Lecture 2 - Innate Immunity PDF

Lecture 2 Innate (non-Specific) immunity Innate immunity is the first line of defense against infections, the elements of the innate immune system include anatomical barriers, secretory molecules and cellular components. Among the mechanical anatomical barriers are the skin and internal epithelial...

Lecture 2 Innate (non-Specific) immunity Innate immunity is the first line of defense against infections, the elements of the innate immune system include anatomical barriers, secretory molecules and cellular components. Among the mechanical anatomical barriers are the skin and internal epithelial layers, the movement of the intestines and the oscillation of broncho- pulmonary cilia. Associated with these protective surfaces are chemical and biological agents. A. Anatomical barriers to infections 1. Mechanical factors The epithelial surfaces form a physical barrier that is very impermeable to most infectious agents. Thus, the skin acts as our first line of defense against invading organisms. The desquamation of skin epithelium also helps remove bacteria and other infectious agents that have adhered to the epithelial surfaces. Movement due to cilia or peristalsis helps to keep air passages and the gastrointestinal tract free from microorganisms. The trapping effect of mucus that lines the respiratory and gastrointestinal tract helps protect the lungs and digestive systems from infection. The flushing action of tears and saliva helps prevent infection of the eyes and mouth 2. Chemical factors Fatty acids in sweat inhibit the growth of bacteria. Lysozyme and phospholipase found in tears, saliva and nasal secretions can breakdown the cell wall of bacteria and destabilize bacterial membranes. The low pH of sweat, gastric secretions, vagina and urine prevents growth of bacteria. Defensins (low molecular weight proteins) found in the lung and gastrointestinal tract have antimicrobial activity. Surfactants in the lung act as opsonins (substances that promote phagocytosis of particles by phagocytic cells). Spermine found in seminal fluid, inhibits growth of G+ve bacteria. Cerumen in the ear has antimicrobial properties. 3. Biological factors The normal flora of the skin and in the gastrointestinal tract can prevent the colonization of pathogenic bacteria by competing with pathogenic bacteria for nutrients or attachment to cell surfaces. B. Humoral barriers to infection The anatomical barriers are very effective in preventing colonization of tissues by microorganisms. However, when there is damage to tissues the anatomical barriers are breached and infection may occur. Once infectious agents have penetrated tissues, another innate defense mechanism comes into play, namely acute inflammation. Humoral factors play an important role in inflammation, which is characterized by edema and the recruitment of phagocytic cells. These humoral factors are found in serum or they are formed at the site of infection. 1. Complement system – The complement system is the major humoral non-specific defense mechanism. Once activated complement can lead to increased vascular permeability, recruitment of phagocytic cells, and lysis and opsonization of bacteria. 2. Coagulation system – Depending on the severity of the tissue injury, the coagulation system may or may not be activated. Some products of the coagulation system can contribute to the non-specific defenses because of their ability to increase vascular permeability and act as chemotacic agents for phagocytic cells. In addition, some of the products of the coagulation system are directly antimicrobial. For example, beta-lysin, a protein produced by platelets during coagulation can lyse many Gram positive bacteria. 3. Lactoferrin and transferrin – By binding iron, an essential nutrient for bacteria, and these proteins limit bacterial growth. 4. Interferon – Interferon are proteins that can limit virus replication in cells. 5. Interleukin-1 – (IL-1) induces fever and the production of acute phase proteins, some of which are antimicrobial because they can opsonize bacteria. C. Cellular barriers to infection Part of the inflammatory response is the recruitment of polymorphonuclear eosinophiles and macrophages to sites of infection. These cells are the main line of defence in the non-specific immune system. 1. Neutrophils – Polymorphonuclear cells (PMNs) are recruited to the site of infection where they phagocytose invading organisms and kill them intracellularly. 2. Macrophages – monocytes are found predominantly in the blood and macrophages are primarily in tissues macrophages functions include phagocytosis and intracellular killing of microorganisms. Furthermore, macrophages act as antigen- presenting cells, which are required for the induction of specific immune responses. 3. Natural killer (NK) can non-specifically kill virus infected and tumor cells. This cells are not part of the inflammatory response but they are important in nonspecific immunity to viral infections and tumor surveillance. 4. Eosinophils – Eosinophils have proteins in granules that are effective in killing certain parasites. Specific (Adaptive) Immune System The immunity is specific against one type of microorganism (It become stronger after many exposures to the microorganism because there is memory cells) Adaptive immunity is often sub-divided into two major types depending on how the immunity was introduced. 1- Naturally acquired immunity A- Naturally acquired active immunity Naturally acquired active immunity occurs when a person is exposed to a live pathogen, and develops a primary immune response, which leads to immunological memory. This type of immunity is “natural” because it is not induced by deliberate exposure. B- Naturally acquired passive immunity Maternal passive immunity is a type of naturally acquired passive immunity, and refers to antibody-mediated immunity conveyed to a fetus by its mother during pregnancy. Maternal antibodies (MatAb) are passed through the placenta to the fetus by an FcRn receptor on placental cells. This occurs around the third month of gestation. IgG is the only antibody isotype that can pass through the placenta. Passive immunity is also provided through the transfer of IgA antibodies found in breast milk that are transferred to the gut of the infant, protecting against bacterial infections, until the newborn can synthesize its own antibodies. 2- Artificially acquired immunity A-Artificially acquired active immunity Artificially acquired active immunity can be induced by a vaccine, a substance that contains antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease. B- Artificially acquired passive immunity Artificially acquired passive immunity is a short-term immunization induced by the transfer of antibodies and immune cells, passive transfer is used prophylactically in the case of immunodeficiency diseases and cancers. It is also used in the treatment of several types of acute infection, and to treat poisoning.