BMS PPT 3 Quiz
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Questions and Answers

What is the primary function of perforins?

  • To kill tissue cells invaded by viruses and cancer cells (correct)
  • Suppressor T cells
  • To mediate dominant immunologic tolerance
  • To help protect against autoimmune response

    • Which of the following cell types are NOT involved in nonspecific immunity?

  • Suppressor T cells (correct)
  • Eosinophils
  • Mononuclear phagocytes
  • Polymorphonuclear phagocytes (neutrophils)

    • Which statement accurately describes the role of the Fc portion of immunoglobulin molecules in the monocyte-macrophage system?

  • It directly interacts with the target cell, causing lysis.
  • It activates the complement cascade directly.
  • It binds to the receptor on macrophages, triggering phagocytosis. (correct)
  • It helps suppress the immune response.

    • Which of the following is NOT a characteristic of suppressor T cells?

    <p>Directly killing infected cells through perforins (C)</p> Signup and view all the answers

    Which of the following is NOT a cell type involved in the monocyte-macrophage cell system?

    <p>Helper T cells (B)</p> Signup and view all the answers

    How does the complement component C3b contribute to the immune response?

    <p>It opsonizes pathogens, making them more easily recognized and phagocytosed by macrophages. (D)</p> Signup and view all the answers

    What is the primary function of the reticuloendothelial system?

    <p>To filter and remove foreign substances from the body (C)</p> Signup and view all the answers

    Which of the following describes the correct order of steps involved in a cytotoxic T cell targeting a virus-infected cell?

    <p>1, 3, 2, 4 (C)</p> Signup and view all the answers

    Which statement correctly describes the role of macrophages in the immune system?

    <p>Macrophages are involved in both nonspecific and specific immune responses. (C)</p> Signup and view all the answers

    Which of the following is NOT a key characteristic required for a pathogen to successfully cause disease?

    <p>The ability to photosynthesize and produce energy (D)</p> Signup and view all the answers

    Which of the following is a primary difference between pathogenicity and virulence?

    <p>Pathogenicity is a general term related to the ability to cause disease, while virulence refers to the degree or severity of that disease (C)</p> Signup and view all the answers

    Which of the following is NOT considered a factor of virulence?

    <p>Ability to produce an antibiotic resistance gene (B)</p> Signup and view all the answers

    Which virulence factor directly prevents phagocytosis by host immune cells?

    <p>Coagulase (C)</p> Signup and view all the answers

    Which of the following is an example of a bacterial disease categorization?

    <p>Gram-negative bacterial infections (A)</p> Signup and view all the answers

    Which of the following is NOT a characteristic of resident flora?

    <p>They are always harmful to the host (B)</p> Signup and view all the answers

    Which of the following is a major reason why the presence of resident flora is advantageous to the host?

    <p>All of the above (D)</p> Signup and view all the answers

    Which of the following is an example of a virulence factor that contributes to invasiveness?

    <p>All of the above (D)</p> Signup and view all the answers

    Which of the following is a key difference between exotoxins and endotoxins?

    <p>Exotoxins are released into the environment, while endotoxins are components of the bacterial cell wall (B)</p> Signup and view all the answers

    Which of the following is NOT an example of a parasitic disease?

    <p>Ringworm (E)</p> Signup and view all the answers

    What makes Mycobacterium tuberculosis difficult to treat?

    <p>Its resistance to certain chemicals and dyes. (A)</p> Signup and view all the answers

    What is a key characteristic that differentiates Mycobacterium tuberculosis from other bacteria?

    <p>It possesses a high degree of resistance to certain chemicals and dyes. (C)</p> Signup and view all the answers

    Which of the following bacteria groups is NOT classified as Gram-positive?

    <p>Pseudomonas aeruginosa (A)</p> Signup and view all the answers

    Which of the following is NOT a typical characteristic of Mycobacterium tuberculosis?

    <p>Has a typical cell wall structure (D)</p> Signup and view all the answers

    What is the primary mode of transmission for Mycobacterium tuberculosis?

    <p>Inhalation of airborne droplets (B)</p> Signup and view all the answers

    Which of the following statements accurately describes the pathogenicity of Mycobacterium tuberculosis?

    <p>It can cause infection in various tissues and organs due to its high resistance to host defenses. (D)</p> Signup and view all the answers

    What is the characteristic difference between Mycobacterium tuberculosis and other bacteria like Staphylococcus aureus and Escherichia coli?

    <p>Mycobacterium tuberculosis has a waxy, lipid-rich cell wall. (D)</p> Signup and view all the answers

    Which of the following is a TRUE statement about Mycobacterium tuberculosis?

    <p>It is highly resistant to the immune system. (A)</p> Signup and view all the answers

    What is the primary reason Mycobacterium tuberculosis infections can be difficult to treat?

    <p>Its highly resistant cell wall structure and unique metabolism. (B)</p> Signup and view all the answers

    Which of the following is NOT a potential site of infection for Mycobacterium tuberculosis?

    <p>Intestines (B)</p> Signup and view all the answers

    Which of these statements regarding the roles of T cells in immunity is NOT accurate?

    <p>CD4+ T cells primarily target intracellular pathogens like viruses and some bacteria. (A)</p> Signup and view all the answers

    Which of the following accurately describes the activation process for B cells?

    <p>B cells require interaction with a CD4+ T cell to become fully activated and differentiate into plasma cells. (D)</p> Signup and view all the answers

    What role does the thymus play in the maturation of T cells?

    <p>The thymus serves as a site where T cells develop and gain the ability to recognize and respond to a specific antigen. (A)</p> Signup and view all the answers

    Which of the following accurately describes a key distinction between innate and acquired immunity?

    <p>Innate immunity is faster and less specific, while acquired immunity is slower but highly specific to individual pathogens. (B)</p> Signup and view all the answers

    Which of these cells is NOT considered a part of the adaptive immune system?

    <p>Natural killer cells (A)</p> Signup and view all the answers

    What is the primary function of antibodies produced by plasma cells?

    <p>To bind to and neutralize foreign antigens, preventing them from damaging host cells. (D)</p> Signup and view all the answers

    Which of the following cell types is NOT directly involved in recognizing and binding to antigens?

    <p>Plasma cells (C)</p> Signup and view all the answers

    What is the primary role of neutrophils in the immune response against atypical mycobacteria?

    <p>They directly phagocytose and destroy the pathogen. (C)</p> Signup and view all the answers

    Which of the following is NOT a characteristic of Mycobacterium leprae infection?

    <p>The ability to infect only the skin and peripheral nerves. (D)</p> Signup and view all the answers

    What is the primary mechanism by which antibodies generated against viral spikes neutralize the virus?

    <p>Antibodies block the viral spikes from interacting with host cell receptors. (B)</p> Signup and view all the answers

    Which of the following accurately describes the replication process of DNA viruses?

    <p>DNA viruses replicate in the nucleus, using host RNA polymerase for transcription and viral DNA polymerase for replication. (D)</p> Signup and view all the answers

    What is the primary difference between the immune response to TB bacilli and atypical mycobacteria?

    <p>TB bacilli primarily stimulate T cell-mediated immunity, while atypical mycobacteria trigger an IFN-mediated response. (D)</p> Signup and view all the answers

    Flashcards

    Innate Defenses

    Non-specific defenses that resist damaging organisms and toxins.

    Acquired Defenses

    Specific immunity involving activation of B and T cells.

    B Cells

    Lymphocytes that produce antibodies, best for fighting bacteria.

    T Cells

    Lymphocytes that seek and destroy infected or cancerous cells.

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    CD8+ T Cells

    Cytotoxic T cells effective against intracellular microbes.

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    B-Cell Receptor (BCR)

    Antibody on B cell surface that interacts with antigens.

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    Plasma Cells

    Activated B lymphocytes that produce large amounts of antibodies.

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    Perforins

    Proteins secreted by killer cells to create holes in target cell membranes.

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    Cytotoxic substances

    Toxic substances that are injected into cells by killer cells to induce death.

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    Killer cells

    Cells that destroy tissue cells invaded by viruses or cancerous cells.

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    Suppressor T Cells

    T cells that prevent over-reaction of the immune system and help avoid autoimmunity.

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    B-lymphocyte production inhibition

    The process by which suppressor T cells reduce the production of B-lymphocytes.

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    Macrophages

    Cells that participate in phagocytosis and inflammation as part of the immune system.

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    Phagocytosis

    The process by which cells engulf and digest pathogens or debris.

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    Monocyte-macrophage system

    A component of the immune system involving monocytes and macrophages in nonspecific immunity.

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    Reticuloendothelial System

    Network of cells including macrophages found throughout the body, important in immunity.

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    Pathogen

    An organism that can cause disease in a host.

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    Pathogenicity

    Ability of a microbial species to produce disease.

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    Virulence

    Ability of microbial strains to produce disease.

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    Infectious Disease Characteristics

    Pathogens must enter, multiply, damage tissues, and evade defenses.

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    Adhesion

    Ability of pathogens to attach to host tissues.

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    Invasiveness

    Ability of pathogens to penetrate host tissues.

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    Toxigenicity

    Ability to produce toxins that harm the host.

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    Communicability

    Ability of a pathogen to spread from one host to another.

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    Resident Flora

    Microbes that live in the body without causing infection.

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    Pathogens

    Disease-causing microbes.

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    Burgdorferi characteristics

    Burgdorferi do not produce toxins or destructive models.

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    Host immune response

    Symptoms from Burgdorferi infections are due to the host's immune response.

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    Nontypical bacteria

    Bacteria like Mycobacterium have atypical cell walls.

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    Acid-fast stain

    A staining technique for identifying acid-fast organisms like Mycobacteria.

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    Aerobic bacteria

    Bacteria that require oxygen to grow, like Mycobacterium tuberculosis.

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    Mycobacterium tuberculosis

    Causative agent of human tuberculosis, transmitted via aerosol.

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    Dissemination of TB

    Mycobacterium tuberculosis can infect various body locations beyond the lungs.

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    Primary target of TB

    The lungs are the primary target of Mycobacterium tuberculosis.

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    Non-motility in Mycobacteria

    Mycobacteria are typically non-motile and rod-shaped.

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    Resistance of Mycobacteria

    Mycobacteria exhibit high resistance to chemicals and dyes.

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    TB Bacilli Pathophysiology

    TB bacilli are phagocytosed by alveolar macrophages, triggering immune response.

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    Atypical Mycobacteria Response

    Macrophages produce IL-12, enhancing IFN to activate neutrophils for pathogen destruction.

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    Mycobacterium leprae and Leprosy

    Leprosy, caused by M. leprae, leads to skin sores and nerve damage, transmitted through droplets.

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    Types of Infectious Diseases

    Categorizes diseases into bacterial, viral, fungal, and parasitic based on causative agents.

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    Virus Structure

    Viruses are tiny agents with DNA or RNA in a protein coat, often enveloped, relying on host cells.

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    Study Notes

    Heme/Onc/ID Basic Medical Science I

    • This course covers innate and acquired immunity.
    • It details bacterial, mycobacterial, viral, fungal, and parasitic infections, covering their normal physiology, etiology, and pathophysiology.
    • Taxonomy of pathogenic human viruses, stages of viral infection, and viral gene expression, viral replication, and cytopathic effect at the cellular level.
    • The biology of HIV, molecular structure, replicative cycle, and epidemiology, pathogenesis, and transmission.
    • The student will define and differentiate various fungi based on normal physiology, etiology, and pathophysiology.
    • The section also examines the various types of parasites (protozoa and helminthic) and their related diseases.

    Objectives

    • Characterize the difference between innate and acquired immunity.
    • Define and differentiate Gram-positive, Gram-negative bacteria, spirochetes, and atypical bacteria.
    • Define and differentiate mycobacterial diseases, tuberculosis, and atypical mycobacterial diseases.
    • Describe the taxonomy of pathogenic human viruses.
    • Identify and characterize the stages of viral infection and viral gene expression.
    • Identify and describe viral replication, and cytopathic effect at the cellular level.
    • Describe the biology of HIV, molecular structure and replicative cycle.
    • Describe the epidemiology, pathogenesis, and transmission of HIV.
    • Differentiate superficial, subcutaneous, and systemic mycoses.
    • Differentiate protozoa and helminthic parasites.

    The Body's Defenses

    • Innate defenses are non-specific defenses.
    • Ability to resist damaging organisms and toxins.
    • Barriers (skin/gastric acid).
    • Cells (neutrophils & macrophages).
    • Chemicals (lysozyme, complement).
    • Processes (fever, phagocytosis, inflammation).
    • Acquired or Adaptive Defenses are specific immunity.
    • B cell: humoral or antibody-mediated immunity.
    • T cell: cellular or cell-mediated immunity.

    B-Cells

    • First made in the liver during mid-fetal life.
    • Red bone marrow takes over production late fetal life and after birth.
    • Activated B lymphocytes (plasma cells) produce antibodies.
    • Best at fighting bacteria and/or toxin bacteria.
    • Can help identify viral antigens extracellularly or when on the surface of an infected cell.
    • Antibodies combine with and destroy foreign antigens (microbes).

    T-Cells

    • T lymphocytes start in the red bone marrow but must move to the thymus to mature.
    • Become CD4+ or CD8+ T-lymphocytes before leaving the thymus.
    • Cells divide rapidly.
    • Each lymphocyte reacts to only one antigen.
    • Thousands of antigens can potentially be recognized.
    • CD8+ T cells are best at fighting intracellular microbes.

    T-Cell Activation

    • T cells must interact with another cell in the body (cell-mediated immunity).
    • T cells only recognize a foreign antigen when that foreign antigen is presented on the surface of a target cell.
    • An activated T cell can produce cytotoxic cytokines or use cytokines to signal other cells to the area

    Lymphocytes: Review

    • 20-30% of circulating WBCs.
    • Migrate in and out of the blood.
    • Before activation, are small cells with a spherical nuclei, taking up a majority of the cell.
    • Most are located in lymphatic organs & tissue.
    • Most are Specific Defenses (adaptive/acquired immunity).

    B-Cells: Further Details

    • A mature B cell has the markers CD19 & CD20.
    • B lymphocytes, once activated (called Plasma cells), secrete antibodies (or immunoglobins).
    • Antibodies combine with and destroy foreign antigens (microbes).
    • An antibody is first a B-cell receptor (BCR) attached to the surface of a B cell.
    • Once the antibody is needed, the BCR is cleaved from the surface of the B-cell and is an antibody.
    • The now active Plasma cell produces more of this same antibody.
    • BCR can directly interact with microbe, toxins from a microbe or can receive help from CD4 cells.

    Plasma Cells

    • Activated B lymphocytes enlarge.
    • Form plasma cells.
    • Proliferate to 500+ cells per precursor during an infection.
    • Gamma globulin antibodies are produced at 2000/sec.
    • Form new B lymphocytes, including memory cells.
    • Takes weeks or months between immunizations.
    • Response is rapid once activated.
    • More potent response on re-exposure.

    Overview of Antibody Production

    • Antigen presented to T cell and processed.
    • Presented to B cell.
    • B cell produces specific antibody (immunoglobulins [Ig], gamma globulin).
    • Antibody attaches to specific antigen.

    Basic Structure of Immunoglobulins

    • An antibody contains both a heavy chain & light chain organized into: Fab (variable region).
    • The “Y” end of the Fab contains antigen binding site.
    • Fc (constant region) determines biological properties of the immunoglobulin (Ig).

    Direct Action of Antibodies

    • Neutralization – cover toxic site of antigenic agent (bind & inactivate).
    • Agglutination – binds multiple particles with antigens together into a clump.
    • Precipitation – soluble antigen and antibody form a large insoluble complex (e.g., tetanus toxin).
    • Complement – bind to membranes of invading agents to cause cell rupture.
    • Opsonization – facilitate phagocytosis of foreign substances.

    The Complement System

    • Complement system (C1-C9) activated by microbes works to enhance immune system parts.
    • Primarily proteins produced in the liver and present in the plasma.
    • Three primary functions: -Lysis of antibody coated cells, such as bacteria and RBCs through a series of proteins which creates pores in the cell membrane.
      • Mediation of opsonization, the preparation of foreign cells for phagocytosis.
      • Generation of peptide fragments that regulate features of the inflammatory response.

    Complement Pathway

    • Membrane lesions = MAC complex
    • Opsonization (tag for phagocytosis)

    Antibodies: IgM

    • First antibody produced.
    • Important in the primary immune response.
    • 5-15% total of antibodies produced.
    • Does bind complement.

    Antibodies: IgG

    • 75% total of antibodies produced.
    • Can cross the placenta.
    • Major line of defense for first few weeks of baby's life.
    • Predominant in the secondary immune response.
    • IgM is converted to IgG to become a better antibody.
    • Does bind complement.
    • Four subclasses (IgG₁, IgG₂, IgG3 and IgG4).

    Antibodies: IgA

    • Found in body exocrine fluid (e.g., tears, saliva, colostrum breast milk, nasal, bronchial & intestinal secretions).
    • Important role in protection of the respiratory, urinary tract, & bowel infection.
    • Does not bind complement.

    Antibodies: IgE

    • Trace levels (0.004%); except with invading parasite.
    • Does not fix complement.
    • Allergic reactions, histamine release.
    • Fc region binds strongly to mast cells & basophils, triggering histamine release.

    Antibodies: IgD

    • Less than 1%.
    • Does not fix complement.
    • Primarily a cell-bound immunoglobulin.
    • Found on the surface of B cells.
    • Little is known, may help CD4 Th cells.

    Immune Response

    • Shows primary and secondary responses to antigens.

    MHC on the Surface of All Cells

    • MHC proteins are found on the surface of cells.
    • MHC variation is determined by genetic variation.
    • Function of MHC:
      • bind fragments of pathogens and display them on the surface of cells
      • T cells require MHC to initiate T cell activation against foreign pathogens (including virus)
      • This process is important for self-tolerance
    • Important so our T cells tolerate "self."
    • Human leukocyte antigen (HLA) is the MHC in humans.
    • MHC class I is present on all nucleated cells
    • MHC class II is present on antigen presenting cells (APCs) like dendritic cells, macrophages & some B cells.

    T-Cell & MHC

    • MHC class I: presents foreign peptides to cytotoxic T cells.
    • MHC class II: presents foreign peptides to helper T cells.
    • Cytotoxic T Cells (CD8): kill infected cells by secreting toxic cytokines.
    • Helper Cells (CD4): secrete cytokines to activate macrophages, CD8 cells, and B-cells.
    • Suppressor T Cells regulate T-cell activity.

    T Lymphocyte Activation

    • Antigen Presenting cells (macrophages, dendritic cells) are in lymphoid organs.
    • Ingest antigen and present antigenic peptides to helper T cells.
    • Secrete IL-1, other cytokines that promote lymphocyte growth and differentiation.
    • Helper T cells produce additional cytokines that stimulate B and T cell proliferation and differentiation.
    • B and T cells need antigenic stimulation to proliferate.

    T Helper Cells (CD4+)

    • ~70% of T cells.
    • Destroyed by AIDS virus.
    • Lymphokines of helper T cells
    • IL2 – proliferation of cytotoxic and suppressor T cells; positive feedback to activate helper T cells
    • IL3
    • IL4, IL5, IL6 – B cell growth factors
    • GM-CSF
    • Interferon-γ

    Cytotoxic T Cells (CD8+)

    • Killer cells directly attack micro-organisms.
    • Secretion of perforins – cell membrane.
    • Fluid flows into the cell.
    • Cytotoxic substances are injected into the cell.
    • Killer cell pulls away from its victim.
    • Kill tissue cells invaded by viruses.
    • Kill cancer cells.
    • Kill heart transplant cells.

    Suppressor T Cells

    • CD25+.
    • Prevent over-reaction of the system.
    • Help protect against autoimmune response.
    • Inhibit B-lymphocyte production.
    • Mediation of dominant immunologic tolerance.
    • T cell-mediated suppression might be responsible for low level of chronic infection seen with many pathogens.

    Monocyte-Macrophage Cell System

    • Macrophages participate in phagocytosis, inflammation, and cellular immunity.
    • Macrophages are mainly involved in nonspecific immunity.
    • Phagocytic cells include mononuclear phagocytes (e.g., neutrophils) and polymorphonuclear phagocytes (e.g., eosinophils, basophils, & mast cells).

    Monocyte-Macrophage Cell System (Details)

    • Derived from stem cells in the bone marrow.
    • Monocytes circulate to sites of inflammation or migrate to various tissues.
    • Macrophages have cell surface receptors (one for the Fc portion of IgG).
    • Tissue macrophages possess a receptor for the complement component C3b (& C5b) = opsonization.

    Reticuloendothelial System

    • Cells of the immune system are found in the blood, body tissues, thymus, spleen, liver, lymph nodes, and body areas exposed to the external environment.
    • These organs comprise the reticuloendothelial system (RES).
    • Components: monocytes, fixed tissue macrophages or mobile macrophages, specialized endothelial cells.

    Types of Inflammation

    • Acute inflammation: Short duration, edema, mainly neutrophils.
    • Granulomatous inflammation: Distinctive pattern of chronic inflammation, activated macrophages predominate, +/- Multinucleated giant cells.
    • Chronic inflammation: Longer duration, lymphocytes & macrophages predominate, fibrosis, new blood vessels (angiogenesis).

    Inflammation: Constitutive Defense of the Body

    • Non-specific response to crossing the 1st line of defense.
    • Signs: heat (calor), erythema (rubor), pain (dolor) & swelling (tumor).
    • Typical localized response.
    • Activates complement system, chemical mediators (histamine, bradykinin), and pro-inflammatory cytokines (TNF, IL-1, IL-6, IL-8).

    Inflammatory Response

    • Macrophages are mobile macrophages.
    • Neutrophils: Margination – diapedesis – chemotaxis within the first hour; Neutrophilia -> 4000 to 5000 cells become 15,000+ cells – released from bone marrow in 4 to 5 hours
    • Monocyte invasion -> macrophages → develop lysosomes -> 8 hours or more.
    • Bone marrow produces granulocytes and monocytes within 3 to 4 days.

    Basophils: Medical Application (Review)

    • Immediate Hypersensitivity (Type I).
    • Mast cell degranulation through allergen-specific IgE.
    • Reactions take place in minutes.
    • Sneezing, runny nose, itching eyes, itching throat.
    • Anaphylaxis or Anaphylactic shock (Systemic Type I): Life-threatening.

    Hypersensitivity Reaction

    • Allergic (Type I).
    • Cytotoxic (Type II).
    • Immune complex (Type III).
    • Delayed (Type IV)

    Immunization

    • Active immunity via different vaccine platforms, inactivated/dead organisms, toxoids, subunit/conjugate or recombinant subunit, and mRNA.
    • Live attenuated virus platform.

    Infections

    • Infection is the lodgment & multiplication of organism in the tissue of the host.
    • Characteristics:
    • Pathogenicity: ability of microbial species to produce disease.
    • Virulence: ability of microbial strains to produce disease.

    Factors of Virulence

    • Molecules produced by the pathogen that enable them to evade, colonize, and attach to the host.
    • Adhesion, invasiveness, toxigenicity (exotoxins & endotoxins), communicability, coagulase, and fibrinolysin.

    Infectious Diseases: Categorization

    • Bacterial diseases: gram-positive, gram-negative, spirochetes, atypical, and mycobacterial organisms.
    • Viral diseases: DNA, RNA, and retroviral agents.
    • Fungal diseases: superficial and systemic mycoses.
    • Parasitic diseases: protozoal and helminthic infections.

    Microbes: Residents

    • Microbes that live in or on the body are resident microbes in non-sterile areas without causing infection.
    • Skin, mucous membrane, bowel, rectum, and vagina.
    • These are often protective, and there is a delicate balance.

    Microbes: Bacteria

    • Single-celled microorganisms.
    • Highly adaptable.
    • Aerobic, anaerobic, or both.
    • Cocci, bacilli, or spirochetes.

    Bacteria Structure

    • Indiscreet nucleus.
    • Cytoplasm-Cytosol
    • Cell Envelope/Cell Wall
    • Protein and DNA synthesis
    • Cell Division

    Bacteria Shapes

    • Gram-positive rods.
    • Gram-negative rods.
    • Gram-positive cocci.
    • Gram-negative cocci.

    Aerobic Bacteria

    • Obligate bacteria require oxygen to thrive
    • Know specific examples when also covered in Med Practice: • Gram positive: Nocardia, Bacillus • Gram negative: Pseudomonas aeruginosa • Acid fast: Mycobacterium tuberculosis.

    Anaerobic Bacteria

    • Grow where oxygen is not present.
    • Infections include intra-abdominal, soft tissue, abscesses, wound, and aspiration pneumonia.
    • Known specific pathogens • Gram-negative: Bacteroides, Fusobacterium • Gram-positive: Clostridia

    Functions of the Bacteria Cell Wall

    • Maintaining the cell's characteristic shape.
    • Countering the effects of osmotic pressure.
    • Providing attachment sites.
    • Providing a rigid platform for surface appendages (flagella, fimbriae, and pili).
    • Playing an essential role in cell division.
    • Being the sites of major antigenic determinants of the cell surface.
    • Resistance to Antibiotics.

    Gram-positive cell wall

    • Thick, homogeneous sheath of peptidoglycan (20-80 nm thick). • Tightly bound acidic polysaccharides (e.g., teichoic acid and lipoteichoic acid). • Retain crystal violet and stain purple.

    Gram-negative cell wall

    • Outer membrane containing lipopolysaccharide (LPS). • Thin shell of peptidoglycan. • Periplasmic space. • Inner membrane. • Lose crystal violet and stain pink.

    Gram Reaction: Cell Wall Type

    • Gram-positive = thicker cell wall, less permeable
    • Gram-negative = thinner cell wall, more permeable

    Gram-Positive Cell Wall (Details)

    • Thick, homogeneous sheath of peptidoglycan.
    • One layer.
    • 20-80 nm thick.
    • No outer membrane.
    • Narrow periplasmic space.
    • More permeable to molecules.
    • Contains teichoic acid & lipoteichoic acid.
    • Function in cell wall maintenance & enlargement during cell division.
    • Move cations across the cell envelope.
    • Stimulate a specific immune response.

    Gram-Negative Cell Wall (Details)

    • Two layers: outer membrane & thin peptidoglycan layer.
    • Thinner (8-11 nm).
    • Outer membrane contains lipopolysaccharides (LPS) & lipoproteins.
    • May function as receptors .
    • May block immune response.
    • Contains porin proteins to regulate molecules entering.
    • Leaving the cell.
    • Periplasmic space above & below peptidoglycan.
    • Site for enzymes (β-lactamases) that degrade penicillins & other β-lactam drugs.

    LPS

    • Lipid A of lipopolysaccharide (LPS) is responsible for endotoxin activity.

    The Gram Stain

    • Differential stain to distinguish gram-positive from gram-negative cell walls.
    • Gram-positive retain crystal violet (purple).
    • Gram-negative lose crystal violet & stain red (safranin).
    • Important basis for bacterial classification/identification.
    • Aids in diagnosing infection, suggesting appropriate drug treatment.

    Gram Positive Bacteria

    • Includes bacilli and cocci.
    • Examples include Staphylococcus aureus(coagulase + catalase +) & Streptococcus (coagulase - catalase)
    • Additional features are used for further classification.

    Clostridial Diseases

    • Family: Clostridiaceae; Genus: Clostridium
    • Includes species such as Clostridium tetani, Clostridium perfringens, Clostridium botulinum, and Clostridium difficile.

    Botulism

    • Caused by Clostridium botulinum.
    • Obligate anaerobic bacterium.
    • Rod-shaped
    • Gram-positive.
    • Neurotoxic protein is produced.
    • Physiopathology: Blocks the release of ACh from motor neurons; skeletal muscle cannot contract without release of ACh
    • Requires zinc.

    Tetanus

    • Caused by Clostridium tetani
    • Obligate anaerobic bacterium.
    • Gram-positive.
    • Neurotoxin splits carboxy terminal to gangliosides on neuronal membranes.

    Staphylococcus species

    • Two species associated with staphylococcal diseases in humans.
      • Staphylococcus aureus (more virulent; carriers in nose & on skin).
      • Staphylococcus epidermidis (coagulase-negative; normal microbiota).

    Streptococci

    • Gram-positive cocci, occur in pairs or chains.
    • Non-motile.
    • Virulence factors include lipoteichoic acid for attachment; hyaluronic acid capsule inhibiting phagocytosis.
    • Catalase negative.
    • Facultative anaerobes (only ferment, do not respire using oxygen).

    Lancefield Groups

    • Grouping system for Streptococcus species based on carbohydrate antigens.
    • Common groups are A, B, C, G, and D, frequently causing disease.

    Gram-Negative Bacteria

    • Includes various shapes (coccobacilli).
    • Requires specific growth requirements (like X & V factors).
    • Multiple examples are presented in this section, including those that are aerobic, and those that are anaerobic (examples are provided).

    Rickettsia rickettsii

    • Very tiny (non-motile), weak gram-negative bacteria requiring special stain.
    • Obligate intracellular pathogens.
    • Can not survive independently outside of host cells.
    • Transmitted via bite (wood tick).
    • Rocky Mountain spotted fever.
    • Endemic typhus.

    RMSF: Pathophysiology

    • R. rickettsia organisms inoculated into dermis after 6-10 hrs. • Spread lymphohematogenously. • Leads to inflammation/edema, increased vascular permeability, loss of barrier function, and consumption of platelets (thrombocytopenia).

    Spirochetes

    • Elongate, motile, flexible spiral-shaped bacteria.
    • Not classified as either gram-positive or gram-negative, except Borrelia burgdoferi.
    • Genus Treponema pallidum causes syphilis: disease of blood vessels; can lead to diffuse, (multiple) organ chronic inflammation.
    • Borrelia burgdoferi: Lyme disease.
    • Leptospira causing Leptospirosis (Weil's Disease).

    Lyme Disease: Pathophysiology

    • Transmission via tick saliva.
    • B. burgdorferi tightly controls protein expression to evade early host immunity.
    • Doesn't produce toxins, but secretes proteases.
    • Symptoms are secondary to the elicited host immune response; spread via lymphatics and/or blood to organs.

    Nontypical Bacteria Cell Walls

    • Some lack typical cell wall structure (e.g., mycobacteria).
    • Gram-positive cell wall with lipid mycolic acid (cord factor).
    • High degree of resistance to chemicals/dyes.
    • Acid-fast stain for diagnosis.

    Acid-fast: Mycobacteria

    • Aerobic non-motile, rod-shaped, slow growers.
    • Outer membrane but no cell wall.
    • Do not have capsules.
    • Adapt to grow on simple substrates.
    • Difficult to treat
    • Examples include Mycobacterium tuberculosis (causative agent for human tuberculosis) and Leprosy is also the result of a myobacterium.

    Mycobacteria: Mycobacterium tuberculosis

    • Caused by Mycobacterium tuberculosis.
    • Inhaled aerosol droplets.
    • Can infect many different body locations (e.g., meninges, brain, bone, kidney, and essentially any organ).

    Primary Tuberculosis (TB) in summary

    • Organisms transmitted via aerosol.
    • TB bacilli lodge in alveoli or lung alveolar ducts.
    • Most bacilli phagocytosed by alveolar macrophages.
    • Macrophages migrate to lymph nodes and generate T cell-mediated immune response.

    Atypical Mycobacteria: Pathophysiology

    • Initially phagocytosed by macrophages.
    • Macrophages produce IL-12, up-regulating IFN.
    • IFN activates neutrophils and macrophages.
    • Neutrophils and macrophages destroy pathogens.

    Mycobacteria: Mycobacterium Leprosy

    • Leprosy: disfiguring skin sores; nerve damage to extremities; caused by Mycobacterium leprae.
    • Multiples slowly, incubation period of 5 yrs.
    • Transmitted via droplets.
    • Can infect skin, eyes, peripheral nerves, and mucosa of the upper respiratory tract.

    Overview: Chapter 6 Sherris Microbiology

    • Viruses are the smallest form of replicating intracellular microorganisms
      • Consists of Sets of genes (DNA or RNA) packaged in a protein coat (capsid), may have a lipid envelope.
      • Viruses are dependent upon host structural components for replication.
      • Viruses have surface spikes binding to host cell receptors & antibodies that neutralize the virus; DNA viruses replicate in the nucleus. RNA viruses replicate in the cytoplasm, except RNA viruses (influenza) & retroviruses.
    • Viral-infected cells may result in cell death/tissue damage (pathology) in acute infections
    • A viral infection can persist as chronic or latent, with few evident pathologic changes in target cells.
    • The major genetic changes (i.e., mutation & recombination) undergone by viruses that allow viruses to escape immune responses & persist in the host.
    • Viral latency presents challenge for antiviral drugs.

    Viruses

    • Interrupt host cellular activity (infect healthy cells); certain cell functions & release of modified particles called virions.
    • Difficulty to treat; dramatic immune responses limit/eradicate infection.
    • Latency; chronic illness.
    • Virus integrates itself into the host genetic material.
    • Does not respond to antibiotics.

    Viruses: Definitions

    • Smallest infectious particle.
    • Obligate intracellular parasite.
    • Viruses cannot make energy or proteins independently of a host cell.
    • Size, shape, structure (capsid, envelope), and nucleic acid.

    Viruses: Shapes

    • Spherical/Icosahedral Viruses.
    • Helical Viruses.
    • Polyhedral Viruses.
    • Complex Viruses.

    Viruses: Details

    • Nucleic acid surrounded by one or more proteins.
    • May have an outer membrane envelope.
    • Encode proteins for replication (rest of necessary material found within the host cell).
    • Do not multiply by division; must be infectious to survive.
    • Genome with either DNA or RNA (not both).
    • Can be ss (single-stranded) or ds(double-stranded) DNA, RNA.

    Viral Life Cycle

    • Attachment, Entry (Fusion or endocytosis), Replication & Expression (copying & producing viral components), Assembly, and Release (exiting host cell).

    Naked (Non-enveloped) Viruses: Pathogenesis

    • Stable in hostile environments.
    • Not damaged by drying, acid, detergent, or heat (envelope-damaging factors).
    • Released by lysis of host cells.
    • Can remain in the GI tract/survive acid & bile.
    • Can spread easily via hands, dust, fomites.
    • Can stay dry and remain infectious.
    • Neutralizing antibodies needed to control infection.

    Viral Infection

    • Attachment to cell surface.
    • Penetration of cell membrane via fusion or endocytosis.
    • Release of viral nucleoprotein into cell cytoplasm.
    • Viral genome is copied & reproduced; viral proteins are formed.

    Course of Viral Infection

    • Primary Replication.
    • Systemic Spread.
    • Secondary Replication.

    Routes of Viral Entry

    • Skin: Breach in physical integrity; vectors (e.g., mosquitoes, ticks)
    • Conjunctiva & mucous membranes: Relatively unprotected.
    • Respiratory tract
    • Gastrointestinal tract: Hostile environment, requiring host adaptation.
    • Genitourinary tract: Relatively less hostile.

    Classification of DNA Viruses

    • Double-stranded DNA viruses.
    • Single-stranded DNA viruses.
    • Complex DNA viruses.

    Herpesviridae Family: dsDNA viruses

    • Herpesviruses: more than 100 known; 8 routinely infect humans.
    • All can establish latent infections within specific tissues (characteristic for each virus).
    • Double stranded DNA genome.
    • Icosahedral outer shell.

    Human Herpesvirdae Family: HHV

    • HHV-1 (Herpes Simplex Virus 1): Herpes labialis, cold sores, primary infection of epithelial cells, recurrent infection in ganglion neurons, can reactivate.
    • HHV-2 (Herpes Simplex Virus 2): Genital herpes, primary infection of epithelial cells, recurrent infection in ganglion neurons, can reactivate.
    • HHV-3 (Varicella-Zoster Virus): Chickenpox and shingles; Primary infection (chickenpox) replicates in the nasopharynx; latency established in dorsal root ganglia, highly contagious, Secondary infection (shingles) via reactivation of latent VZV infection.
    • HHV-4 (Epstein-Barr Virus): Primary agent of infectious mononucleosis; replicates in epithelial cells of the oropharynx & in B lymphocytes, transmitted via saliva, often asymptomatic; down-regulates cell adhesion molecules (CAMs) involved in immune recognition.
    • HHV-5 (Cytomegalovirus): Replicates in salivary glands & kidneys (the virus replicates continuously in the body at a very low level [persistence]).

    HPV: Papillomaviridae

    • More than 170 types, causing genital & skin warts, cervical cancer, & others.
    • Non-enveloped.
    • Double stranded DNA.
    • Icosahedral capsid.

    DNA vs RNA Virus

    • Factors influencing mutation rate include genome size, single vs. double stranded, polymerase activity, proofreading, & post-replicative repair.

    Classification of RNA Viruses

    • Multiple combinations of genome & capsid structure; typically single-stranded, except Reoviridae.
    • All non-enveloped viruses have icosahedral capsid structure.

    Filoviridae RNA Virus: Ebola

    • Ebola virus disease (EVD): Filoviridae family, often branched; enveloped ssRNA, helical shape.
    • High virulence pathogen causing hemorrhagic fever.
    • Capable of rapid mutation & evasion of host defenses; adaptable to environmental changes.

    Ebola Pathophysiology

    • Fruit bat is animal reservoir; transmission via contact with animal tissues/body fluids, or ingestion of contaminated plants/water.
    • Direct mucous membrane or percutaneous exposure to infected body fluids.
    • Virus infects monocytes, macrophages, & dendritic cells via surface glycoprotein.
    • Travels to lymph nodes, spleen, & liver. Leads to systemic inflammation/fever.
    • Infected cells lose ability to function as antigen-presenting cells (APCs).
    • Adaptive immune response failure.

    Rhabdoviridae RNA Virus: Rabies

    • Enveloped ssRNA
    • Distinct “bullet” shape, helical.
    • Entry: infected saliva.
    • Encephalitic rabies: inflammation of the brain.
    • Causes cytoplasmic eosinophilic inclusion bodies (Negri bodies) in neuronal cells.
    • Virus replicates in muscle cells, travels via nerves to the CNS, then to skin, cornea, and salivary glands.
    • Paralytic rabies: muscle weakness.

    Orthomyxoviridae Family: Influenza

    • Orthomyxoviridae family, enveloped negative-stranded RNA virus.
    • Glycoprotein spikes with haemagglutinin (HA) and neuraminidase (NA).
    • Self-limiting infection.
    • Transmitted in respiratory secretions
    • Important variations in virus types (e.g., subtypes of HA).

    Coronaviridae Family: COVID-19

    • Coronaviridae family, enveloped positive-single stranded RNA virus.
    • Binds to ACE2 (and other proteins) & virus binds to many different cell types, especially respiratory epithelial cells.
    • SARS-CoV-2 (COVID-19) pandemic.

    Coronaviridae Family: COVID-19 (Details)

    • SARS-CoV-2 causes respiratory illness (from no to mild to severe).
    • Enveloped, positive-single-stranded RNA virus.
    • Has glycoprotein surface E2 spike protein to allow it to bind to host cells.
    • Transmitted through respiratory secretions.

    Flaviviridae Family: Zika Virus

    • Flaviviridae family.
    • Enveloped, single-stranded RNA virus, icosahedral outer shell.
    • Closely related to dengue, yellow fever, and West Nile viruses.
    • Transmitted by infected Aedes mosquito bites (female).

    Flaviviridae Family: Zika Pathophysiology

    • Suspected link with Guillain-Barré syndrome.
    • Muscle weakness/numbness due to nerve cell damage.
    • Infectious pathogens mimic peripheral nerve myelin protein.
    • Immune system responds to attack pathogen by now attacking the real myelin protein.

    Retroviruses

    • Family of RNA viruses.
    • Contain reverse transcriptase (RT).
    • RT makes a complementary DNA (cDNA) copy of the viral RNA.
    • cDNA is integrated into host DNA.

    Retroviridae Family: HIV Virus

    • HIV-1 (more virulent) & HIV-2 are retroviruses.
    • Enveloped retrovirus (SSRNA) with a genome but a retrovirus.
    • Technically not a RNA virus because it uses DNA intermediates for replication.
    • Target cells: CD4 helper T cells (T tropic), macrophages, & dendritic cells.
    • Enters host cells via CD4 receptor & chemokine co-receptors (primarily CCR5 & CXCR4).
    • Transmission via sexual, blood, semen, vaginal secretions, maternal-fetal, breast milk.

    Overview of HIV Life Cycle

    • Binding & Fusion.
    • Viral attachment protein (VAP) entry.
    • Reverse transcription (unique to retroviruses).
    • Integration.
    • Viral RNA & protein expression.
    • Assembly & budding.
    • Maturation.
    • HIV targets host cells (CD4 T cells, macrophages,& dendritic cells).

    HIV Pathogenesis

    • Profound immunosuppression.
    • Due to depletion of T4 helper lymphocytes.
    • Initially high levels of HIV antigen & RNA in the blood then settles to a low level during incubation period (set point).
    • Massive turnover of CD4 cells.
    • AIDS develops when CD4 cells can no longer be replenished (witnessed by high HIV-RNA, HIV-antigen, and low CD4 counts).

    Host CD4+ Lymphocytes Decline

    • HIV replicates in infected CD4+ T cells.
    • Activation of uninfected CD4+ T cells.
    • Expression of HIV peptides on infected CD4+ T cells.
    • Death of infected cells (cytopathic effect of virus).
    • Activation-induced cell death (apoptosis).
    • Killing of infected cells by virus-specific CTLs.

    Viral Infection and the Immune System

    (1) Transmission & entry of virus into host. (2) Spread in host: systemic infection. (3) Tropism (cellular/tissue specificity): viral surface proteins interacting with host cell receptors (e.g., CD4). (4) Virulence & cytopathogenicity: relative ability of virus to cause disease; extent of pathogenicity. (5) Patterns of viral infection & disease: - Infection vs disease (some infections not symptomatic) - Common infections vs uncommon diseases (6) Host factors: immune status, genetic background, age, nutrition influence infection outcome.

    Viral Infection and the Immune System (Host Defense)

    • Host innate & adaptive immune responses (interferons, natural killer cells, macrophages, phagocytosis, mucociliary clearance, & fever) fight infection.
    • Adaptive immune response (humoral/B-cells & cell-mediated/T-cells) involves virus-specific CTLs destroying virus-infected cells.
    • Virus-induced immunopathology: occurs when immune cells can't stop viral infections (high cell infection).
    • Emerging viruses like SARS-CoV-2 (COVID-19) can cause multiorgan damage with excessive viral load & cytokine release.

    Infectious Diseases: Categorization

    • Diseases caused by bacteria, viruses, fungi, or parasites.

    Mycoses (Fungal Infections): Types

    • Superficial: confined to outer skin layers (skin, hair, & nails).
    • Cutaneous: affect deeper skin layers; relatively common in tropical regions.
    • Subcutaneous: introduced via skin trauma & remains in localized areas (sporotrichosis).
    • Systemic: invasive, often asymptomatic initially. -Opportunistic infections in immuno-compromised patients.

    Mycoses (Fungi): Yeasts

    • Unicellular.
    • Sometimes form pseudohyphae (networks that connect different cells).
      • Grows as a single cell or by budding off a smaller daughter cell (asexual reproduction).

    Mycoses (Fungi): Molds

    • Multicellular.
    • Consist of hyphae (filaments), creating a thread-like (fuzzy) appearance.
    • Spores are airborne and dispersed; can remain alive in dormant state.
    • Can use sexual (meiosis) or asexual (mitosis) reproduction.
    • Degrade material using enzymes as an energy source.

    Dimorphic Fungi

    • Have 2 distinct morphological forms: yeast or mold.
    • Able to survive in various environments by adjusting their form (e.g., response to changes in nutrient availability & temperature).

    Ways to Classify Mycoses

    • Site of infection (superficial, cutaneous, subcutaneous, systemic).
    • Route of acquisition (airborne, cutaneous).
    • Type of virulence of fungus.

    Site of Infection: Superficial & Cutaneous Mycoses

    • Usually confined to outer skin layers (hair, nails).
    • Do not invade living tissues.
    • Common examples include tinea versicolor (yeast overgrowth).
    • Dermatophytes (fungi) are the main culprits.

    Site of Infection: Subcutaneous Mycoses

    • Introduced after trauma (e.g. puncture, wound).
    • Infections often remain localized at entry site but can sometimes spread to surrounding tissue.
    • Often minimal or asymptomatic.

    Site of Infection: Systemic Mycoses

    • Caused by pathogenic & opportunistic fungal pathogens.
    • More likely in immunocompromised patients.
    • Spread to surrounding tissue
    • May remain asymptomatic initially.
    • Often characterized by slowly progressive dissemination (widespread infection throughout the body)
    • examples include Histoplasmosis, Coccidioidomycosis, Blastomycosis, Candidiasis, Aspergillosis, Cryptococcosis, Pneumocystis jirovecii. (Previously called Pneumocystis carinii).

    Fungi: Candidiasis

    • Approx 20 species causing infection.
    • Candida albicans = most common.
    • Can be strict aerobe or facultative anaerobe.
    • Favors moist surfaces (e.g., gut, genitals, lungs).
      • Superficial (e.g.; oral); Deep infections
    • Invading host via adhesins promotes retention; secretory IgA destruction also promotes this.
    • Overcoming host barriers (e.g., in IV catheters); widespread in immunocompromised individuals.

    Fungi: Cryptococcus

    • Cryptococcus species ("hidden sphere/berry") are often referred to as yeasts.
    • Often inhaled (microscopic fungus).
    • Pathogenic; commonly C. neoformans or C. gattii.
    • Invasive infection often occurs in immunocompromised individuals.

    Fungi: Pneumocystis

    • Use to be called P. carinii (now more commonly referred to as P. jirovecii).
    • Classified as a protozoa (formerly).
    • Pathogenic yeast-like fungus.
    • Usually causes few symptoms in non-immunocompromised individuals. Immunocompromised (e.g., HIV) individuals are highly susceptible to infection.

    Fungi: Histoplasmosis

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