Innate immunity

• Neval Yurttutan, M.D. discusses immune response, which involves microbes attempting to get into the body must first get past the skin and mucous membranes, which are rich in scavenger cells and IgA antibodies.
• Microbes that get past the skin and mucous membranes must elude a series of 1st line defenses, which include patrolling phagocytes, complement, and various other enzymes and chemicals.
• Infectious agents that get past these barriers must confront specific immune response tailored just for them, both antibodies and cells.
• All multicellular organisms possess intrinsic mechanisms for defending themselves against microbial infections.
• Innate immunity provides the early defense against infections and instructs the adaptive immune system to respond to different microbes.
• Adaptive immunity response often uses mechanisms of innate immunity to eradicate infections.
• Microorganisms and tumor cells can be internalized by phagocytosis and degraded by NK cells.
• The 2nd line of defense consists of immunologic mechanisms in which lymphocytes recognize the presence of foreign agents or substances: antigens and eliminate them.
• Either destroy the antigen or target it for destruction by other cells.
• If an organism is able to pass the first line of defense mechanisms, it encounters the 2nd line of defense.
• Elimination can occur by direct lymphocytic destruction of the antigens or by formation of specialized proteins called antibodies.
• NK cells respond to IL-12 produced by macrophages and secrete IFN-γ, which activates the macrophages to kill phagocytosed microbes.
• NK cells kill host cells infected by intracellular microbes, thus eliminating reservoirs of infection.
• There is a constant bidirectional cross talk between innate and adaptive immunity.
• Innate immune system has no memory function and does not react against the host because it has inherent specificity for microbial structures and mammalian cells express regulatory molecules to prevent innate immune reactions.
• Skin and mucosa are physical and chemical barriers in the innate immune system.
• Cells of the innate immune system include phagocytes, neutrophils, monocytes/macrophages, and NK cells.
• The skin is the first line of immunological defense, made up of the epidermis, outer layer, and dermis.
• The epidermis is comprised of tightly packed cells rich in keratin, which impedes water from entering the skin and is slightly acidic which inhibits bacterial growth.
• The dermis contains the sebaceous glands from which hairs grow, and from which sebum is secreted, which inhibits the growth of some type of bacteria and fungi.
• Mucus secreted by the respiratory and gastrointestinal tract serves to protect the host by trapping many microorganisms.
• Phagocytes generally patrol the body searching for pathogens, but are also able to react to a group of highly specialized molecular signals, called cytokines, produced by other cells.
• The lysosome contains enzymes and acids that kill and digest the particle or organism.
• Monocytes turn into macrophages when they enter the tissues, they have the ability to do phagocytosis.
• To phagocytose a particle or pathogen, a phagocyte extends portions of its plasma membrane, wrapping the membrane around the particle until the entire particle is enveloped (i.e
• Once inside the cell, the invading pathogen is contained inside a vacuole called fagosome which merges with another type of vacuole called a lysosome.
• PMNL (neutrophils) are the mature phagocytes, they are non-dividing short lived cells with a multilobed nucleus, they migrate through tissues to destroy microbes and respond to inflammatory stimuli.
• Pattern recognition receptors have evolved as a protective adaptation to potentially harmful microbes.
• Phagocytes are immune cells that engulf, or eat, pathogens or particles.
• Innate immune system receptors are nonclonally distributed, identical receptors are expressed on all the cells of a particular type, such as macrophages.
• The major function of the neutrophil is to stop or retard the action of foreign matter or infectious agents, it accomplishes this by moving to the area of inflammation or infection, phagocytozing (ingesting) the foreign material, and killing and digesting the material.
• Monocytes are large mononuclear phagocytes, they are the immature stage of the macrophages, they form from the stem cell in the bone marrow, they develop into monocytes and enter the blood circulation, the nucleus is often band shaped (horseshoe), or reniform (kidney-shaped), vacuoles may be present.
• Mononuclear phagocytes develop in the bone marrow, circulate in the blood as monocytes, and are resident in all tissues of the body as macrophages, they may differentiate into specialized forms in particular tissues.
• The total population of lymphocytes can recognize over a billion different antigens, in contrast all the receptors of innate immunity probably recognize less than a thousand microbial patterns.
• Bacterial infection can result in a leukomoid reaction, white cell counts of 100000 X 10^6/L (normal WBC=4000 to 10000 X 10^6/L).
• PMNL comprise 40-75 % of the peripheral leukocytes, the cytoplasm is abundant with a few nonspecific granules and a full complement of rose-violet specific granules.
• The flushing action of saliva, tears, and urine mechanically expels pathogens.
• Pathogens are mechanically expelled from the lungs through a process known as ciliary action.
• Saliva and tears contain antibacterial enzymes, such as lysozyme, which destroy bacterial cell walls.
• Vaginal secretions become slightly acidic following menarche, while semen contains spermine and zinc which repels some pathogens.