LECTURE 14  IMMUNE  SYSTEM


I. Introduction
 

II. Non-Specific Defense Against Microbial Invasion
 

    A. Barriers:  The skin and mucous, physical and chemical defense,
                        the first line barriers to infection.

    B. Inflammatory Response:
        1.  Phagocytic cells, inflammation, and antimicrobial proteins form the
             second-line barriers to infection.

            Phagocytosis:  the ingestion of invading organisms by certain white blood cells. (neutrophils, monocytes

                                  (macrophage), and eosinophils)

        2. Inflammatory response:  infected tissue -à chemical molecules –à  capillary dilation and permeability --à phagocytic

                                                 cells  arrives --- > the tissue heals

        3. Natural Killer Cells:  Attacking invader’s cell membrane, causing it to burst open.

        4. Antimicrobial proteins:
            lysozyme (tears, saliva..)  20 serum proteins

              Interferons:  inhibit viral reproduction.

 

II. Specific Immune System

    A. General Characteristic:

        1.  Lymphocytes, key cells of the immune system, the third-line of defense.  Originated from pluripotent stem cells in the

            bone marrow or liver of a developing fetus.

        B lymphocytes (B cells):  Lymphocytes remain in the bone marrow and continue their maturation become B cells.

        T lymphocytes ( T cells):  Lymphocytes that migrate from the bone marrow to the thymus, develop into T cells.

        2. Four Important Characteristics:

            a) Specificity
 
            b) Diversity

            c) Memory

            d) Identification of self:  self-tolerance.

            B cells and T cells and antigens interact with them provide these characteristics

            Antigen:  a foreign molecule that elicits a specific response by lymphocytes.

            Antibody:  when antigen invaded the body, they activate lymphocyte cells to secrete proteins to interact with them,         these proteins…

            Antigen receptors are numerous (about 100, 000) and diversified.

    B. The Defenders:

        1. B cells:  Production of antibodies in response to foreign proteins of bacteria, viruses, and tumor cells.

                a) Plasma cell:  produced by B cell, a population of identical effector cells.
 
                b) Clonal selection:  selected by a small number of selected cells by antigens gives rise to clones of thousands of

                                               cells, all specific for and dedicated to eliminating that antigen.
                c) Primary immune response 10 ~ 17 days
                d) Second immune response 2 ~ 7 day

        2. Memory B Cell:
            From primary response to second response
            Immunological Memory.

        3. T cells

                Lymphocytes mature in thymus…

                a):  Major Histocompatibility Complex
                      (MHC)

                     a family of genes coding for a collection of cell surface glycoproteins (proteins with attached sugar chains), which

                    identify “self” to the immune system.
 

                   Class I MHC:  found on all nucleated cells.

                   Class II MHC: restricted to macrophages, B cells, activated T cells, and interior cells of  thymus.

                   Function of MHC molecules:  antigen presentation

               b):  Killer T cell (cytotoxic T cell):
                        have antigen receptors that bind to antigens displayed by   MHC I molecules

               c):  Helper T cell:
                        have receptors that bind to antigens displayed  by MHC II   molecules.  Helper T cells modulate both

                        humoral (B-cell) and cell mediated (cytotoxic T cell) immune responses through the secretion of different

                        cytokines---- Interleukin-2 (IL-2)
 
                d):  Suppressor T cell: (Ts)
                      function in turning off the immune response, once antigen   has been eliminated from the body.

                e):  Memory T cell:   a long lived descendant of T cell
                      that contact with antigen, which can respond rapidly to the same antigen when re-exposed to it.

            4. Macrophages:  a cell, derived from white blood cells, called monocytes, whose functions is to consume foreign

                                        particles, including bacteria.  It is part of the non-specific defense system.

            5. Antibodies:  a protein, produced by cells of the immune system, that combines a specific antigen and usually

                                   facilitates destruction of the antigen.

   C. Identification of Self, --Self tolerance

Lymphocytes bearing receptors specific for molecules already present in the body are either rendered nonfunctional or destroyed by programmed cell death (apoptosis), leaving only lymphocytes that react to foreign molecules.  Fails to have the self tolerance, lead to multiple sclerosis.
 

    D. Humoral Immunity

        Involves B cell activation and results from the production of antibodies that circulate in the blood plasma and lymph.

   Fig.  43.13
T-dependent antigen --> MHC II protein, macrophage -->CD4 (T cell surface protein), Helper T cell--->Activated helper T

cell -- >IL2 and other cytokines--> B cell --> memory B cells and plasma cells --> Secreted antibodies.

        1. T – dependent antigen:

            In humoral immunity, antigens that can activate B cell proliferation and cause them to different into a clone of

            antibody-secreting plasma cells, only with help from TH  (Helper T cell).  The response is usually strong and memory

            B cells are generated in this process.  Most antigens are T-dependent antigens.

        2. T--independent antigen:
            Antigens that can activate B cell proliferation and differentiation without help from TH  (Helper T cell).  The response

            is usually weaker and no memory B cells are generated in this process.

    E. Cell – mediated Immunity
        Immunity to some infections could be passed along only if T lymphocytes were transferred.

        Fig 43.12

        Cytotoxic T cells, MHC I protein, and CD8 (Tc surface protein), antigen---> IL2 from helper T cell---> active killer cells (cytotoxic T cells)---> Tc release perforin to lyse the target cell.

    F. An Overview of the Immune Response:
        Fig.  43.10
 

    G. Helper T lymphocytes function in both humoral and cell-mediated immunity.

       Fig. 43.11
 

III. Immunization

Also known as vaccination, which artificially provide active immunity to human body.

    A. Vaccines:  inactivated bacterial toxins, killed microbes, parts of microbes, and viable but weakened microbes.

    Vaccines:  agents can no longer cause disease, but they retain the ability to act as antigens, and stimulating an immune

                    response, more importantly stimulate the immunological memory, which leads to the quick secondary immune

                    response.  Measles, whooping cough, and smallpox.

    Active immunity: Depends on the response of the infected person’s own   immune system.

    Passive immunity:  Antibodies can be transferred from one individual to another, providing passive immunity.

    B. Antisera:  a high concentration of antibodies taken from the blood of an individual who has been exposed to a particular

                        pathogen.

        Some antisera occurs naturally, mother’s IgG antibodies pass through the placenta to her fetus.

    C. Interferons:  a type of proteins, produced by white blood cells, that serves as defense against viruses by interfering

        with viral replication.

    D.    Monoclonal antibody:  a defensive protein produced by cells descended from a single cell; an antibody secreted by a

           clone of cells and consequently, is specific for a single antigenic determinant.
 

IV. Acquired Immune Deficiency Syndrome (AIDS)

     AIDS is an immuneno deficiency disease caused by a virus.

    A. Molecular Biology of HIV
        A retrovirus  HIV-1, and HIV-2: the reverse transcribed RNA directing the synthesis of a viral DNA, which is integrated   into the host cell genome, the viral genome would direct the production of new virus particles, CD4 molecules on helper T cells function as the major receptor for the virus instead, not functioning in the normal immune system, helping the helper T cells, therefore disable the immune system.

    B. HIV infection:  body fluid containing infected cells, such as semen or blood.

    C. The scope of the HIV epidemic.

        HIV was first identified in 1983,
 
        HIV entered the U.S. population in the late 1970s.

       513,486 cases of people with AIDS had been reported to CDC  in the U.S. as of DEC.31, 1995.

       319,849 had died by the end of 1995, a leading killer of people aged 25 to 44 in the U.S.
 

        Worldwide, an estimated 27.9 million had become HIV-infected through mid-1996, and 7.7 million had developed

        AIDS.

        Projection indicated that 40 to 110 million people worldwide will be HIV-infected in the 21st century.

    D. AIDS Therapies and Vaccines

        Combination Therapy.

        In the United States, doctors can prescribe eleven anti-HIV drugs.

        These eleven drugs full into three groups:

        1.  Nucleoside analog reverse transcriptase inhibitors:  Five drugs.

        2.  Non-nucleoside reverse transcriptase inhibitors: Two drugs.

        3.  Protease inhibitors: Four drugs.

More information about AIDS, Go TO:  http://www.aegis.com/topics/basics/hivandaids.html