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 host cell entry and increase 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.

Steps of the Lytic Cycle:

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

Lysogenesis: Allows the virus to persist in the host genome, evading immune detection. Environmental stress or immune suppression can trigger reactivation to the lytic cycle.

Viral Genomes and Replication Enzymes

Viruses may have one of six types of genomes: dsDNA, ss(+)DNA, ss(-)DNA, dsRNA, ss(+)RNA, ss(-)RNA.
Key enzymes involved in viral replication:
- 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 host cells, making it a good antiviral target)
- RDDP: RNA-dependent DNA polymerase (reverse transcriptase; makes DNA from RNA, as in retroviruses)

Replication Pathways:

dsDNA Virus: Uses host DDRP to make mRNA and DDDP to replicate DNA.
ss(+)DNA Virus: DDDP makes (-)DNA, DDRP makes mRNA, DDDP replicates DNA.
ss(-)DNA Virus: DDRP makes mRNA, DDDP makes (+)DNA, then (-)DNA.
ss(+)RNA Virus: Acts as mRNA, translated directly; RDRP synthesizes (-)RNA as template for more (+)RNA.
ss(-)RNA Virus: RDRP (carried in virion) makes (+)RNA for translation and genome replication.
dsRNA Virus: RDRP synthesizes mRNA and replicates RNA genome.
ss(+)RNA Retrovirus: RDDP (reverse transcriptase) makes (-)DNA, DDDP makes (+)DNA, viral DNA integrates into host genome.

Note: Human cells do not possess RDRP, making it an ideal antiviral drug target.

Antimicrobial Drugs: Mechanisms and Effects

Antibiotic Targets and Examples

Antibiotics exploit differences between bacterial and human cells to selectively inhibit or kill bacteria.

Cell Wall Synthesis: Targeted by β-lactams (e.g., penicillin); effective mainly against Gram-positive bacteria. MOA: Inhibit peptidoglycan synthesis.
Protein Synthesis: Target bacterial ribosomes (70S) but may affect mitochondrial ribosomes (similar to prokaryotic ribosomes).
- Tetracycline: Binds 30S subunit; side effect: brown teeth (binds calcium in developing teeth).
- Azithromycin: Binds 50S subunit; side effect: blocks Ca2+ channels, may cause arrhythmia.
- Gentamycin: Binds 30S subunit; side effects: nephrotoxicity, hearing loss (mitochondrial toxicity).
DNA Replication: Bacteria use DNA gyrase (targeted by ciprofloxacin); humans use topoisomerase.
Metabolic Pathways: Sulfa drugs (e.g., trimethoprim) inhibit folate synthesis (not used by humans).

Side Effects and Clinical Considerations

All antibiotics carry risks and side effects (e.g., allergic reactions, GI upset, organ toxicity).
Antibiotic selection is based on infection severity and risk-benefit analysis.
Development of new antibiotics is limited by economic factors and short product lifespan.

Antibiotic Risk Ranking (Lowest to Highest)

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

Microbial Growth: Plate Count Assays

Calculating Colony-Forming Units (CFU)

Plate count assays estimate the number of viable bacteria in a sample using serial dilutions and colony counts.

Formula: $\text{CFU/mL} = \frac{\text{Number of Colonies}}{\text{Volume Plated (mL)} \times \text{Dilution Factor}}$
FDA Standard: Count plates with 30–300 colonies for accuracy.

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, rapid) and adaptive (specific, slower but more effective) branches.

Innate Immunity: First line of defense; includes skin, macrophages, dendritic cells, mast cells, complements, and cytokines.
Adaptive Immunity: Involves B cells (antibody production), T cells (cell-mediated immunity), and memory cells.

Cells and Organs of the Immune System

Bone Marrow: Produces pluripotent stem cells (can become lymphoid or myeloid progenitors).
Lymph Nodes: Filter blood and house immune cells.
Thymus: Site of T cell maturation and selection.

Innate Immune Cells

Macrophages: Phagocytose pathogens, present antigens (APCs).
Dendritic Cells: APCs, activate naive T cells.
Mast Cells: Release histamine, mediate inflammation and allergy.
Neutrophils: First responders, phagocytose bacteria.
Eosinophils: Attack antibody-coated parasites.
Basophils: Mediate inflammation and allergic responses.
Natural Killer (NK) Cells: Kill infected or tumor cells without prior activation.

Adaptive Immune Cells

B Cells: Produce highly specific antibodies.
T Cells: Helper T cells (CD4+) coordinate immune response; Killer T cells (CD8+) destroy infected cells.
Memory Cells: Provide rapid, robust response upon re-exposure to antigen.

Major Histocompatibility Complex (MHC)

MHC I: Present on all nucleated cells; present endogenous antigens to CD8+ T cells.
MHC II: Present on APCs (macrophages, dendritic cells); present exogenous antigens to CD4+ T cells.

Immune Cell Differentiation

Pluripotent Stem Cells: Differentiate into myeloid (innate) or lymphoid (adaptive) progenitors.
Myeloid Progenitors: Give rise to erythrocytes, platelets, neutrophils, monocytes (macrophages), eosinophils, basophils, and dendritic cells.
Lymphoid Progenitors: Give rise to B cells, T cells, and NK cells.

Phagocytosis and Inflammation

PAMPs (Pathogen-Associated Molecular Patterns): Recognized by macrophages, trigger cytokine release and inflammation.
Diapedesis: Movement of white blood cells from blood vessels to tissues.
Inflammation Symptoms: Edema, redness, heat, pain (due to increased blood flow and vascular permeability).

Antibodies (Immunoglobulins)

Structure and Function

Regions: Variable (antigen specificity), 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 enhanced phagocytosis.
Opsonization: Coating pathogens to enhance phagocytosis.
Neutralization: Blocking toxins or pathogen attachment.
Complement Activation: Formation of Membrane Attack Complex (MAC) for cell lysis.

Hypersensitivity Reactions

Types of Hypersensitivity

Type	Mechanism	Antibody/Cell	Examples
I (Immediate)	IgE-mediated, mast cell degranulation	IgE	Allergies, anaphylaxis
II (Cytotoxic)	Antibody binds cell surface, complement activation	IgG, IgM	Hemolytic anemia, thrombocytopenia
III (Immune Complex)	Antigen-antibody complexes deposit in tissues	IgG, IgM	Serum sickness, nephritis
IV (Delayed)	T cell-mediated cytotoxicity	T cells	Contact dermatitis, TB test

Mechanisms and Clinical Features

Type I: Sensitization on first exposure (IgE binds mast cells), rapid reaction on second exposure (histamine, leukotrienes, anaphylaxis).
Type II: Antibodies bind to cells (e.g., RBCs, platelets), activate complement, cause cell lysis (e.g., penicillin-induced hemolysis, Rh incompatibility).
Type III: Immune complexes deposit in capillaries, activate complement, cause inflammation (e.g., post-strep nephritis, dust-induced alveolitis).
Type IV: T cell-mediated, delayed onset (24–72 hrs), no antibodies involved (e.g., poison ivy, latex allergy).

Key Terms and Concepts

Opsonization: Enhanced phagocytosis via antibody or complement coating.
Plasma Cells: Differentiated B cells that secrete antibodies.
Memory Cells: Long-lived cells for rapid secondary response.
Autoimmunity: Failure of self-tolerance (e.g., diabetes, multiple sclerosis).

Summary Table: Antibody Classes

Class	Structure	Main Functions	Special Features
IgM	Pentamer	Agglutination, complement activation	First antibody produced
IgG	Monomer	Opsonization, neutralization, crosses placenta	Most abundant in blood
IgA	Dimer	Agglutination, antiviral	Secreted in mucosa
IgE	Monomer	Histamine release, allergy	Binds mast cells
IgD	Monomer	Membrane-bound, unknown function	On B cell surface

Additional info:

Antibody-dependent cell-mediated cytotoxicity (ADCC) is a mechanism where antibodies direct immune cells to kill target cells, considered safer than chemotherapy or radiation for some therapies.
Gene expression, not DNA sequence, determines cell type (e.g., muscle vs. nerve cell).