Immunology Dr. Hal Sternberg MCB 135E Lecture 29-30

DEVELOPMENT OF IMMUNE SYSTEM - GESTATIONAL TOLERANCE (PREVENTING REJECTION) - FETAL/NEONATAL PROTECTION - VACCINATION/IMMUNIZATION

VACCINATIONS BIRTH BCG (BACILLUS CALMETTE-GUERIN) ORAL POLIO HEPATITIS 6 WEEKS DPT (DIPHTHERIA, TETANUS, PERTUSSIS ORAL POLIO 2 ND DOSE HEPATITIS 2 ND 10 WEEKS DPT (DIPHTHERIA, TETANUS, PERTUSSIS) ORAL POLIO 3 RD 14 WEEKS DPT 3 RD ORAL POLIO 4 TH 6-9 MONTHS ORAL POLIO 5 TH HEPATITIS B 9 MONTHS MEASLES MONTHS MMR (MEASLES, MUMPS, RUBELLA) DPT booster dose ORAL POLIO 6 TH 5 YEARS DPT 2 ND booster ORAL POLIO 7 TH 10 YEARS TT (TETANUS) 3 RD booster HEPATITIS B booster YEARS TETANUS booster

** Taken from the Scientist;17(2004) ….. Progression of Vaccine Development **

Function of Immune System is PROTECTION against: 1.Bacteria 2.Virus 3.Fungus/ multicellular parasites 4.Cancer 5.Toxins 6.( 5,000 daltons--protein/lipid/CHO/nucleic acids)

Tissues and Organs Important for Immune Function Cells derived from stem cells: liver, bone marrow Cells are stored, multiply, interact, and mature in: thymus, spleen, lymph nodes, blood Transport: lymphatic vessels Accessory Organs Appendix, tonsils, intestines

Cell Types 1.Lymphocytes: derived in bone marrow from stem cells include both T cells and B cells

A) T cells: stored & mature in thymus-migrate throughout the body -Killer Cells Perform lysis (infected cells) Cell mediated immune response -Helper Cells Enhance T killer or B cell activity -Suppressor Cells Reduce/suppress immune activity May help prevent auto immune disease Lymphocytes (cont.)

B)B-Cells: stored and mature in spleen secrete highly specific Ab to bind foreign substance (antigen: Ag), form Ab-Ag complex responsible for humoral response perform antigen processing and presentation differentiate into plasma cells (large Ab secretion) Lymphocytes (cont.)

2.Neutrophils- found throughout body, in blood -phagocytosis of Ab-Ag CX

3.Macrophages- throughout body, blood, lymphatics -phagocytose non-specifically (non Ab coated Ag) -phagocytose specifically Ab- Ag CX -have large number of lysosomes (degradative enzyme) -perform Ag processing and presentation -present Ag to T helper cell -secrete lymphokines/ cytokines to stimulate T helper cells and immune activity

4. Natural Killer Cells-in blood throughout body -destroy cancer cells -stimulated by interferons

Bacterial Infection Macrophage Bacteria

Complement Series of enzymes which are sequentially activated and result in lysis of cell membrane of infected cell at bacterium Permeabilizes membrane leaky Complement binding and activation ~35 enzymes and factors involved in cascade

CDC involves: 1) recognition, 2) attachment of complement-fixing antibodies to tumor specific surface antigens, 3) complement activation, 4) formation of MAC resulting in transmembrane pores (perforins) that disrupt the osmotic barrier of the membrane and lead to osmotic 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.

Thymus Involution Repertoire of lymphocytes shift with aging (membrane components shift)

ORGAN AND T-CELL DEVELOPMENT YOLK SAC LIVER (4 Weeks) BONE MARROW (4-5 Weeks ) THYMUS (7-10 Weeks) BLOOD LYMPH (14 Weeks) SPLEEN (16 Weeks) T-cells migrate and appear in tissues with development and increase in number throughout Gestation

B-CELLS FIRST appear in immature state - Liver at 7 weeks LATER –appear mature by weeks CAN DIFFERENTIATE INTO IMMUNOLOGICALLY COMPETENT ANTIBODY-PRODUCING PLASMA CELLS

NATURAL KILLER CELLS FIRST APPEAR IN FETAL BONE MARROW AROUND 13 WEEKS GESTATION FOUND THROUGHOUT BODY NK CELLS HAVE DIMINISHED ACTIVITY BEFORE BIRTH COMPARED TO ADULT STIMULATED BY INTERFERON AFTER 27 WEEKS

COMPLEMENT PROTEINS ARISE FROM LIVER FIRST DETECTED 5-6 WEEKS GESTATION INCREASE GRADUALLY IN CONCENTRATION AT ABOUT 28 WEEKS COMPLEMENT PROTEINS ARE AROUND 2/3 THAT OF ADULT CONCENTRATIONS INDIVIDUAL VARIATION

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)