The Immune System

1. The Immune System • I. Specific Immunity • A. Humoral Mediated: • (B-Cell immunity; Free Ig’s) • Antibodies react to bacteria by:1. Binding directly with bacterial toxins to neutralize them • 2. Coat bacteria to enhance the phagocytosis be non-specifics components (monocytes, etc.,). • Immunoglobulin subclass: IgG, IgA, IgM, IgD, & IgE

2. The Immune System • I. Specific Immunity • B. Cell Mediated: ( T-cell immunity; membrane receptors) • Viruses, parasites, fungi, etc., are reacted by: • 1. Helper - T • 2. Cytotoxic - Tcells • 3. Macrophages • 4. Tranfer factor • 5. Cytokines (lymphokines/interleukins) • II. Non-specific Immunity

3. Phagocyte: Neutrophis Monocytes Tissue macrophages (histiocytes) Kupffer cells Alveclar macrophages Microgia Location: Blood & all tissues Blood & tissues All tissues ( including spleen, lymph nodes, bone marrow) Liver Lungs Central nervous system Table 15.2 Phagocytic Cells and Their Locations

4. Thymus Bone T-lymphocytes B-lymphocytes Sensitized lymphocytes Cellular Immunity Plasma cells Humoral Immunity Development of the Immune System Yolk sac/Bone Hematopoietic stem cells Etrythrocytes Granulocytes Monocytes Megokaryocytes Lymphoid stem cells

5. Immunology Review Antigen macrophage Immune System Immunoglobulins (immediate hypersensitivity) Transfer factor Delayed hypersensitivity B-cells Humoral Bone (Gut associated lymphoid tissue) T-cells Cellular thymus Advanced lymphcytes Plasma Cells

6. Table 15.5 Immunology ReviewImmunoglobulins • IgC most abundant Ig of internal body fluids, particularly extravascular. Where they combat micro-organisms and their toxins • IgA major Ig insero-mucus secretions where it defends external body surfaces • IgM very effective agglutinator; produced early in immune response - effective first line of defense vs. bacteraemia • IgD present on lymphocytes surface of newborn • IgE raised in parasitic infections. Responsible for symptions of atopic allergy

7. light S S S X S S S Antigen binding sites heavy heavy X light Table 15.5 Immunology ReviewImmunoglobulins • Antibody model proposed by R.E. Porter withtwo heavy and two light polypeptide chains held by interchain disulphide bonds

8. Birth IgM 100 IgG % Adult Level 50 IgA, IgD, IgE 0 -3 0 6 12 18 Mother Infant Age in months Development of serum immunoglobulin levels in the human.

9. The Complement SystemMechanism of Action • 1. IgG & IgM-antigen complexes bind with C-1 to activate the enzyme system. • 2. Activated C-1 converts C-4 into C-4a & C-4b. • 3. C-4b binds to the antigen’s membrane (is fixed) and causes theconversion of C-2 into C-2a & C-2b. • 4. C-2a attaches to C-4b and causes the cleaving of C-3 into C-3a & C-3b. The C-3b attaches to the complex while C-3a is secreted.

10. The Complement SystemMechanism of Action • 5. Activated C-5 through C-9 become fixed to the antigen & create large pores in the membranes of the antigens allowing H20 influx. The cells (bacterial) swell and burst. • 6. C-3a & C-5a produce chemotaxic substances which: • A) attract phagocytes • B) cause opsonization-stimulates phagocytes • C) cause release of histamine from mast cells

11. The Complement System(continued) • Summary • 1. Recognition: (C-1) • 2. Activation: (C4, C2 + C3) • 3. Attack: (C5 -C9)

12. Development of the T-cell System • Lymphocyte precursors originate in the yolk sac and migrate into the fetus. The lymphoid stem cells then migrate to the thymus under the influence of an “attraction factor.” The cells then become “programmed” and become immunocompetent. • PUTATIVE PROCESS: • 1. Thymic hormones thyopoietin I & II transform the stem cells into T-cells in the thymic cortex • 2. Thymic hormone thymosin promotes the maturation of T-cells in the thymic medulla & other lymphoid tissue. • 3. Some of the T-cells enter the blood and travel to other lymphoid tissues and establish colonies (germinal centers) where they divide by clonal growth.

13. Helper T-cell Killer T-cell T-cell receptor Foreign antigen CD4 coreceptor CD8 coreceptor Class-2 MHC molecule Class-1 MHC molecule Antigen presenting cell Target cell Figure 15.18 Coreceptors on helper and killer T cells . A foreign antigen is presented to T lymphocytes in association with MHC Molecules. The CD4, on helper T cells and CD8 corecepters on killer T cells, permit each type of T cell to interact only with a specific class of MHC molecule

14. HIV life cycle: Viral Infection Free Virus Attachment Penetration CD4 Viral RNA Reverse transcriptase Reverse Transcription Proviral DNA Cell Nucleus Integration Cellular DNA

15. HIV life cycle:phase of viral expression Free Virus Budding Packaging Viral proteins translation Genomic RNA splicing Cell Nucleus Viral RNA Transcription Proviral DNA

16. Acquired Immune Deficiency Syndrome (AIDS) • Caused by Human Immunodeficiency Virus (HIV) • Classes: • 1. Oncornaviruses (cause tumors, but not AIDS) • a. HTLV-1 • b. HTLV-2 • 2. Cytopathic Virus (Lenti-viruses) cause AIDS • a. HIV-1 worldwide • b. HIV-2 less pathogenic (geographically restricted)

17. Acquired Immune Deficiency Syndrome (AIDS) (continued) • Modes of transmissions: • 1. Sexual contact with an HIV-infected person • 2. Transfusion of HIV contaminated blood • 3. In utero from infected mother to baby • 4. Injected drug use • 5. Mucocutaneous exposure (one case from kissing)

18. Acquired Immune Deficiency Syndrome (AIDS) (continued) • Risk of HIV Transmission: • A person is at risk of HIV infection anytime s/he comes into contact with the following fluids of an infected individual: • Blood • Semen • Vaginal fluid • Breast milk

19. Blood Serum/plasma Semen Vaginal secretions Cerebrospinal fluid Vitreous fluid Human Breast Milk Synovial fluid Pleural fluid Pericardial fluid Peritoneal fluid Amniotic fluid Wound exudates Table 1 Body Fluids to which Universal Precautions Apply In Relationship to “Bloodborne” Pathogens

20. Table 2 Body Fluids to which Universal Precautions Apply If Containing Visible Blood In Relationship to “Bloodborne” Pathogens • Saliva • Feces • Vomitus • Urine • Nasal secretions • Sputum • Sweat • Tears

21. Table 3 Handling of Medical Devices / Equipment for Reuse Method of Reprocessing: Decontaminate only use intermediate or low-level germicide or simple wash with soap and water Decontaminate, then preferably sterilize at a minimum do high level disinfection by soaking 10 - 20 minutes in an EPA approved chemical agent Decontaminate and sterilize by cold sterilization (12) or preferably by heat steam or gas following the recommendations of the sterilizer • Use of Device: • Contact with skin • Contact with mucous membrane • Penetrate skin

22. Florida HIV Statistics as of 1/1/95 • U.S.A. 1 in 250 est. to be HIV+ • FLA. 1 in 100 est. to be HIV + • Dade 1 in 40 est. to be HIV+ • Orlando 1 in 20 est. to be HIV+ • HIV leading cause of death among women • aged 15 - 25 in USA • 1 women infected every 1 -2 minutes Worldwide • 1 women dies due HIV every 2 minutes

23. AIDS/HIV Statistics as of 1/1/95 • 18,000 children have lost their mothers to HIV • # of teens contracting HIV doubles every 14 months • 6,500,000 teenagers contract a STD in USA each year • 30,000 HIV infected teens in USA 1/1/94 • FLA is: #1 Heterosexual trasnsmission • #2 Injectable drug transmission • #2 Teenage & pediatric cases • #3 Total AIDS cases

24. AIDS/HIV Statistics as of 1/1/95 • AIDS leading Counties Cities • Dade 13,654 Miami • Broward 6,909 Ft. Lauderdale • Palm Beach 3,775 West Palm Beach • Hillsborough 2,585 Tampa • Duval 2,225 Jacksonville • Orange 2,249 Orlando • Total cases 43,242 Fla • 401,749 USA

25. RNA or Thymic hormone Lymphokine Lymphokine Lymphokine B-cell: Ig helper effect B-cell: No Ig Suppressor effect T-cell: Blastogenesis Activiated marcophage Macrophage migration inhibition Chemotoxis Other cells: Viral resistance Cytotoxic inactivation Characteristics of Lymphokines Macrophage: