Immunology PDF

What if the innate immune response is not enough to control a pathogen infection? If the innate immune response cannot control pathogen growth, then the adaptive immune response is induced. Bone marrow stem cells are the source for all immune cells, including lymphocyt...

What if the innate immune response is not enough to control a pathogen infection? If the innate immune response cannot control pathogen growth, then the adaptive immune response is induced. Bone marrow stem cells are the source for all immune cells, including lymphocytes. B and T lymphocytes provide adaptive immunity and are produced from a different lineage from innate immune cells. All the immune system characteristics that we are familiar with (memory, specificity, diversity, tolerance) are associated with adaptive immunity. However, the adaptive immune response can’t work by itself; it is dependent upon innate immune function. Antibodies (Immunoglobulin) are proteins secreted by B lymphocytes that provide highly specific immunity: they are heterodimers composed of ‘heavy’ and ‘light’ polypeptide chains that together form binding sites for pathogen structures known as “antigens”. Different antibodies can have very Antibody structure different antigen binding sites Any molecule that provokes an adaptive immune response is called an “antigen”. Antibodies bind specific areas (epitopes) on larger molecules. All types of molecules can be recognized as antigens, including proteins, carbohydrates, lipids, and nucleic acids. Pathogens include numerous antigens, and each typically has multiple epitopes.  The diversity of the adaptive immune response depends upon generating a huge population of lymphocytes, each with a different specificity. Each mature B cell is capable of secreting antibodies that bind a pathogen structure which is different from the structures bound by antibodies secreted by other B cells. Stem cell in bone marrow Pool of mature B cells The immune system has the potential to produce as many as 1011 different antibody specificities  Clonal Selection Mechanism Exposure to pathogen antigens stimulates the proliferation and differentiation of only those lymphocytes that can bind the antigens. Most activated lymphocytes provide anti-pathogen response, e.g. antibody secretion, while a few become long-lived memory cells. B lymphocytes can produce antibodies (immunoglobulin) Clonal Selection Mechanism Immunoglobulin structure The immune system generates a huge pool of lymphocytes, each with a different specificity. Exposure to pathogen antigens stimulates the proliferation and differentiation of only the antigen-binding lymphocytes. Diverse antibody specificities are generated by recombination of immunoglobulin (Ig) gene segments in individual cells during the development of B cells in the bone marrow. Random combination of V, D, J gene segments creates a unique Ig gene coding for a unique antigen binding site.  Gene segment recombination occurs for both antibody heavy and light chain genes during development of B cells in the bone marrow. The unique combination of gene segments generated in each B cell creates antibodies with unique binding specificity. The heavy and light chains generated in each B cell combine to make a complete antibody molecule with unique antigen binding sites. Antibodies provide immunity in a several different ways. Directed cytotoxicity  Proliferation and activation of mature B cells takes place in 2° lymphoid tissue, e.g. lymph nodes, and depends upon antigen recognition by immunoglobulin expressed as a receptor on the cell surface. Receptor aggregation signals activation. B cell antigen receptor structure: immunoglobulin chains associated with Iga and b signaling subunits B cells almost always need help from T cells to become activated. Cytokines cytokines T cells supply signals through cytokines and cell surface receptor interactions. B cell activation is accompanied by maturation into antibody- secreting Plasma cells, or long-lived Memory cells.  B cell activation can also result in changing the isotype (class) of antibody that is produced by individual B cells. B cells start out producing IgM, but can switch to the IgG, IgA, or IgE class. These classes differ in their heavy chain constant region (Fc). Fc region The constant region gene segment is switched by deletion of Fc regions determine structural intervening DNA sequences without and functional differences. changing the antigen binding site.  IgG class antibodies can be recognized by immune cells with receptors for the IgG Fc region. Macrophages have IgG Fc receptors which allows them to efficiently ingest antibody coated (opsonized) pathogens Natural killer cells also have IgG Fc receptors which allows them to efficiently kill pathogen infected cells bound by IgG antibodies.  Dimeric IgA is transported across the intestinal epithelium (transcytosis). In the lumen of the intestine IgA is able to block pathogen binding or the action of toxins. Transcytosis of IgA also occurs in salivary glands  The Fc region of both IgM and IgG classes of antibody serve as attachment sites for complement proteins when the antibodies are bound to pathogen surfaces. Recruitment of complement initiates pore formation in the pathogen membrane. Complement proteins kill pathogens by forming pores in their membranes  IgE class of antibodies are bound by Fc receptors on Mast cells. Binding of antigen (allergens) to the bound IgE induces Mast cells to release mediators, such as histamine, which elicit an allergic reaction. Development of memory B cells means that a second response to the same antigen occurs faster, with more Ig produced, and with a larger fraction of non-IgM antibody classes.