Medical Microbiology: Virology, Microbiome, Pathogenesis, and Immunology

Comprehensive practice flashcards reviewing medically important viruses, human microbiome ecology, microbial pathogenesis and virulence factors, antibody biology, and innate host defenses.

Antigenic Drift

Minor annual genetic variations in the influenza virus genome caused by the accumulation of mutations introduced by its error-prone RNA-dependent RNA polymerase (RdRP), providing partial protection from previous infection or vaccination.

Antigenic Shift

A major genetic reassortment resulting from the combination of RNA segments from influenza viruses with different host ranges (such as swine flu and bird flu), producing novel strains that lead to severe outbreaks due to low herd immunity.

Provirus

A dormant stage of a retrovirus (such as HIV) in which viral double-stranded DNA is permanently integrated into the host cell's nuclear chromosome, which can later be reactivated by signals such as IL-2.

Reverse Transcriptase

A retroviral enzyme that converts viral single-stranded RNA into double-stranded DNA prior to integration into the host genome; this enzyme is inhibited by nucleoside analogs.

TMPRSS2

A host cell transmembrane serine protease that cleaves the SARS-CoV-2 spike protein, exposing the fusion domain to mediate fusion between the viral envelope and the host plasma membrane.

Positive-Sense RNA (+RNA)

A single-stranded viral RNA genome that functions directly as messenger RNA (coding strand) and can be immediately translated by host ribosomes to synthesize viral proteins, such as RNA-dependent RNA polymerase (RdRP).

Negative-Sense RNA (-RNA)

A single-stranded viral RNA genome complementary to mRNA that cannot be directly translated by the host cell; the virion must package its own RNA-dependent RNA polymerase to synthesize translatable $+\text{RNA}$ strands.

Molnupiravir

An oral nucleoside analog manufactured by Ridgeback (indicated for individuals aged $18+$) that incorporates into viral RNA during transcription to induce lethal viral mutagenesis.

Veklury (Remdesivir)

An intravenous nucleoside analog manufactured by Gilead (indicated for individuals aged $12+$) that inhibits viral RNA-dependent RNA polymerase, halting viral mRNA production.

Human Microbiome Project (HMP)

An NIH Common Fund initiative established to characterize the microbial communities residing across five major human body habitats (nasal passages, oral cavities, skin, gastrointestinal tract, and urogenital tract) and analyze their connection to health and disease.

Operational Taxonomic Unit (OTU)

A pragmatic definition of a bacterial species or group used in metagenomic 16S rRNA analysis, grouped based on a $97\%$ sequence similarity threshold.

Alpha Diversity

A measure of microbial biodiversity referring specifically to the total number of distinct types of organisms (species richness) present within a single given environment or site.

Beta Diversity

A comparative ecological measure that determines the difference or similarity in microbial community composition between two distinct environments or samples.

Collector's Curve

A graphical representation plotting the cumulative number of OTUs identified against the total number of sequenced clones, where flattening slopes estimate community species richness.

Short-Chain Fatty Acids (SCFAs)

Bacterial fermentation end products of dietary fiber (primarily butyrate, propionate, and acetate) that nourish intestinal epithelial cells, regulate proteins like PPAR-$\gamma$, and promote regulatory T cell (Treg) activation.

Dysbiosis

An ecological disruption or imbalance between the host immune system and the resident microbiota, resulting in diminished microbial diversity and associated with disorders like inflammatory bowel disease (IBD).

Polysaccharide A (PSA)

A capsular carbohydrate produced by Bacteroides fragilis that stimulates the development and proliferation of helper T ($\text{T}_\text{H}$) cells in the gut and suppresses inflammation in models of colitis.

Fecal Microbiota Transplantation (FMT)

The transfer of processed stool from a healthy donor into a patient to restore microbial diversity in the colon, yielding a $94\%$ cure rate with a $10\%$ relapse rate for recurrent Clostridioides difficile infection.

Human Milk Oligosaccharides (HMOs)

Prebiotic complex carbohydrates found in breast milk that selectively promote the colonization of Bifidobacterium longum infantis, which produces SCFAs for gut integrity and sialic acid for brain development.

Probiotic

A formulation of live microorganisms, such as Lactobacillus casei Shirota found in Yakult, consumed to transiently benefit host health by influencing microbial gene expression and reducing inflammation.

Pathogenicity

The intrinsic qualitative ability of a microbial agent to cause disease in a host organism.

Virulence

The quantitative measure of the severity or degree of disease produced by a pathogen, often governed by virulence factors encoded on plasmids or lysogenic phages.

$$\text{ID}_{50}$$

The infectious dose per unit of time required to establish infection in $50\%$ of an experimental host population.

$$\text{LD}_{50}$$

The lethal dose of an organism or toxin required to kill $50\%$ of an experimental host population.

Bacteremia

The transient presence of viable bacteria circulating within the bloodstream without active microbial replication.

Septicemia

The active multiplication and growth of pathogenic bacteria within the bloodstream, often triggering systemic inflammation and severe clinical disease.

Coagulase

A bacterial enzyme produced by Staphylococcus aureus that induces the clotting of fibrinogen into fibrin, creating a protective wall that shields the pathogen from host immune defenses.

Streptokinase

A fibrinolytic enzyme produced by Streptococcus pyogenes that digests fibrin clots, facilitating bacterial escape and dissemination into adjacent tissues and blood vessels.

Hyaluronidase

An extracellular spreading enzyme produced by pathogens like Streptococcus pyogenes that degrades hyaluronic acid in connective tissues, facilitating tissue invasion.

Leukocidin

A bacterial pore-forming cytotoxin that destroys host white blood cells (leukocytes), contributing to tissue damage and pus formation.

Botulinum Toxin

An AB-type bacterial neurotoxin produced by Clostridium botulinum that acts at the motor end plate to block the release of acetylcholine from synaptic vesicles, resulting in flaccid paralysis.

Limulus Amoebocyte Lysate (LAL) Assay

A sensitive diagnostic assay utilizing blood amoebocytes from the horseshoe crab Limulus polyphemus, which undergo degranulation and clot formation upon exposure to Gram-negative bacterial lipopolysaccharide (endotoxin).

B-Cell Receptor (BCR)

A membrane-bound immunoglobulin (monomeric IgM or IgD) complexed with Ig$\alpha$ and Ig$\beta$ signal transduction proteins on the B-cell surface that specifically binds an antigen epitope.

Complementarity-Determining Regions (CDRs)

Three hypervariable peptide loops found within the variable domains of immunoglobulin heavy and light chains that form the three-dimensional antigen-binding cleft.

V(D)J Recombination

The somatic gene rearrangement process in developing B lymphocytes that enzymatically fuses one Variable (V), one Diversity (D), and one Joining (J) gene segment together, deleting intervening DNA to generate primary antibody diversity.

Clonal Deletion

The programmed apoptotic death of developing immature lymphocytes that bind strongly to self-antigens in central lymphoid organs, thereby establishing central self-tolerance.

Immunoglobulin M (IgM)

The initial antibody class secreted during a primary immune response; forms a pentameric structure joined by disulfide bonds and a single J chain, possessing $10$ antigen-binding sites.

Immunoglobulin G (IgG)

The predominant immunoglobulin class in human serum (accounting for approximately $80\%$ of circulating antibodies), which dominates the secondary immune response and mediates opsonization, complement activation, and neutralization.

Class Switching

A secondary somatic DNA recombination event occurring in proliferating mature B cells that alters the heavy chain constant region exon to change the antibody class (e.g., from IgM to IgG, IgA, or IgE) without modifying antigen specificity.

Opsonization

The coating of microbial pathogens by antibody molecules (such as IgG) or complement fragments (such as C3b) to facilitate recognition and ingestion by phagocytes displaying Fc or complement receptors.

Lysozyme

An antibacterial enzyme present in bodily secretions such as tears and saliva that hydrolyzes the $\beta(1 \rightarrow 4)$ glycosidic bonds linking NAG and NAM in bacterial peptidoglycan.

Diapedesis

The active extravasation process whereby circulating leukocytes (such as neutrophils) adhere to activated capillary endothelial cells and squeeze between them to migrate into inflamed tissues.

Pathogen-Associated Molecular Patterns (PAMPs)

Conserved, invariant molecular motifs found on microbes (such as lipopolysaccharide, flagellin, peptidoglycan, and lipoteichoic acid) that are recognized by host pattern recognition receptors.

Toll-Like Receptors (TLRs)

A family of pattern recognition receptors expressed on the plasma membrane or endosomal membranes of phagocytes that bind PAMPs and trigger an intracellular kinase signaling cascade leading to immune gene transcription.

NF-$\kappa\text{B}$

A key pro-inflammatory transcription factor held inactive in the cytoplasm by I$\kappa\text{B}$; phosphorylation of I$\kappa\text{B}$ via TLR kinase cascades allows active NF-$\kappa\text{B}$ to enter the nucleus and initiate transcription of cytokine genes.

Respiratory Burst

A rapid surge in oxygen consumption occurring in phagocytes following phagolysosome formation, generating antimicrobial reactive oxygen intermediates such as superoxide ($\text{O}_2^{\bullet-}$), hydrogen peroxide ($\text{H}_2\text{O}_2$), and hypochlorous acid ($\text{HOCl}$).

Membrane Attack Complex (MAC)

A cylindrical pore assembly formed by complement proteins that inserts into eukaryotic membranes or Gram-negative outer membranes, inducing osmotic lysis of the target cell.

Natural Killer (NK) Cells

Innate cytotoxic lymphocytes that evaluate target cells by checking for MHC Class I molecules; if MHC Class I is absent or down-regulated and stress proteins are expressed, NK cells release perforins and granzymes to induce apoptosis.

Interferons (IFNs)

Antiviral regulatory cytokines produced by virus-infected cells that bind surface receptors on neighboring uninfected cells, activating intracellular pathways that degrade viral double-stranded RNA and inhibit protein synthesis.