Immunotoxicity

Question 1

What is immunotoxicity also called?

Answer 1

Immune mediated toxicity

Question 2

What does immunotoxicology involve?

Answer 2

The study of adverse effects on the immune system resulting from exposure to drugs or chemicals

Question 3

What can the adverse effects associated with immunotoxicology affect?

Answer 3

The immune system itself, or lead to non-immune organ damage

Question 4

What are the main lymphocytes?

Answer 4

B cells and T cells

Question 5

What are the main leukocytes (polymorphonuclear granulocytes)?

Answer 5

Neutrophils, eosinophils, basophils

Question 6

What do B cells do?

Answer 6

Produce antibodies and have highly specific receptors for foreign material (antigens)

Question 7

What do T cells do?

Answer 7

Produce cytokines and have highly specific receptors for foreign material (antigens)

Question 8

What are the cellular components of innate immunity?

Answer 8

Macrophages, dendritic cells (DCs), granulocytes, mast cells, NK cells

Question 9

What are the cellular components of adaptive immunity?

Answer 9

T cells and B cells

Question 10

What are the efferent mechanisms of innate immunity?

Answer 10

Cytokine production, inflammatory response, phagocytosis, pathogen killing

Question 11

What are the efferent mechanisms of adaptive immunity?

Answer 11

Antibody production, cytokine production, cell killing

Question 12

What type of immunity has memory?

Answer 12

Adaptive immunity

Question 13

What is the purpose of innate immunity?

Answer 13

Alert other innate and adaptive immune cells to pathogen presence, directly kill pathogen, encourage the development of an adaptive immune response

Question 14

What is the purpose of adaptive immunity?

Answer 14

Assist in efficacy of innate immune response, produce highly specific ligands for pathogens

Question 15

Where are macrophages found?

Answer 15

In tissues all over the body

Question 16

What are Kupffer cells?

Answer 16

Resident macrophages in the liver, largest macrophage population in the body, function is to remove foreign material from portal circulation that streams into the liver

Question 17

What is the duality of macrophages?

Answer 17

Can be protective or cause damage to host tissues, synthesize and release proinflammatory mediators (cytokines, ROS, RNS)

Question 18

What are the mechanisms of damage by macrophages?

Answer 18

NADPH oxidase, NO production, protease release, cytokine release (TNF alpha, IL-1beta/8)

Question 19

What can cytokine release by macrophages signal?

Answer 19

Neutrophil recruitment (cathepsin G, elastase)

Question 20

What is idiosyncratic drug-induced liver injury?

Answer 20

Rare disease that develops independently of drug dose, route, or duration of administration

Question 21

What are preexisting disease states associated with idiosyncratic DILI?

Answer 21

Alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), cirrhosis, autoimmune hepatitis

Question 22

What are examples of drugs that can be involved in idiosyncratic DILI?

Answer 22

Alkylating agents, thioacetamide, acetaminophen

Question 23

What are M1 macrophages?

Answer 23

Macrophages that encourage inflammation via ROS, RNS, chemokines, etc., leading to cytotoxicity and tissue injury

Question 24

What are M2 macrophages?

Answer 24

Decrease inflammation and encourage tissue repair, lead to immune suppression and tissue repair

Question 25

What are causes of immunosuppression?

Answer 25

Chemotherapy, drugs, infections, radiation, autoimmune disease, aging, malnutrition

Question 26

What are examples of immune suppression agents?

Answer 26

Xenobiotic-induced impairment of maturation and development of immune cells, halogenated aromatic hydrocarbons (TCDD)

Question 27

What is the phenotype of immunosuppression?

Answer 27

Pancytopenia, neutropenia, anemia, thymic atrophy/involution, decrease in T cell production, decrease in proliferation, differentiation, cytokine production, cell responses

Question 28

What are the consequences of immunosuppression?

Answer 28

Tumor promotion, opportunistic infections, worsening of underlying conditions

Question 29

What is TCDD?

Answer 29

Dioxin, a halogenated aromatic hydrocarbon that causes a decrease in thymus mass, leading to T cell depletion and less T cell differentiation

Question 30

What receptor is important in immunity and why?

Answer 30

AhR, as thymus has increased expression of AhR, and mice without AhR in thymus are resistant to thymic atrophy caused by TCDD

Question 31

What are PFAS and PFOS?

Answer 31

'Forever' chemicals that can cause a variety of diseases/infections/damage and can reduce antibody formation in response to vaccines

Question 32

What is a proinflammatory Th17 cell?

Answer 32

Stimulates AhR transactivation via binding to transcription factors and stimulating inflammatory agents

Question 33

What do regulatory T cells (Tr1 cells) do?

Answer 33

Encourage stabilization of suppressive activity by lacking inflammatory mediator release

Question 34

What is hypersensitivity?

Answer 34

An exaggerated response by the immune system to a particular substance, part of adaptive immunity

Question 35

What is type 1 hypersensitivity?

Answer 35

IgE mediated hypersensitivity occurring within 1 hour, can lead to anaphylaxis

Question 36

What is type 2 hypersensitivity?

Answer 36

Antibody mediated cytotoxic hypersensitivity mediated via IgG or IgM, cytotoxic, occurring hours to days, can cause hemolytic anemia

Question 37

What is type III hypersensitivity?

Answer 37

Immune complex mediated, occurring 1-3 weeks, associated with serum sickness and systemic lupus erythematosus (SLE)

Question 38

What is type IV hypersensitivity?

Answer 38

T cell mediated (cell mediated), occurring days to weeks, can cause rash or Stevens-Johnson syndrome (SJS)

Question 39

What does protein covalent binding cause?

Answer 39

Immunogen/allergen/antigen formation

Question 40

What is a hapten?

Answer 40

A small molecule that can chemically modify a large molecule to cause antibody production specific to that modified protein

Question 41

What is an antigen in the context of hapten?

Answer 41

The haptenated protein to which antibodies are produced

Question 42

What is an example of an agent that causes hypersensitivity?

Answer 42

Penicillin

Question 43

What are therapeutic drugs causing autoimmunity?

Answer 43

Hydralazine, isoniazid, procainamide, all cause SLE type syndrome (type III hypersensitivity)

Question 44

What is the difference between parent drug and metabolite?

Answer 44

Can be either that interact with leukocytes and cause a response; reactive metabolites can be formed, affecting cellular proteins

Question 45

What is the assessment of immunotoxicity?

Answer 45

Need to extrapolate prior to studying in humans; animal models are being replaced in some industries; machine learning and predictive approaches will accelerate findings

Question 46

What should immunotoxicity consider?

Answer 46

The balance between too little (hypoimmunity) and too much (hyperimmunity)

Question 47

What are some drugs used to treat type I hypersensitivity?

Answer 47

Antihistamines, cromolyn sodium, theophylline, epinephrine, cortisone

Question 48

How do antihistamines work?

Answer 48

Block histamine receptors on target cells

Question 49

How does cromolyn sodium work?

Answer 49

Blocks Ca2+ influx into mast cells and blocks degranulation of mast cells

Question 50

How does theophylline work?

Answer 50

Prolongs high cAMP levels in mast cells by inhibiting PDE, cleaves cAMP to 5'-AMP and blocks degranulation of mast cells

Question 51

How does epinephrine work?

Answer 51

Stimulates cAMP production by binding to beta-adrenergic receptors on mast cells and blocks degranulation of mast cells

Question 52

How does cortisone work?

Answer 52

Reduces histamine levels by blocking conversion of histidine to histamine and stimulates mast cell production of cAMP