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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
12-6 Cytokines: Sources and Functions in Immune Regulation | IL-12
Source: DCs Macrophages Physiological Actions: Activates NK cells Induces Th1 responses
26
12-6 Cytokines: Sources and Functions in Immune Regulation | IL-13
Source: Th2 cells Physiological Actions: Stimulates B-cell growth Inhibits Th1 responses
27
12-6 Cytokines: Sources and Functions in Immune Regulation | IL-17
``` Source: Th17 NK cells gamma delta T cells Neutrophils ``` Physiological Actions: Proinflammatory Inhibits Tregs
28
12-6 Cytokines: Sources and Functions in Immune Regulation | IFN-alpha/beta (Type I IFN)
Source: Leukocytes DCs Fibroblasts Physiological Actions: Induction of MHC I expression Antiviral activity Stimulation of NK cells
29
12-6 Cytokines: Sources and Functions in Immune Regulation | IFN-gamma
Source: T cells NK cells Physiological Actions: Induction of MHC I and MHC II Activates macrophages
30
12-6 Cytokines: Sources and Functions in Immune Regulation | TGF-beta
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
12-6 Cytokines: Sources and Functions in Immune Regulation | GM-CSF
Source: Macrophages Endothelial cells Fibroblasts Physiological Actions: Stimulates growth and differentiation of monocytes and granulocytes
32
``` 12-7 Models of Host Resistance Bacterial Parasite Fungal Viral Tumor ```
Model: Pathogen Bacterial: Listeria monocytogenes Streptococcus pneumoniae Parasite: Trichinella spiralis Fungal: Candida albicans Viral: Influenza A2 Tumor: B16F10 melanoma
33
12-8 Possible Mechanisms of Chemical-Induced Immune Modulation Direct: Functional changes
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
12-8 Possible Mechanisms of Chemical-Induced Immune Modulation Direct: Structural changes
Mechanism: Structural changes Examples: Alterations in surface receptors or ligands Histopathological changes in lymphoid organs
35
12-8 Possible Mechanisms of Chemical-Induced Immune Modulation Direct: Compositional changes
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
12-8 Possible Mechanisms of Chemical-Induced Immune Modulation Direct: Metabolic activation
Mechanism: Metabolic activation Examples: Conversion to a toxic metabolite
37
12-8 Possible Mechanisms of Chemical-Induced Immune Modulation Indirect: Effects secondary to other target organ toxicity
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
12-8 Possible Mechanisms of Chemical-Induced Immune Modulation Indirect: Hormonal changes
Mechanism: Hormonal changes Examples: Alteration in neuroendocrine regulation Alteration in autonomic output from the CNS Altered release of steroids from sex organs
39
12-9 Cellular Models of Immunotoxicology | T cell type
``` 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
12-9 Cellular Models of Immunotoxicology | B cell type
``` 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
12-9 Cellular Models of Immunotoxicology | Macrophage
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
12-10 Tier Approach for Immunotoxicology Testing | Tier 1
``` 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
12-10 Tier Approach for Immunotoxicology Testing | Tier 2
``` Procedures: Surface marker analysis Secondary (IgG) AFC assay CTL assay DTH response Host resistance studies ```
44
12-11 Suggested Testing Configurations: Three Tests with 100% Concordance
``` 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
``` 12-12 Chemical Agents know to be associated with autoimmunity Drugs antigenic chemical: methyl dopa hydralazine isoniazid procainamide halothane ```
``` 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
``` 12-12 Chemical Agents know to be associated with autoimmunity Nondrug chemicals: Vinyl chloride Mercury Silica ```
``` 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
12-13 Chemicals Implicated in Autoimmunity Scleroderma Systemic lupus erythematosus
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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