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Transcript
Immunology Review Part One Immune Responses Innate Immunity • First line of defense in preventing foreign substances from entering body. • Available at birth (innate or natural). • Generalized, nonspecific reaction. Innate Immunity • No prior exposure to foreign substance required. • Response doesn’t change with further exposure. • Influenced by: – Age – Stress – Fatigue – Nutritional status Elements Of Innate Immunity • Skin • Tears, saliva, secretions • Mucus • Chemicals • pH • • • • • • Normal flora Temperature Cough Reflex Toll-like receptors Phagocytes Inflammation Phagocytosis • Monocyte, macrophage, eosinophil or neutrophil drawn in to area by chemotactic factors such as complement or cytokines. • Receptors on phagocyte make contact with foreign material. – May be enhanced by CRP, complement or antibodies. (Opsonins) • Phagocyte engulfs foreign material to form phagosome. • Phagosome merges with granules in cytoplasm. Granules contain chemicals that digest foreign material. • Waste material is expelled from phagocyte (exocytosis). Inflammation • Capillaries dilate and blood accumulates in the affected area, leading to redness and increased temperature. • Fluid accumulates, causing edema. • Phagocytes migrate into the tissue and destroy foreign invaders. Cells Alive! • To see the interaction between elements of innate immunity, please go to http://www.cellsalive.com/ouch1.htm • View “Anatomy of a Splinter”. Acquired (Adaptive) Immunity • Forms only after exposure to foreign substance. • Response is specific to the foreign stimulus. • Recognizes self vs. non-self. • Displays memory. • 2 forms: – Cell mediated – Humoral Cell Mediated Immunity Cell Mediated Immunity • Controlled by T lymphocytes. – Influence other parts of the immune system (including the humoral response) through the release of cytokines. • Responsible for such processes as delayed hypersensitivity, transplant immunity, and tumor rejection. Cell Mediated Process • Foreign matter is broken down into smaller peptides. • Peptides combine with the Major Histocompatibility Complex (MCH) antigens. Major Histocompatibility Complex • Found on the membrane of every nucleated cell. • Three classes: – I (A, B, C loci) – II (DR, DQ, DP loci) – III (complement , Tumor Necrosis Factor [TNF]) • MHC Class I and II antigens each have an antigen binding groove which carries foreign peptides. Major Histocompatibility Complex Class II Class I Antigen Binding Groove Antigen Binding Groove Pathogen Recognition • MHC Class I antigens are found on almost every nucleated cell in the body • These antigens bind peptides that are produced within the cell – Tumors, viruses, intracellular bacteria – These peptides are termed endogenous antigens Pathogen Recognition • MHC Class II molecules are found on monocytes, macrophages, dendritic cells, and B lymphocytes. – Termed Antigen Presenting Cells (APC) • Class II molecules bind foreign peptides that come from bacteria, virus, or parasites that have been ingested by the APC. – Termed exogenous antigens Pathogen Recognition • T cells possess receptors (TCR) that recognize foreign antigen when it is bound to MHC antigen. – T cytotoxic lymphocytes (Tc cells) interact with Class I antigens. – T helper lymphocytes (TH cells) interact with Class II antigens. • TCR is coupled to CD3. • CD3 signals the interior of the T cell that antigen is present. • T cell then secretes cytokines that effect surrounding cells. • Some T cells mature into memory T cells. These assist with rapid recognition of the foreign antigen the next time it is encountered, thus speeding up the immune response. T Lymphocyte Subsets • T helper cells (TH) – – – – Make up 2/3’s of the T lymphocyte population CD4 positive React with MHC class II proteins Stimulate both the cytotoxic and the humoral responses • T cytotoxic cells (TC) – CD8 positive – React with MHC class I proteins Cytotoxic T Cells • TC cell recognizes the foreign peptides associated with the Class I MHC antigen. – Recognition via the TCR and CD8. • TC produces perforin, a protein that causes disruption of the membrane of the affected cell. • The affected cell dies by apoptosis. – Cell fragments into smaller particles. – Fragments are engulfed by phagocytes. • Cytokines TNF and interferon are released by the TC to prevent spread of virus. – May injure healthy tissue. Cells Alive! • Please go to http://www.cellsalive.com/ctl.htm • View “The Cytotoxic T Lymphocyte”. Humoral Immunity Humoral Immunity • Major cell involved is the B cell. • Develops into plasma cells and memory cells. • Influenced by T helper cells. The Humoral Process • Foreign antigen is introduced to host. • Antigen Presenting Cells (APCs) process antigen into peptide fragments, then present it to the TH lymphocyte. – Dendritic cells and macrophages function as APCs – Foreign peptides bind to MHC Class II antigens • The TH recognizes the foreign antigen through its T Cell Receptor (TCR) and CD4. The Humoral Process • The B cell has also recognized the foreign antigen via the B cell receptor (BCR), and processed the foreign antigen. – Foreign peptide is then expressed on the surface MHC class II molecules. • TH recognizes that the peptide seen by its TCR and the peptide presented by the B cell are the same. • TH releases cytokines to stimulate B cell. The Humoral Process • B cells divide into plasma cells or memory cells. – Plasma cells produce and secrete antibody. – The antibody produced is specific for one antigenic determinant! – Memory cells recall previous encounter with foreign antigen. Persist in circulating lymphocyte pool for months up to years. Cells Alive! • Please go to http://www.cellsalive.com/antibody.htm • View “Making Antibodies”. The Humoral Process • Signals from the TH influence the class of antibody produced by the B cell and the ability to switch immunoglobulin classes. – Interleukins – Transforming growth factor • IgM is the first immunoglobulin produced. • Most B cells switch from IgM production to IgG, the most prevalent immunoglobulin. Primary vs. Secondary Humoral Response IgG IgM IgM IgG First exposure to antigen Second & subsequent exposures to the same antigen Primary Response • First time the host encounters the foreign antigen. • Latency period: Lag time between exposure to antigen and production of antibodies. • IgM is the main class of antibody (immunoglobulin) produced. – Some IgG is made. Primary Response • Concentration of antibody (titer) is relatively low. • Antibody titer drops off quickly. Secondary Response • Also called the anamnestic or memory response. • A repeat encounter with the same foreign antigen. • Usually takes a smaller dose of antigen to stimulate the response. • Memory cells hasten the immune response. Secondary Response • IgG is the primary immunoglobulin produced. – Some IgM is also made. • Response is faster. • Antibody titer is higher. • Antibody detectable for a longer period of time. Secondary Response Faster, Higher, Stronger, Longer This concludes “Immunology Review, Part One: Immune Responses” Please complete the exercise “Comparing Immune Response Mechanisms”
