Virology Quiz Questions

Viruses, Viroids, and Prions

• Viruses are genetic information composed of DNA or RNA contained within a protective protein coat
  • Inert particles, no metabolism, no replication, hijack host cell's replication machinery
  • Infectious agents, but not alive
• Viral genome is either DNA or RNA, never both, and affects replication strategy
• Viral protein components are used for attachment, with phages having tail fibers and animal viruses having spikes
• Viruses have three shapes: icosahedral, helical, and complex
• Virus families end in the suffix -viridae, and genus ends in -virus
• Viruses are often categorized informally, such as by route of infection (e.g., oral-fecal, respiratory, zoonotic)

Bacteriophages

• There are three general types of bacteriophages: lytic, temperate, and lysogenic
• Lytic phages exit the host after replicating, causing the host cell to lyse, and involve a five-step process: attachment, genome entry, synthesis, assembly, and release
• Temperate phages have the option of the lytic life cycle or the incorporation of their DNA into the host cell genome
• Lambda phage is a model for the lysogenic life cycle, where the phage DNA circularizes and can direct lytic infection or integrate into the host chromosome

Roles of Bacteriophages in Horizontal Gene Transfer

• Generalized transduction results from packaging errors during phage assembly, and can transfer any gene from the donor cell
• Specialized transduction results from excision mistakes during the transition from lysogenic to lytic cycle, and only transfers genes next to the integrated phage DNA

Bacterial Defenses Against Phages

• Restriction-modification systems protect bacteria by degrading phage DNA using enzymes, and modification enzymes protect host DNA from restriction enzymes

Methods Used to Study Bacteriophages

• Viruses multiply only inside living cells, and must be cultivated in suitable host cells to grow
• Plaque assays are used to quantitate phage particles in samples, and involve counting plaque-forming units (PFU)

Animal Virus Replication

• Animal virus replication involves a five-step infection cycle: attachment, penetration and uncoating, synthesis, assembly, and release
• Attachment involves binding to specific receptors on the host cell surface
• Penetration and uncoating involve the fusion of the virus with the host cell membrane or endocytosis
• Synthesis involves the expression of viral genes and the production of viral structural and catalytic proteins
• Replication strategies vary depending on the type of genome: DNA, RNA, or reverse-transcribing

Categories of Animal Virus Infections

• Acute infections have a rapid onset and short duration
• Persistent infections continue for years or a lifetime, and may be chronic or latent
• Chronic infections involve continuous production of low levels of virus particles, while latent infections involve the integration of the viral genome into the host chromosome

Viruses and Human Tumors

• Viruses can cause tumors by interfering with host cell growth control mechanisms
• Some viruses have oncogenes that are similar to host proto-oncogenes, and can induce tumors

Cultivating and Quantitating Animal Viruses

• Viruses must be grown in an appropriate host, such as cell culture or tissue culture
• Embryonated chicken eggs were historically used, but are now less common

Other Infectious Agents: Prions

• Prions are proteinaceous infectious agents composed solely of protein, with no nucleic acids
• Prions are linked to slow, fatal human diseases and animal diseases, and are usually transmitted within species
• Prion proteins accumulate in neural tissue, causing neurons to die and tissues to develop holes

Immune System: Innate and Adaptive Immunity

• Innate immunity is routine protection, and involves pattern recognition of specific molecules
• Adaptive immunity develops throughout life, and is more specialized, involving antigens and the production of antibodies

Overview of the Innate Defenses

• The first line of defense involves physical barriers, such as skin and mucous membranes
• The second line of defense involves sensor systems, blood cells, and phagocytosis

First-Line Defenses

• Physical barriers, such as skin and mucous membranes, prevent microbe entry into the body
• Antimicrobial substances, such as salt, lysozyme, and defensins, also protect the body
• Normal microbiota, the community of microorganisms that live in and on the body, can also prevent pathogen growth

Second-Line Defenses

• Blood cells, including granulocytes, mononuclear phagocytes, and lymphocytes, are important in host defenses
• Granulocytes, such as neutrophils and basophils, engulf and destroy bacteria and other material
• Mononuclear phagocytes, such as macrophages and dendritic cells, differentiate from monocytes and play a key role in host defenses### The Cells of the Immune System
• Dendritic cells: sentinel cells that function as "scouts" and engulf material in tissues, bringing it to cells of the adaptive immune system for "inspection"
• Lymphocytes: responsible for adaptive immunity, highly specific in recognition of antigen, found in lymph nodes and lymphatic tissues
  • B cells: produce antibodies in response to antigen
  • T cells: highly specific in recognition of antigen, including natural killer (NK) cells that lack specificity

Cell Communication

• Communication between blood cells allows for a coordinated response to microbial invasion
• Surface receptors: "eyes" and "ears" of cell, proteins that span the membrane, connecting outside to inside
• Binding to specific ligand induces response
• Cytokines: "voices" of cell, produced by one cell, diffuse to others, bind to appropriate cytokine receptors to induce changes
• Adhesion molecules: allow cells to stick to other cells, e.g. endothelial cells adhere to phagocytic cells in the blood, allowing them to exit the bloodstream

Pattern Recognition Receptors (PRRs)

• Allow the body's cells to detect signs of microbial invasion
• Three types: Toll-like receptors, NOD-like receptors, and RIG-like receptors
• Toll-like receptors (TLRs): anchored in membranes of sentinel cells, detect compounds, send signals to nucleus, induce gene expression, and cause a response
• NOD-like receptors (NLRs): found in cytoplasm, detect bacterial components, initiate a series of events to protect the host, sometimes damaging the host cell
• RIG-like receptors (RLRs): found in cytoplasm, detect viral RNA, induce production of interferons, which diffuse to neighboring uninfected cells, causing them to express inactive antiviral proteins

The Complement System

• Assists activities of adaptive immune system
• Complement proteins are inactive proteins circulating in blood and bathing tissues
• Proteins are activated in response to signals indicating microbial invasion
• Activation leads to a cascade of activation, resulting in three major outcomes: opsonization, inflammatory response, and lysis of foreign cells
• Three pathways of activation: alternative, lectin, and classical

Phagocytosis

• Phagocytes engulf and digest material and pathogens
• Chemotaxis: phagocytes are recruited by chemoattractants
• Recognition and attachment: phagocytes bind to pathogen
• Engulfment: pseudopods surround the pathogen, then fuse to form a phagosome
• Phagosome maturation and phagolysosome formation: phagosome fuses with lysosome, pH is lowered, and lysosomes deliver enzymes
• Destruction and digestion: toxic ROS produced, pH decreases, enzymes degrade, defensins damage membrane of invader
• Exocytosis: phagolysosome fuses with plasma membrane, and expels any undigested material

The Inflammatory Response

• Tissue damage results in inflammation
• Inflammation contains the site of damage, localizes the response, eliminates the invader, and restores tissue function
• Triggers cause host cells to release inflammatory mediators
• Inflammation results in swelling, redness, heat, pain, and sometimes loss of function
• Acute inflammation is short-term, macrophages clean up damage by ingesting dead cells and debris
• If acute fails, chronic inflammation results, macrophages and giant cells accumulate, and granulomas form

Fever

• Important host defense mechanism
• Strong indicator of infectious disease, especially bacterial
• Temperature-regulation center in brain normally holds at 37°C, but raises during infection in response to pyrogens
• Increased temperature slows bacterial growth, allows more time for host defenses

Adaptive Immunity

• Develops and matures throughout life
• Takes a week or more to build effective immunity following first exposure to a pathogen
• Adaptive immunity has memory, giving a stronger response to re-exposure to a pathogen
• Adaptive immunity also has molecular specificity, protection against one pathogen does not protect against others
• It is also tolerant, must distinguish between "healthy self" cells and "dangerous" cells such as pathogens and cancer cells

Strategy of the Adaptive Immune Response

• Depends on lymphocytes: B cells and T cells

• First response to an antigen is the primary response

• Adaptive immune system then "remembers" the mechanism that proved effective against that specific antigen

• If encountered again, a stronger secondary response results

• Two basic strategies exist: humoral immunity and cell-mediated immunity

• Humoral immunity: B cells produce antibodies, which eliminate extracellular antigens

• Cell-mediated immunity: T cells eliminate antigens residing within a host cell### T-Cell Function

• T cells secrete cytokines that help in activation of B cells and macrophages

• T cells secrete “death packages” that lead to death of infected host cells and cancer cells

B Lymphocytes and the Antibody Response

• B-cell activation by T-dependent antigens involves:
  • B-cell receptor binding to antigen
  • Antigen internalization via endocytosis and degradation into peptide fragments
  • Fragments delivered to MHC class II molecules at the B cell surface for inspection by TH cells
  • Antigen presentation, which leads to activation of B cells by TH cells
• Characteristics of Primary Response:
  • Takes 10-14 days for substantial antibody accumulation
  • Person may be sick during this time
  • Additional exposure to antigen leads to a much faster secondary response
• Characteristics of Primary Response (continued):
  • Some B cells differentiate to form plasma cells
  • Plasma cells generate antibodies
  • Activated B cells continue proliferating and differentiating in the presence of antigen
  • Antibody titer steadily increases
• Class Switching:
  • All plasma cells initially secrete IgM
  • TH cells can induce some activated B cells to become plasma cells that secrete other antibody classes (usually IgG)
• Characteristics of Secondary Response:
  • Significantly faster and more effective than primary response
  • Pathogens are usually eliminated by this response before causing harm
  • Memory B cells are responsible for the secondary response
  • Antibodies produced by these cells bind antigen effectively

The Response to T-Independent Antigens

• Some antigens can lead to B cell activation without the help of TH cells
• These antigens have multiple identical epitopes, which are bound by groups of B-cell receptors
• This leads to activation, but the response is not very immunogenic in young children

T Lymphocytes: Antigen Recognition and Response

• T cells play a different role from B cells
• T cells never produce antibodies
• Effector T cells directly interact with target cells
• T cells recognize peptide-MHC complexes
• MHC class I molecules present endogenous antigens
• MHC class II molecules present exogenous antigens
• Cytotoxic T cells recognize antigen presented on MHC class I molecules
• Helper T cells recognize antigen presented on MHC class II molecules
• TH cells have CD4 proteins, which are receptors for HIV
• TC cells have CD8 proteins

Effector Functions of TC (CD8) Cells

• TC cells induce apoptosis in infected “self” cells and cancer cells
• TC cells recognize infected or cancerous cells by the MHCI molecules
• They release proteases and cytotoxins to induce apoptosis

Effector Functions of TH (CD4) Cells

• TH cells coordinate the immune response
• They recognize peptide presented by a B cell or a macrophage and release cytokines to activate those cells
• They control the activities of activated B cells and macrophages
• They also control the activities of other T cells

Role of TH Cells in B Cell Activation

• TH cells recognize antigen presented on MHCII from antigen-presenting cells and activate that cell with cytokines

Role of TH Cells in Macrophage Activation

• TH cells recognize peptides presented by a macrophage on MHCII molecules
• They activate the macrophage by releasing cytokines, which increases its power
• Activated macrophages have increased size and metabolism, and produce toxic compounds

Natural Killer (NK) Cells

• NK cells induce apoptosis in “self” cells
• NK cells recognize host cells with foreign proteins in the membrane bound by antibodies through antibody-dependent cellular cytotoxicity (ADCC)
• NK cells also recognize and destroy stressed host cells lacking MHCI
• Some viruses interfere with antigen presentation and prevent host cells from displaying MHCI, which allows NK cells to recognize and destroy them