Comprehensive Study Notes: Viruses, Antimicrobial Drugs, Immunology, and Hypersensitivity

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Viruses: Structure and Replication

Basic Viral Structure

Viruses are acellular infectious agents that require a host cell to replicate. All viruses share certain structural features, with some possessing additional components that enhance their infectivity.

Genetic Material: Can be DNA or RNA, single- or double-stranded.
Capsid: Protein shell that encases the genetic material.
Envelope (optional): Lipid membrane derived from the host cell, helps evade immune detection.
Spike Proteins (optional): Glycoproteins protruding from the envelope, facilitate attachment and entry into host cells.

Viral Envelope: Mimics host cell membrane, allowing immune evasion. Spike Proteins: Function as attachment factors, acting as 'fake' cell receptors to mediate entry into host cells. Both structures increase viral virulence.

Viral Replication Pathways

Lytic Cycle: The primary method of viral replication, resulting in host cell lysis and release of new virions.
Lysogenic Cycle (Lysogenesis): Viral genome integrates into host chromosome, replicating with the host cell and remaining latent until triggered to enter the lytic cycle.

Goals of a Virus: (1) Copy genetic material, (2) Assemble new viral particles.

Lytic Cycle Steps

Attachment: Virus binds to host cell surface.
Uncoating: Viral capsid is removed, releasing genetic material into the host cell.
Assembly: New viral genomes and proteins are synthesized and assembled into new virions.
Lysis: Host cell bursts, releasing new viruses.

Lysogenic Cycle

Viral genome integrates into host DNA, replicating passively with the host.
Provides immune evasion and survival under unfavorable conditions.
Can reactivate to lytic cycle if host immunity weakens.

Viral Genomes and Replication Enzymes

Possible viral genomes: dsDNA, ss(+)DNA, ss(-)DNA, dsRNA, ss(+)RNA, ss(-)RNA.
Key enzymes:
- DDDP: DNA-dependent DNA polymerase (makes DNA from DNA)
- DDRP: DNA-dependent RNA polymerase (makes RNA from DNA)
- RDRP: RNA-dependent RNA polymerase (makes RNA from RNA; not found in humans)
- RDDP: RNA-dependent DNA polymerase (reverse transcriptase; makes DNA from RNA)

Replication Pathways by Genome Type

dsDNA Virus: Uses host DDRP to make mRNA from (-) strand; DDDP copies DNA genome.
ss(+)DNA Virus: DDDP makes (-) DNA, DDRP makes mRNA from (-) DNA, DDDP copies DNA.
ss(-)DNA Virus: DDRP makes mRNA from (-) DNA, DDDP copies DNA.
ss(+)RNA Virus: (+) RNA acts as mRNA; RDRP synthesizes (-) RNA, which is then used to make more (+) RNA.
ss(-)RNA Virus: RDRP (carried in virion) makes (+) RNA (mRNA), which is translated and used to make more (-) RNA.
dsRNA Virus: (+) RNA is translated; RDRP copies RNA genome.
ss(+)RNA Retrovirus: RDDP (reverse transcriptase) makes (-) DNA, DDDP makes (+) DNA, viral DNA integrates into host genome.

Note: RDRP is an ideal antiviral target because it is not present in human cells.

Antimicrobial Drugs

Antibiotic Targets and Mechanisms

Antibiotics are designed to target structures or processes unique to bacteria, minimizing harm to human cells.

Cell Wall Synthesis: e.g., Penicillin (a β-lactam) inhibits peptidoglycan synthesis; effective mainly against Gram-positive bacteria.
Protein Synthesis (Ribosomes): Bacterial ribosomes are 70S (30S + 50S subunits), while eukaryotic ribosomes are 80S. Examples:
- Tetracycline: Targets 30S subunit; side effect: brown teeth in children (binds calcium).
- Azithromycin: Targets 50S subunit; side effect: blocks Ca2+ channels, may cause arrhythmia.
- Gentamycin: Targets 30S subunit; side effects: nephrotoxicity, hearing loss (mitochondrial toxicity).
DNA Replication: Bacteria use DNA gyrase (targeted by ciprofloxacin); humans use topoisomerase.
Metabolic Pathways: e.g., Sulfa drugs (trimethoprim) inhibit folate synthesis (not used by humans).

Side Effects and Risks

All antibiotics carry risks and side effects (e.g., allergic reactions, GI upset, Stevens-Johnson Syndrome).
Antibiotic selection is based on infection severity and risk-benefit analysis.

Antibiotic Risk Ranking (Lowest to Highest)

Drug	Relative Risk
Penicillin	Lowest
Tetracycline	Low
Azithromycin	Moderate
Gentamycin	High
Ciprofloxacin	Higher
Sulfa Drugs	Highest

Microbial Growth and Quantification

Plate Count Assays

Plate count assays are used to estimate the number of viable bacteria in a sample by serial dilution and plating.

Colony-Forming Units (CFU): Each colony represents a single viable bacterium.
Acceptable Plate Range: 30-300 colonies per plate (FDA standard).

CFU Calculation Formula

To calculate the original concentration:

$\text{CFU/mL} = \frac{\text{Number of Colonies}}{\text{Volume Plated (mL)} \times \text{Dilution Factor}}$

Examples

Milk sample: 54 colonies from 1 mL of 1:1000 dilution → 54,000 CFU/mL
Well water: 83 colonies from 1 mL of 1:10,000 dilution → 830,000 CFU/mL
Ocean water: 191 colonies from 0.1 mL of 1:100 dilution → 191,000 CFU/mL

Immunology: Innate and Adaptive Immunity

Overview of the Immune System

The immune system protects against pathogens (bacteria, viruses, fungi, parasites) and environmental threats. It is divided into innate (nonspecific) and adaptive (specific) branches.

Innate Immunity: First line of defense, rapid but nonspecific (e.g., skin, macrophages, dendritic cells, mast cells, complement, cytokines).
Adaptive Immunity: Slower but highly specific and has memory (e.g., B cells, T cells, memory cells).

Key Immune Organs

Bone Marrow: Produces pluripotent stem cells.
Lymph Nodes: Filter blood and house immune cells.
Thymus: Site of T cell maturation.

Cells of the Immune System

Cell Type	Origin	Function
Macrophage	Myeloid	Phagocytosis, antigen presentation
Dendritic Cell	Myeloid/Lymphoid	Antigen presentation, activates T cells
Mast Cell	Myeloid	Histamine release, inflammation
Neutrophil	Myeloid	Phagocytosis, first responder
Eosinophil	Myeloid	Attack parasites
Basophil	Myeloid	Inflammation, allergy
B cell	Lymphoid	Antibody production
T cell	Lymphoid	Cell-mediated immunity
Natural Killer Cell	Lymphoid	Kill infected/tumor cells

Stem Cell Differentiation

Pluripotent Stem Cell: Can become myeloid or lymphoid progenitor.
Myeloid Progenitor: Gives rise to erythrocytes, platelets, granulocytes, monocytes, dendritic cells.
Lymphoid Progenitor: Gives rise to B cells, T cells, natural killer cells.

Major Histocompatibility Complex (MHC)

MHC I: Present on all nucleated cells (not RBCs); presents endogenous antigens to CD8+ T cells (Killer T cells).
MHC II: Present on antigen-presenting cells (macrophages, dendritic cells); presents exogenous antigens to CD4+ T cells (Helper T cells).

Immune Response Activation

Antigen Presentation: Macrophages and dendritic cells present antigens to T cells.
Double-Check System: B cells present antigen to Helper T cells for confirmation before launching a full immune response (prevents autoimmunity).
Memory: Adaptive immunity retains memory of pathogens for faster secondary response.

Antibodies (Immunoglobulins)

Structure and Function

Regions: Variable (antigen specificity) and constant (antibody class).
Classes:
- IgM: Pentamer; agglutination, complement activation.
- IgD: Membrane-bound; function not fully understood.
- IgE: Monomer; binds mast cells, triggers histamine release (allergy).
- IgA: Dimer; agglutination, antiviral properties.
- IgG: Monomer; most abundant, crosses placenta, opsonization, neutralizes toxins.

Antibody Functions

Agglutination: Clumping of pathogens for easier phagocytosis.
Opsonization: Enhanced phagocytosis via antibody/complement binding.
Neutralization: Blocking pathogen binding sites or toxins.
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Antibodies flag infected cells for destruction by NK cells.

Hypersensitivity Reactions

Types of Hypersensitivity

Type	Mechanism	Antibody Involved	Onset	Examples
I	Immediate, IgE-mediated, mast cell degranulation	IgE	Minutes	Allergies, anaphylaxis
II	Antibody binds to cell surface antigen, complement activation	IgG, IgM	Hours	Hemolytic anemia, thrombocytopenia
III	Immune complex deposition, complement activation	IgG, IgM	Hours	Serum sickness, nephritis
IV	Cell-mediated (T cells, macrophages)	None	24-72 hrs	Contact dermatitis, TB test

Type I (Immediate) Hypersensitivity

First exposure: Sensitization, IgE produced and binds mast cells.
Second exposure: Antigen cross-links IgE, mast cell degranulation (histamine, leukotrienes), causing anaphylaxis (bronchoconstriction, hypotension, hives).

Type II (Cytotoxic) Hypersensitivity

Antibodies bind to antigens on RBCs or platelets, activating complement and leading to cell lysis (e.g., penicillin-induced hemolytic anemia, Rh incompatibility).

Type III (Immune Complex) Hypersensitivity

Antigen-antibody complexes deposit in tissues (e.g., kidneys, lungs), activating complement and causing inflammation (e.g., nephritis after strep, dust-induced alveolitis).

Type IV (Delayed) Hypersensitivity

T cell-mediated; no antibodies involved.
Examples: Contact dermatitis (poison ivy), TB skin test, latex allergy.
Onset: 24-72 hours after exposure.
Treatment: Steroids.

Key Terms and Concepts

PAMP: Pathogen-associated molecular patterns (e.g., peptidoglycan, LPS) recognized by innate immune cells.
Diapedesis: Movement of white blood cells from blood vessels into tissues.
Opsonization: Process by which pathogens are marked for phagocytosis.
Agglutination: Clumping of pathogens by antibodies, facilitating clearance.
ADCC: Antibody-dependent cell-mediated cytotoxicity; safer than chemotherapy or radiation for targeting infected cells.

Additional info: These notes synthesize and expand upon the provided material, ensuring coverage of all major concepts relevant to college-level microbiology, including viral structure and replication, antimicrobial mechanisms, immune system organization, and hypersensitivity reactions.