equilibrium of the tumour cells as they are under constant pressure from CD8 and NK cells releasing INF-gamma and IL-12

Question 32

what are the main factors that cause a tumour to move form an equilibrium phase to escaping the immune defences?

Answer 32

- the tumour is no longer recognised by the adaptive immune system -the tumour cells become insensitive to immune effector mechanisms -the tumour microenvironment induces an immunosuppressive state

Question 33

what are tumour-specific antigens?

Answer 33

antigenic peptides presented by MHC I markers that are solely found on cancerous/ tumour cells and no other cells

Question 34

what are tumour-associated antigens?

Answer 34

antigenic peptides presented on MHC I markers that are either: - reactivated embryonic genes not normally expressed on cells -over-expression of self peptides causing T cell recognition

Question 35

explain the escape mechanism of LOW IMMUNOGENICITY

Answer 35

it is the failure to properly activate T cells due to the lack of MHC, adhesion and co-stimulatory molecules on the tumour cell surface, therefore leading to a lack of TILs so little to no mounted immune response 'hiding from the immune system by switching off their visibility to T cells'

Question 36

explain the escape mechanism of TUMOUR TREATED AS SELF ANTIGEN

Answer 36

lack of co-stimulatory signals expressed by the APCs presenting the tumour antigens to T cells may cause a failed response/ lead to tolerance -> treatment of tumour as self

Question 37

explain the escape mechanism of ANTIGENIC MODULATION

Answer 37

it is a mechanism whereby T cells are able to recognise some immunogenic antigens produced by the rapidly mutating tumour cells, but due to the TAA heterogeneity and downregulaiton of MHC molecules on some tumour cells, they are able to escape the immune response. 'creates too many too soon for the immune cells to control'

Question 38

explain the escape mechanism of TUMOUR-INDUCED IMMUNE SUPPRESSION

Answer 38

it is a mechanism whereby the tumour cells produce cytokines (TGF-b and IL-10 to recruit Tregs) enzymes (IDO - starve the T cells, tilting the balance towards tolerance) and express cell surface proteins (PD-L1) in order to create an immunosuppressive environment allowing them to escape

Question 39

explain the escape mechanism of TUMOUR-INDUCED PRIVILEGED SITE

Answer 39

it is where tumour cells induce/ secrete stromal cells or cells with a stromal composition as they have immunological properties, to form a region with vascularisation and therefore nutrients safe from immune cells. Thus the tumour cells recruit and form their own little happy place with all they need allowing them to proliferate without being attacked by the immune system. 'they form a immune privileged site'

Question 40

what are the three symptoms of T cell exhaustion

Answer 40

- low cytokine production (IFN-gamma, TNF-a) - decreased cytotoxicity (granzymes/preforins dysfunction) - poor proliferative capacity

Question 41

memory B cells vs long lived plasma cells?

Answer 41

- Memory B cells can be created at many stages during the B cell response - 'complete' B cell response produces long lived plasma cells (different to Bm cells Long lived plasma cells produce highly specific antibodies to the antigen. If the antigen mutates its GG bro. This is where Bm creation at many stages comes in clutch because they can recognize broader ranges of antigens

Question 42

What is tolerance? what are the 4 methods in which we maintain tolerance?

Answer 42

tolerance is not reacting to self antigens it is maintained by: deletion, anergy, inhibition, and ignorance

Question 43

describe the intrinsic and extrinsic pathways of apoptosis/deletion within tolerance

Answer 43

extrinsic = Fas/FasL > recruitment of death domain > caspase activity > apooptosis intrinsic = Lack of IL2/7 > upreg of p53 > protectors inhibited and executionerrs activated > apoptosis

Question 44

describe the anergy pathway within tolerance

Answer 44

anergy = long lived state of low proliferation + cytokine production weak signaling to T cells w/o co-stimulation > disrupts LAT pathway > T cell activation & signalling reduced

Question 45

describe the two inhibition pathways within tolerance

Answer 45

CTLA4 competitively binds CD80/86 > stops CD28 (on T cell) from binding it. IE. decreases co-stimulation OR PD-1 (on T cell) binds to PD1L (on APCs) > activation of ITIM in T cell > reduced T cell signaling, proliferation and possibly even cell lysis

Question 46

describe the two way which tolerance can be broken

Answer 46

1. molecular mimicry - pathogen is engulfed, processed, and presented by DCs to immune cells. However, the peptide it presents looks similar to other self antigens so we prime against ourselves 2. alloreactivity - Direct Allorecognition: Recipient T cells recognize intact donor MHC on donor APCs. - Indirect Allorecognition: Recipient APCs process donor MHC molecules and present donor peptides on self-MHC to T cells.

Question 47

Describe T reg generation pathways

Answer 47

Thymic = CD4+ on the cusp of negative selection in the prescence of IL2 > upregulation of Foxp3 = Foxp3+tTreg Peripheral = Foxp3-CD4 encounters RA (secreted by DCs), TGFb, and IL2 > Foxp3+iTreg OR if DC is activated by TLR can secrete IL6, which in combination with TGFb can stimulate TH17 (inflammatory)

Question 48

describe the 4 effector functions of antibodies

Answer 48

1. Neutralization: IgG/IgA can bind antigens via (variable) Fab region 2. Opsonisation: Fab region binds to pathogen, macrophages bind to the Fc regions sticking out causing crosslinking and phagocytosis. 3. antibody-dependent cell-mediated cytotoxicity: the exact same as opsonisation but just NK cells instead of macrophages 4. degranulation (sensitisation): antibodies bind mast cells via Fc region, easily crosslinked by pathogens in future

Question 49

How do antibodies cross membrane to infiltrate deep into tissues?

Answer 49

polymeric immunoglobulin receptors OR neonatal Fc receptors

Question 50

If we have Long-lived plasma cells in the BM, why do we need B memory cells?

Answer 50

LLPC produce Ab constitutively at relatively low amounts. If infection gets out of control Bm can be activated go to germinal centres make more plasma cells and undergo affinity maturation and help produce lots of Ab with good specificity. IE back reservoir of Ab.