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The immune system and toxic effects Flashcards

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1
Q

What is immunotoxicology?

A

The study of adverse effects on the immune system resulting from exposure to drugs, environmental chemicals, and biological materials

Immunotoxicology examines how these exposures disrupt immune function.

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2
Q

What are the components of the immune system?

A

Lymphoid organs, cellular populations, and soluble factors

These components work together to provide immunity against nonself substances.

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3
Q

Define innate immunity.

A

A first-line defense response with little immunological memory

Innate immunity includes physical and biochemical barriers.

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4
Q

Define acquired (adaptive) immunity.

A

Characterized by antigen specificity and immunological memory

The response is faster and more robust upon subsequent exposure to the same antigen.

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5
Q

What is the role of hematopoietic stem cells (HSC)?

A

They are pluripotent and self-renewing cells from which all other hematopoietic cells are derived

HSCs originate in the bone marrow and differentiate into various immune cells.

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6
Q

What are cytokines?

A

Soluble factors produced by immune cells for cell-cell communication

Cytokines regulate immune responses and include interleukins (ILs), interferons (IFNs), and tumor necrosis factor (TNF).

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7
Q

What is the function of neutrophils?

A

Phagocytic cells that eliminate microorganisms via reactive oxygen species (ROS)

Neutrophils are a primary line of defense against pathogens.

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8
Q

List the two main types of macrophages.

A
  • Classically activated macrophages (M1)
  • Alternatively activated macrophages (M2)

M1 macrophages are pro-inflammatory, while M2 macrophages are involved in tissue repair.

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9
Q

What are dendritic cells (DC)?

A

Antigen presenting cells that bridge innate and adaptive immunity

They play a crucial role in the detection of pathogens and initiation of immune responses.

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10
Q

What is the complement system?

A

A system of about 30 serum proteins that destroy infectious agents’ membranes

It facilitates phagocytosis and promotes inflammation.

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11
Q

What are the primary functions of natural killer (NK) cells?

A
  • Cytokine production
  • Destruction of virus-infected or neoplastic cells

NK cells are important for innate immunity and can act independently of antibodies.

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12
Q

What are pathogen-associated molecular patterns (PAMPs)?

A

Molecules derived from pathogens that are recognized by the immune system

PAMPs trigger immune responses through pattern recognition receptors.

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13
Q

What is the significance of the membrane attack complex (MAC)?

A

It disrupts the membrane integrity of target cells

MAC is formed by the final components of the complement cascade.

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14
Q

What are danger-associated molecular patterns (DAMPs)?

A

Cell-derived molecules produced in response to cellular stress

DAMPs help the immune system recognize damaged or dying cells.

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15
Q

Define antigen.

A

A nonself substance that can be recognized by the immune system.

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16
Q

What are the five types of immunoglobulins?

A
  • IgM
  • IgD
  • IgG
  • IgE
  • IgA
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17
Q

What is the role of the variable regions in antibodies?

A

Determine antibody specificity and interact with antigens.

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18
Q

What are the two regions of an antibody molecule?

A
  • Fab region
  • Fc region
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19
Q

List some functions of antibodies.

A
  • Opsonization of pathogens
  • Initiation of complement-mediated lysis
  • Neutralization of viral infection
  • Enhancement of specificity of CMI
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20
Q

What are antigen-presenting cells (APCs)?

A

Cells that process and present antigens to T lymphocytes.

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21
Q

Which cells are considered professional APCs?

A
  • B cells
  • Macrophages
  • Dendritic cells
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22
Q

What is the major pathway for detecting and killing virally infected cells?

A

MHCI antigen processing and presentation.

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23
Q

What are the key events following antigen encounter for T and B cells?

A
  • Specific antigen recognition
  • Cellular activation
  • Clonal expansion
  • Differentiation into effector and memory cells
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24
Q

What are the two subdivisions of acquired immunity?

A
  • Humoral immunity
  • Cell-mediated immunity (CMI)
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25
What is the role of B cells in the immune response?
Produce antigen-specific antibodies.
26
What is the role of the spleen in the immune system?
Filters blood, removing foreign antigens and dead cells.
27
What is humoral immunity?
Part of the acquired immune system involving antibodies ## Footnote It is responsible for eliminating extracellular invaders.
28
What is cell-mediated immunity (CMI)?
Part of the acquired immune system involving effector cells ## Footnote CMI performs various functions to eliminate intracellular invaders.
29
What is the primary antibody produced during a secondary immune response?
IgG ## Footnote IgG has a higher affinity for the activating antigen compared to IgM.
30
What are the three ways cell-mediated cytotoxicity can occur?
* MHC-dependent recognition by CTLs or iNKT cells * Indirect recognition by NK cells via Fc receptors * Receptor-mediated recognition by macrophages of complement-coated targets
31
What initiates inflammation?
Release of chemotactic factors following injury or insult ## Footnote This is followed by increased blood flow and capillary permeability.
32
What are the major cellular contributors to an inflammatory response?
* Macrophages * Neutrophils * ILCs * T Cells
33
What do pro-inflammatory cytokines induce?
* Fever * Activation of T cells and macrophages * B- or T-cell proliferation * Neutrophilia * Increased vascular permeability or apoptosis
34
What are the two main types of immune-mediated diseases?
* Hypersensitivity * Autoimmunity
35
What is Type I hypersensitivity characterized by?
IgE-mediated response ## Footnote It often leads to immediate allergic reactions.
36
What mediates Type II hypersensitivity?
IgG or IgM antibodies ## Footnote It involves cytotoxic responses to foreign antigens on cell surfaces.
37
What distinguishes Type III hypersensitivity reactions?
Formation of circulating antigen-Ig complexes ## Footnote These complexes can cause widespread tissue damage.
38
What are the three classes of Type IV hypersensitivity responses?
* Contact hypersensitivity * Tuberculin-type hypersensitivity * Hypersensitivity pneumonitis
39
What is the primary mechanism of sensitization in Type IV hypersensitivity?
Development of activated and memory T cells ## Footnote This occurs instead of antibody production.
40
What is the difference between hypersensitivity and autoimmunity?
Hypersensitivity involves an exaggerated immune response, while autoimmunity occurs when the immune system attacks the body's own tissues ## Footnote Autoimmune diseases can be tissue-specific or tissue-non-specific.
41
What are the prerequisites for autoimmune disease to occur?
1. An autoreactive clone must escape central tolerance 2. Peripheral tolerance mechanisms must fail 3. The autoreactive clone must induce a detrimental immunological response
42
What is the consequence of senescence of immunity?
Reductions in both innate and acquired immune responses to antigens ## Footnote This is associated with aging and a decrease in the production of newly formed immune cells.
43
What is the significance of defects in immune system development?
They can lead to devastating consequences due to impaired immune development ## Footnote Effects of chemicals on critical immune organ genesis in developing fetuses may have significant implications.
44
What role do cytokines and neuropeptides play in neuroendocrine immunology?
They mediate interactions between the CNS, endocrine, and immune systems ## Footnote This includes the modulation of immune activity by chemicals acting on the nervous or endocrine systems.
45
What are xenobiotics?
Substances that can exert significant effects on the immune system ## Footnote Xenobiotics include drugs, chemicals, and environmental pollutants.
46
What unique quality does the immune system possess?
The ability of immune cells to be removed from the body and to function in vitro.
47
What parameters are included in standard toxicological studies?
* Body and selected organ weights * General observations of overall animal health * Selected serum chemistries * Hematologic parameters * Bone marrow ability to generate specific colony-forming units * Histopathology of lymphoid organs.
48
Define innate immunity.
Immunologic responses not induced through antigen receptors, with limited immunological memory.
49
What are some responses included in innate immunity?
* Phagocytosis of pathogens * Release of ROS by macrophages, neutrophils, and monocytes * Recognition of tumor cells by NK cells * Lytic activity of the complement cascade.
50
How can phagocytic activity be measured?
Using plate-based or flow cytometric methods to quantify engulfed fluorophore-labeled particles.
51
What is the T-cell-dependent antibody response (TDAR)?
An antibody response requiring T cells to help B cells make antibodies.
52
What are T-cell-independent antigens?
Antigens that can elicit antibody production by B cells without T-cell help.
53
What is flow cytometry used for?
To analyze large numbers of individual cells based on light scatter, fluorescence, and absorbance.
54
What factors can affect the results of host resistance studies?
* Strain, route of administration, and challenge levels of the pathogen * Strain, age, and sex of the host * Physiologic state of the host and the pathogen * Time of challenge with the pathogen.
55
What is developmental immunotoxicology (DIT)?
The study of how changes in the developing immune system may uniquely respond to chemical perturbation.
56
What are the three types of differences that might occur in developmental immunotoxicology?
* Qualitative difference * Quantitative difference * Temporal difference.
57
What are the five critical windows of vulnerability in the development of the immune system?
* Hematopoietic stem cell formation * Migration of hematopoietic cells * Establishment of bone marrow and thymus * Functional development of the immune system * Manifestation of mature immune responses ## Footnote Each window represents a specific developmental phase where exposure to toxic chemicals can have significant effects.
58
What type of immune response is typically triggered by respiratory sensitizers?
IgE response ## Footnote This response is associated with a Th2-dependent response and specific cytokines.
59
What is the role of molecular biology in immunotoxicology?
Identification of gene expression changes due to xenobiotic exposure ## Footnote Techniques such as RT-PCR and RNA-Seq are commonly used for these assessments.
60
What is the first step in characterizing mechanisms of immunotoxic action by xenobiotics?
Identifying the cell type(s) targeted by the agent ## Footnote This helps in selecting appropriate methods for further investigation.
61
What is one method for achieving gene-specific silencing?
RNA interference or CRISPR-Cas9 ## Footnote Both methods have limitations related to transfection efficiency.
62
What are xenobiotics?
Chemical substances that are foreign to the biological system ## Footnote Xenobiotics can include drugs, pollutants, and dietary components.
63
How can xenobiotics indirectly affect immune competence?
Through the release of immunomodulatory factors from cells or tissues other than the immune system ## Footnote The liver is often involved in this indirect modulation.
64
What is the role of the liver in immune modulation?
Source of diverse proteins, including acute-phase proteins that downregulate the immune system ## Footnote These proteins help maintain immune homeostasis.
65
What is the hypothalamic-pituitary-adrenal axis?
A regulatory system that controls stress responses and hormone release ## Footnote Deregulation can lead to decreased immune competence.
66
What is a common effect of pesticide exposure?
Occupational exposure leading to potential immunotoxicity ## Footnote Pesticides include insecticides, rodenticides, and herbicides.
67
How do metals exert their toxic effects?
By interacting with enzyme systems, membranes, or cellular organelles ## Footnote Most metals act as immunomodulators.
68
What are mycotoxins?
Secondary metabolites of fungi that can produce immune stimulation or suppression ## Footnote Examples include aflatoxin and ochratoxin.
69
What is the role of sex hormones in immune function?
They exhibit sexual dimorphism, affecting antibody responses and autoimmune disease incidence ## Footnote Estrogens enhance while androgens suppress certain immune functions.
70
What is a significant concern with drug abuse and immune function?
Certain drugs exhibit immunosuppressive actions ## Footnote This includes cannabinoids, opioids, and cocaine.
71
How do opioids suppress immune responses?
Through Gi-coupled opioid receptors (µ, κ, and δ) and opioid receptor–independent actions ## Footnote Opioids affect the CNS, autonomic nervous system, and hypothalamic-pituitary-adrenal axis.
72
What immune responses are altered by cocaine and its derivatives?
Humoral and cell-mediated immune responses, disruption of Th1/Th2 balance ## Footnote Cocaine affects host resistance and the stress response.
73
What is the effect of methamphetamine on the immune system?
Suppression of both cell-mediated immunity (CMI) and humoral immunity in vivo ## Footnote Methamphetamine is known for its immunotoxicity.
74
What is the association between ethanol exposure and pulmonary infection?
Increased incidence of pulmonary infection ## Footnote Ethanol significantly changes peripheral blood mononuclear cells (PBMC) and suppresses signaling through TLRs.
75
Which substances may induce autoimmunity, including schleroderma?
Vinyl chloride, organic solvents, crystalline silica, and hexachlorobenzene ## Footnote These substances can perturb the immune system.
76
What are biologics in the context of immunotoxicity?
Therapies derived from living organisms that can modulate the immune system ## Footnote They include monoclonal antibodies and recombinant proteins.
77
What are the potential adverse effects of biologics?
Immunosuppression leading to infections or malignancies, infusion reactions, cytokine storms, or autoimmunity ## Footnote Biologics can also elicit an immune response against themselves.
78
What are the mechanistic categories of monoclonal antibodies?
1. Bind and neutralize specific cytokines 2. Trigger lysis by the adaptive immune response 3. Block costimulation signals 4. Stimulate costimulatory receptors or block inhibitory receptors 5. Block lymphocyte trafficking ## Footnote Each category represents a different mechanism of action.
79
What is a key challenge in immunotoxicology?
Characterization of the risk associated with xenobiotic-induced immunotoxicity ## Footnote This includes understanding dose-response relationships and exposure amounts.

Medical Toxicology (13 decks)

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