Immune and Inflammatory Responses - NCM 106 PDF

IMMUNE AND INFLAMMATORY RESPONSES NCM Lecturer: Mr. Mark Cristino I Date: Sept. 26, 2024 106 I Week # 2...

IMMUNE AND INFLAMMATORY RESPONSES NCM Lecturer: Mr. Mark Cristino I Date: Sept. 26, 2024 106 I Week # 2 Gastrointestinal Tract (GI) Genitourinary Tract (GU) - Acts as a physical barrier to invasion. Respiratory Tract - Lined with tiny, hairlike processes called cilia. The cilia sweep any captured pathogens or foreign materials upward toward the mouth, where they will be swallowed. The cilia also can move the captured material to an area causing irritation, which leads to removal by coughing or sneezing. GI Tract - Protective coating, preventing erosion of GI cells by the acidic environment of the stomach, the digestive enzymes of the small intestine, and the waste products that accumulate in the BARRIER DEFENSES large intestine. - Serves as a lubricant throughout the GI tract to facilitate movement of the food bolus and waste products. - Act as a thick barrier to prevent foreign pathogens from penetrating the GI tract and entering the body. GU Tract - Provides direct protection against injury and trauma - Traps any pathogens in the area for the destruction by the body/ Gastric Acid - aids in digestion - destroys many would-be pathogens that are either ingested or swallowed after removal from the respiratory tract Exist to: Major Histocompatibility Complex - Prevent the entry of foreign pathogens - Serve as important lines of defense in - Ability to distinguish between self-cells and protecting the body foreign cells. - Skin and mucous membranes, gastric acid, - Produces several proteins called and the Major Histocompatibility Complex histocompatibility antigens or human leukocyte (MHC) antigens(HLAs). These antigens are located on the cell membrane and allow the body to Skin recognize calls as being self-cells. - First line of defense THE IMMUNE RESPONSE - Acts as a physical barrier to protect the internal tissues and organs of the body. o An immune response is what the immune system does when confronted by an antigen. - Glands in the skin secrete chemicals that destroy or repel many pathogens. o An immune response is an elaborate interplay - The top layer of the skin falls off daily, which between antigen, non-specific defenses, and B and T makes it difficult for any pathogen to colonize lymphocytes. on the skin. - The normal bacterial flora of the skin helps to o The process involves direct contact (cells, molecules destroy many disease-causing pathogens. bind to receptors on cell surfaces) and cytokines Mucous Membrane (messenger molecules) that also bind to receptors on cell surfaces. - Line the areas of the body that are exposed to external influences but do not have the benefit More specific invasion can stimulate a more specific of skin protection: response through the immune system. As Respiratory Tract mentioned previ-ously, stem cells in the bone marrow produce lymphocytes that can develop into GROUP L  IMMUNE AND INFLAMMATORY RESPONSES NCM Lecturer: Mr. Mark Cristino I Date: Sept. 26, 2024 106 I Week # 2 (so T lymphocytes named because they migrate PRODUCTION OF ANTIBODIES from the bone marrow to the thymus gland for activation and maturation) or B lymphocytes (so Immune response is brought about by three named because they are activated in the bursa of types of cells: 1 APC macrophages, dendritic Fabricius in the chicken, although the specific point cells, 2 T Cells and 3 B cells. of activation in humans has not been identified). The first step is capture and processing of Other identified lymphocytes include natural killer antigens by APC and their presentation with the cells and lymphokine-activated killer cells Both of association of appropriate MHC molecule to T these cells are aggressive against neoplastic or cells. cancer cells and promote rapid cellular death. They do not seem to be programmed for specific However some polysaccharides and simple identification of cells. molecules with repeating epitopes do not require T Cell participation Research in the area of lymphocyte identification is relatively new and continues to grow. There may be other lymphocytes with particular roles in the STAGES OF ANTIBODY MEDIATED IMMUNE RESPONSE immune response that have not yet been identified. 1. The entry of antigen, its distribution and fate in the tissues and its contact with appropriate RESULTS OF IMMUNE RESPONSE immunocompetent cells 2. The secretion of antigen by cells and the o Beneficial, Indifferent, Injurious. control of the antibody forming process Reactions follow against any antigen either living or 3. The secretion of antibodies, its distribution in dead. tissues and body fluids and manifestations of May respond in its effects. ➔ Specific (body acts on that specific microorganism), No reactivity (ex. due to being immunocompromised), or Tolerance. CLASSIFICATION OF IMMUNE RESPONSE 1. Humoral 2. Cell Mediated Type May work together. May work in the opposite way. One may be more active than the other. HUMORAL CELL MEDIATED Active against most Protects against fungus, extracellular bacterial viruses IC bacterial infections pathogens Viruses Rejection of homograft, GVH HUMORAL IMMUNE RESPONSE Produces Antibodies B Cell ○ Plasma cell Antigen Presented to Immunocompetent cells Processed - Secretion of Antibodies, GROUP L  IMMUNE AND INFLAMMATORY RESPONSES NCM Lecturer: Mr. Mark Cristino I Date: Sept. 26, 2024 106 I Week # 2 PATHOGENS DAMAGE TISSUES IN VARIETY WAYS HOW LONG CAN AN ANTIBODY BE ACTIVE The duration of the lag phase and persistence of the antibody depends on the nature of the antigen. In diphtheria toxoid the lag phase in the primary response may be as long as 2-3 weeks. In pneumococcal polysaccharides antigens the antibodies are detected in a few hours. PRIMING AND BOOSTER DOSES The first injection is known as priming dose and subsequent injection as booster dose. With live vaccines, a single dose is sufficient as multiplication of the organisms in the body provides a continuous antigenic stimulus that PRIMARY AND SECONDARY IMMUNE RESPONSES acts as both the priming and booster dose. FACTORS INFLUENCING ANTIBODY PRODUCTION A single injection of antigen helps in sensitizing or priming of an immunocompetent cell Under genetic control, producing particular antibody than in the actual May be responder or non-responder. - defines elaboration of high levels of antibody. the capacity of the individual to respond or not Effective levels of antibody are usually induced respond by only subsequent injection of Ir (Immune response genes) control this property. Age. The embryos is immunologic ally immature During the embryonic life the developing lymphoid cells come into contact with all the tissue antigens of the body released by cellular breakdown - lead to elimination of self antigens. IMMUNITY IN NEONATES Early mechanisms of self tolerance. -> 3-6 months Maternal antibodies, Ig G 5-7 years Ig A 10-15 years B cell responses to most proteins and other T cells dependent develop early. TYPES OF ANTIBODY RESPONSE The responses to most Polysaccharide and Initial Antigenic Stimulus (Primary Response other T cell independent antigens develop later. IgM HUMORAL IMMUNITY IN VIVO USES Response is slow and short lived, Secondary Response IgG Response is Prompt, Powerful and Prolonged Higher level of antibodies and lasts longer GROUP L  IMMUNE AND INFLAMMATORY RESPONSES NCM Lecturer: Mr. Mark Cristino I Date: Sept. 26, 2024 106 I Week # 2 IgA can stop colonization of Immunoglobulin mucosal surface. It interferes with the attachment molecular adhesions present on the bacterial surface. Depends on Nature of Antigenic stimulus Bacterial exotoxins are inhibited - as the Best developed after following infection with antibodies can prevent interaction of enzymes intracellular parasites with substrate. Live vaccines highly stimulating Antibodies can kill bacteria. Killed vaccine not very effective Antibodies can affect the specific transport But effective if it contains Freund type adjuvant. systems and deprive the energy needs of the bacteria. FUNCTIONS OF T CELLS Affect the motility Reduces the invasion Antibodies can cause agglutination Only T cell dependent antigens lead to Stimulate the phagocytosis, and complement development of CMI activity. Certain chemicals which come in contact with skin induces Delayed hypersensitivity T Cell contain the specific receptor (TCR ) USES OF ADMINISTRATION OF ANTIBODIES One epitope ( Antigen) on contact with receptor undergoes blast transformation Passive administration of antibodies Leads to Clonal proliferation eg. Hyper immune globulins, Cytotoxic T cells (AKA CD8 Cells) recognize antigen on surface of virus infected cells, tumor cells, allograft Sensitization issues in Rh negative mothers cells with MHC I and sectored Lymphokines and destroy The effect occurs due to feedback mechanism target celLs The antibody may also combine with antigen and prevent its availability for the immunocompetent cells. Rh -ve mothers + Rh+ ve fetus administration of anti-Rh globulin immediately following delivery The stimulated cells undergoes blast transformation, Clonal proliferation Leads to Effectors cells and Memory cells ADMINISTRATION OF IMMUNOGLOBULINS T cell react on presentation with MHC Helper T cells (AKA CD4 Cells) when presented IV administration has immunomodulation on surface of macrophages or other cells effect complexes with Administered in Thrombocytopenia and autoimmune hemolytic anemia. INTRODUCTION OF CELL MEDIATED IMMUNITY GROUP L  IMMUNE AND INFLAMMATORY RESPONSES NCM Lecturer: Mr. Mark Cristino I Date: Sept. 26, 2024 106 I Week # 2 - leads to release of Biological MHC Il molecule Cytokines may act on the cells that secrete Mediators Lymphokines - activate them (Autocrine action), on nearby cells Macrophages and kills intracellular (Paracrine action), or in some instances on distant cells (Endocrine action) BROAD VIEW ON CYTOKINES PAIN Definition: An unpleasant sensory and emotional Cytokines are a category of signalling proteins and experience. glycoproteins that, like hormones and neurotransmitters, are used extensively in cellular Subjective: sensation and emotion communication. Not necessarily correlated with a stimulus CYTOKINES Purposeful: Tells you that damage is being done to the Cytokines have been classed as Lymphokines, body. interleukins, and chemokines, based on their presumed function, sell secretion, or target of action. because Seek care cytokines are characterised by considerable Stop the destructive behavior redundancy and pleiotropism, such distinctions, allowing for exceptions, are obsolete. NEUROPHYSIOLOGY OF PAIN Lymphokines biologically active substance Pain Transduction - pain stimulus released by activated T Lymphocytes Pain Transmission - nerve conduction Monokines - substances secreted by Pain Modulation - running interference monocytes and macrophages Pain Perception Interleukins - produced by lymphocytes which exert a regulatory effect on other cells All above grouped under cytokines Autocrine - if the cytokine acts on the cell that secretes it. Paracrine - if the target is restricted to the immediate vicinity of a cytokine’s secretion. Endocrine - if the cytokine diffuses to distant regions of the body (carried by blood or plasma) It seems to be a paradox that cytokines binding to antibodies have a stronger immune effect than the cytokine alone. This may lead to lower TYPES OF PAIN therapeutic doses. Concepts WHAT ARE CYTOKINES ○ Pain Threshold They are peptide mediators, intracellular ○ Pain Tolerance messengers, which regulate immunological, Acute - autonomic hyperactivity inflammatory and reparative host cell ○ Catecholamine release: Tachycardia, responses. tachypnea, increased BP, irritability They are potent hormones active even at ○ Local muscle rigidity Fetomolar concentrations produced by widely ○ There is sudden feeling of pain distributed cells Chronic (Lymphocytes, Macrophages, Platelets, and ○ Continuous or intermittent Fibroblasts) ○ Little or no autonomic hyperactivity ○ Gradual increasing feeling of pain GROUP L  IMMUNE AND INFLAMMATORY RESPONSES NCM Lecturer: Mr. Mark Cristino I Date: Sept. 26, 2024 106 I Week # 2 PAIN MANAGEMENT ADVERSE EFFECTS Stop the stimulus GI: Pain vs Ulcer (you should have full stomach Introduce competing stimulus (Gate Theory) or take it after meals because it can cause Induce natural endorphins ulcer) Increase brain modulation to produce ○ Adjuvant preventive therapy endogenous opioids Bleeding Pharmacologic Approaches Renal Impairment COX INHIBITORS Salicylism Reye’s Syndrome Major classes Pregnancy: Cat D ○ Inflammatory inhibiting agents (NSAIDS) both pain and anti- Hypersensitivity inflammation KEY DIFFERENCES WITH OTHER COX-1 ○ Non-inflammatory inhibiting agent For ASA binds irreversibly to COX-1 pain only ○ Inhibition of platelets NSAIDS: NON-STEROIDAL ANTI-INFLAMMATORY DRUGS Non-aspirin products do not protect against MI NSAIDS OTHER COX-1 INHIBITORS ○ Generic term to mean any drug that inhibits inflammation but does not Ibuprofen (Advil, Motrin) affect cortisol receptors Ketoprofen (Orudis) ○ Work by inhibiting COX Naproxen (Aleve) ○ Selectivity - inhibit both COX-1 and Diclofenac (Voltaren) COX-2 Ketorolac (Toradol) can be given IM ○ More selective for COX-2, fewer Indomethacin (Indocin) undesirable side effects. ○ Dual action-anti inflammation and pain Nabumetone (Relafen) perception COX-2 INHIBITORS ○ Not harmful to our liver except Acetaminophen More selective for COX-2 ○ You cannot take NSAIDS along with Reduce pain and inflammation warfarin (it is an antiplatelet drug), Do not produce platelet effects steroids such as glucocorticoids, and while drinking alcohol GI side effects? TYPICAL NSAIDS CV safety? “Nonselective” COX inhibitors Drugs: ○ Celecoxib: Celebrex (need to know) ○ Aspirin ○ Rofecoxib: Vioxx (off the market) ○ Ibuprofen ○ Valdecoxib: Bextra (off the market) ○ Naproxen ○ Diclofenac ACETAMINOPHEN ○ Indomethacin Inhibits COX, but only in the CNS ○ Sulindac ○ Ketorolac Reduces fever and pain COX-2 Inhibitors more on pain management Does not inhibit inflammation ○ Celecoxib, Valdecoxib, Rofecoxib Maximum Dosage: 4gm/day Toxic metabolite may damage liver in large doses given over time GROUP L  IMMUNE AND INFLAMMATORY RESPONSES NCM Lecturer: Mr. Mark Cristino I Date: Sept. 26, 2024 106 I Week (Tylenol) Acetaminophen # 2 is used to treat moderate to use and overdose and is related to direct toxic effects mild pain and fever and often is used in place of the on the liver. The dose that could prove toxic varies with NSAIDs or salicylates. It has been the most frequently the age of the patient, other drugs that the patient might used drug for managing pain and fever in children. It is be taking, and the underlying hepatic function of that widely available OTC and is found in many combination patient. When overdose occurs, acetylcysteine can be products. It can be extremely toxic. It causes severe used as an antidote. Life support measures may also liver toxicity that can lead to death when taken in high doses. T-HELPER CELLS Therapeutic Actions and Indications Acetaminophen acts directly on the thermoregulatory cells in the hypothalamus to cause sweating and Saan na pro-produce ang ating white blood cells? or vasodilation; this in turn causes the release of heat and where does your blood form? - in your bone marrow, lowers fever. The mechanism of action related to the dba? lahat ng form ng blood, or types of blood whether analgesic effects of acetaminophen has not been it is an RBC, WBC, or platelet. And that bone marrow identified. produces your myeloid and lymphoid stem cells. Acetaminophen is indicated for the treatment of pain Lymphoid produces lymphocytes. and fever associated with a variety of conditions, including influenza; for the prophylaxis of children receiving diphtheria-pertussis-tetanus immunizations (aspirin may mask Reye syndrome in children); and for the relief of musculoskeletal pain associated with arthritis. Pharmacokinetics Acetaminophen is rapidly absorbed from the GI tract, reaching peak levels in 0.5 to 2 hours. It is extensively metabolized in the liver and excreted in the urine, with a half-life of about 2 hours. Caution should be used in patients with hepatic or renal impairment, which could interfere with the metabolism and excretion of the drug, leading to toxic levels. Acetaminophen crosses the placenta and enters breast milk; it should be used cautiously during pregnancy or lactation because of the potential adverse effects on the fetus or neonate Contraindications and Cautions Acetaminophen is contraindicated in the presence of an allergy to acetaminophen because of the risk of hypersensitivity reactions. It should be used cautiously in pregnancy or lactation because of the potential for adverse effects on the fetus or baby and in hepatic dysfunction or chronic alcoholism because of associated toxic effects on the liver. Adverse Effects Adverse effects associated with acetaminophen use include headache, hemolytic anemia, renal dysfunction, skin rash, and fever. Hepatotoxicity is a potentially fatal adverse effect that is usually associated with chronic GROUP L