NURS 314 Infection and Immunity

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Terms in this set (73)
the collection of all the microorganisms living in association with the human body. These communities consist of a variety of microorganisms including eukaryotes, archaea, bacteria and viruses. Bacteria in an average human body number ten times more than human cells, for a total of about 1000 more genes than are present in the human genome. Because of their small size, however, microorganisms make up only about 1 to 3 percent of our body mass (that's 2 to 6 pounds of bacteria in a 200-pound adult). These microbes are generally not harmful to us, in fact they are essential for maintaining health. For example, they produce some vitamins that we do not have the genes to make, break down our food to extract nutrients we need to survive, teach our immune systems how to recognize dangerous invaders and even produce helpful anti-inflammatory compounds that fight off other disease-causing microbes. An ever-growing number of studies have demonstrated that changes in the composition of our microbiomes correlate with numerous disease states, raising the possibility that manipulation of these communities could be used to treat disease
The immune response: collective and coordinated response of cells of the immune system

Protects host from foreign invaders such as pathogens, bacteria, parasites, viruses

Distinguishes self from non-self (Cancer, autoimmune reactions, transplants)

Mediates healing (i.e. Inflammatory response, wound repair)

Dysfunction ➔ autoimmunity, immunodeficiency, allergies, hypersensitivity, transplant pathology

Mostly protective but can produce undesirable effects such as when response is excessive (allergies) or when it recognizes self tissue as foreign (autoimmune disease)
Innate Immunity (First line of defense)Immunity that is present before exposure and effective from birth Does not distinguish between different microbes Physical barriers: -Skin -Linings of the gastrointestinal, genitourinary, and respiratory tracts Epithelial cell-derived chemical barriers- Synthesized and secreted saliva, tears, ear wax, sweat, and mucus, Antimicrobial peptides, Normal bacterial flora Attacks non-self microbesInflammation (Second Line of Defense)(first immune response to injury) Caused by a variety of materials -Infection, mechanical damage, ischemia, nutrient deprivation, temperature extremes, radiation, etc. Local manifestations -Redness, heat, swelling, pain, loss of function Vascular Stage -Increased blood flow (vasodilation) -Structural changes (↑ vascular permeability) Cellular Stage -Emigration of leukocytes (neutrophils) from microcirculation to accumulate at site of injury or infectionEndothelial CellsSingle cell -Produce antiplatelet and antithrombotic agents to maintain vessel patency -Produce vasodilators and vasoconstrictors to regulate blood flow -Provide selective permeability barrier to exogenous (microbial) and endogenous inflammatory stimuli -Regulate leukocyte extravasation by expression of adhesion molecules and receptors -Synthesize and release inflammatory mediators -Regulate immune cell proliferation through secretion of hematopoietic CSF's -Participate in repair process of inflammation by production of growth factors that stimulate angiogenesis and extracellular matrix synthesisPlateletsRelease potent inflammatory mediators that increase vascular permeability and alter chemotactic, adhesive, and proteolytic properties of endothelial cells Platelet activation= release of greater than 300 proteins; many of which are inflammatory mediatorsAdaptive ImmunityDestroys infectious microorganisms that are resistant to inflammation Re-exposure produces a faster, greater, and more prolonged response Inducible, Specific Creates memory cells like: Immunoglobulins Lymphocytes (T cells, B cells) Two types: Cell-mediated (cellular) Antibody-mediated (humoral)B LymphocytesForm in the bone marrow and release antibodies that fight bacterial infectionsCytolytic T LymphocytesCytolytic T cells, CD8 cells Do not produce antibodies Attack and kill target cells directlyHelper T LymphocytesHelper T cells, CD4 cells -Antibody production by B cells -Required for an effective immune response -Activation of cytolytic T cells (CD8 cells) -Promote type IV sensitivity reactions, also known as delayed-type hypersensitivity (DTH)MacrophagesBegin in bone marrow, enter blood as monocytes, and infiltrate tissues, where they evolve into macrophages Principal scavengers of the body Specific acquired immunity Activation of T cells Final mediators of delayed type hypersensitivity (DTH) rxn Phagocytize cells tagged with antibodies Also play key roles in natural immunity and inflammationDendritic cellsMulti-origin, especially relevant to HIV transmissionMast cells and basophilsMediate immediate hypersensitivity reactionsNeutrophilsPolymorphonuclear leukocytes (PMNs) Phagocytize bacteria and other foreign particlesEosinophilsAttack and destroy foreign particles that have been coated with antibodies of the immunoglobulin (Ig) E classAntibodiesAlso called Immunoglobulins or Gamma globulins Family of structurally related glycoproteins Mediate humoral immunity Recognize and bind with specific antigens Produced by B lymphocytesIgMInvolved with ABO blood antigens On surface of naïve B cells and serves as antigen receptor for initiating differentiation of B cells 1st Ig made in response to antigenIgAFound in saliva, tears, colostrum, mucosal secretions Prevents attachment of bacteria and viruses to epithelial cells a secretory Ab (bronchial, pancreatic, vaginal secretions, etc.), 1st line of defense in mucosal tissuesIgDServes as antigen receptor on B cellsIgGMost abundant AB; binds bacteria, toxins, extracellular viruses Present in bodily fluids and enters tissues Only Ig to cross placenta Activates complement system can also bind receptors on NK cells and macrophages leading to lysis of target cellIgEInvolved in inflammation, allergic responses, and parasitic infections Binds to mast cells/basophils and triggers release of histamineMajor Histocompatibility Complex MoleculesA set of cell surface proteins essential for the acquired immune system to recognize foreign molecules MHC molecules become expressed on the surface of all cells Play a key role in the activation of helper and cytotoxic T lymphocytes Guide cytotoxic T lymphocytes toward target cells Provide the basis for distinguishing between self and nonselfClass I MHC moleculesFound on virtually all cells except erythrocytes Located on the surface of antigen-presenting cells (APCs) Help initiate immune responses by "presenting" antigen to cytotoxic T cellsClass II MHC moleculesFound primarily on B cells and APCs (macrophages and dendritic cells) Located on the surface of APCs Help initiate immune responses by presenting antigen to helper T cellsCytokineAny mediator molecule (other than an antibody) released by any immune system cell Lymphokine: Cytokine released by a lymphocyte Monokine: Cytokine released by a mononuclear phagocyte (monocyte or macrophage)Antibody-Mediated (Humoral) ImmunityProduction of antibodies Interaction of three types of cells: -Antigen-presenting cells (macrophage or dendritic)- Activate CD4 cells -Helper T cells (CD4 cells)- Stimulate B cells -B cells- Make antibodies Antibody effector mechanisms Opsonization of bacteria (Binding of antibodies enhances to phagocytosis) Activation of the complement system (Response involving ~30 proteins in cascade resulting in MAC on the surface of bacteria ) Neutralization of viruses and bacterial toxinsCell-Mediated (Cellular) ImmunityDelayed-type hypersensitivity-Mediated by macrophages and helper T cells Cytolytic T lymphocytes (CTLs, CD8 cells)-Mediated by cytolyticT cells -Recognition of virally infected target cells -Mechanism of cell kill -Cause target cell lysisImmunizatonThe most effective method to protect against infectious diseases is to create a highly immune population Universal vaccine is the goal -Herd Immunity: 93% of population needs to be vaccinated Vaccines carry risk, but risks of disease are much greaterActive ImmunityAntibodies produced by one's own immune system against a specific disease -usually permanent (because of memory cells) Acquired by: 1. contracting a disease 2. vaccination against a diseasePassive ImmunityAntibodies from another human being or animal Effective but limited, diminishes over time Example: Maternal antibodies passed to infants protect them for the first 4-6 months of lifeVaccineWhole or fractionated microorganisms; either killed or live (but attenuated, or weakened) vaccines Attenuated vaccines are not given to infants, the elderly, or immunocompromised personsToxoidBacterial toxin that has been changed to a nontoxic formSerologyThe study of blood serum with regard to immune response After exposure to an infectious agent, the body produces antibodies and the antibody titer rises IgM: rises during the acute phase, then falls IgG: remains elevated after the acute phasePrimary Immune Response-Takes 10-17 days to occur after first exposure -Symptoms of illness occurs during these days -Antigen-selected B and T cells proliferate and differentiate into effector cellsSecondary Immune Response-Subsequent exposures to antigen -Takes 2-7 days to occur -Greater magnitude response and prolonged -Occurs due to presence of memory cells B memory cells respond to a specific antigen immediately Plasma antibody levels rise within days Booster shots cause a secondary immune response so antibody levels will be high before the disease is encounteredLive-Attenuated Influenza VaccinesIntranasal vaccine that contains living microorganisms that have been altered so that they don't cause diseaseInactivated Influenza VaccineIntramuscular injection of a vaccine that contains microorganisms that have been killed by heat, chemicals, or radiationImmunization RecordsNational Childhood Vaccine Act of 1986 requires a permanent record of each mandated vaccination including: -Date of vaccination -Route and site of vaccination -Vaccine type, manufacturer, lot number, expiration date -Name, address, title of person administering the vaccine Required to ensure appropriate vaccination and avoid over-vaccination Vaccine Adverse Event Reporting System (VAERS)Adverse effects of immunizationImmunocompromised people are at special risk from live vaccines -Congenital immunodeficiency -Human immunodeficiency virus (HIV) infection -Leukemia -Lymphoma -Generalized malignancy -Therapy with radiation -Cytotoxic anticancer drugs -High-dose glucocorticoidsImmunity in Older AdultsImpaired function of innate immune cells (phagocytes) Impaired inflammation likely a result of chronic illness Diabetes, cardiovascular disease, etc. Decreased inflammatory response due to chronic medication intake Diminished healing response d/t skin's loss of regenerative ability More common infection and chronic inflammationBacteriaSingle-celled organisms that lack a membrane bound nucleus or organelles (prokaryotes) Can live independently Use infected organisms for food and shelterAntibiotic TargetsCell wall synthesis Protein synthesis Nucleic acid synthesis Bacterial metabolism This selects for bacteria that can: Inactivate antibiotics Change antibiotic binding sites Use different metabolic pathways Change their walls to keep antibiotics outSelective toxicityThe ability of a drug to injure target cell/organism without injuring others (like beneficial flora) Based on differences between microbes and humans -Disruption of cell wall (PCN, cephalosporins)- high solute concentration in bacteria= high osmotic pressure. Without cell wall, microbes would swell and lyse -Inhibition of enzymes unique to bacteria (sulfonamides)- microbes require folic acid and cannot obtain it directly from the environment. They take up the precursor to folic acid (PABA: para-aminobenzoic acid) and convert it to folic acid via enzyme -Disruption of protein synthesis (aminoglycosides)- microbes have different ribosomes than humans for protein synthesisClassification of DrugsDrugs are classified by the susceptibility (drug is toxic to organisms) Dose and route of administration must result in adequate levels of drug at infected site for sufficient time. Organism must be susceptible to concentration of drug at infected siteAcquired Antimicrobial ResistanceMicrobes become resistant to drug = ↓ or no susceptibility Prolonged hospitalization, significant morbidity, excessive mortality Major culprits: Staphylococcus aureus (MRSA) Clostridium difficile (C. diff) Enterobacter species (VRE) Klebsiella species (G- Rods) Acinetobacter (AB) Tuberculosis (TB) HIVIdentification of Infective OrganismID infective organism so right drug can be selected Variety of modalities: rapid tests, culture on agar Culture can take days to weeks Treatment may be initiated prior to culture results Based on presumption of what organism may likely be Empirical treatment Broad spectrum before ID of organism type + susceptibility = crucial Empiric treatment based on most likely organism and suspected susceptibility based on site, sx, etc. prior to culture results returning Need culture prior to starting abx Adjust treatment regimen once culture results receivedMechanisms of ResistanceDecrease drug concentration at site of action -Cease active uptake of drug -Increase active transport out of cell Alteration of drug target molecules -Structural changes in targets of drugs (e.g., ribosomes) Antagonist production -Synthesize compound that antagonizes drug action Drug inactivation -Synthesize drug metabolizing enzymes -Examples: Penicillinase and Beta-lactamases (inactivates drugs that have a beta lactam ring (PCN, cephalosporins, carbapenems))How Bacteria Acquire ResistanceSpontaneous Mutation- confers resistance to one drug Conjugation- horizontal transfer of extrachromasomal DNA between or across species -Plasmid transfer: gene circle encodes for beta-lactamases and other resistance determinants (efflux pumps, enzymes for inactivation) -Confers multiple drug resistance (MDR) -Can acquire from normal floraWhy Bacteria Acquire ResistanceUse of antibiotics, which kill off sensitive microbes and facilitate survival of drug resistant microbes -No longer subject to other microbes' toxins -Loss of competition for available nutrients -Create condition favorable for overgrowth of resistant microbes Broad-spectrum antibiotics will kill more competing organisms than narrow spectrum, therefore facilitate more overgrowth Nosocomial infectious pathogens can be very resistant because so much abx used in hospitals Important to Note: Can cause overgrowth of flora with resistance that can be transferred to pathogens Dosing: to ensure adequate blood levels, abx should be given around the clock q4, q8, etc. and given on an empty stomach without co-administration with other medsSuprainfectionsA new infection that appears during course of treatment for a primary infection Develops as antibiotics eliminate inhibitory influence of normal flora, allowing secondary infectious agent to flourish More likely with broad-spectrum antibiotics because they kill more normal flora Caused by drug resistant microbe that is resistant to abx being used to treat primary infection Ex: C. diffCDC's (2002) Campaign to Prevent Antimicrobial Resistance1. Prevent infection -Vaccinate -Remove catheters 2. Diagnose and treat infection effectively -Target pathogen (limit broad-spectrum) -Access experts 3. Use antimicrobials wisely -Treat infection, not colonization or contamination 4. Prevent transmission Degree of misuse of abx: 50% of abx rx inappropriate or unnecessaryAmoxicillinFunctional class: beta-lactam antibiotic, a penicillin Indications: Wide range of gram-positive staph, strep and pneumococcal infections, including syphilis, and Lyme disease Mechanisms of Action (MOA): disrupts the synthesis of the peptidoglycan layer of bacterial cell walls Side Effects (SE): Gastrointestinal upset and diarrhea -Serious: Allergy with anaphylactic reactions (wheezing, rash, fever) Nursing Considerations: Allergies (to PCN), renal disorders, lactation. -Evenly space doses in 24 hour cycle -Take the full course of therapy; do not stop because you feel better. -Specific for this problem and should not be used to self-treat other infectionsVirusParticles that insert their genome into a host cell Protein coat surrounding nucleic acid core Have no metabolic enzymes of their own Use cell's metabolic machinery to make new virusesAntiviral DrugsAntiviral Agents Block: 1. Viral binding to cells 2. Viral RNA or DNA synthesis 3. Integration of viral DNA 4. Production of protein coats (capsids) of new viruses Not virucidalRETROvirusesInject viral RNA rather than DNA into the host cell. Require transcription from the single strand RNA to single strand DNA before replication. Each strand of viral RNA is associated with a molecule of reverse transcriptase used in the transcription of viral RNA to DNA. Integrate viral DNA into host cell DNAHIV and Adolescent YMSM1 in 3 Baltimore City young African American men who have sex with men (YMSM) are living with HIV. YMSM in Maryland represent the fastest growing population of new HIV infections.What HIV DoesDestroys T-cells faster than they can replicateMarkersViral load -number of viruses circulating in the blood -rate of replication CD4s (found on T-cells) -Destroyed during virus replication -Measure how much damage to immune system -Predict risk for disease progression -CD4 count <200 = AIDSNatural History of HIV InfectionStage 1: Primary (Acute) HIV Infection 2-4 weeks after transmission Flu-like illness Large amount of virus in blood Very contagious Stage 2: Clinical latency (Chronic HIV Infection) Low levels of HIV in blood - 10 years or longer May have no symptoms Can reach viral suppression ("undetectable") on medication Stage 3: AIDS decreased CD4 count (<200 cells/mm), increased viral load 3 year survival without treatment Chills, sweats, lymphadenopathy, weakness, weight loss May be very contagiousSeroconversionPeriod of time between when you're exposed and when you develop antibodiesRate of ProgressionWithout treatment, seroconversion to death is 10-12 years Survival prolonged by: Highly Active Anti-Retroviral Therapy (HAART or ART) Pneumocystis jiroveci prophylaxis Mycobacterium avium prophylaxis Care by experienced HIV providersCDC Testing Recommendations for HIVEveryone ages 13 to 64 At least once as part of routine care Yearly if high risk Newly pregnant and third trimester Opt-out vs. Opt-in Decreases stigma and anxiety Late diagnosis can lead to complications and death Previous targeted risk approach was ineffective in reaching heterosexuals, youth African Americans, Latinx, rural residents Routine testing has been shown to be effective Reduced perinatal transmission Age <18 Can consent to treatment or advice re: STIs or HIV Does NOT need parental consent Can be confidential (provider does not need to inform parent) BUT Communicate the following: Charges will appear on insurance EOB Mandatory reporting requirementsReproductive Cycle of HIVStep 1 represents HIV-1 entry into the host cell, which involves the binding of the viral envelope protein, glycoprotein 120 (gp120), to the CD4 molecule, followed by a conformational change in gp120 that allows binding to the chemokine host-cell receptor (e.g., CCR5 or CXCR4). Glycoprotein 41 (gp41), also part of the virus envelope, then mediates HIV-cell fusion to permit viral entry. The fusion inhibitor, enfuvirtide, blocks fusion between the virus (through gp41) and the CD4 molecule, and the CCR5 coreceptor antagonist, maraviroc, blocks viral binding (through gp120) to CCR5. Step 2 is reverse transcription, in which the single-stranded HIV-1 RNA is transcribed into double-stranded DNA by the HIV enzyme (polymerase) called reverse transcriptase. This step is the site of action of nucleoside and nucleotide reverse-transcriptase inhibitors (NRTIs) and nonnucleoside reverse-transcriptase inhibitors (NNRTIs). Step 3 is the migration of HIV DNA into the nucleus and its integration into the DNA of the host cell, a process catalyzed by the viral enzyme integrase. Integrase strand-transfer inhibitors (INSTIs) target this step. Step 4 is the transcription of the HIV-1 DNA into HIV messenger RNA (mRNA) and HIV genomic RNA. Step 5 is the transport of the HIV-1 RNA out of the nucleus and the translation of HIV-1 mRNA into viral polyproteins. Step 6. To be functional, the transcribed proteins must be cleaved into smaller component proteins, a process that occurs through the action of the HIV-1 enzyme protease. This is the site of action of protease inhibitors. Step 7 is the assembly of viral genomic RNA and viral enzymes (reverse transcriptase, integrase, and protease) into viral particles. Step 8 is the budding and maturation of new viral particles, which then go on to infect other host cells.Truvada(emtricitabine/tenofovir) Functional Class: Antiretroviral, nucleoside reverse transcriptase inhibitor (NRTI) Indications: Used as part of antiretroviral therapy (ART )in HIV infection, and for prophylaxis if HIV negative (PEP and PrEP) MOA: inhibits the activity of the HIV-1 reverse transcriptase (RT) by competing with a natural substrate and by being incorporated into nascent viral DNA which results in chain termination. SE: Nausea, vomiting, diarrhea, headache, dizziness, trouble sleeping, back pain, or change in the color of skin on your palms or soles of the feet may occur. Fat redistribution. -Serious: Guillain-Barre Syndrome (symptoms: difficulty breathing/swallowing/moving your eyes, drooping face, paralysis, slurred speech) Nursing considerations: Patients already infected with HIV should only take Truvada with other HIV meds. Patient support necessary for successful ongoing drug therapy. A Cochrane review found that both tenofovir alone, as well as the tenofovir/emtricitabine combination, decreased the risk of contracting HIV by 51%Opportunities to Impede HIV ReplicationInhibit attachment and fusion Inhibit reverse transcription Inhibit DNA integration Impair assembly and budding off