Immunotoxicology

Question 1

What are the primary lymphoid organs?

Answer 1

Lymphatic vessels
Thymus
Appendix
Bone Marrow

Question 2

What are the Secondary lymphoid organs?

Answer 2

Tonsils
Lymph Nodes
Spleen
Lymphatic vessels

Question 3

What are the 5 types of leukocyte?

Answer 3

Eosinophil
Neutrophil
Basophil
Lymphocyte
Monocyte

Question 4

What is the function of Eosinophils?

Answer 4

Phacocytotic/Allergy

Question 5

What is the function of Neutrophils?

Answer 5

Bacteriai phacocytosis/Inflammation

Question 6

What is the function of Basophils?

Answer 6

Allergy/Inflammation

Question 7

What is the function of Lymphocytes?

Answer 7

B Cells: Antibody production

T Cells: Cell cytotoxicity

Question 8

What is the function of Monocytes?

Answer 8

Phagocytic/Macrophage precursors

Question 9

What is the difference between Humoral and Cell-mediated Adaptive (acquired) immunity?

Answer 9

Humoral: B cells target EXTRACELLULAR MICROBES with antibodies and are phagocytosed by macrophages

Cell-meidated: T cells target INTRACELLULAR MICROBES by their antigen and release cytokines which activate cytotoxic T cells, causing lysis of the infected cell

Question 10

What are the 5 antibodies?

Answer 10

IgG (most abundant)
IgE (allergies) 
IgD
IgA
IgM (first responder)

Question 11

Which components of the immune system are a target for xenobiotics/toxicants?

Answer 11

All of them

Question 12

Define immunotoxicity

Answer 12

Any adverse effect on the structure or function of the immune system, or on other systems as a result of immune system dysfunction

Question 13

What are the two extremes of immunomodulation and what are the symptoms of each?

Answer 13

Immunosuppresion - Impaired immunity, enhanced susceptibility to infection/neoplasm

Immunoenhancement - Autoimmunity, hypersensitivity (chronic inflammation)

Question 14

What is Azathioprine typically prescribed for?

Answer 14

Rheumatoid arthritis, IBD

Question 15

What is Azathioprine converted into?

Answer 15

6-mercaptopurine

Question 16

How is 6-mercaptopurine cleared from the body?

Answer 16

TPMP methylates it

Question 17

What is the active metabolite of 6-mercaptopurine?

Answer 17

6-thioguanine nuclotides

Question 18

What is the effect of 6-thioguanine nucleotides?

Answer 18

Immunosuppression

Question 19

What is neutropenia?

Answer 19

A low neutrophil count

Question 20

What can cause neutropenia?

Answer 20

Impaired proliferation (eg anticancer drugs)
Cell viability (cytotoxicity)
Can be idiosyncratic or drug induced

Question 21

How can clozapine cause Neutropenia?

Answer 21

Idiosyncratic Drug-Induced Neutropenia (IDIN)
Unpredictable, adverse reaction to drugs
Specific to the individual, impossible to predict

Question 22

How does cigarette smoke cause inflammation?

Answer 22

Bu targeting neutrophils, macrophages and CD8+ cells

Question 23

What are the 3 effects of inflammation in the lungs?

Answer 23

Alveolar wall destruction
Mucous Hypersecretion
Abnormal tissue repair

Question 24

What is an effect cigarette smoke on immune cells?

Answer 24

Decreased phagocytosis

Question 25

The constituents of cannabis (cannabinoids and noncannabinoids) are typically (inflammatory/noninflammatory)

Answer 25

anti-inflammatory

Question 26

Which Cannabinoid receptor is responsible for the anti-inflammatory response?

Answer 26

CB2

Question 27

How does selective CB2 activation cause immunosuppression?

Answer 27

By promoting efferocytosis (ability to clear apoptosis cells)

Question 28

What is a potential mechanism of immunosuppression via cannabinoids?

Answer 28

T-Cell apoptosis

Question 29

What is another name for Halogenated Aromatic Hydrocarbons?

Answer 29

Dioxin-like Chemicals (DLCs) or dioxins

Question 30

How are humans exposed to Dioxins?

Answer 30

(sources: combustion of industry materials) Through air, soil/sediment, water table End up in our food, bioaccumulates in fatty tissue

Question 31

How else are people exposed to dioxins?

Answer 31

Used as herbacide

Question 32

What is TCDD?

Answer 32

A DLC

Question 33

What is an effect of TCDD on humans?

Answer 33

Immune toxicity (Chloracne)

Question 34

What immune organ does TCDD act on?

Answer 34

The Thymus

Question 35

What is the function of the thymus?

Answer 35

Site of T-cell maturation (immature T cells migrate from bone marrow)

Question 36

What does TCDD do to the thymus?

Answer 36

Causes thymic atrophy

Question 37

How does TCDD cause thymic atrophy?

Answer 37

By binding AhR (and many others), translocating into nucleus, and causing Ahr-induced gene battery

Question 38

True/False? Exposure to TCDD alters plasma antibody profile durin influenza infection (in mice)

Answer 38

True, increases mortality rate

Question 39

How did plasma IgG levels differ in people contaminated by Saveso's TCDD accident?

Answer 39

Lower amounts of TCDD

Question 40

True/False? Exposure to TCDD increased the incidence of infectious disease

Answer 40

False

Question 41

What is the underlying cause of most autoimmune diseases?

Answer 41

We don't know

Question 42

What is the putative mechanism of chemical-induced autoimmunity?

Answer 42

1. Toxicant-induced aberrant cell death 2. Covalent binding of now-exposed cellular material to tissue proteins (results in formation of neoantigens 3. Inflammation/tissue injury

Question 43

What is Systemic lupus erythematosus characterized by?

Answer 43

Dysfunction of T cells, B cells, and DC: production of anti-nuclear antibodies

Question 44

What caused Subacute Cutaneous lupus erthyematosus in some cases?

Answer 44

Lamisil (athlete's food)

Question 45

What are the 3 categories of asthma?

Answer 45

Atopic (allergic, extrinsic) Non-Atopic (non-allergenic, intrinsic) Other

Question 46

What is atopic asthma characterised by?

Answer 46

Evidence of allergic sensitization (most common form)

Question 47

What is non-atopic asthma characterized by?

Answer 47

Asthma where there is inflammation of the airways that is not caused by exposure to an antigen Common triggers are viruses and inhaled pollutents

Question 48

What is TDI?

Answer 48

Hi production volume chemical Occupational exposure Most common cause of work-related asthma