Unit 4 Micro Study Guide

Immune Deficiencies and Autoimmunity

• Primary Immunodeficiency: Genetic, present at birth, affects immune system development (e.g., SCID).
• Secondary Immunodeficiency: Acquired, caused by external factors (e.g., HIV, malnutrition).
• Autoimmunity: Immune system attacks body's own tissues.
• Autoimmune Disorder: Disease resulting from autoimmunity (e.g., lupus).
  • Characteristics: chronic inflammation, flare-ups, autoantibodies, tissue damage.
• Challenges in diagnosis: mimic other conditions, lengthy process, requires multiple tests.
• Treatment focuses on symptom management; immunosuppressants increase infection risk.

Type I Hypersensitivities

• Immediate allergic reaction, mediated by IgE.
• Sensitizing Exposure:
  • First exposure to allergen leads to IgE production and binding to mast cells/basophils.
• Subsequent Exposures:
  • Allergen binds to IgE, triggers degranulation and release of inflammatory mediators (histamine).
• Cells: Mast cells, basophils, Th2 cells
• Antibody: IgE
• Mediators: Histamine, leukotrienes, prostaglandins
• Portal of Entry:
  • Inhaled: Respiratory symptoms.
  • Ingested: Gastrointestinal symptoms.
  • Injected: Systemic symptoms.
  • Skin: Localized hives.
• Localized Anaphylaxis: Mild, affects one area.
• Systemic Anaphylaxis: Life-threatening, multiple systems involved.
• Treatment: Avoidance, antihistamines, corticosteroids, epinephrine, desensitization.

Type II Hypersensitivities

• Cytotoxic, IgG or IgM bind to antigens on host cells.
• Mechanisms: Complement activation, opsonization, ADCC.
• Antibodies: IgG, IgM
• Targets: Antigens on host cell surfaces (e.g., RBCs).
• ABO Transfusion Reactions:
  • Incompatible blood leads to IgM-mediated attack on donor RBCs.
• Rh Incompatibility (HDN):
  • Rh- mother, Rh+ fetus; maternal IgG destroys fetal RBCs.
  • Prevention: RhoGAM injection.

Type III Hypersensitivities

• Immune complex-mediated; complexes deposit in tissues.
• Antibody: IgG (mainly), sometimes IgM
• Cells: Neutrophils, macrophages, complement proteins
• Mechanism: Immune complex deposition triggers inflammation and tissue damage by neutrophils.
• Examples: serum sickness, lupus, rheumatoid arthritis.

Type IV Hypersensitivities

• Delayed-type; T-cell mediated, not antibody-mediated.
• Cells: Th1 cells, CTLs, macrophages
• Mechanism: T cells release cytokines, activate macrophages, and CTLs destroy host cells.
• Examples: Tuberculin skin test, contact dermatitis, graft rejection, type 1 diabetes.

Vaccine-Preventable Diseases: Re-Emergence

• Factors: Vaccine hesitancy/misinformation, decreased vaccination rates, global travel, conflict, poverty, pathogen evolution, anti-vaccine movements.

Immunology Principles Underlying Vaccination

• Antigen Exposure: vaccines introduce antigens to stimulate an immune response without causing disease.
• Activation of the adaptive immune system: activation of B cells and T cells after antigen exposure
• Formation of Memory Cells: memory B and T cells for long-term protection.
• Primary Immune Response: IgM and IgG produce after lag period
• Secondary Immune Response: faster and stronger response upon re-exposure
• Herd Immunity: Protects unimmunized people.
• Induction of Long-Lasting Immunity: vaccines generate long-lasting immunity
• Tolerance and Safety: vaccines are designed to stimulate the immune system without harmful inflammation

Herd Immunity

• High percentage of population immune, reducing disease spread.
• Threshold: 70-95% immunity.
• Protects unimmunized individuals.

Types of Vaccine Formulations

• Live Attenuated: Weakened pathogen; strong immunity, but risky for immunocompromised.
• Inactivated (Killed): Safe, but weaker response; needs boosters.
• Subunit, Recombinant, Conjugate: Fragments of pathogen; safe, may need adjuvants.
• Toxoid: Inactivated toxins; long-lasting, needs boosters.
• mRNA: Rapid development; new, requires cold storage.

COVID-19 Vaccines Overview

• mRNA Vaccines: Pfizer-BioNTech (Comirnaty),Moderna (Spikevax)
• Protein Subunit Vaccines: Novavax (Nuvaxovid)
• Viral Vector Vaccines: Johnson & Johnson (Janssen)
• Inactivated Virus: Sinovac (CoronaVac), Sinopharm (BBIBP-CorV)

Recommended Vaccines

• Childhood: HBV, DTaP, IPV, MMR, Hib, Varicella, HepA, Menin, HPV.
• Adult: Flu, Tdap, HPV, Zoster, Pneumococcal, HBV, Meningococcal.
• Special Populations: Flu, Tdap, HBV, Meningococcal, Pneumococcal, HPV, Rabies.

Immunological Diagnostic Tools: ELISA

• Purpose/Rationale: Enzyme-linked immunosorbent assay.
• Detection Antibody and Reporter Enzyme: Detect and quantify target substance.
• Direct, Indirect, Sandwich ELISA: Different formats for antigen detection.
• Molecular Diagnostic Tool: PCR
  • PCR and RT-PCR: Amplify and detect DNA or RNA.
  • Component Analyzed: Microbe/pathogen genetic material.
  • Primer Function: Initiate DNA amplification.

Antimicrobial Drugs

• Broad-spectrum: Wide range of microorganisms.
• Narrow-spectrum: Specific group of microorganisms.
• Bacteriostatic: Inhibits bacterial growth.
• Bactericidal: Kills bacteria.
• Natural: Produced by microorganisms.
• Semisynthetic: Chemically modified natural antibiotics.
• Synthetic: Man-made antimicrobials.
• Antibiotic: Natural compound that kills or inhibits microorganisms.
• Antimicrobial Drug: natural, semisynthetic, or synthetic agent used to treat infections
• Therapeutic Index: Ratio of toxic dose to effective dose.
• Selective toxicity: ability of a drug to target harmful microbes without damaging the host's cells

Antibacterial Drug Targets

• Inhibition of cell wall synthesis (e.g., penicillins).
• Inhibition of protein synthesis (e.g., tetracyclines).
• Disruption of plasma membrane (e.g., polymyxins).
• Inhibition of nucleic acid synthesis (e.g., rifampin).
• Inhibition of metabolic pathways (e.g., sulfonamides).

Developing Drugs Against Viruses and Eukaryotic Pathogens

• Viruses: Few unique targets, high mutation rates.
• Eukaryotic Pathogens: Similar to human cells, higher toxicity risk.

Antimicrobial Resistance

• Microbe's ability to survive antimicrobial drugs.
• Intrinsic: Natural resistance.
• Acquired: Resistance through mutation or gene transfer.
• Antimicrobial use selects for resistant microbes.
• Misuse spreads resistance in agriculture and clinics.

Reducing Antimicrobial Resistance

• Healthcare Workers: Prescribe when necessary, select appropriate antibiotic, educate patients, ensure infection control.
• Patients: Take as prescribed, don’t demand, never share, practice hygiene, vaccinate.

Control of Microbial Growth

• Decontamination: Reduces harmful microorganisms.
• Sterilization: Complete removal of microbial life.
• Disinfection: Eliminates pathogens on objects.
• Bacteriostatic: Inhibits growth.
• Bactericidal: Kills bacteria.
• Disinfectant: disinfet inanimate objects.
• Antiseptic: disinfect living tissues.
• Methods of Physical Control:
  • Boiling: Ineffective against spores.
  • Autoclave: 121°C at 15 psi for 15-20 minutes.
  • Pasteurization: Reduces microbial load.
    • Batch: 63°C for 30 minutes.
    • HTST: 72°C for 15 seconds.
• Radiation:
  • Ionizing: Damages DNA.
  • Non-ionizing: UV, forms thymine dimers.
• Filtration: Removes microorganisms.