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 2ND DOSE• HEPATITIS 2ND

• 10 WEEKS• DPT (DIPHTHERIA, TETANUS,

PERTUSSIS)• ORAL POLIO 3RD

• 14 WEEKS• DPT 3RD

• ORAL POLIO 4TH

• 6-9 MONTHS• ORAL POLIO 5TH

• HEPATITIS B

• 9 MONTHS

• MEASLES

• 15-18 MONTHS

• MMR (MEASLES, MUMPS, RUBELLA)

• DPT booster dose

• ORAL POLIO 6TH

• 5 YEARS

• DPT 2ND booster

• ORAL POLIO 7TH

 

• 10 YEARS

• TT (TETANUS) 3RD booster

• HEPATITIS B booster

 

• 15-16 YEARS

• TETANUS booster

** Taken from the Scientist;17(2004)

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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 Types1. Lymphocytes: derived in bone marrow from stem

cells include both T cells and B cells. 1012

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A) T cells: stored & mature in thymus-migrate throughout the body

-Killer Cells Perform lysis (infected cells)Cell mediated immune response

-Helper CellsEnhance T killer or B cell activity

-Suppressor CellsReduce/suppress immune activityMay 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

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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

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

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Bacterial Infection

Macrophage

Bacteria

ComplementSeries 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

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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, milkvariable 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.

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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 14-20 weeks

• CAN DIFFERENTIATE INTO IMMUNOLOGICALLY COMPETENT ANTIBODY-PRODUCING PLASMA CELLS

NATURAL KILLER CELLS • FIRST APPEAR IN FETAL BONE MARROW

AROUND 13 WEEKS GESTATION

• 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)