Pathophysiological Concepts Chapter 8: Infection & Defects in Mechanisms of Defence

Mechanisms of Immune Response

• Immune deficiency results in increased susceptibility to infections, ranging from mild to life-threatening.
• Hypersensitivity responses can be exaggerated against environmental substances (allergies), misdirected against self-cells (autoimmunity), or directed against beneficial tissues (alloimmunity).

Infection Factors

• Communicability: Ability of a pathogen to spread; highly communicable diseases include measles and pertussis, while HIV is less so.
• Infectivity: Capacity of a pathogen to invade and multiply in the host; e.g., Herpes simplex can remain latent.
• Virulence: The severity of disease caused by a pathogen; rabies virus is highly virulent, while measles shows low virulence.
• Pathogenicity: Ability to produce disease influenced by communicability, infectivity, virulence, and extent of tissue damage (e.g., HIV's effect on T cells).
• Portal of Entry: Routes include direct contact, inhalation, ingestion, or bites from animals/insects.
• Toxigenicity: Ability to produce toxins that enhance virulence.

Bacterial Diseases

• Bacteria are prokaryotic organisms; environmental or immune factors influence their survival.
• Staphylococcus aureus: Opportunistic pathogen, leading to skin infections, abscesses, or septicemia; antibiotic resistance is a concern (e.g., MRSA).

Toxins

• Exotoxins: Enzymes damaging host cell membranes or inhibiting protein synthesis.
• Endotoxins: Trigger inflammatory responses and fever, often released by Gram-negative bacteria leading to conditions like sepsis and cardiovascular shock.

Viral Diseases

• Viruses are the most common human afflictions; replication relies on host cell infection.
• Spread via aerosol, blood, sexual contact, or vectors.
• Viral replication involves host cell attachment, penetration, uncoating, replication, assembly, and release.
• Some viruses (e.g., herpes) can remain latent within the host.

Influenza Variability

• Undergoes antigenic variation necessitating annual vaccinations.
• Minor changes are termed antigenic drift; major changes are referred to as antigenic shift.

Fungal Infections

• Eukaryotic organisms existing as yeasts or molds; pathogenicity involves environment adaptation and immune suppression.
• Candida albicans: Common opportunistic pathogen, found in normal microbiomes; can cause localized or disseminated infections, leading to complications like thrush.

Parasitic Infections

• Ranges from unicellular protozoa to multicellular worms; common in developing countries.
• Damage may arise from infestation and inflammatory responses.

Countermeasures Against Infections

• Infection control, antimicrobials, active immunization (vaccines), and passive immunotherapy are vital for managing infections.

Active Immunization

• Vaccines stimulate protective antibodies or cellular immunity without causing disease.
• Goal is to induce long-lasting immunity and achieve herd immunity (85% vaccination rate increases public protection).

Immunodeficiencies

• Primary: Congenital genetic defects affecting immune function.
• Secondary: Acquired conditions like infections, cancer, or aging leading to increased infection susceptibility.
• Clinical signs include recurrent severe infections and specific immune cell deficiencies.

Evaluation of Immunity

• Complete blood count (CBC) provides cellular information; quantitative immunoglobulin testing screens for antibody levels.

Treatment for Immunodeficiencies

• Options include gamma-globulin therapy, stem cell transplants, transfusions, and gene therapy.

HIV and AIDS

• AIDS is a secondary immune deficiency caused by HIV, which targets CD4+ T-helper cells.
• HIV leads to a decreased T-cell count, resulting in a generalized immune deficiency.
• New treatments allow for better management of HIV, turning it into a chronic illness rather than a terminal condition.

Epidemiology of AIDS

• Transmitted via blood, IV drug use, sexual contact, or maternal transmission.
• Over half of those living with HIV/AIDS are women, with heterosexual activity being the most common transmission pathway.

Clinical Manifestations of AIDS

• Presentation includes serologically negative or positive states, early stages of HIV disease, or full-blown AIDS.
• Early symptoms are typically mild (headache, fever, fatigue) but worsen with disease progression.

Treatment and Prevention of HIV and AIDS

• Highly active antiretroviral therapy (HAART) involves combinations of medications tailored to individual patients.
• Long-term use of these therapies can elevate risks for cardiovascular and metabolic conditions.

Hypersensitivity

• Characterized by an altered immune response resulting in host damage; classified into allergies, autoimmunity, and alloimmunity.

Types of Hypersensitivity

• Four mechanisms:
  • Type I: IgE mediated (common allergies)
  • Type II: Tissue-specific reactions
  • Type III: Immune complex mediated
  • Type IV: Cell-mediated

Type I Hypersensitivity

• Immediate allergic reactions mediated by IgE against environmental antigens.
• Symptoms include asthma, hives, and gastrointestinal disturbances.
• Treatment options include avoidance of allergens and antihistamines.

Autoimmunity

• Characterized by a breakdown of tolerance leading to the immune system misidentifying self-antigens as foreign.
• Can be triggered by infectious diseases.

Example of Autoimmune Disease

• Systemic Lupus Erythematosus (SLE): Autoimmune condition with multisystem involvement; symptoms include butterfly rash, arthritis, and presence of antinuclear antibodies.

Alloimmunity

• Immune responses against tissue from another individual, observable in transfusions and transplants.
• ABO Blood Group: Type O is a universal donor; Type AB is a universal recipient.
• Rh incompatibility can lead to hemolytic disease of the newborn; RhoGAM injections prevent complications during pregnancy.

Transplant Rejection

• Classified by timing:
  • Hyperacute: Immediate, rare rejection due to pre-existing antibodies.
  • Acute: Cell-mediated response to unmatched human leukocyte antigens.
  • Chronic: Develops over months/years due to weak immune reactions against minor HLA differences.