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DABT > Immune Tox C&D 8 > Flashcards

Immune Tox C&D 8 Flashcards

1
Q

12-2 Organization of the Immune System: Lymphoid Tissue

Primary Lymphoid Organs

A

Classification:
Primary

Lymphoid Organs:
Bone Marrow
Thymus

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2
Q

12-2 Organization of the Immune System: Lymphoid Tissue

Secondary Lymphoid Organs

A

Classification:
Secondary

Lymphoid Organs:
Spleen
Lymph nodes
Peyer's patches
Skin-associated lymphoid tissue (SALT)
Mucosal lamina propria (MALT)
Gut-associated lymphoid tissue (GALT)
Bronchial-associated lymphoid tissue (BALT)
Nasal-associated lymphoid tissue (NALT)
Cells lining the genitourinary tract
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3
Q

12-2 Organization of the Immune System: Lymphoid Tissue

Tertiary Lymphoid Organs

A

Classification:
Tertiary

Lymphoid Organs:
Lymphoid neogenesis in nonlymphoid organs

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4
Q

12-3 Innate vs Acquired Immunity
Characteristic:
Cell involved

A

Characteristic:
Cell involved

Innate Immunity:
Neutrophils
Macrophages
NK/NKT cells
DC
Acquired Immunity:
T cells
B cells
Macrophages (accessory cell)
DC (accessory cell)
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5
Q

12-3 Innate vs Acquired Immunity
Characteristic:
Primary soluble mediators

A

Characteristic:
Primary soluble mediators

Innate Immunity:
Complement
Perforin/granzyme
Acute-phase proteins
IFN-alpha/beta
Other cytokines

Acquired Immunity:
ANtibody
Cytokines
Perforin/granzyme

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6
Q

12-3 Innate vs Acquired Immunity
Characteristic:
Specificity of response

A

Characteristic:
Specificity of response

Innate Immunity:
Limited

Acquired Immunity:
Yes (very high specificity)

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7
Q

12-3 Innate vs Acquired Immunity
Characteristic:
Receptors

A

Characteristic:
Receptors

Innate Immunity:
TLR
Complement receptors
NLR
Fc
TCRgamma delta

Acquired Immunity:
TCRalpha beta
TCRgamma delta
Ig alpha beta

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8
Q

12-3 Innate vs Acquired Immunity
Characteristic:
Response enhanced by repeated antigen challenge

A

Characteristic:
Response enhanced by repeated antigen challenge

Innate Immunity:
No

Acquired Immunity:
Yes

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9
Q

12-4 Properties of Immunoglobulin Classes and Subclasses

Class: IgG

A

Biological Properties:
Complement fixation (selected subclasses)
Crosses placenta

Mean Serum Conc (mg/ml) & Human half-life (days)
IgG1-  9 (21d)
IgG2-  3 (20d)
IgG3-  1 (7d)
IgG4-  1 (21d)
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10
Q

12-4 Properties of Immunoglobulin Classes and Subclasses

Class: IgA

A

Biological Properties:
Secretory antibody

Mean Serum Conc (mg/ml) & Human half-life (days)
3 (6d)

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11
Q

12-4 Properties of Immunoglobulin Classes and Subclasses

Class: IgM

A

Biological Properties:
Complement fixation
Efficient agglutination

Mean Serum Conc (mg/ml) & Human half-life (days)
1.5 (10d)

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12
Q

12-4 Properties of Immunoglobulin Classes and Subclasses

Class: IgD

A

Biological Properties:
Possible role in antigen-triggered lymphocyte differentiation

Mean Serum Conc (mg/ml) & Human half-life (days)
0.03 (3d)

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13
Q

12-4 Properties of Immunoglobulin Classes and Subclasses

Class: IgE

A 
Biological Properties:
Allergic responses (mast-cell degranulation)

Mean Serum Conc (mg/ml) & Human half-life (days)
0.0001 (2d)

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14
Q

12-5 Characteristics of Selected Immune Cells

Macrophage

A

Properties:
Phagocytosis
Adherence

Surface receptors:
Complement
Fc region of Ig

Surface markers:
CD16
CD11b
CD64

Proliferation in response to:
CD40L+ cytokines

Effector functions:
Cytokine production
Bactericidal activity
Tumor cell cytotoxicity
Suppressor activity
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15
Q

12-5 Characteristics of Selected Immune Cells

DC

A

Properties:
Phagocytosis
Adherence

Surface receptors:
Complement
Fc region of Ig

Surface markers:
CD11c
CD11b

Proliferation in response to:
CD40L+ cytokines

Effector functions:
Cytokine production
Bactericidal activity
Tumor cell cytotoxicity

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16
Q

12-5 Characteristics of Selected Immune Cells

T Cells

A

Properties:
No Phagocytosis
No Adherence

Surface receptors:
Antigen receptors
No Complement
Some Fc region of Ig

Surface markers:
CD4
CD8
CD3

Proliferation in response to:
Allogeneic cells (MLR)
PHA
ConA
Anti-CD3 + IL-2
Effector functions:
Cytokine production
Tumor cell cytotoxicity
Immunological memory
Suppressor activity
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17
Q

12-5 Characteristics of Selected Immune Cells

B cells

A

Properties:
Phagocytosis
No Adherence

Surface receptors:
Antigen receptors
Complement
Fc region of Ig

Surface markers:
Ig
CD19
B220

Proliferation in response to:
LPS
Anti-Ig + IL-4
CD40 + cytokines

Effector functions:
Antibody production
Cytokine production
Immunological memory
Suppressor activity
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18
Q

12-5 Characteristics of Selected Immune Cells

NK cells

A

Properties:
No Phagocytosis
No Adherence

Surface receptors:
Complement
Fc region of Ig

Surface markers:
CD16
CD11b

Proliferation in response to:
N/A

Effector functions:
Cytokine production
Tumor cell cytotoxicity

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19
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IL-1

A

Source:
Macrophages
Epithelial cells

Physiological Actions:
Activation and proliferation of T cells
Proinflammatory
Induces fever and acute-phase proteins
Induces synthesis of proinflammatory cytokines
20
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IL-2

A

Source:
T cells

Physiological Actions:
Primary T-cell growth factor
Growth factor for B cells and NK cells

21
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IL-4

A

Source:
Th2 cells
Mast cells

Physiological Actions:
Proliferation of activated Th2 and B cells
B-cell differentiation and IgE isotype switching
Antagonizes IFN-gamma
Inhibits Th1 responses

22
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IL-5

A

Source:
Th2 cells
Mast cells

Physiological Actions:
Proliferation and differentiation of eosinophils

23
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IL-6

A 
Source:
Macrophages 
Th2 cells
B cells
Endothelial cells

Physiological Actions:
Enhances B-cell differentiation and Ig secretion
Induction of acute-phase proteins by liver
Proinflammatory
Proliferation of T cells and increased IL-2 receptor expression

24
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IL-10

A

Source:
Tregs
Bregs
Macrophages

Physiological Actions:
Inhibits T-cell and macrophage responses

25
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IL-12

A

Source:
DCs
Macrophages

Physiological Actions:
Activates NK cells
Induces Th1 responses

26
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IL-13

A

Source:
Th2 cells

Physiological Actions:
Stimulates B-cell growth
Inhibits Th1 responses

27
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IL-17

A 
Source:
Th17
NK cells
gamma delta T cells
Neutrophils

Physiological Actions:
Proinflammatory
Inhibits Tregs

28
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IFN-alpha/beta (Type I IFN)

A

Source:
Leukocytes
DCs
Fibroblasts

Physiological Actions:
Induction of MHC I expression
Antiviral activity
Stimulation of NK cells

29
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

IFN-gamma

A

Source:
T cells
NK cells

Physiological Actions:
Induction of MHC I and MHC II
Activates macrophages

30
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

TGF-beta

A

Source:
Macrophages
Megakaryocytes
T cells

Physiological Actions:
Enhances monocyte/macrophage chemotaxis
Enhances wound healing: angiogenesis, fibroblast
Proliferation, deposition of extracellular matrix
Inhibits T- and B- cell proliferation
Inhibits antibody secretion
Primary inducer of isotype switch to IgA

31
Q

12-6 Cytokines: Sources and Functions in Immune Regulation

GM-CSF

A

Source:
Macrophages
Endothelial cells
Fibroblasts

Physiological Actions:
Stimulates growth and differentiation of monocytes and granulocytes

32
Q 
12-7 Models of Host Resistance
Bacterial
Parasite
Fungal
Viral
Tumor
A

Model: Pathogen

Bacterial:
Listeria monocytogenes
Streptococcus pneumoniae

Parasite:
Trichinella spiralis

Fungal:
Candida albicans

Viral:
Influenza A2

Tumor:
B16F10 melanoma

33
Q

12-8 Possible Mechanisms of Chemical-Induced Immune Modulation
Direct:
Functional changes

A

Mechanism:

Functional changes

Examples:
Altered antibody-mediated responses
Altered cell-mediated responses
Altered release of preformed mediators
Altered host resistance
Inability of one or more cell types to perform a required activity, for examples:
production of antibody
release of cytokines
processing and presentation of antigen
proliferation and differentiation
receptor-mediated signal transduction
34
Q

12-8 Possible Mechanisms of Chemical-Induced Immune Modulation
Direct:
Structural changes

A

Mechanism:

Structural changes

Examples:
Alterations in surface receptors or ligands
Histopathological changes in lymphoid organs

35
Q

12-8 Possible Mechanisms of Chemical-Induced Immune Modulation
Direct:
Compositional changes

A

Mechanism:

Compositional changes

Examples:
Alterations in CD3+, CD4+, CD8+, B220+, and/or Ig+ in spleen
Alterations in CD4+, CD8+, CD4+/CD8+, and/or CD4-/CD8- in thymus
Changes in hematological cellular parameters
Alterations in circulating Ig
Alterations in CFU profile in bone marrow

36
Q

12-8 Possible Mechanisms of Chemical-Induced Immune Modulation
Direct:
Metabolic activation

A

Mechanism:

Metabolic activation

Examples:
Conversion to a toxic metabolite

37
Q

12-8 Possible Mechanisms of Chemical-Induced Immune Modulation
Indirect:
Effects secondary to other target organ toxicity

A

Mechanism:

Effects secondary to other target organ toxicity

Examples:
Induction of acute-phase proteins as a result of liver injury
Increased corticosteroid release from the adrenal gland

38
Q

12-8 Possible Mechanisms of Chemical-Induced Immune Modulation
Indirect:
Hormonal changes

A

Mechanism:

Hormonal changes

Examples:
Alteration in neuroendocrine regulation
Alteration in autonomic output from the CNS
Altered release of steroids from sex organs

39
Q

12-9 Cellular Models of Immunotoxicology

T cell type

A 
Cell line (species):
EL-4 (mouse)
Jurkat E6 (human)

Effector Response:
IL-2

Stimulus:
EL-4: Phorbol ester
Jurkat: Phorbol ester + Ca ionophore
or anti-CD3 + anti-CD28

40
Q

12-9 Cellular Models of Immunotoxicology

B cell type

A 
Cell line (species):
CH12.LX (mouse)
BCL-1 (mouse)
SKW (human)
Daudi (human)

Effector Response:
IgM
Daudi: NONE (signal transduction)

Stimulus:
LPS
SKW: LPS or alpha IgM + CD40L
Daudi: alpha IgM

41
Q

12-9 Cellular Models of Immunotoxicology

Macrophage

A

Cell line (species):
RAW 264.7 (mouse)
J774.1 (mouse)
U937 (human)

Effector Response:
RAW: Nitric oxide, IL-1
J744.1: Nitric oxide, IFN-gamma
U937: TNF-alpha, IL-1alpha, IL-6, IL-8

Stimulus:
LPS

42
Q

12-10 Tier Approach for Immunotoxicology Testing

Tier 1

A 
Procedures:
Hematology
Body weight
Organ weights (spleen, thymus, kidney, liver)
Spleen cellularity
Bone marrow cellularity and CFU
Immunopathology
AFC assay
Proliferative responses
NK assay
43
Q

12-10 Tier Approach for Immunotoxicology Testing

Tier 2

A 
Procedures:
Surface marker analysis
Secondary (IgG) AFC assay
CTL assay
DTH response
Host resistance studies
44
Q

12-11 Suggested Testing Configurations: Three Tests with 100% Concordance

A 
AFC, DHR, Surface markers
AFC, NK, DHR
AFC, NK, Thymus: body weight
AFC, DHR, Thymus: body weight
Surface markers, NK, DHR
Surface markers, DHR, T-cell mitogens
Surface markers, DHR, Thymus: body weight
Surface markers, DHR, LPS response
45
Q 
12-12 Chemical Agents know to be associated with autoimmunity
Drugs
antigenic chemical:
methyl dopa
hydralazine
isoniazid
procainamide
halothane
A 
Antigenic Chemical:
Clinical Manifestations (determinant):
Methyl dopa:
Hemolytic Anemia (Rhesus antigens)

Hydralazine:
SLE-like syndrome (Myeloperoxidase)

Isoniazid:
SLE-like syndrome (Myeloperoxidase)

Procainamide:
SLE-like syndrome (DNA)

Halothane:
Autoimmune hepatitis (liver microsomal proteins)
46
Q 
12-12 Chemical Agents know to be associated with autoimmunity
Nondrug chemicals:
Vinyl chloride
Mercury
Silica
A 
Antigenic Chemical:
Clinical Manifestations (determinant):

Vinyl chloride:
Scleroderma-like syndrome (abnormal protein synthesized in liver)

Mercury:
Glomerular neuropathy (glomerular basement membrane protein)

Silica:
Scleroderma (most likely acts as an adjuvant)

47
Q

12-13 Chemicals Implicated in Autoimmunity

Scleroderma

Systemic lupus erythematosus

A

Scleroderma:

Solvents (toluene, xylene)
Tryptophan
Silicones

Systemic lupus erythematosus:

Phenothiazines
Penicillamine
Propylthiouracil
Quinidine
L-DOPA
Lithium carbonate
Trichloroethylene
Silicones

DABT (6 decks)

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