MCB 135E: Discussion November 15-19, 2004

Immunology Development Function Important Aspects Bacterial Infection Complement Viral Infection Classes of Ig SCID

Development Gestational Tolerance Fetal/Neonatal Protection Vaccination/Immunization Thymus Involution Organ and T-Cell Development B-Cell Development Natural Killer Cells Complement Proteins

Function/Origination Protection Against: –Bacteria –Virus –Fungus / parasites –Cancer –Toxins –Molecules greater than 5Kd size Utilizes –Cells derived from stem cells Liver, Bone Marrow –Cells are stored, multiply, mature in: Thymus Spleen Lymph Node –Transport Blood Lymph Vessels

Important Aspects Cell Types Lymphocytes –T-Cells Killer Cells Helper Cells Suppressor Cells –B-Cells Secrete highly specific Ab Humoral Response Differentiate to Plasma Cells Cell Types Neutrophils Macrophages Natural Killer Cells

Macrophage Bacterial Infection

1.Bacteria enters body and is phagcytosed by macrophage 2.Macrophage processes bacteria and produces class II MHC that binds portion of bacteria and presents on cell surface 3.MHC II complex binds T Cell Receptor / CD4 on T H Cell and secretes IL-I 4.T H Cell undergoes activation or anergy

Bacterial Infection 5.Activated T H Cell binds B Cell via TCR/MHC II Interaction 6.Activated T H Cell is secreting IL-II that leads to differentiation of B-Cell  Plasma Cell (Secretes Ab)  B- Memory 7.Antibody-Antigen Complex triggers complement lysis

Viral Infection

5 classes of Ig IgG: 150,000 m.w. most abundant in blood, cross placental barrier, fix complement, induce macrophage engulfment IgA: associated with mucus and secretory glands, respiratory tract, intestines, saliva, tears, milk variable size IgM: 900,000 m.w. 2nd most abundant, fix complement, induce macrophage engulfment, primary immune response

5 Classes of Ig IgD: Low level in blood, surface receptor on B- cell IgE: Binds receptor on mast cells (basophils) secretes histamine, role in allergic reactions Increased histamine leads to vasodilation, which leads to increase blood vessel permeability. This induces lymphocyte immigration swelling and redness.

SEVERE COMBINED IMMUNODEFICIENCY DISEASE (SCID) CHARACTERISTICS: GENERALLY CAUSED BY DEFECT OF SINGLE GENE NEEDED FOR T-CELL AND B-CELL FUNCTION —SUBJECT EXHIBITS NO CELL MEDIATED RESPONSE ––SUBJECT CANNOT MAKE ANTIBODIES ABOUT 25% OF CASES INVOLVES DEFECTIVE GENE FOR THE ENZYME ADENOSINE DEAMINASE (REQUIRED FOR PURINE BREAKDOWN)

SEVERE COMBINED IMMUNODEFICIENCY DISEASE (SCID) TREATMENT OPTIONS: GERM FREE ENVIRONMENT BONE MARROW TRANSPLANT ROUTINE INJECTIONS OF ADENOSINE DEAMINASE ENZYME (ADA) GENE THERAPY USING SUBJECTS OWN CELLS (RETROVIRUS CONTAINING ADA TO “INFECT” SUBJECTS BONE MARROW STEM CELLS)