Inflammation, Infection, & Immunity Allie Arguello Inflammation and Causes • Innate & automatic • Response to cell injury • Causes • Trauma • Infection • Ischemia • Extreme heat & cold This Photo by Unknown author is licensed under CC BY-SA. Cardinal signs Rubor (redness) Tumor (swelling) Calor (heat) Thi s Photo by Unknown author is l icensed under CC BY-SA. Dolor (pain) Functio laesa (loss of function) Cell of Inflammation • Endothelial Cells • Line blood vessels • Produce vasoactive substances • Selectively permeable • Platelets • Release inflammatory mediators • Affect endothelial permeability and alter endothelial properties (more sticky) • Clotting • Aspirin is an anti-platelet This Photo by Unknown author is licensed under CC BY-SA-NC. Cells of Inflammation • Granulocytes 1. Neutrophils: First to appear, most numerous 2. Eosinophils: appear later; allergic rxns 3. Basophils: allergic rxns by IgE (antibody) 4. Mast Cells: activated to release histamine and cytokines • Agranulocytes 1. Monocytes: circulate and differentiate into macrophages when needed 2. Macrophages: phagocytosis This Photo by Unknown author is licensed under CC BY-SA. Vascular Stage Acute Inflammation • Vasodilation • Permeability Cellular Stage • Leukocytes migrate Leukocyte Activation and Phagocytosis • Opsonization • Microbe killing Immediate and brief vasoconstriction • Stops bleeding Vascular Stage 2. Vasodilation • Increases blood flow • Redness & warmth 3. Increased Capillary Permeability • Allows exudate (filled with proteins and mediators) to escape into tissue to do work • Swelling, pain, and loss of function Cellular Stage 1. Margination: Leukocytes "roll" along endothelial cells 2. Adhesion: Adhere to vessel wall 3. Transmigration: Slip between cells to get into tissues • Chemotaxis guides the cell to the point of injury • Cytokines and other mediators "tell" WBCs where to go through chemical signaling This Photo by Unknown author is licensed under CC BY-SA. Leukocyte Activation and Phagocytosis This Photo by Unknown author is licensed under CC BY. • Opsonization: "flagging" invading microbes • Makes it easier for phagocytes to find and kill • Phagocytosis • Engulf, kill, and digest using enzymes This Photo by Unknown author is licensed under CC BY-SA. Inflammatory mediators • Leukotrienes: Contract smooth muscle, constrict airways, increase vessel permeability • Prostaglandins: Vasodilate, increase permeability, mediate pain and swelling, bronchoconstrict, attract leukocytes • Thromboxane: Clotting (promotes platelets), bronchoconstrict, vasoconstrict • Histamine: Vasodilate, increase permeability, pro-inflammatory • Complement: Plasma protein cascade, promotes leukocytes and phagocytosis • Bradykinin: Increase permeability; cause pain Corticosteroids and NSAIDS • Corticosteroids: Inhibit Arachidonic Acid • No leukotrienes, prostaglandins, or thromboxane • Aspirin and NSAIDS: Inhibit Cyclooxygenase Pathway • No prostaglandins or thromboxane This Photo by Unknown author is licensed under CC BY-SA. Types of Exudates • Serous: watery, low protein • Hemorrhagic: contains RBCs/blood • Purulent: pus, cellular debris • Infection! • Fibrinous: fibrinogen; thick meshwork Chronic vs Acute Inflammation Acute • Short, limited • Neutrophils primarily present Chronic • Continual, weeks to years • Macrophages and lymphocytes come in and stay • Fibroblasts This Photo by Unknown author is licensed under CC BY. Systemic Inflammation • Affects the ENTIRE body • GI, respiratory, weight, BP, HR • Acute phase response • WBCs go up or down • Fever • Sepsis/shock This Photo by Unknown author is licensed under CC BY. Fever • Hypothalamus tries to kill microbes by increased body temperature • Cooling, fluids, antipyretics (COX inhibitors) • Elderly: Change in mental status • Slight alterations can mean big problems; baseline is lower • Children • Very common, often no cause This Photo by Unknown author is licensed under CC BY-NC-ND. Sepsis and Shock • Overwhelmed with microbes • Inflammation is out of control • Extreme release of mediators • Systemic vasodilation: BP drop • Systemic capillary permeability: BP drop This Photo by Unknown author is licensed under CC BY-NC-ND. Question Time! Answer: A, B, D • The nurse is teaching a client experiencing inflammation. Which sign of inflammation should the nurse include in the teaching? (Select all that apply.) A. Pain B. Swelling C. Paresthesia D. Redness E. Paralysis Answer: B, C, E • The nurse is caring for a client with localized inflammation. Which finding should the nurse expect to assess in this client? (Select all that apply.) A. White blood cell count of 15,000 B. Palpable warmth of the extremity C. Tenderness with palpation or movement D. Oral temperature of 101 degrees °F E. Localized edema Answer: D • A nurse in the acute care setting is caring for a patient who has rubor (flush) of an area of injury on the left lower extremity. What is the cause for this finding? A.) Exudate B.) Neutrophils C.) Extravasation D.) Vasodilation Answer: C • A patient arrives in the emergency department reporting fever for 24 hours and lower right quadrant abdominal pain. After laboratory studies are performed, what does the nurse determine indicates the patient has a bacterial infection? a.) Increased platelet count b.) Decreased blood urea nitrogen c.) Increased number of band neutrophils d.) Increased number of segmented myelocytes Answer: B • What is the body's initial response to injury? a. immune response b. inflammatory response c. repair and regeneration d. hyperplasia and hypertrophy Answer: C • The directed movement of white blood cells to the area of injury is called? a. pavementing b. margination c. chemotaxis d. hyperemia Answer: C • All of the following are systemic manifestations of inflammation except? a. leukocytosis b. fever c. hyperemia and erythema d. lymphadenopathy Answer: vasodilation, permeability Histamine causes ___ of arterioles and increase the ___ of venules Answer: Acute • A parent brings a child to the emergency department with newly formed blisters from touching a hot pan covering the majority of both palms; they are red and feel hot to the touch. Which type of inflammatory manifestation is this? Answer: C,D,F • Which of the following are symptoms of a systemic infection? (Select all that apply.) a. Redness. b. Edema. c. Fatigue. d. Fever. e. Pain or tenderness. f. Nausea and vomiting. Answer: B • Edema occurs in inflammation due to: A. Constriction of small veins in the surrounding area. B. Leakage of plasma from capillaries. C. Increased phagocytic action of white blood cells. D. Concentration of injurious agents. Answer: A • The nurse assesses a surgical patient the morning of the first postoperative day. Signs of a local inflammatory response that the nurse EXPECTS to find include: • A. Slight redness and heat of the incision. • B. Leukocytosis with elevated monocytes. • C. Pain and serous drainage of the incision. • D. Fever and increased pulse and respiratory rate. Immunity • Innate • Natural • Born with • Adaptive • Slower • More effective and specific Innate vs Adaptive This Photo by Unknown author is licensed under CC BY. Mediators • Cytokines: both innate and adaptive • Tumor necrosis factor a: inflammation, fever, acute-phase response • Kills through apoptosis • Activates neutrophils and endothelial cells • Chemokines: for migration and activation of immune/inflammatory cells • Colony-stimulating factors: growth and development of bone marrow progenitors • Produce more neutrophils, RBCs • Bone marrow suppression= decreased cell production This Photo by Unknown author is licensed under CC BY-NC. Innate Immunity 1. Epithelial barrier • Skin 2. Phagocytic Cells • Neutrophils and macrophages 3. Dendritic Cells • Translate innate into adaptive immunity • Capture "image" of pathogen 4. NK Cells • Early defense against foreign cells (especially virally infected and cancer cells) 5. Plasma Proteins MHC and NK Cells • Major histocompatibility complex: shown on normal cells to recognize as self (like a lock and key) • Virally infected/tumor cells don't have this complex • NK cells notices the MHC receptor isn't present • Cell gets killed This Photo by Unknown author is licensed under CC BY-SA-NC. Innate Mediators • Opsonin • Make phagocytosis easier • Cytokines • Acute-phase proteins • C-Reactive protein • Increases with chronic inflammation (ex. High cholesterol) • Complement System • In blood • Cytolysis, opsonization, chemotaxis, anaphylaxis • Aggregates bacteria=easier to kill Adaptive Immunity • Recognizes invaders • Remembers invaders • Second exposure=Faster and larger response; more effective defense This Photo by Unknown author is licensed under CC BY-SA-NC. • Lymphocytes: B and T cells • Humoral and CellMediated Immunity Humoral vs. CellMediated • Humoral • B lymphocytes • Extra-cellular microbes and toxins • Cell-Mediated • T lymphocytes • Intracellular microbes and viruses Antigens and Antibodies • Antigen: foreign substance • Cause immune response • Examples? • Antibody: recognize antigens • Made by B-cells This Photo by Unknown author is licensed under CC BY-NC. APCs • Macrophages and Dendritic Cells • Find antigen, capture it, present it to T cells to start adaptive immunity This Photo by Unknown author is licensed under CC BY. T-Lymphocytes • CD4 and CD8 • CD4=Helper T cells; direct signals • CD8=Cytotoxic T cells; destroy • Regulatory T-cells: inhibit harmful lymphocyte growth • Activate T and B cells • Intracellular viral infections (HIV) • Reject foreign tissue • Delayed hypersensitivity rxns This Photo by Unknown author is licensed under CC BY. B-Lymphocytes • Plasma cells • Release antibodies • Memory cells • Remember antigens for quicker response • Antibodies • Recognize and bind pathogens and to alert body This Photo by Unknown author is licensed under CC BY-SA-NC. Immunoglobulins • IgG: protect newborn (crosses placenta) • IgA: body secretions (breast milk) • IgM: early immunity; first encounter with pathogen • IgD: on B-lymphocytes, mature B cells • IgE: parasitic, allergic, and hypersensitivity rxns • Mast cells, basophils https://www.toppr.com/ask/ content/concept/immunoglo bulins-268707/ Active vs Passive Immunity • Active: long lasting; memory cells respond to next exposure • Immunization • Flu shot • Having disease • Having flu in the past • Passive: short-term • Transferred from another source • Mother to infant through breast milk (IgG) • Antibody serum • Injected with antibodies not made by you This Photo by Unknown author is licensed under CC BY-SA. Lymphoid Organs • Central • Bone marrow: Produce both lymphocytes; B-cells mature • Thymus: T-cells mature • Peripheral • Trap and process antigens • Increased likelihood of making a defense • Lymph nodes, tonsils This Photo by Unknown author is licensed under CC BY-SA. Immune Response in the Older Adult • More susceptible • Less adaptation and immunity • Less T-cells This Photo by Unknown author is licensed under CC BY. Questions Answer: A • Enhancement of phagocytosis is called? a. opsonization b. abfraction c. transudate d. chemotaxis Answer: E • Antibody mediated immunity (Humeral immunity) complements the inflammatory response because: a. It is specific and has the ability to recognize previous antigens b. Is quick acting, responding to a recognized antigen within 6 hours c. Is delayed in its response to a recognized antigen, taking 1-3 days d. a&b e. a&c Answer: C • In the course of the normal immune response, antigens of any type are: a. Reproduced. b. Strengthened. c. Neutralized. d. Changed to "memory cells" Answer: B • You are caring for a patient who has a severe rash and itching from poison ivy in the lower legs. This reaction is best understood as an example of cell mediated immunity. The cell type involved in this type of immunity are: a. B lymphocytes b. T lymphocytes c. Natural killer cells d. Antibodies Answer: B • Your adult patient is scheduled to receive an influenza vaccination. She asks "how do those things work anyway?" Select the best response. a. "They work by giving you antibodies so you will be immune immediately if exposed in the future to the same antigen." b. "Immunizations work by sensitizing your body to prepare antibodies against this virus if exposed in the future to the same antigen." c. "Trust me, they work and you need one!" d. "Immunizations work by activating cytokines which are part of the immune response." Answer: C • The complement system is responsible for a.) blood clotting b.) production of pain c.) destruction of microorganisms d.) increased extracellular fluid volume Answer: A • Antibodies are produced by a.) memory B-lymphocytes b.) helper T-lymphocytes c.) macrophages d.) plasma cells Answer: B • Which cells of the innate immune system stimulate specific response from the adaptive immune response? a.) cytotoxic T-lymphocytes b.) macrophages c.) memory T-lymphocytes d.) helper T-lymphocytes Answer: D • Which T-lymphocytes activate the B-cell response? a.) suppressor T-cells b.) cytotoxic T-cells c.) memory T-cells d.) helper T-cells Answer: Thymus; bone marrow • T-lymphocytes mature in ________ ; and B-lymphocytes mature in _____ Answer: C • The level of this antibody is raised in allergic reactions a.) IgA b.) IgG c.) IgE d.) IgM Answer: IgG • This antibody can cross the placenta Answer: IgM • The first antibody to arrive is usually _____ Hypersensitivity Disorders • Type I, IgE-mediated disorders • Type II, antibody-mediated disorders • Type III, complement-mediated immune disorders • Type IV, T-cell–mediated disorders Type 1: IgE Mediated • First exposure: Makes antibodies (IgE) • Second Exposure: allergen binds to antibodies • Causes mast cells to degranulate (histamine)=tissue injury • Immediate and confined • Fixed antibody on mast cells, freely floating antigen • Examples • Allergic asthma, allergic rhinitis, hives • Food allergies Type 2: Cytotoxic Hypersensitivity • IgG or IgM • Antigen is on cell, marks it for attack • Fixed antigen, freely floating antibody • Complement gets activated • Forms Membrane Attack Complex (MAC) • Macrophage destroys This Photo by Unknown author is licensed under CC BY-SA-NC. • Examples • Mismatched blood transfusion reactions • Hemolytic disease of the newborn (Rh incompatibility) • Myasthenia Gravis Type 3: Immune Complex Allergic Disorders • Antigen and antibody come together=inflammatory response • IgG and IgM • Immune complexes deposit on walls of blood vessels and tissues and activate complement • DepositThe deposit site gets damaged • Examples • Systemic lupus erythematosus • Serum sickness • Arthus rxn This Photo by Unknown author is licensed under CC BY-SA-NC. Type 4: Cell Mediated Hypersensitivity • Delayed-type • T-cells, not antibodies • T helper cells release cytokines, activate macrophages • Examples • Contact dermatitis (latex, poison ivy) • Multiple sclerosis This Photo by Unknown author is licensed under CC BY-SA-NC. MHC 1 vs 2 • MHCs function to identify self vs. non-self cells • Bind fragments of antigen and display them on their cell surface so that T-lymphocytes can recognize them MHC 1 MHC 2 On most cells Only on APCs Intracellular pathogens Extracellular pathogens Best review videos!! • Type 1 Hypersensitivity • Type 2 Hypersensitivity • Type 3 Hypersensitivity • Type 4 Hypersensitivity Transplanted Tissue Types 1. Allogeneic • Related or unrelated; but similar HLA types 2. Syngeneic • Identical twins 3. Autologous • Same person This Photo by Unknown author is licensed under CC BY-SA-NC. Questions!! Answer: Anaphylactic/ Type 1 • After receiving an intravenous dose of Vancomycin, your patient begins to complain of shortness of breath and tongue swelling. This would be an example of what type of reaction? Answer: B • The nursing instructor asks the student nurse to explain a type IV hypersensitivity reaction. Which statement by the student best describes type IV hypersensitivity? A. "It is a reaction of immune globulin (Ig)G with the host cell membrane or antigen." B. "The reaction of sensitized T-cells with antigen and release of lymphokines activate macrophages and induce inflammation." C. "It results in release of mediators, especially histamine, because of the reaction of IgE antibody on mast cells." D. "An immune complex of antigen and antibodies is formed and deposited in the walls of blood vessels." Answer: C • Which statement is true about pathologic conditions of the immune system? a. Allergies result when the immune system loses its ability to react to antigens. b. In immunodeficiency, the body's immune system overreacts to foreign antigens. c. In autoimmune diseases such as Lupus or Rheumatoid Arthritis, the body's immune system treats some of the body's own tissues as foreign invaders. d. None of the above. Answer: B • A nurse is reviewing the chart of a newborn treated for hemolytic disease. Which statement shows the nurse's understanding of the cause of the disease? A. "Neutrophils attempt to phagocytize the RBCs." B. "antibodies bound with an antigen activate the cascade destroying the RBCs." C. "Complement activation causes the release of inflammatory chemical mediators resulting in RBC destruction." D. "Endogenous antigens stimulate a type II reaction resulting in lysis of the RBC." Answer: Type 3 • Which hypersensitivity reaction damages tissues through the deposition of immune complexes in tissue walls? HIV • Virus that attacks CD4 cells • Immunity becomes compromised • Transmission • Sexual contact, blood-blood contact, mother to child • Phases 1. Primary Infection • Flu-like • Days-weeks after contracting 2. Chronic • Latent, asymptomatic • Years 3. AIDS • CD4 count <200 • Very vulnerable to infections Modes of Transmission • Penetration • Ex. Infected splinter • Direct Contact • Ex. Kissing --> mononucleosis • Ingestion • Ex. E. coli food poisoning • Inhalation • Ex. Influenza Sources • Nosocomial=from hospital • Community acquired=outside of hospital • Endogenous: from inside body, normal flora becomes infectious • Exogenous: from outside body • Fomite: inanimate object containing an infection • Ex. Table surface Disease Course 1. Incubation • Infection -> Symptom onset; where infection grows 2. Prodromal • Early, nonspecific symptoms • Usually becomes contagious, but often unaware of illness 3. Acute • Peak symptoms • Immune response in full force 4. Convalescent • Recovery, starting to feel better 5. Resolution • Symptoms and infection gone This Photo by Unknown author is licensed under CC BY. Bioterrorism • Category A: highest risk; easily transmitted, high mortality, harder treatment • Plague, Anthrax, Smallpox, Tularemia, Viral hemorrhagic agents (Ebola), Botulism • Category B: 2nd priority • Food/water-borne diseases (Salmonella, E.coli), zoonotic infections, Viral encephalitis, castor bean toxin aka Richin toxin • Category C: 3rd priority, includes emerging pathogens of note • Mycobacteria Tuberculosis, Nipah and hantavirus, tick-borne disease, yellow fever, Cryptosporidium parvum Questions! Answer: D • A patient tests positive for COVID-19 but has not yet begun showing symptoms. What stage of infection is this patient in? • a.) Prodromal • b.) Convalescent • c.) Nonspecific • d.) Incubation