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.

Example: Influenza virus has an envelope and spike proteins (hemagglutinin and neuraminidase).

Viral Envelope and Spike Proteins

Viral Envelope: Mimics host cell membrane, allowing the virus to evade immune detection.
Spike Proteins: Function as ligands for host cell receptors, mediating viral entry and increasing virulence.

Viral Replication Pathways

Lytic Cycle: Main method of viral replication, resulting in host cell lysis and release of new virions.
Lysogenic Cycle (Lysogenesis): Viral genome integrates into host chromosome, replicates with host cell, can later reactivate to lytic cycle.

Steps of Lytic Replication:

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

Lysogenic Cycle: Virus integrates into host DNA, remains dormant until triggered (e.g., by weakened immunity), then reenters lytic cycle.

Viral Genomes and Replication Enzymes

Possible 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 human cells).
- RDDP: RNA-dependent DNA polymerase (reverse transcriptase; makes DNA from RNA).

Replication Pathways:

dsDNA Virus: Uses host DDRP to make mRNA; DDDP copies DNA genome.
ss(+)DNA Virus: DDDP makes (-)DNA, DDRP makes mRNA, DDDP copies DNA.
ss(-)DNA Virus: DDRP makes mRNA, DDDP makes (+)DNA, then (-)DNA.
ss(+)RNA Virus: Acts as mRNA, translated directly; RDRP makes (-)RNA, then (+)RNA.
ss(-)RNA Virus: RDRP (carried in virion) makes (+)RNA, which is translated; RDRP makes more (-)RNA.
dsRNA Virus: (+)RNA is translated; RDRP copies RNA genome.
ss(+)RNA Retrovirus: RDDP makes (-)DNA, DDDP makes (+)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), eukaryotic ribosomes are 80S.
- Tetracycline: Inhibits 30S subunit; side effect: brown teeth in children (binds calcium).
- Azithromycin: Inhibits 50S subunit; side effect: blocks Ca2+ channels, may cause arrhythmia.
- Gentamycin: Inhibits 30S subunit; side effects: nephrotoxicity, hearing loss (mitochondrial toxicity).
DNA Replication: Bacteria use DNA gyrase, humans use topoisomerase.
- Ciprofloxacin: Inhibits DNA gyrase; side effects: tendon rupture, agitation, seizures.
Metabolic Pathways: e.g., Sulfa drugs (trimethoprim) inhibit folate synthesis (not used by humans); side effects: Stevens-Johnson Syndrome, arrhythmia.

Antibiotic Risk Ranking (Lowest to Highest): Penicillin, Tetracycline, Azithromycin, Gentamycin, Ciprofloxacin, Sulfa drugs.

Antibiotic Resistance and Prescribing

Antibiotics have a limited shelf life; pharmaceutical companies may prioritize other drugs.
Drug choice depends on infection severity and risk-benefit analysis.

Microbial Quantification: Plate Count Assay

Principles and Calculations

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

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

Examples:
- 54 colonies from 1 mL of 1:1000 dilution: 54,000 CFU/mL
- 83 colonies from 1 mL of 1:10,000 dilution: 830,000 CFU/mL
- 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 and harmful substances. 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, complements, cytokines).
Adaptive Immunity: Slower but highly specific and has memory (e.g., B cells, T cells, 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 dead cells; site of lymphocyte activation.
Thymus: Site of T cell maturation and selection.

Innate Immune Cells

Macrophages: Phagocytize pathogens, present antigens (APCs).
Dendritic Cells: APCs, activate naive T cells.
Mast Cells: Release histamine, cause inflammation and vasodilation.
Neutrophils: Most abundant, first responders, phagocytize bacteria.
Eosinophils: Attack antibody-coated parasites.
Basophils: Mediate inflammation and allergic responses.
Complements: Plasma proteins forming the Membrane Attack Complex (MAC) to lyse bacteria.
Cytokines: Signaling proteins, induce inflammation and fever.

Adaptive Immune Cells

B Cells: Produce antibodies, present antigens to T cells.
T Cells: Helper T cells (CD4) coordinate immune response; Killer T cells (CD8) destroy infected cells.
Natural Killer (NK) Cells: Kill tumor and infected cells without prior activation.
Memory Cells: Provide rapid response upon re-exposure to the same antigen.

Immune Cell Development

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.

Major Histocompatibility Complex (MHC)

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

Immune Response Activation

Antigen Presentation: APCs present antigens to T cells in lymph nodes.
Double-Check Mechanism: Both B and T cells must recognize antigen to initiate adaptive response, preventing autoimmunity.
Memory: Adaptive immunity is faster and stronger upon second exposure due to memory cells.

Antibodies (Immunoglobulins)

Structure and Function

Regions: Variable (antigen specificity) and constant (antibody class).
Classes:
- IgM: Pentamer; main agglutinator, activates complement.
- IgD: Membrane-bound; function not fully understood.
- IgE: Monomer; triggers histamine release, involved in allergies.
- IgA: Dimer; agglutination, antiviral properties.
- IgG: Monomer; most abundant in blood, crosses placenta, neutralizes toxins, opsonization.

Antibody	Structure	Main Functions	Special Features
IgM	Pentamer	Agglutination, complement activation	First antibody produced
IgD	Monomer	Membrane receptor	Function unclear
IgE	Monomer	Histamine release	Allergy, parasitic defense
IgA	Dimer	Agglutination, antiviral	Secretions (mucus, milk)
IgG	Monomer	Opsonization, neutralization, crosses placenta	Most abundant

Hypersensitivity Reactions

Types and Mechanisms

Type I (Immediate, IgE-mediated): Allergies, anaphylaxis. First exposure sensitizes, second exposure triggers mast cell degranulation (histamine, leukotrienes).
Type II (Cytotoxic, IgG/IgM-mediated): Antibodies bind to cell surfaces (e.g., RBCs, platelets), activate complement, cause cell lysis (e.g., hemolytic anemia, thrombocytopenia, Rh incompatibility).
Type III (Immune Complex): Antigen-antibody complexes deposit in tissues, activate complement, cause inflammation (e.g., serum sickness, nephritis).
Type IV (Delayed, Cell-mediated): T cell-mediated, no antibodies; occurs 24–72 hours after exposure (e.g., contact dermatitis, TB test, poison ivy).

Type	Immune Component	Onset	Examples
I	IgE, mast cells	Minutes	Allergies, anaphylaxis
II	IgG/IgM, complement	Hours	Hemolytic anemia, Rh disease
III	Immune complexes	Hours	Serum sickness, nephritis
IV	T cells, macrophages	24–72 hrs	Contact dermatitis, TB test

Key Features and Examples

Type I: Requires prior sensitization; second exposure causes rapid symptoms (bronchoconstriction, hypotension, hives).
Type II: Antibodies target cells; e.g., penicillin-induced hemolysis, Rh incompatibility in pregnancy.
Type III: Immune complexes deposit in tissues; e.g., post-strep nephritis, dust-induced alveolitis.
Type IV: T cell-mediated cytotoxicity; e.g., poison ivy, latex allergy. Can occur on first exposure.

Clinical Relevance

Anaphylaxis: Life-threatening, requires immediate treatment (epinephrine).
Autoimmunity: Failure of thymic deletion can lead to diseases like diabetes or multiple sclerosis.
Treatment: Type IV hypersensitivity is treated with steroids.

Additional info:

Opsonization enhances phagocytosis by marking pathogens for immune recognition.
Antibody-dependent cell-mediated cytotoxicity (ADCC) is a targeted, less toxic alternative to chemotherapy.
Gene expression, not DNA sequence, determines cell type (e.g., muscle vs. nerve cell).