1. PHL 633 Immunotoxicology First and second Lectures By Abdelkader Ashour, Ph.D. Phone: 4677212Email: aeashour@ksu.edu.sa

2.  Xenobiotics can cause immune suppression  Xenobiotics can interact with the immune system to either cause or exacerbate allergic disease  Xenobiotics could have some involvement in autoimmune disease Immunotoxicology, Overview  Immunotoxicology “The study of undesired effects resulting from the interactions of xenobiotics with the immune system”  Immunotoxicity “Adverse health effect of xenobiotics on components and functions of the immune system”  Immune System It defends the body against infectious agents (bacteria, viruses, fungi, parasites), ubiquitous in our environment, as well as certain tumor cells A crucial part of this function is the ability to distinguish endogenous components “self ” from potentially harmful exogenous components “non- self”

3.  Immune Stimulation The immune system may react to foreign substances that would otherwise be relatively innocuous, such as certain chemicals, pollens and house dust  The resulting allergic reactions can produce an array of pathologies ranging from skin rashes and rhinitis to more life-threatening asthmatic and anaphylactic reactions Immunotoxicology, Overview  Immune Suppression Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more susceptible to infections and certain types of cancer

4. Immunotoxicology, Overview  In addition, although the immune system can generally distinguish between “self ” and “non-self” in some circumstances it may mistakenly react against “self ” components, resulting in another type of immune-mediated health effect, autoimmune disease  Xenobiotic compounds and physical stressors, such as UV and ionizing radiation can modulate immune function by acting as immunosuppressants, allergens or potentiators of allergic disease  There is also growing evidence that xenobiotic exposures are associated with autoimmune disease

5. Immune System

6. Immune system  Overview :  The immune system defends the body against infectious agents (bacteria, viruses, fungi, parasites), which are ubiquitous in our environment  It also has a role in defending the body against certain tumor cells that may arise spontaneously or as the result of environmental insults (viral, radiation, and chemical)

7. Organs of the Immune System

9.  Secondary organs which include: I.Spleen II.lymph nodes (scattered throughout the body) III.Tonsils IV.adenoids Organs of the Immune System  Organs of the Immune System include:  Primary organs which include: I.Bone marrow: from which immune cells are derived II.Thymus: has a major role in the differentiation of T lymphocytes  There are also lymphoid aggregates in the three major portals of entry for environmental agents: I.Lung: Bronchus-associated lymphoid tissue (BALT) II.Gut: Gut-associated lymphoid tissue (GALT) III.Skin: Skin-associated lymphoid tissue (SALT)

10. Important Definitions

12.  Sites of action:  Protection from pathogens Extracellular Intracellular Immune system  Function:  Protection from pathogens Intracellular (viruses, some bacteria and parasites) Extracellular (most bacteria, fungi, and parasites)  Elimination of modified or altered “self” Cancer or transformed cells

13.  Intracellular pathogens:  Cell-mediated responses are primary defense Antibodies are ineffective Two scenarios: I.Pathogen in cytosol  Cytotoxic T cell (CD8) II.Pathogen in vesicles  Th1 (CD4) releases cytokines  Activates macrophages Immune Response to Pathogens  Extracellular pathogens  Antibodies are primary defense Neutralization Opsonization Complement activation

14. Cells of the Immune System