1 1 N5315 Advanced Pathophysiology Immune System and Infectious Disease Immune System Physiology There are five types of immunity: • Natural Immunity (AKA Innate Resistance/Immunity). This is resistance that exists prior to exposure to a microbe. We are born with this resistance and it is based on our genotypes and species. For example, humans cannot become infected with canine distemper. Dogs/cats can’t be infected with West Nile virus. Natural immunity is provided by nonspecific barriers to infection such as the skin, mucous membranes, certain cells (NK cells), certain proteins (complement, cytokines), and involves inflammation and phagocytosis. It does not improve after exposure. It functions to kill invading microorganisms and activates acquired immunity. The cells of innate immunity include phagocytic cells, antigen presenting cells, natural killer cells, and complement. o Phagocytic cells include neutrophils, macrophages, and dendritic cells. ▪ Neutrophils are present during acute inflammation and are responsible for engulfing microbes and kills them by using a cytoplasmic myeloperoxidase which is toxic to pathogens. ▪ Macrophages are derived from monocytes, which leave the blood stream and differentiate in tissues. ▪ Dendritic cells engulf antigens in the epithelia of the skin, GI and respiratory tracts. o Antigen presenting cells include dendritic cells, macrophages and B cells. APC ingest and process antigens. The peptides are loaded on to their major histocompatibility complex II molecule and are presented to the T-cell. o Natural Killer Cells contain granules that attack and kill virus-infected or cancerous cells. o Complement is comprised of a collection of proteins which are formed by a cascade of events. It is not important to know the steps in the production of the complement system. Ultimately, they form the membrane attack complex and lyse a pathogen’s cell membrane. • Acquired Immunity is the state of immunity that is obtained after exposure to an antigen. It improves with repeat exposure and it is specific. Active acquired immunity is produced by the host after exposure to an antigen or an immunization. This is the basis of vaccinations.2 2 • Passive acquired immunity is that immunity acquired via the transfer of antibodies, or T-cells to the recipient. Natural Passive immunity occurs via mother to fetus. Antibodies cross the placenta or in the breast milk. Artificial Passive Immunity occurs when antibodies are given to a recipient to provide immunity. This is used to treat rabies, tetanus, hepatitis, and snake bites. It is a good way to fight infection, it provides immediate protection, but the immunity only lasts as long as the antibodies, approximately 2 weeks. • Humoral immunity is that immunity conferred by the B-Cells. It provides immunity against some viral infections, toxin induced diseases and diseases caused by pneumococci, meningococci, or Haemophilus. • Cell-Mediated immunity is that immunity conferred by T-Cells. Immunity is active against cells infected with intracellular bacteria or viruses. It defends against cancer, fungal infections, parasitic infections, tumors, and is responsible for organ transplantation rejection. Organs of the Immune System Review The bone marrow, thymus, spleen, lymph nodes, tonsils and peyer patches all have a role in immunity. The bone marrow is responsible for the production of immune cells and the maturation of B cells. As we grow, the thymus shrinks, but it provides a site for T -cell differentiation, maturation and selection. The spleen is a lymphoid organ and contains blood filled sinuses which filter antigens and cells from the blood. The red pulp is the location of red blood cell storage and turnover. The white pulp is the site where immune cell interaction occurs. Antigen presenting cells present antigens to the lymphocytes in the spleen which triggers the immune response. Persons who have had their spleen removed or have a nonfunctional spleen as is the instance with persons with sickle cell disease are at an increased risk for infection, particularly infections caused by streptococcal bacteria. These individuals require the pneumococcal vaccine. The lymph nodes, tonsils, and peyer patches are also sites where antigens interact with immune cells. Cell Mediated Immune Response Cell-Mediated Immunity/Response is governed by T-Cells. T-cells are differentiated (named) by the expression of antigens on their cell membrane called “cluster of differentiation” (CD). There are many different types of CD cells but what I want you to know is in this lecture. CD4 cells are aka T-helper or T4 cells. They function to activate macrophages, B-cells, cytotoxic T-cells and other CD4 cells. They release lymphokines that begin the inflammatory process and they mediate delayed hypersensitivity reactions such as the TB skin test. These functions are performed by a subgroup of CD4 cells called TH1 and TH2. These are the cells that release lymphokines.3 3 CD8 cells are cytotoxic T-cells, AKA CD8 Cells, Killer T’s, T8 cells. They function to kill virus infected cells, tumor cells and allograft cells (transplant tissue) directly through the release of cytotoxic chemicals which destroy the cell membrane or induce apoptosis. Memory T-cells allow the host to remember antigens and respond quicker and more vigorously after the initial exposure. They live for many years and can reproduce themselves. T-regulatory cells slow or stop the immune response once the invader is defeated Activation of T-Cells: • Antigen presenting cells include B-lymphocytes, macrophages, and dendritic cells. • Antigen enters host → Macrophage (or other APC) engulfs antigen → antigen expressed on MHC class II → secretes IL 1 to attract CD4 cells → presents it to CD4-cells → CD4 differentiates into Th1 and Th2→ Th1 releases IL2 → activated cytotoxic T-cells (Tc) → Tc receptor connects with MHC class I receptor on invader → cytotoxic chemicals released → invader killed. Th2 releases IL4 → activates the humoral immune system Humoral Immune Response Is governed by B-Cells. B-cells mature into plasma cells that then produce antibodies There are 5 classes of antibodies (glycoproteins): • IgG is the most prominent immune globulin. It binds with viruses, bacteria and toxins. It activates complement and binds to macrophages. It is the primary antibody in the secondary
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