Host defense mechanisms - Lecture guide PDF

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HOST DEFENSE MECHANISMS Humans, as well as other higher organisms, have developed mechanisms to prevent entry of microorganisms from environment in the body. In addition, if any microorganism overcomes these obstacles and enters the body, nonspecific and specific immune responses are activated in order to destroy microorganism and build up immunity against it. These mechanisms are usually classified in three lines of defense that are elaborated in chapters 14 and 15 of the textbook – “Host Defenses I -Overview and Nonspecific Defenses” and “Host Defenses II – Specific Immunity and Immunization”. Please, read these chapters and focus on the following topics (it will be expected from you to know about these topics after this lecture): 

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Three lines of defense – list the components of the three lines of host defense against microorganisms. o 1st line of defense- includes any barrier that blocks invasion at the portal of entry. Limits access to the internal tissues of the body  Physical barriers, chemical barriers o 2nd line of defense- an internalized system of protective cells and fluids that includes inflammation and phagocytosis. It acts rapidly at both the local and systemic levels once the first line of defense has been breached  Phagocytosis, inflammation, fever, antimicrobial proteins o 3rd line of defense- acquired on an individual basis as each foreign substance is encountered by WBCs. The reaction with each different microbe produces unique protective substances and cells that can come into play if that microbe is encountered again. Provides long-term immunity.  B cells, T cells First line of defense – describe components of the first line of defense. What is the role of keratin in the first line of defense? What is lysozyme and what is its role in host defense against microorganisms? o Skin  The skin and mucous membranes of the respiratory and digestive tracts have several built-in defenses. The outermost layer is composed of keratin, which is a thick, tough layer that is highly impervious and waterproof. Few pathogens can penetrate this.  In addition, outer layers of skin are constantly sloughing off, taking associated microbes with them.  Other barriers include hair follicles and skin glands. o Digestive, urinary, and respiratory  The mucous coat on the free surface of some membranes impedes the entry and attachment of bacteria  Blinking and tear production flush the eye’s surface with tears  Flow of saliva  Vomiting and defecation  Nasal hair  Flow of mucus and fluids that occurs in allergy and colds  Coughing

Lysozyme- an enzyme that hydrolyzes the peptidoglycan in the cell wall of bacteria  The high lactic acid and electrolyte concentrations of sweat and the skin’s acidic pH and fatty acid content are also inhibitory to many microbes. Components of immune system – list components of human immune system. Explain the role of components of lymphatic system (lymph, lymphatic vessels, and lymphoid organs and tissues). Explain classification of white blood cells and the role of the main classes. o Components  The mononuclear phagocyte system- a collection of monocytes and macrophages scattered throughout the extracellular spaces that function to engulf and degrade foreign molecules  The spaces surrounding tissue cells that contain ECF  The bloodstream  The lymphatic system- a system of vessels and organs that serve as sites for development of immune cells and immune reactions. It includes the spleen, thymus, lymph nodes, and GALT  To provide an auxiliary route for the return of ECF to the circulatory system proper  To act as a “Drain-off” system for the inflammatory response  To provide surveillance, recognition, and protection against foreign materials through a system of lymphocytes, phagocytes, and antibodies  Lymph- tiny capillaries that transport fluid  Lymph nodes- tributary system of vessels and filters o Lymphoid organs and tissues  Thymus- thymocytes develop specificity and are released into the circulation as mature T cells. The T cells migrate to and settle in other lymphoid organs where they occupy specific sites  lymph nodes- filter out materials that have entered the lymph and for providing appropriate cells and niches for immune reactions  spleen- serves as filter for blood. Primary function is to remove worn-out red blood cells from circulation, its most important function is the filtering of pathogens from the blood and then having them destroyed by resident macrophages  clusters of tissues that appear in mucosal surfaces o WBCs  Granulocytes- have granules  Agranulocytes- lacking granules Phagocytosis – describe the process of phagocytosis (pay attention to the role of chemotaxis, different receptors, and lysosome in this process). What are blood cells which can destroy microorganisms through the phagocytosis? o To survey the tissue compartments and discover microbes, particulate matter, and injured or dead cells o To inject and eliminate these materials o To recognize immunogenic information in foreign matter o Steps: o

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Chemotaxis- recognizing microorganisms as foreign b/c of various signal molecules that the molecules have on their surface  Pathogen-associated molecular patterns- molecules shared by many microorganisms and therefore serve as “red flags” for phagocytes  Pattern recognition receptors- recognize and bind PAMPs  Collectins- soluble molecules that roam through blood and tissues, bind to microbial PAMPs, and mark them for phagocytic destruction  Ingestion- on the scene of an inflammatory reaction, phagocytes often trap cells or debris against fibrous network of connective tissue of the wall of blood and lymphatic vessels. Extends pseudopods that enclose cells or particles in a Pocket and internalize them in a vacuole called a phagosome  Phagolysosome formation- lysosome fuses with phagosome  Destruction- oxygen dependent system involved several damaging substances. Release of lactic acid, lysozyme, and nitric oxide.  Excretion- debris released from macrophage by exocytosis Inflammation – what is inflammation? What is the role of inflammation as a part of innate immunity? o Inflammation- reaction to any traumatic event in the tissues. o Serve as important warning that injury has taken place and set in motion responses that save the body from further injury.  To mobilize and attract immune components to the site of the injury  To set in motion mechanisms to repair tissue damage and localize and clear away harmful substances  To destroy microbes and block their further invasion o Rubor- redness//increased circulation and vasodilation in the injured tissues o Tumor- swelling//increased fluid escaping into the tissues o Dolor- pain //stimulation of nerve endings o Calor- heat//heat given off by increased flow of blood Fever – Should we use medications to reduce fever below 101.5°F? Explain your answer. What are benefits of fever as a part of innate immunity? o No. fever can be seen as the body’s attempt to make the internal environment less hospitable to the virus and lowering the body temp. may allow the virus to proliferate. Antimicrobial proteins – what is the role of interferons in an immune response? What is complement? How does the complement contribute to the host defense against microorganisms? Explain the mode of antimicrobial action of antimicrobial peptides. o Interferon- a small protein produced naturally by certain white blood and tissue cells; used in therapy against certain viral infections and cancer. Also involved in defenses against other microbes and in immune regulation and intercommunication o Complement- serum protein components that act in a definite sequence when set in motion either by an antigen-antibody complex or by factors of the alternative pathway.  End product is a large protein termed the membrane attack complex. This complex can digest doles in the cell membranes of bacteria, cells, and enveloped viruses, thereby destroying them. 

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Antimicrobial peptides- short proteins that have the capability of inserting themselves into bacterial membranes. They kill microbes.  The peptide inserts itself into pathogen membranes using a positive charge plus a hydrophobic tail Receptors in specific immunity – Explain roles of the major histocompatibility complex and lymphocyte receptors (immunoglobulins and T-cell receptors) in immune response. Explain the origin of diversity of lymphocyte receptors. o Major histocompatibility complex- a set of genes in mammals that produces molecules on surfaces of cells that differentiate among different individuals in the species  Plays a vital role in recognition of self by the immune system and in rejection of foreign tissue o Lymphocyte receptors T cells have receptors that bind antigens that have been processed and complexed with MHS molecules on the presenting cells surface.  Secrete cytokines that help destroy pathogens and regulate immune responses, but do not produce antibodies o Immunoglobin- large glycoprotein molecules that serve as the antigen receptors of B cells and, if they are secreted, antibodies Antigens and clonal proliferation – what are antigens? Explain the process of clonal selection. o Antigen- substance that provokes an immune response in specific lymphocytes. o Clonal selection- the recognition by a single clone of a B or T cell of a foreign antigen o When this antigen enters the immune surveillance system, it encounters specific lymphocytes ready to recognize it. Such contact stimulates that clone to undergo mitotic divisions and expands it into a larger population of lymphocytes, all bearing the same specificity. This increases the capacity of the immune response to respond to that antigen. Presentation of antigens – what is presentation of antigens and where does it occur? What immune cells are involved in this process? o Presentation of antigen- process by which the protein antigen is presented to lymphocutes in the form of short peptide fragments. o Presented on antigen-presenting cell o Dendritic cells- process antigen material Cell-mediated immunity – describe only the main steps in activation of T-cells. What are the main components of T-cell response? o B-cell response – explain activation of B-cells in an immune response. Describe the ways how antibodies can contribute to elimination of invading microorganisms. o Steps  Binding of antigen Antigen processing and presentation  B cell/Th cell cooperation and recognition  B-cell activation  Differentiation  Clonal expansiono

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Some antigens are capable of activating naïve B cells simply by binding to their antigen receptors Immunization – what is immunity? Explain the difference between natural and artificial immunity. Explain the difference between active and passive immunization. o Active- occurs when an individual receives an immune stimulus that activates the B and T cells, causing the body to produce immune substances such as antibodies  Creates a memory that renders the person ready for quick action upon reexposure to that same antigen  Requires several days to develop  Lasts for long time o Passive- occurs when and individual receives immune substances that were produced actively in the body of another human or animal donor  Lack of memory for original antigen  Lack of production of new antibodies against that disease  Immediate protection  Short term effects o Natural- encompasses any immunity that is acquired during the normal biological experiences of an individual rather that medical intervention o Artificial immunity- protection from infection obtained through medical procedures.  Vaccines or administration of immune system o

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