Lecture 15 and 16: Immunopharmacology

Question 1

Rheumatoid arthritis

Answer 1

autoreactive T cell and antibodies against antigen localized to joint synovium
joint inflammation and destruction

Question 2

Transplant rejection

Answer 2

difference in MHC between donor and recipient
results from unwanted immune response

Question 3

Corticosteroids

Answer 3

decrease production of inflammatory cytokines
increase production of IL-10 in some cases
broadly immunosuppressive
dirty drug

extreme changes in transcriptional activity
prevent NF-kB nuclear translocation, no inflammatory cytokines
have anti-inflammatory cytokines

Question 4

-omab

Answer 4

fully mouse
recognized as foreign in human

Question 5

-ximab

Answer 5

chimeric

Question 6

-zumab

Answer 6

humanized (not 100% human)

Question 7

-umab

Answer 7

fully human

Question 8

2 strategy to use mAbs to treat autoimmune disease

Answer 8

1. destroy T-cells by binding an antibody that can be recognized by Nk cell Fc receptor
2. block IL-2 receptor signalling, reduce T-cell activation

Question 9

Muromonab-CD3

Answer 9

first monoclonal antibody (mouse IgG2 isotype) approved for use in humans
extremely potent immunosuppression
Binds to CD3 and cause clustering activation
T-cell activation initially
later cause internalization of muromonab CD3:CD3 complex

useful in organ transplant, can cause cytokine release syndrome

Question 10

Basiliximab

Answer 10

human IgG1 isotype
antagonist of alpha subunit of IL-2 receptor
prevent maturation of T-cells
reduce antibody production from B-cell because reduce CD4 T-cells

Question 11

Infliximab, adalimumab, golimumab

Answer 11

Anti-TNFa
binds to TNFa directly, not receptor
broadly immunosuppressive

Question 12

Tumor infiltrating lymphocytes (TIL)

Answer 12

more = hot tumor, higher survival, better disease prognosis in anti-cancer therapies
less = cold tumor, less survival

Question 13

Imiquimod

Answer 13

TLR7 (endosomal) agonist
cause NF-kB cytokine genes transcription
induce local inflammation

Question 14

Traztuzumab

Answer 14

against HER2
highly expressed on breast cancer
recruit NK cell through Fc receptor (CD16) clustering

Antibody-drug conjugate deliver Mertansine (toxic payload) to cancer cell that express HER2

Question 15

Rituximab

Answer 15

treats autoimmune disease
against cell surface protein CD20 (highly expressed on B-cell)
cause NK cell directed cancer cell lysis

Question 16

2 Immune checkpoint receptors

Answer 16

CTLA-4 and PD-1
CTLA-4 inhibit CD40
PD-1 binds to PD-L1

Question 17

Bispecific antibody

Answer 17

link T cell and tumor cell to enforce interactions

Question 18

Etanercept

Answer 18

chimeric protein that binds to TNF-a and inactivates it
fusion to Fc greatly improves half-life

Question 19

CAR-T cell therapy

Answer 19

engineered T-cell to bind to cancer biomarker to induce killing
can cause cytokine release syndrome (CRS)
give Tocilizumab to prevent binding of IL-6
decrease global inflammation allow patient to recover

Question 20

Adjuvants

Answer 20

provided in vaccines to induce innate immune response (initiate antigen presentation)

Question 21

mRNA vaccines

Answer 21

mRNA codes for antigen (spike protein)
stimulate immune response
mRNA acts as both adjuvant and antigen

Question 22

3 steps to initiate innate immunity

Answer 22

1. LPS (PAMPs) binds to TLR
2. clustering of TLRs
3. Activate NF-kB and rapid production of cytokines

Question 23

TNFa and CXCL8 (IL-8)

Answer 23

released by macrophages
instruct neutrophils to extravasate and enter site of infection

Question 24

Function of TNFa

Answer 24

induce ICAM-1 expression
increase vascular permeability

Question 25

Function of neutrophils

Answer 25

Phagocytosis ROS inside neutrophils destroy engulfed pathogens

Question 26

Function of dendritic cells

Answer 26

Uptake antigen and load on MHC-II at site of infection travels to lymph nodes and mature into professional antigen presenting cells (APCs) PAMPs provide 'mature and present this' signal

Question 27

3 signals for T-cell activation

Answer 27

1. recognizes antigen presented on MHC 2. requires costimulation from CD28 (T-cell) to CD80/86 (DC) 3. cytokines produced by dendritic cells catalytic (single DC can activate many T-cells)

Question 28

8 steps in T-cell signalling cascade that leads to T cell differentiation

Answer 28

1. T-cell activation 2. CD3 activation 3. Ca2+ influx 4. activates calcineurin 5. activates NFAT 6. promotes IL-2 transcription 7. activates mTOR 8. T-cell differentiation (mature)

Question 29

CD4+ T-cells

Answer 29

helper T-cell help other cell mount immune response, binds to MHC-II

Question 30

CD8+ T-cells

Answer 30

cytotoxic T-cell kill cell directly MHC-I restricted

Question 31

Th1 cells

Answer 31

release IFN-gamma promote macrophage activation and pathogen killing

Question 32

Th2 cells

Answer 32

activate granulocytes such as basophils and eosinophils against helminths

Question 33

Th17 cells

Answer 33

release IL-17 combat bacteria and fungi

Question 34

Tregs

Answer 34

release IL-10 and TGF-B antigen-specific immunosuppression

Question 35

CD4 T-cells and B cells

Answer 35

B-cell presents antigen to CD4 T-cells CD4 T-cells promote B cell differentiation into plasma cells leading to antibody production memory cells too

Question 36

CD16 (receptor) on NK cells

Answer 36

binds to Fc region of antibody cause clustering of CD16 initiate killing through the release of cytotoxic material (ADCC)

Question 37

IgG 1-4

Answer 37

neutralization: All IgG opsonization: 1,3 /low in 4 NK cell activation: 1 and 3 half life: 1,2,4 similar / 3 short half life