Infection & Defects in Mechanisms of Defence PDF

Infection & Defects in Mechanisms of Defence Chapter 8 Infection & Defects in Mechanisms of Defence An inadequate response (immune deficiency) may range from relatively mild defects to life-threatening severity. Inappropriate responses (hypersensitivity) may be: 1. Exaggerated against no...

Infection & Defects in Mechanisms of Defence Chapter 8 Infection & Defects in Mechanisms of Defence An inadequate response (immune deficiency) may range from relatively mild defects to life-threatening severity. Inappropriate responses (hypersensitivity) may be: 1. Exaggerated against non-infectious environmental substances (allergies) 2. Misdirected against the body’s own cells (autoimmunity) 3. Directed against beneficial foreign tissues, such as transfusions or transplants (alloimmunity) Factors for Infection 1. Communicability: Ability to spread from one individual to others and cause disease (ex. measles and pertussis spread very easily; HIV is of lower communicability) 2. Infectivity: Ability of pathogen to invade and multiply in the host (ex. Herpes simplex virus can survive for long periods in a latent stage) 3. Virulence: Capacity of a pathogen to cause severe disease (ex. measles virus is of low virulence while rabies virus is highly virulent) 4. Pathogenicity: Ability of an agent to produce disease. Success depends on communicability, infectivity, extent of tissue damage, and virulence (ex. HIV can kill T cells) 5. Portal of Entry: Route by which a pathogenic microorganism infects the host (ex. direct contact, inhalation, ingestion, bites of an animal or insect) 6. Toxigenicity: Ability to produce soluble toxins or endotoxins, factors that greatly influence the pathogen’s degree of virulence Bacterial Disease Bacteria are prokaryotes (lack a discrete nucleus) Survival & growth depend on the effectiveness of the body’s defence mechanisms and the bacteria’s ability to resist the defences Staphylococcus aureus - Opportunistic pathogen in that it is well-equipped to act as a life-threatening pathogen when the opportunity arises. - Starts out as a skin infection at site of trauma, but can develop into abscess and boils, and may lead to septicemia (infection in bloodstream). - Antibiotic resistance is a major problem (MRSA) Toxin Production Exotoxins Enzymes that can damage the plasma membranes of host cells or can inactivate enzymes critical to protein synthesis Endotoxins Activate the inflammatory response and produce fever Bacterial Virulence and Infectivity Bacteremia (presence) or septicemia/sepsis (growth) Result of a failure of the body’s defence mechanisms Usually caused by Gram-negative bacteria Endotoxins released into the blood activate the complement and clotting systems, leading to a degree of capillary permeability sufficient to permit escape of large volumes of plasma into surrounding tissue, contributing to hypotension and, in severe cases, cardiovascular shock Viral Disease Most common affliction of humans (common cold, cold sores, AIDS) Replication depends on ability to infect host cell Simple organism Usually self-limiting Transmission: Aerosol, Infected blood, Sexual contact, Vector Viral Replication Not capable of independent reproduction Need permissive host cell: Attachment, Penetration, Uncoating, Replication, Assembly, Release Copies of genetic material made New virions released from cell to infect other host cells Some remain latent in host cell until activated by stress, hormonal changes, disease (e.g., herpes virus and “cold sore”) Influenza Goes through antigenic variation; when the viral surface antigens change! - This is why there are yearly vaccines with different strains - Minor change = antigenic drift - Major change = antigenic shift Fungal Infection Eukaryotes Exists as single-celled yeasts, multi-celled molds, or both Reproduce by simple division or budding Pathogenicity: - Adapt to host environment (wide temperature variations, & low oxygen) - Suppress the immune defences - Usually controlled by phagocytes, T lymphocytes - Candida albicans (Yeast) - Most common cause of fungal infections - Opportunistic - Found in normal microbiome of skin, GI tract, and vagina of many individuals - Localized infection if overgrowth occurs - Disseminated infection if immunocompromised - May involve deep infection - High mortality rates - Thrush = accumulation on the lining of your mouth Parasitic Infection Symbiotic Unicellular protozoa to large worms (helminths; tapeworms) Protozoa include malaria, amoebae, flagellates More common in developing countries Spread human to human via vectors Usually ingested Tissue damage is secondary to infestation itself with toxin damage or from inflammatory/immune response Countermeasures Against Infectious Microorganisms 1. Infection control measures 2. Antimicrobials 3. Active immunization 4. Passive immunotherapy Active Immunization Vaccines: biological preparations of antigens that when administered, stimulate production of protective antibodies or cellular immunity against a specific pathogen without causing potentially life-threatening disease GOAL is to induce long-lasting protective immune responses under safe conditions - Creation of antibodies, and T cells Another GOAL is herd immunity. Where ~85% of the population should be immunized to achieve protection of the total population. Inactivated virus vs weakened (attenuated) virus Deficiencies in Immunity Immune Deficiency (Immunodeficiency): the failure of the immune or inflammatory response to function normally, resulting in increased susceptibility to infections Primary (congenital) genetic defects Secondary (acquired) other conditions such as cancer, infection, or aging Clinical presentation: - Development of unusual or recurrent, severe infections - T-cell, B-cell, and phagocyte deficiencies Evaluation of Immunity Complete blood count (CBC) with a differential CBC provides information and the numbers of RBC, WBC, platelets Differential provides quantities of lymphocytes, granulocytes, and monocytes Quantitative determination of immunoglobulins Screening for antibodies (IgA, IgG, IgM, IgE, IgD) Treatment for Immunodeficiencies Gamma-globulin therapy; Intravenous immune globulin (IVIg) Stem cell transplantation Transfusion of erythrocytes (RBC) Bone marrow transplants Gene therapy Acquired Immune Deficiency Syndrome (AIDS) & Human Immunodeficiency Virus (HIV) Acquired Immune Deficiency Syndrome (AIDS): A secondary immune deficiency that develops in response to viral infection ○ Human Immunodeficiency Virus (HIV) infects and destroys the CD4+ T-helper (Th) cells which are necessary for the development of both plasma cells and T-cytotoxic cells ○ The decreasing number of CD4+ cells is a key immunological finding in AIDS **HIV suppresses the immune response against itself and secondarily causes a generalized immune deficiency by suppressing the development of immune responses against other pathogens and opportunistic microorganisms, leading to the development of AIDS** HIV & AIDS New developments have made the HIV infection more of a chronic illness, when the condition is well managed - Immune modifiers & antiviral agents - Many people live with HIV infection for long periods without it progressing to AIDS Epidemiology of AIDS HIV is a blood-borne pathogen, transmitted by: - Blood or blood products - Intravenous medication abuse - Both heterosexual and homosexual activity - Maternal-child transmission before or during birth Most common route world wide is heterosexual activity Women constitute more than half of those living with HIV/AIDS Clinical Manifestations of AIDS At the time of diagnosis the individual will present with one of the following: ○ Serologically negative (no detectable antibody) ○ Serologically positive (positive for antibody against HIV proteins), but asymptomatic ○ Early stages of HIV disease ○ AIDS Depletion of CD4+ cells. Early stage S/S: mild & nonspecific (headache, fever, fatigue) Treatment & Prevention of HIV and AIDS Highly active antiretroviral therapy (HAART) - Combination of medications from different classes & specific regimens - Based on age, secondary clinical symptoms (hepatic or renal insufficiency), CD4+ Th cell levels, viral load, specific co-infections, pre-existing cardiac risk factors, past history of treatment failure, and suspected medication resistance Medication therapies are NOT curative; therefore medications may have to be taken for the individual's lifetime Longtime use of these medications can increase risk for cardiovascular disease, metabolic disorders, and organ failure Hypersensitivity: Allergy, autoimmunity, & alloimmunity Hypersensitivity: Altered immunological response to an antigen that results in disease or damage to the host Allergy: refers to a hypersensitivity to environmental allergens; can include medicines, natural products (bees, pollens), and anything else not naturally found in the individual Autoimmunity: a disturbance in the immunological tolerance of self-antigens; the immune system does not recognize the individuals own antigens. Many clinical disorders are associated with autoimmunity & are generally referred to as autoimmune diseases Alloimmunity: when the immune system of one individual produces an immunological response against the tissues of another individual; can be observed during transfusions, transplanted tissues, or the fetus during pregnancy Hypersensitivity 4 mechanisms: Type I IgE mediated Type II Tissue-specific reactions Type III Immune complex mediated Type IV Cell mediated Types of reactions: - Immediate hypersensitivity reaction (minutes to a few hours) - Anaphylaxis (severe & life threatening) - Delayed hypersensitivity reaction (several hours & maximal severity days after the exposure) Type I Hypersensitivity: IgE mediated Most common allergic reactions; usually against environmental antigens Acting through H1 receptors histamine has several effects ○ Contracts bronchial smooth muscles (bronchial constriction; asthma) ○ Increases vascular permeability (edema) ○ Causes vasodilation (increased blood flow) H2 receptors and histamine results in ○ Increased gastric acid secretion S/S: gastric (N/V, adbo pain), urticaria (hives), conjunctivitis, rhinitis, asthma, bronchospasm, thick secretions from lungs Treatment: avoiding antigens, antihistamines Autoimmunity Genetic, environmental, and random factors Breakdown of tolerance - Body recognizes self-antigens as foreign - Self-antigens not normally seen by the immune system Infectious disease can be the initiator of autoimmune disease (rheumatic fever) Systemic Lupus Erythematosus (SLE) Chronic multisystem inflammatory disease Produces a large amount of antibodies against self-antigens including - Nucleic acids, Erythrocytes (RBCs) and Platelets Clinical Findings: - Facial rash confined to the cheeks (malar or butterfly rash) - Discoid rash (raised patches, scaling) - Photosensitivity - Oral or nasopharyngeal ulcers - Nonerosive arthritis of at least 2 peripheral joints - Serositis (inflammation of membranes of lung or heart) - Renal, neurological, hematological, or immunological disorders - Presence of antinuclear antibody (ANA) Malar or Butterfly Rash Alloimmunity: Transfusion Reactions ABO blood group A and B carbohydrate antigens (Can be simultaneously expressed) Blood types based on which erythrocytes expressed: A, B, O (neither expressed), AB (both expressed) Example: Person with blood type A receives type AB or B blood, transfused erythrocytes are destroyed **Type O—universal donor / Type AB—universal recipient** ABO blood group (letters) Rh blood group (-/+) - Antigens expressed only on RBCs - Rh-positive & Rh-negative *if Rh-negative mothers create antibodies against their Rh-positive fetuses, it can cause hemolytic disease of the newborn* RhoGAM is an injection provided to prevent Rh incompatibility from developing during pregnancy Transplant Rejection Classified according to time between transplantation and rejection Hyperacute ○ Immediate and rare ○ Pre-existing antibody to the antigens of the graft Acute ○ Cell-mediated immune response against unmatched HLA (human leukocyte antigen) Chronic ○ Months or years ○ Result of a weak cell-mediated reaction against minor HLA