Microbiology 2 - Innate & Adaptive Immunity.pdf

Microbiology Innate & Adaptive Immunity Microbiology| Innate & Adaptive Immunity Contents : Historical Perspective 8 Innate and Adaptive Components 11 Phagocytosis and Intracellular Killing 19 Response of phagocytes to infection 22 Initiation of Phagocytosis 24 Respiratory burst and intracellular ki...

Microbiology Innate & Adaptive Immunity Microbiology| Innate & Adaptive Immunity Contents : Historical Perspective 8 Innate and Adaptive Components 11 Phagocytosis and Intracellular Killing 19 Response of phagocytes to infection 22 Initiation of Phagocytosis 24 Respiratory burst and intracellular killing 30 Microbiology| Innate & Adaptive Immunity The immune system is a defense system that has evolved to protect animals from invading pathogenic microorganisms and cancer. It is able to generate enormous variety of cells and molecules capable of specifically recognizing and eliminating an apparently limitless variety of foreign invaders. Microbiology| Innate & Adaptive Immunity These cells and molecules act together in a dynamic network whose complexity resemble that of the nervous system. Functionally, an immune response can be divided into two related activities recognition and response. Immune recognition is remarkable for its specificity. Microbiology| Innate & Adaptive Immunity The immune system is able to recognize subtle chemical differences that distinguish one foreign pathogen from another. Furthermore, the system is able to discriminate between foreign molecules and the body’s own cells and proteins. Microbiology| Innate & Adaptive Immunity Response: Once a foreign organism has been recognized, the immune system recruits a variety of cells and molecules to mount an appropriate response, called an effectors' response, to eliminate or neutralize the organism. Microbiology| Innate & Adaptive Immunity In this way the system is able to convert the initial recognition event into a variety of effector responses, each uniquely suited for eliminating a particular type of pathogen. Later exposure to the same foreign organism induces a memory response, characterized by a more rapid and heightened immune reaction that serves to eliminate the pathogen and prevent disease. Microbiology| Innate & Adaptive Immunity Historical Perspective : The discipline of immunology grew out of the observation that individuals who had recovered from certain infectious diseases were thereafter protected from the disease. The Latin term immunis, meaning “exempt,” is the source of the English word immunity, meaning the state of protection from infectious disease. Microbiology| Innate & Adaptive Immunity The first recorded attempts to induce immunity deliberately were performed by the Chinese and Turks in the fifteenth century. Various reports suggest that the dried crusts derived from smallpox pustules were either inhaled into the nostrils or inserted into small cuts in the skin (a technique called variolation) Microbiology| Innate & Adaptive Immunity the English physician Edward Jenner, in 1798, Intrigued by the fact that milkmaids who had contracted the mild disease cowpox were subsequently immune to smallpox, which is a disfiguring and often fatal disease, Jenner reasoned that introducing fluid from a cowpox pustule into people (i.e., inoculating them) might protect them from smallpox. Pasteur extended these findings to other diseases, demonstrating that it was possible to attenuate, or weaken, a pathogen and administer the attenuated strain as a vaccine Microbiology| Innate & Adaptive Immunity The Immune System Includes Innate and Adaptive Components : Immunity: the state of protection from infectious disease, it has both a less specific and more specific component. The less specific component, innate immunity, provides the first line of defense against infection. Most components of innate immunity are present before the onset of infection and constitute a set of disease-resistance mechanisms that are not specific to a particular pathogen but that include cellular and molecular components that recognize classes of molecules peculiar to frequently encountered pathogens. Microbiology| Innate & Adaptive Immunity Microbiology| Innate & Adaptive Immunity Although the innate and adaptive immune systems both function to protect against invading organisms, they differ in a number of ways. The adaptive immune system requires some time to react to an invading organism, whereas the innate immune system includes defenses that, for the most part, are constitutively present and ready to be mobilized upon infection. Microbiology| Innate & Adaptive Immunity Second, the adaptive immune system is antigen specific and reacts only with the organism that induced the response. In contrast, the innate system is not antigen specific and reacts equally well to a variety of organisms. Finally, the adaptive immune system demonstratesimmunological memory. It “remembers” that it has encountered an invading organism and reacts more rapidly on subsequent exposure to the same organism. In contrast, the innate immune system does not demonstrate immunological memory. Microbiology| Innate & Adaptive Immunity Innate (Non-Specific Immunity) Anatomical barriers to infections Humoral barriers to infection Cellular barriers to infection Microbiology| Innate & Adaptive Immunity Anatomical Barrier Mechanical factors Chemical factors Biological factors Microbiology| Innate & Adaptive Immunity Humoral barriers to infection Complement Coagulation B lysin Lactofrrin & transferrin IFN Lysozyme IL1 Microbiology| Innate & Adaptive Immunity Cellular barriers to infection Neutrophils (PMNs) Macrophages NK (LAK) Eosinophils Microbiology| Innate & Adaptive Immunity Phagocytosis and Intracellular Killing : A. Phagocytic cells 1. Neutrophils/Polymorphonuclear cells PMNs are motile phagocytic cells that have lobed nuclei. They can be identified by their characteristic nucleus or by an antigen present on the cell surface called CD66. They contain two kinds of granules the contents of which are involved in the antimicrobial properties of these cells. Microbiology| Innate & Adaptive Immunity Primary or Azurophilic Granules Secondary or Specific Granules Contain cationic proteins & defensins that can kill Bacteria Lysozyme Proteolytic enzymes like elastase, and cathepsin G to breakdown proteins NADPH oxidase components, which are involved in the generation of toxic oxygen products Lysozyme to break down bacterial cell walls Myeloperoxidase, which is involved in the generation of bactericidal compounds Lactoferrin, an iron chelating protein B12-binding protein Microbiology| Innate & Adaptive Immunity 2. Monocytes/Macrophages Macrophages are phagocytic cells that have a characteristic kidney-shaped nucleus. They can be identified morphologically or by the presence of the CD14 cell surface marker. Unlike PMNs they do not contain granules but they have numerous lysosomes which have contents similar to the PNM granules. Microbiology| Innate & Adaptive Immunity Response of phagocytes to infection : Circulating PMNs and monocytes respond to danger signals generated at the site of an infection. signals include: 1. N-formyl-methionine containing peptides released by bacteria. 2. clotting system peptides. 3. Complement products and cytokines released from tissue macrophages that have encountered bacteria in tissue. Microbiology| Innate & Adaptive Immunity 4. Some signals stimulate endothelial cells near the site of the infection to express cell adhesion molecules such as ICAM-1 and selectins which bind to components on the surface of phagocytic cells and cause the phagocytes to adhere to the endothelium. 5. Vasodilators produced at the site of infection cause the junctions between endothelial cells to loosen and the phagocytes then cross the endothelial barrier by “squeezing” between the endothelial cells in a process called diapedesis. 6. Once in the tissue spaces some of the signals attract phagocytes to the infection site by chemotaxis (movement toward an increasing chemical gradient). Microbiology| Innate & Adaptive Immunity Initiation of Phagocytosis : Phagocytic cells have a variety of receptors on their cell membranes through which infectious agents bind to the cells. Microbiology| Innate & Adaptive Immunity 1. Fc receptors: Bacteria with IgG antibody on their surface have the Fc region exposed and this part of the Ig molecule can bind to the receptor on phagocytes. Binding to the Fc receptor requires prior interaction of the antibody with an antigen. Binding of IgG-coated bacteria to Fc receptors results in enhanced phagocytosis and activation of the metabolic activity of phagocytes (respiratory burst). Microbiology| Innate & Adaptive Immunity 2. Complement receptors: Phagocytic cells have a receptor for the 3rd component of complement, C3b. Binding of C3b-coated bacteria to this receptor also results in enhanced phagocytosis and stimulation of the respiratory burst. 3. Scavenger receptors: Scavenger receptors bind a wide variety of polyanions on bacterial surfaces resulting in phagocytosis of bacteria. Microbiology| Innate & Adaptive Immunity 4. Toll-like receptors: Phagocytes have a variety of Toll-like receptors (Pattern Recognition Receptors or PRRs) which recognize broad molecular patterns called PAMPs (pathogen associated molecular patterns) on infectious agents. Binding of infectious agents via Toll-like receptors results in phagocytosis and the release of inflammatory cytokines (IL-1, TNF-alpha and IL-6) by the phagocytes. Microbiology| Innate & Adaptive Immunity Phagocytosis : After attachment of a bacterium, the phagocyte begins to extend pseudopods around the bacterium. The pseudopods eventually surround the bacterium and engulf it, and the bacterium is enclosed in a phagosome. Microbiology| Innate & Adaptive Immunity During phagocytosis the granules or lysosomes of the phagocyte fuse with the phagosome and empty their contents. The result is a bacterium engulfed in a phagolysosome which contains the contents of the granules or lysosomes. Microbiology| Innate & Adaptive Immunity Respiratory burst and intracellular killing : During phagocytosis there is an increase in glucose and oxygen consumption which is referred to as the respiratory burst. The consequence of the respiratory burst is that: 1. a number of oxygen-containing compounds are produced which kill the bacteria being phagocytosed. This is referred to as oxygen-dependent intracellular killing. 2. In addition, bacteria can be killed by pre-formed substances released from granules or lysosomes when they fuse with the phagosome. This is referred to as oxygenindependent intracellular killing. Microbiology| Innate & Adaptive Immunity Microbiology| Innate & Adaptive Immunity Oxygen-independent intracellular killing : 1. cationic proteins (cathepsin) released into the phagolysosome can damage bacterial membranes. 2. Lysozyme breaks down bacterial cell walls. 3. Lactoferrin chelates iron, which deprives bacteria of this required nutrient. 4. Hydrolytic enzymes break down bacterial proteins. Microbiology| Innate & Adaptive Immunity Thus, even patients who have defects in the oxygen-dependent killing pathways are able to kill bacteria. However, since the oxygen-dependent mechanisms are much more efficient in killing, patients with defects in these pathways are more susceptible and get more serious infections. Microbiology| Innate & Adaptive Immunity Non-specific Killer Cells : A. Natural killer (NK): cells are also known as large granular lymphocytes (LGL) because they resemble lymphocytes in their morphology, except that they are slightly larger and have numerous granules. Microbiology| Innate & Adaptive Immunity NK cells can be identified by the presence of CD56 and CD16 and a lack of CD3 cell surface markers. NK cells are capable of killing virus-infected and malignant target cells but they are relatively inefficient in doing so. Microbiology| Innate & Adaptive Immunity However, upon exposure to IL-2 and IFN-gamma, NK cells become lymphokineactivated killer (LAK) cells, which are capable of killing malignant cells. Continued exposure to IL-2 and IFN-gamma enables the LAK cells to kill transformed as well as malignant cells. LAK cell therapy is one approach for the treatment of malignancies. Microbiology| Innate & Adaptive Immunity How do NK and LAK cells distinguish a normal cell from a virus-infected or malignant cell? NK and LAK cells have two kinds of receptors on their surface – a killer activating receptor (KAR) and a killer inhibiting receptor (KIR). When the KAR encounters its ligand, a killer activating ligand (KAL) on the target cell the NK or LAK cells are capable of killing the target. However, if the KIR also binds to its ligand then killing is inhibited even if KAR binds to KAL. Microbiology| Innate & Adaptive Immunity The ligands for KIR are MHC-class I molecules. Thus, if a target cell expresses class I MHC molecules it will not be killed by NK or LAK cells even if the target also has a KAL which could bind to KAR. Microbiology| Innate & Adaptive Immunity Normal cells constitutively express MHC class I molecules on their surface, however, virus infected and malignant cells down regulate expression of class I MHC. Thus, NK and LAK cells selectively kill virus-infected and malignant cells while sparing normal cells. Microbiology| Innate & Adaptive Immunity B. Kill cell: Killer (K) cells are not a morphologically distinct type of cell. Rather a K cell is any cell that mediates antibody-dependent cellular cytotoxicity (ADCC). In ADCC antibody acts as a link to bring the K cell and the target cell together to allow killing to occur. Microbiology| Innate & Adaptive Immunity K cells have on their surface an Fc receptor for antibody and thus they can recognize, bind and kill target cells coated with antibody. Killer cells which have Fc receptors include NK, LAK, and macrophages which have an Fc receptor for IgG antibodies and eosinophils which have an Fc receptor for IgE antibodies.