MCB 135 E Discussion November 15 19 2004

MCB 135 E: 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 5 Kd 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

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 / CD 4 on TH Cell and secretes IL-I 4. TH Cell undergoes activation or anergy

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

Viral Infection

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

5 Classes of Ig Ig. D: Low level in blood, surface receptor on Bcell Ig. E: 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 (ADA) • • • GENE THERAPY USING SUBJECTS OWN CELLS (RETROVIRUS CONTAINING ADA TO “INFECT” SUBJECTS BONE MARROW STEM CELLS) ENZYME