Antibodies therapies

Question 1

How are t-cells different than b-cell repertoire in terms of maturation?

Answer 1

T-cells don’t have affinity maturation, they are born with the same potential repertoire

Question 2

What are the effector functions of t-cellS?

Answer 2

Kill cells through cytotocity or cytokines or recruit other immune cell types to kill the cells

Question 3

What do b-cells do when they meet an antigen and how?

Answer 3

Recognize conformation determinants with the antibodies on their surface that are specific, they develop affinity maturation when producing more antibodies

Question 4

Effector functions of b-cells?

Answer 4

Opsonization, neutralization, complement activation and ADCC

Question 5

What are antibodies made up of? What links them? How many antigen binding sites?

Answer 5

variable region and constant regions that are made up two heavy chains and two light chains. Disulphide bonds
2 antigen binding sites

Question 6

What happens when they don’t add reducing agent with papain what happens?

Answer 6

There is more fragments in the constant regions compared to adding reducing agent

Question 7

What is the importance of FC regions?

Answer 7

They give the antibody it’s class

Question 8

What’s the first antibody b-cells produce?

Answer 8

IGM and IgD

Question 9

What does class switch depend on?

Answer 9

The strength of signal

Question 10

What are the structural differences between IGA, IGM, IGE,IGG? Where is the IGA found?

Answer 10

IGM-pentameric
IGE,IGG-monomeric
IGA-dimeric mucous

Question 11

Which antibodies are good at activating complementation?

Answer 11

IGG,IGM

Question 12

What is the half life of antibodies?

Answer 12

10-20 days

Question 13

What is IGE good at activating?

Answer 13

High affinity to basophils and mast cells

Question 14

How do b-cells affinity mature?

Answer 14

The antibody that binds to antigen it’s strength depends on the activation of b-cells and if re-encounters the antigen it will mutate it’s binding site and the antibodies with the best affinity binding are selected for

Question 15

What does the interaction between the epitope and antigen depend on?

Answer 15

Electrostatic forces, van der waals, hydrogen bonds,shape, hydrphobic forces

Question 16

What is the tradeoff between multimeric and monomeric antibody structure? What is it good for?

Answer 16

Affinity and how easily it transports.

Binds to multiple antigens

Question 17

How are antibodies made?

Answer 17

T helper cells bind to b-cells after it binds to antigen and the t-cell secrete cytokines that makes b-cells to be activated and release antibodies

Question 18

What are thibgs to consider when targetting tumour?

Answer 18

Unique epitope

Overexpression of antigens on tumour cells and less on normal cells

Question 19

How do b-cells mature?

Answer 19

They bind to t-cells and t-cells secret IL-4, which makes them proliferate, they also express CD40L which allows the b-cells to class switch through somatic hypermuation, then the b-cell mature and produce plasma antibody secreting cells and memory cells

Question 20

Which isotype class do TH1 and TH2 induce and what cytokines?

Answer 20

th1-IGG2A and IGG3 by ifn-gamma and TGF-b

TH2-IGG1 and IGE by il-4

Question 21

What are ethe different pathways that activate complementation pathway?

Answer 21

Classical-antibidy- antigen complex
alternative pathway-pathogen surface
lectin pathway-lectin opsonize the surface of pathogen

Question 22

Explain complementation

Answer 22

So soluble c2-c4 cascade of cleavage will activate and recrut the next c protein in the cascade. C3 convertase can mediate inflammation via c3A, and c5a or it can induce killing through recruiting C5-C9 sequentially they form a membrane bound pore and depolarize until cell dies. It can opsonize just by c3 convertase and C3B binding to complement receptor on phagocyte

Question 23

What do CD16, CD32, CD64 and fceRI fcar do? Where are they found?

Answer 23

CD16- is activating induces killing, found on macrophage, mast cells, natural killer cells, neutrophils.
CD32-inhibition if the uptake of signalling, found on macrophage, mast cells and b-cells
CD64-activating of killing, and uptake of signalling. Found on dendritic cells and macrophage
fceRI-binds to IGE secrete granules
fcar-bind to IgA and IgM uptakes them to different tissues

Question 24

How does opsinization work?

Answer 24

C3B binds to complement receptor on the bacteria and antibody also binds to the surface of bacteria, while the antibody recognizes the FC receptor on the macrohphage and binds to, C3B will bind to cR1 on the surface of the macrophage and then the antibody with the bacteria is engulfed and lysed with lysosomes

Question 25

How does ADCC work?

Answer 25

The antibodies bind to the antigens on the cell surface of pathogen and binds to FC receptors(CD16) on NK cells and they release signals that killthe cells

Question 26

What are other fc mediated responses?

Answer 26

Inflammatory responses, phagocyte recruitment

Question 27

What is the difference between active immunization and passive?

Answer 27

Active- administer immunogen | Passive-create anti-bodies in vitro and adminester it inot patients

Question 28

What are the pros and cons in active immunization?

Answer 28

Low cost, polyclonal Difficult to control response Difficult to target self antigen

Question 29

What are the pros and cons in passive immunization?

Answer 29

Its expensive very few good tumour antigen | Very reproducible and good response to self antigens

Question 30

What are some alternative solutions?

Answer 30

Chimeric antibodies transgenic animals human monoclonal antibodies(plasmacytoma and immunize humans)

Question 31

Give examples of monoclonal antibodies being used to treat cancer

Answer 31

Avastin-neutralizes VEGF used to treat CRC Retuximab- Activate the complement pathway and bind to NK cells Pantimumab-Targets HER1 it blocks growth factor receptor and induces apoptosis

Question 32

What are the mechanisms of actions of antibody therapies

Answer 32

adcc Complement mediated lysis neutralization apoptosis

Question 33

What are other approaches in cancer therpay?

Answer 33

Rdiotherapy-less toxic antibody drug conjugates-gets cleared quickly but reduces toxicity Prodrug toxin targeting

Question 34

What rae the positives and negatives of radioimmunotherapy?

Answer 34

Gets cleared quickly, biodistribution, number of cells binding to antibody less toxic to normal cells

Question 35

Positives and negatives of antibody drug conjugates. What is an example what did it bind to?

Answer 35

``` Less toxic to normal cells heterogenity of response of tumour number of drug per cell for killing number of cells binding to AB mylotarg to CD33 on leukimia cells ```