Chapter 15

Specific Defenses of the Host

Specific immunity When the non-specific defense fails, then the third, specific line of immunity is activated Immunity is not innate but adaptive; it is acquired over time It is characterized with a specificity and memory Specificity antibodies against chickenpox is not effective against measles virus During the 2nd encounter with a pathogen, the lymphocytes recall the 1st engagement and attack it again Immunity is a defensive response of the body when a foreign organism or foreign substance invades it. Antigens are substances (proteins or polysaccharides) that provoke immune response Antibodies are proteins produced to inactivate the antigens During the immune response, lymphocytes recognize and bind to the antigen The immune system has two components: 1. Humoral immunity production of antibodies (B-cells) 2. Cell-mediated immunity activation and proliferation of immune system cells (T-cells) Overview of lymphocyte development and interaction There are 5 Stages: 1. Development of B-cells and T-cells 2. Antigen presenting cells present the antigen to lymphocytes (T-helper cells) 3. Lymphocytes activation formation of B and T cells 4. B lymphocytes become plasma cells produce antibodies 5. Activated T cells become Helper T cells and cytotoxic T cells Specificity of the lymphocytes They have receptor sites on the cell surface that can recognize millions of different antigens This great diversity of receptor sites is achieved through genetic recombination of 500 genes The lymphocytes with the receptor sites for self cells are eliminated Upon entry of an antigen, only lymphocytes specific to that antigen proliferate clonal selection Characteristics of Antigens Not a normal constituent of the body They are components of microbial cells (capsule, cell wall, flagella, fimbriae, microbial toxins, and coats of viruses), humans, plants, animals They belong to: proteins, lipoproteins, glycoproteins Good antigens have complex molecules Poor antigens have small and simple molecules Antigens contain specific regions that are recognized by antibodies antigenic determinants or epitopes

Superantigens (bacterial toxins) can trigger a 100 times greater response of immune system toxic shock syndrome Antigen Processing and Presentation Antigen Processing Antigen Processing Cells (APC) ingest a bacterial cell degrade the antigen into smaller peptides The processed antigens are complexed with a cell glycoprotein MHCII (major histocompatibility complex) and transported to the cell surface Antigen Presentation The processed antigens are presented to lymphocytes T cells are activated they release interleukin-2 B-cell activation and antibody synthesis The linked receptor of T-cells and B-cells, and chemical stimulus from the T-cell stimulates the B-cells Proliferation and differentiation of B-cells Two types of cells are formed: memory cells and plasma cells Memory cells play role in future exposure to the same antigen Plasma cells synthesize and release the antibodies Antibody Structure Antibodies are specific proteins (immunoglobulins Ig) developed by the body that is invaded by a specific microorganism The antibody molecule is Y-shaped. It consists of 4 protein chains: 2 identical heavy chains 2 identical light chains Each antibody molecule has two binding sites (site that binds to antigen) Antibody molecule is made up of constant region variable region binds the epitope of the antigen Antibody-Antigen Interactions Complementary fit between antigen and antibody is needed The better the fit the better the stimulation of the lymphocytes Antigen - Antibody Binding Antigens are rendered harmless by different mechanisms: Agglutination - antibodies cross-link the antigens (bacterial cells) forming aggregates that are more easily digested by phagocytes Opsonization - antibodies coat the antigens enhancing the phagocytosis Neutralization - antibodies block the active sites on viruses (or bacteria) preventing their attachment to host cells Immunoglobulin classes IgG 80% of all antibodies; effective against bacteria, toxins, trigger the complement system, long term immunity IgA - Abundant in mucus membranes IgM Large molecule, first to appear, circulate in blood

IgD In small amounts (1%) has no well-defined function, B-cell activation IgE - Play role in allergic reactions

Primary and Secondary Responses to Antigen Primary response There is a latent period Takes longer to reach the maximum Secondary response Memory cells responsible Fast response Higher concentration of immunoglobulins Basis for vaccination T cells and cellular immunity Produced in the bone marrow, mature in thymus gland, and wait for the encounter with antigens in the lymphoid organs Two populations of T cells: Helper T cells (with CD4 receptor) Cytotoxic T cells Recognize peptides that are presented on dendritic cells Helper Cells Activated helper cells produce cytokins Th cells proliferate and produce cytotoxic T cells natural killer cells macrophages Depression of T cell (class CD4) by HIV is responsible for pathology of AIDS Cytotoxic T Cell Recognize and kill the infected cell (some microorganisms multiply inside the host cell) Recognize and kill nonself (tumor) cells Attaches to the target cell and releases perforin (pore-forming protein) Natural Killer Cells Lymphocytes related to T cells They do not have specificity for antigen The first to attack cancer cells and virus infected cells Classifying Specific Immunity Natural active immunity Getting the infection Natural passive immunity Maternal antibodies are transported across placenta Artificial Active Immunity Vaccination Artificial Passive Immunity (Immunotherapy)

Administration of specific antibody obtained by vaccinating animals and extracting the serum

Monoclonal Antibodies Technique by which large amounts of specific antibodies can be produced Vaccines Vaccine is a suspension of microorganisms or their cell components that are injected into a human or animal body in order to induce immunity. The purpose of vaccination is to control microbial diseases and to prevent epidemics Types of vaccines Attenuated whole agent vaccine Use of living but attenuated (weakened) or mutant microbes. Measles, mumps, rubella (MMR) Advantage: more closely mimic an actual infection Disadvantage: can backmutate to virulent form and cause a disease Inactivated whole-agent vaccines Use of killed microbes (rabies, influenza, and polio) Killed by formalin or phenol Toxoids Chemically or thermally modified toxins used to stimulate active immunity Tetanus, diphtheria toxoids requires series of injections Require boosters every 10 years Recombinant vaccines Genetically engineered microorganisms produce the antigenic fraction of the pathogen (Hepatitis B). DNA vaccine Promising technology in vaccine production Gene coding for an antigen is incorporated into a plasmid naked DNA (plasmid) injected Human cells will take up the plasmid Foreign protein (antigen) will be expressed This will stimulate immune response Why to Vaccinate? To protect individuals To establish herd immunity Protection of the whole population Prevention of epidemics Protection of non-immunized individuals