- Basic Concepts in Immunology-


 

I. Immunology -

The study of the body's defense against pathogens (viruses, bacteria, fungi, parasites)

II. History and Overview
 

    A. Edward Jenner (late 1700's) - first vaccination against smallpox:
     

      1. Vaccine - a dead or weakened pathogen used to induce immunity without causing any disease - worldwide smallpox vaccinations eliminated disease in 1979.
       
    B. Louis Pasteur (late 1800's) - developed cholera & rabies vaccines

    C. Innate Immunity - present from birth - fast but nonspecific
     

      1. Macrophages - phagocytic cells discovered by Elie Metchnikoff (late 1880's) that can kill  pathogens.
       
    D. Adaptive immunity - acquired during individual's lifetime - slow but specific
     
      1. Antibodies (Ab) (Immunoglobulins - Ig) - (late 1800's) - substances in serum of infected individuals that bind pathogen

      2. Antigens - substances that bind to antibodies (old definition)

      3. Complement (late 1800's) - substances in the serum that destroy pathogens when combined with antibodies

      4. Lymphocytes - (1960's) - required for all forms of adaptive immunity - each lymphocyte is specific for certain antigen (monospecificity). All lymphocytes specific to a particular antigen are called a clone

      5. Clonal Selection Theory - (1950's) - explains how adaptive immunity works - specific lymphocyte clones exist in small numbers before exposure to pathogen - after exposure, clones specific to pathogen proliferate, increase in number and differentiate into effector cells, such as those that secrete pathogen-specific antibodies

III. Features of Adaptive Immunity

    A. Clonal Selection and Tolerance
     
      1. Receptor repertoire - the receptors on all lymphocytes - recognize all antigens except self-antigens

      2. Tolerance - why we normally don't respond to antigens of our self-antigens - lymphocytes with receptors for self antigens are eliminated early in development (central tolerance)

      3. Immunological memory - when the body re-exposed to pathogen, the adaptive  immunity is faster and stronger because of the increased number of pathogen-specific lymphocytes
       

    B. Lymphocyte Differentiation - Antigen Independent
     
      1. B cells and T cells - B-cells secrete antibody (as plasma cells); T-cells develop into effector cells that either kill pathogen- infected cells or activate other parts of the immune system

      2. Where are lymphocytes found?
       

        a. Central Lymphoid Organs - Bone Marrow and Thymus

        b. Peripheral Lymphoid Organs - Lymph Nodes (LN), Spleen (Spl)

        c. Mucosal Surfaces - e,g, Gut-Associated Lymphoid Tissues (GALT) - tonsils, peyers patches of small intestine

        d. In Circulation - Blood and Lymph
         

      3. Where do lymphocytes mature?  B - cells mature in bone marrow whereas T- cells start  in the bone marrow and finish maturing in the thymus. T-cells and B-cells that have yet to be exposed to antigen are called 'naïve' or 'virgin' lymphocytes

      4. How do lymphocytes make such a large repertoire of receptors? They rearrange  gene segments during differentiation - once rearranged to make a specific type of  receptor, the change is permanent, and all the progeny of those cells will have the same receptor. Many types of receptors can be made in this way - called 'combinatorial diversity'

      5. What is the antigen receptor on B-cells and T-cells? membrane-bound Ig on B-cells, T-cell receptor on T-cells

      6. How are self-reactive lymphocytes eliminated during development?
       

        a. Tolerance - cells that respond to self-Ag are killed in a process called 'clonal deletion'
         
    C. Lymphocyte Differentiation - Antigen Dependent
     
      1. Where in the body do lymphocytes encounter antigen? - in the peripheral (secondary)  lymphoid organs - LN or spleen

      2. How does antigen get from site of infection? - via blood or lymph - lymphocytes  recognize antigens and become effector cells

      3. Filter of the lymph - Lymph nodes

      4. Filter of the blood - Spleen

      5. Characteristics common to Spleen, LN and GALT - There are distinct areas for B cells and T cells - B cells that differentiate into antibody-secreting cells are in germinal centers  near the boundary of B and T cell areas

      6. Activated lymphocytes - differentiate into effector cells - cell proliferation causes clonal expansion (formation of lymphoblasts) followed by differentiation into effectors - clonal expansion is characteristic of adaptive immunity

      7. Co-stimulatory signals required for activation of  lymphocytes
       

        a. B cells - 1st signal is binding of Ag to surface Ig; second signal provided by T cells (soluble factors called "cytokines")

        b. T cells - Ist signal is binding of Ag to T cell receptor (TCR); second signal provided by antigen-presenting cells (APC), which are B-cells, macrophages, or dendritic cells APC trap antigens and present them to T cells

IV. Immune response to pathogens

    A. Humoral Immunity - mediated by Ig - good against extracellular pathogens and toxins (e.g., from bacteria). Antibodies can function in 3 ways:
     
      1. Neutralization - physical binding by Ab

      2. Opsonization - binding of Ab to bacteria causes it to be ingested more rapidly by macrophages

      3. Activation of complement - can lyse and kill bacteria
       

    B. Cellular Immunity - mediated by T cells, macrophages, and other cells - good against cells with intracellular pathogens (e.g., tuberculosis)
     
      1. Cytotoxic T cells - can destroy cells infected with viruses

      2. Helper T-cells - activate other cells of immune system

      3. Macrophages - can be activated by T cells and then kill intracellular pathogens

V. Major Histocompatibility Complex (MHC) Antigens

    A. T cells recognize antigen bound to MHC molecules

    B. MHC Class I bearing cells (most body cells) - interact with CD8 positive 'cytotoxic' T-cells that act by direct cell killing

    C. MHC Class II bearing cells (antigen presenting cells) - interacts with CD4 positive 'helper' T-cells, which activate other T cell and B cell responses

VI. Innate Immunity -

operates during early stages of infection - this immunity is induced, but is nonspecific

    A. Complement - can kill some bacteria even in absence of Ab

    B. Acute Phase Proteins - made by liver - can also kill some bacteria

    C. Macrophages - can phagocytose bacteria in absence of Ab

    D. Neutrophils and others

VII. Immune system in health and disease

    A. 'Good' immunity - resistance against second infections - ability to be immunized - possible cancer treatment

    B. 'Bad' immunity - transplant rejections allergies (immunodeficiency (including AIDS), and autoimmune disease

By Dr. J.A.Wise Dept of Biology, Hampton University