Chapter 08: Infection and Defects in Mechanisms of Defence

Infection

• Infectious diseases are major contributors to global morbidity and mortality rates.
• Pathogens possess distinct characteristics that affect their disease-causing potential.
• Bacteria injure host cells via exotoxins (enzymes damaging cell membranes or inhibiting protein synthesis) and endotoxins (triggering inflammation and fever).
• Septicemia indicates bacteria multiplication in blood, where endotoxins induce vasoactive enzyme release, leading to increased vascular permeability and potential endotoxic shock.
• Viruses infiltrate host cells and exploit their metabolic systems to replicate and induce disease.
• Infected cells may experience reduced protein synthesis, lysosomal disruption, formation of viral nucleic acid inclusions, giant cell formation, altered antigen properties, potential malignant transformation, or increased susceptibility to bacterial infections.
• Mycoses are fungal infections, classified into yeasts (single-celled) and multicellular moulds (filaments).
• Dermatophytes infect skin, hair, and nails, causing conditions like ringworm and athlete's foot.
• Fungi, such as Candida albicans, emit toxins and enzymes harmful to tissues; Candida is the leading cause of fungal infections in humans.
• Parasitic organisms vary from unicellular protozoa to larger worms and are prevalent globally, but less so in Canada and the U.S.
• Transmission of parasites mainly occurs via vectors (e.g., mosquitoes) or contaminated food/water, with diseases like malaria and Chagas disease as notable examples.
• Infection control requires safe food and water, waste management, insect control, vaccination, prudent antimicrobial use, and passive immunotherapy.

Deficiencies in Immunity

• Immune deficiencies occur when self-defense mechanisms fail to function normally.
• Immunodeficiencies are either congenital (genetic origin disrupting lymphocyte development) or acquired (due to diseases or physiological changes).
• Clinical hallmark is susceptibility to rare or severe infections, with infection types correlating with specific immune defects.
• Individuals with cell-mediated immunity defects experience fungal and viral infections; those with humoral defects face bacterial infections.
• Severe Combined Immunodeficiency (SCID) signifies a total absence of T-cell function and significant B-cell dysfunction.
• Wiskott-Aldrich syndrome is linked to reduced IgM antibody production.
• DiGeorge syndrome results from a partial or complete absence of the thymus, impacting T-cell immunity and often associated with hypocalcemia and cardiac issues.
• Antibody deficiencies arise from issues in B-cell maturation or function, as observed in Bruton agammaglobulinemia or selective IgA deficiency.
• Phagocyte defects can arise from inadequate quantities or dysfunctions, affecting bacterial adhesion and killing.
• Deficiencies in complement proteins and mannose-binding lectin are rare but present a higher infection risk.
• Acquired immunodeficiencies stem from conditions like malnutrition, medical treatments, trauma, stress, or infections.
• Treatments typically involve replacement therapies for deficient antibodies or lymphocytes, with ongoing gene therapy trials.
• Acquired Immunodeficiency Syndrome (AIDS) is caused by the retrovirus HIV, targeting and destroying CD4+ Th cells.

Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity

• Hypersensitivity involves misdirected immune responses either against self-tissues (autoimmunity), beneficial foreign tissues (alloimmunity), or exaggerated reactions to environmental antigens (allergy).
• Hypersensitivity mechanisms include type I (IgE-mediated), type II (tissue-specific), type III (immune complex-mediated), and type IV (cell-mediated).
• Reactions can be immediate (occurring within seconds to hours) or delayed (taking hours to days).
• Anaphylaxis is a rapid, severe immediate hypersensitivity reaction that can lead to shock and death upon re-exposure to antigens.
• Type I hypersensitivity occurs when an allergen binds to IgE on mast cells, triggering degranulation and release of histamine.
• Type II hypersensitivity reactions arise from mechanisms like complement-mediated lysis and macrophage phagocytosis.
• Type III hypersensitivity involves immune complexes depositing in tissues, activating complement and attracting neutrophils to inflammatory sites.
• Both systemic (e.g., serum sickness) and localized (e.g., Arthus reaction) immune complex diseases exist.
• Type IV reactions are mediated by sensitized lymphocytes that kill target cells or activate other immune cells.
• Allergens are specific antigens responsible for allergic reactions, predominantly of type I hypersensitivity.
• Autoimmune diseases result from loss of self-antigen tolerance, often with genetic predispositions and associating with type II or type III hypersensitivity reactions.
• Alloimmunity arises when the immune system reacts to antigens on tissues from the same species, as seen in transplant rejections and transfusion reactions.