Immunotoxicity

Question 1

What is immunotoxicity?

Answer 1

Immunotoxicity is an adverse or inappropriate change in the structure and function of the immune system after exposure to a foreign substance.

Question 2

ADAs?

Answer 2

Antibody drug antibodies

Question 3

What route of adminstration is best for multiple dose?

Answer 3

IV not SC because of more immune cells present in the skin to fight foreign species

Question 4

What types of immunogenicities are there?

Answer 4

Immunosuppressive
Autoimmunity
Hypersensitivity (1-4)
Infusion reaction

Question 5

Type I hypersensitivity is related to?

Answer 5

Anaphylaxis

Question 6

Type II hypersensitivity is related to?

Answer 6

Trombocytopenia

Question 7

Type III hypersensitivity is related to?

Answer 7

Serum sickness

Question 8

Type IV hypersensitivity is related to?

Answer 8

Allergy, DRESS, SJS, TEN and AGEP

Question 9

Infusion reactions can manifest as?

Answer 9

Anaplylaxis, anaphylactoid reactions, cytokine release syndrom

Question 10

How can immunosuppression be induced?

Answer 10

IFN-a treatment → blocking hemtological bone marrow colony-forming units leading to myelosuppression

Question 11

What is autoimmunity associated with?

Answer 11

drug-induced lupus DIL

Question 12

How is Type I hypersensitivity mediated

Answer 12

IgE immediate reaction 2-30 min

Question 13

How is Type II hypersensitivity mediated

Answer 13

IgG and IgM cytotoxic reactions 5-8h

Question 14

How is Type III hypersensitivity mediated

Answer 14

(IgG and IgM) Immune complex-mediated reaction 2-8h

Question 15

How is Type IV hypersensitivity mediated

Answer 15

(T) cell-mediated 24-72h

Question 16

Which hypersensitivities are Ab-mediated and which are Cell mediated?

Answer 16

1-3: Ab-mediated: 1:IgE, 2-3: IgG and IgM
4: T cell-mediated

Question 17

Which hypersensitivity is transient and disappears after treatment?

Answer 17

Type III, serum sickness and Type I DI-lupus

Question 18

Why is Type III hypersensitivity called serum sickness

Answer 18

Ig production against soluble Ag unlike type II hypersensitivity → formation of circulating immune complexes

Question 19

Type III hypersensitivity aka complex-mediated hypersensitivity. What is the mechanism?

Answer 19

Antigens in excess:
Ab-Ag complexes deposited in tissue → classic pathway: release of C3a and C5a → recruiting macrophages and neutrophils → inflammatory damage to tissue

Question 20

Anti-venom drugs can induce what hypersensitivity?

Answer 20

Type III
bcs of foreign protein moiety from another species.
Snake venom is made from horse polyclonal antibodies. Snake venom has many active groups making it less cost-efficient to produce mAbs

Question 21

What hypersensitivity has an induction phase and elicitation phase

Answer 21

Type IV

Question 22

Characterize Drug-induced lupus DIL

Answer 22

Autoimmune manifestation: Abs against self Ag, butterfly rash in face and affect many tissues

Question 23

Core cytokine in CRS?

Answer 23

IL-6, IL-10, TNF-a and IFN-gamma are elevated in patients with CRS

Question 24

IL-6 role in CRS?

Answer 24

Induces positive feed back loop for T cell activation

Question 25

Minimum anticipated biological effect lvl required for biopharmaceuticals MABEL as opposed to No observed adverse effect lvl NOAEL for SOMs. Why is MABEL not used for all drugt?

Answer 25

It requires more time and data (experiments) to determine MABEL

Question 26

Any adverse effects experiences by patients during the infusion (bio)pharmalogic agents or any event occuring on the firsts fay of drug adminstration...?

Answer 26

Infusion-related reactions (IRRs)

Question 27

Examples of IRRs

Answer 27

IgE mediated (Type I/Anaphylaxis) Non-IgE mediated (Anaphylactoid) CRS

Question 28

Low immunogenicity risk?

Answer 28

Native human protein Single dose

Question 29

High immunogenicity risk?

Answer 29

Autoimmune disease The presence of host cell proteins or DNA Aggregates Foreign sequences Duration of treatment Multiple dose