Download Lecture 29-30

Immunology
Dr. Hal Sternberg
MCB 135E
Lecture 29-30
DEVELOPMENT OF IMMUNE
SYSTEM
• - GESTATIONAL TOLERANCE
•
(PREVENTING REJECTION)
• - FETAL/NEONATAL PROTECTION
• - VACCINATION/IMMUNIZATION
VACCINATIONS
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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
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14 WEEKS
DPT 3RD
ORAL POLIO 4TH
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6-9 MONTHS
ORAL POLIO 5TH
HEPATITIS B
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9 MONTHS
MEASLES
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15-18 MONTHS
MMR (MEASLES, MUMPS, RUBELLA)
DPT booster dose
ORAL POLIO 6TH
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5 YEARS
DPT 2ND booster
ORAL POLIO 7TH
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10 YEARS
TT (TETANUS) 3RD booster
HEPATITIS B booster
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15-16 YEARS
TETANUS booster
Progression of Vaccine Development **
…..
…..
** Taken from the Scientist;17(2004)
Function of Immune System is
PROTECTION against:
1.
2.
3.
4.
5.
6.
Bacteria
Virus
Fungus/ multicellular parasites
Cancer
Toxins
( 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. 1012
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Lymphocytes (cont.)
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)
2. Neutrophils- found throughout body, in blood
-phagocytosis of Ab-Ag CX
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QuickTime™ and a
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3. Macrophages- throughout
body, blood, lymphatics
-phagocytose non-specifically
(non Ab coated Ag)
-phagocytose specifically AbAg 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
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Macrophage
Bacteria
Bacterial
Infection
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
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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, 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 Bcell
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
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YOLK SAC
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BONE MARROW
• (4-5 Weeks )
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LIVER
(4 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 TCELL 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:
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GERM FREE ENVIRONMENT
BONE MARROW TRANSPLANT
ROUTINE INJECTIONS OF ADENOSINE DEAMINASE
(ADA)
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GENE THERAPY USING SUBJECTS OWN CELLS
(RETROVIRUS CONTAINING ADA TO “INFECT”
SUBJECTS BONE MARROW STEM CELLS)
ENZYME