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

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 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) 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, 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.

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)