Biochemistry & Immunology in Nursing (NRS414) PDF

27/12/2024 2 BIOCHEMISTRY & IMMUNOLOGY LEARNING OBJECTIVES IN NURSING (NRS414)...

27/12/2024 2 BIOCHEMISTRY & IMMUNOLOGY LEARNING OBJECTIVES IN NURSING (NRS414) AT THE END OF THE LESSON, STUDENTS ARE ABLE TO EXPLAIN OR IDENTIFY: I. Terminologies in immunology. II. Innate immunity, its component and reaction. III. Adaptive immunity, its component and reaction. IV. Phagocytosis. V. Molecular defenses. VI. Characteristics of inflammation. NRS421 HS240 VII. Interferon and Complement system. HS260 3 4 Terminologies Immunity: refers to the ability of an organism to recognize and defend itself against infectious agents Susceptibility: opposite of immunity, is the vulnerability of the host to harm by infectious agents Antigen : a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies. Immune system: consists of various cells, especially lymphocytes, and organs such as the thymus gland, that help provide the host with specific immunity to infectious agents 5 6 Types of Immunity Innate immunity (genetic): exists because of genetically determined characteristics All humans have immunity to many infectious agents that cause disease in pets and domestic animals (Specific) Adaptive immunity (acquired): immunity obtained (Non-specific) in some manner other than heredity Naturally acquired adaptive immunity is most often obtained by having a specific disease Artificially acquired adaptive immunity is obtained by receiving an antigen by injection of vaccine or immune serum 1  27/12/2024 7 8 Ex : i. Anti-venom ii. Anti- tetanus iii. Anti-serum COVID 19 9 10 11 12 Innate and Adaptive Immunity Host defenses that produce resistance against infection can be adaptive or innate Adaptive defenses: respond to particular agents called antigens (e.g. viruses and pathogenic bacteria) Innate defenses: those that act against any type of invading agent 2  27/12/2024 13 14 Adaptive Immunity Respond to antigens by producing antibodies Also involve the activation of the lymphocytes Lymphocytes: specific cells of the body’s immune system Antibody and cellular responses are more effective against succeeding invasions by same pathogen than against initial invasions 15 16 Innate Immunity 1) Physical barriers: skin and mucous membranes and chemicals they secrete 2) Chemical barriers: antimicrobial substances in body fluids (e.g. saliva, mucus, gastric juices) and iron limitation mech. 3) Cellular defenses: certain cells that engulf invading microorganisms 4) Inflammation: reddening, swelling, and temperature increases in tissues at sites of infection 5) Fever: elevation of body temperature to kill invading agents and/or inactivate their toxic products 6) Molecular defenses: interferon and complement, that destroy or impede invading microorganisms 17 18 Skin and mucous membranes protect your body and internal organs from injury and infectious agents These two physical barriers are made of cells that line body surfaces and secrete chemicals ex: human beta-defensin-2 on human skin destroys Physical Barriers pathogens by poking holes in bacterial membranes Mucosa covers those tissues and organs of body cavity exposed to exterior 3  27/12/2024 19 20 Physical Reflects Activities Flush harmful microbes by: Coughing and sneezing Vomiting Diarrhea Chemical Barriers Tears Saliva Urinary flow 21 22 Cellular Defenses – Defensive Cells High salt content of sweat inhibits bacteria from growing Blood consists of about 60% liquid called plasma and 40% cells Sweat and sebum produced by sebaceous glands have low pH that inhibits growth of bacteria Cells: erythrocytes, platelets, and leukocytes Acidic pH of stomach is a defense against intestinal pathogens Leukocytes are defensive cells important to adaptive and innate immunity Lysozyme: present in tears, saliva, and mucus, cleaves peptidoglycan linkage in bacterial cell wall 23 24 Granulocytes Granulocytes Have granular cytoplasm and an irregularly shaped, lobed nucleus include: 1. Basophils: release histamine which helps initiate inflammatory response 2. Mast cells: prevalent in connective tissue, release histamine, and associated with allergies 3. Eosinophils: present in large numbers during allergic reactions 4. Neutrophils (polymorphonuclear leukocytes): phagocytic cells that guard skin/mucous membranes against infection 4  27/12/2024 25 26 Agranulocytes Agranulocytes Lack granular cytoplasm with round nuclei Monocytes include: Lymphocytes 1. Monocytes: phagocytic cells derived from myeloid stem cells 2. Lymphocytes: derived from lymphoid stem cells and contribute to adaptive host immunity Lymphocytes circulate in blood and are found in lymph nodes, spleen, thymus and *DC: dendritic cells tonsils 28 Phagocytes Cells that literally eat or engulf materials Patrol, or circulate through body, destroying dead cells and cellular debris Guard the skin/mucous membranes against invasion by microorganisms Macrophages: “big eaters” that destroy not only microorganisms but also larger particles 29 30 The Process of Phagocytosis Chemotaxis Phagocytes in tissues first must recognize Phagocytes digest and destroy invading invading microorganisms microbes and foreign particles by a process called phagocytosis pattern recognition receptors (PRRs) on the phagocytic cells recognize molecular patterns Phagocytic cells must: unique to pathogen 1. Find - chemotaxis Phagocytes release cytokines that have specific 2. Adhere to roles in host defenses 3. Ingest, and 4. Digest the microorganisms Chemokines: a class of cytokines that attract additional phagocytes to site of infection 5  27/12/2024 31 32 Adherence and Ingestion The ability of the phagocyte cell membrane to bind to specific molecules on the surface of the microbe is called adherence Antiphagocytic capsule: the most common means by which bacteria avoid phagocytosis Complement system: coat microbes with antibodies to aid phagocyte in adherence Phagosome: pseudopodia fuse and enclose microorganism within this cytoplasmic vacuole 33 34 Phagocytosis of two bacterial cells by a neutrophil Digestion Phagocytic cells have several mechanisms for digesting and destroying ingested microbes Digestive enzyme - defensin Phagolysosome: lysosomes (cytoplasms of the phagocytes) contain digestive enzymes (called defensins) fuse with phagosome membrane Lysosome + Macrophages use other metabolic products to kill phagosome - ingested microbes: phagolysosome 1. Oxygen to form hydrogen peroxide 2. Nitric oxide and superoxide ions 1. Find 35 36 Inflammation The body’s defensive response to tissue damage from microbial infection. Acute and chronic. Phagocytosis o Acute inflammation – histamine is released by damage tissue. https://www.youtube.com/watch?v=sJ8Sz0CcNKo o Chronic inflammation – the inflammatory agent continues to cause tissue injury Characterized by clinical signs: 1. Calor: an increase in temperature 2. Rubor: redness 3. Tumor: swelling 4. Dolor: pain at infected or injured site 6  27/12/2024 37 38 Characteristics of Inflammation 1) Calor – increase in body temperature – fever. Normal temperature 37oC / 98.6 oF. Fever – endogenous and exogenous. Endogenous – release of cytokines Exogenous – pathogens and their toxins (pyrogens) 2) Rubor – redness – blood vessels dilate. 3) Tumor – swelling (edema) – vasodilation – increase permeability for the reaction of cellular defense mechanism eg. phagocytes. 4) Dolor – pain – production of bradikinin – stimulate pain receptors 39 40 The inflammatory process Initiation leads to a cascade (chain) of events Results in dilation of blood vessels, leakage of fluid from vessels and migration of leukocytes and phagocytes Leakage of phagocytes from blood vessels called diapedesis Certain pro-inflammatory mediators cause the diameter of blood vessels to increase Results in increased blood flow Increased blood flow responsible for signs of inflammation 41 42 Molecular Defenses Involvethe action of interferon and complement Inflammation Interferon: small soluble proteins that act non- specifically to cause cell killing and to https://www.youtube.com/watch?v=Fbzb75HA9M8 stimulate cell to produce anti viral proteins. Interfered with viral replication in other cells Humans have three groups of interferon (alpha (α), beta (β), and gamma (γ)). 7  27/12/2024 43 44 The mechanism interferon alpha and beta in virus infections 1 2 Natural Killer Cells (NK Cells) 3 Increase activity by exposure to interferon and cytokines. In virus infected cells, NK cells recognize specific 9 4 glycoprotein on the cell surface and secrete protein that trigger death of the infected cells. 5 8 Parasite (worm) – too big to be engulfed by neutrophil and 7 macrophages, eosinophil will secrete toxic enzyme e.g major basic protein (MBP) to destroy the worm, then only 6 macrophages engulf the parasites elements. 45 46 Complement Refers to a set of more than 20 large regulatory proteins that play a key role in host defense General functions of the complement system are: 1. Enhance phagocytosis 2. Lyse pathogens directly 3. Generate peptide fragments that regulate inflammation and immune responses Works as a cascade: a set of reactions that amplify some effect 47 48 The Complement System: Complement system ❑ Antibodies ❑ Activated by bind to antigen contact between complement proteins and https://www.youtube.com/watch?v=BSypUV6QUNw polysaccharides at the pathogen surface 3 kinds of molecular defenses 8  27/12/2024 49 50 CLASSICAL COMPLEMENT PATHWAY Activation of the classical complement pathway OPSONISATION Bacteria with capsules or surface proteins can prevent phagocytosis but complement system counteract. Special antibody called opsonin bind to and coat surface of the infectious agents. C1 binds to the antibody (opsonin) and initiate cascade. C1 causes the cleavage of C4 into C4a and C4b. C4b and C1 cause C2 to split into C2a and C2b. C4bC2a complex – leads to the splitting of C3 into C3a and C3b. C3b binds to the surface of the microbe - opsonisation Complement receptors (antibody receptor) on the plasma membrane of the phagocytes recognize C3b molecules and stimulate phagocytosis. 51 52 Inflammation C3a, C4a and C5a enhance the inflammatory reactions by stimulating chemotaxis (abundant phagocytes attracted Opsonization at the site of infection) followed by phagocytosis. https://www.youtube.com/watch?v=6gHjx_hYA14 C3a, C4a and C5a also adhere to the membranes of basophils and mast cells causing them to release histamine and other substances that increase permeability of the blood vessels. 53 54 Immune Cytolysis Complement lesions in cell membranes Through formation of membrane attack complexes (MAC). Cell lysis is triggered by C3b – immune cytolysis. C3b produces lesions in the cell membrane of microorganisms cause cellular contents to leak out. Immune cytolysis – C3b initiates the splitting of C5 into C5a and C5b. C5b binds to C6 and C7 and form C5bC6C7 complex (hydrophobic). Complex inserts into the microbial cell membrane. C8 binds to C5b. C5b,C6,C7,C8 complex causes assembly in the cell membrane up to 15 and form C9 molecule. These proteins form pore – MAC – direct lysis of invading microorganisms 9  27/12/2024 55 56 A Summary of the body’s nonspecific defenses 57 SUMMARY The immune system protects the body through two main defenses: innate immunity, which provides quick, non-specific responses, and adaptive immunity, which targets specific pathogens and remembers them for future protection. Processes like phagocytosis, molecular defenses, and systems such as interferons and the complement system play key roles in fighting infections. Understanding these components helps us appreciate how the body defends itself and highlights the importance of immunity in maintaining health. Thank you for your attention and participation! 10