Download Chapter fifteen notes microbiology and more Study notes Microbiology in PDF only on Docsity!
Chapter 15 15.1 Hypersensitivities: Type I hypersensitivity : Involves IgE antibody against soluble antigen, triggering mast cell degranulation .; Soluble antigen; Allergen-specific IgE antibodies bind to mast cells via their Fc receptor. When the specific allergen binds to the IgE, cross-linking of IgE induces degranulation of mast cells. Ex: Local and systemic anaphylaxis, seasonal hay fever, food allergies, and drug allergies Type II hypersensitivity : Involves IgG and IgM antibodies directed against cellular antigens, leading to cell damage mediated by immune effectors. Cell bound antigen. IgG or IgM antibody binds to cellular antigen, leading to complement activation and cell lysis. IgG can also mediate ADCC with cytotoxic T cells, NKC, macrophages and neutrophils. Ex: RBC destruction after transfusion with mismatched blood types or during hemolytic disease of the newborn. Type III hypersensitivity : Involves IgG, IgM, and occasionally IgA1 antibodies forming immune complexes that accumulate in tissue, causing tissue damage mediated by immune effectors.; Soluble antigen. Antigen-antibody complexes are deposited in tissues. Complement activation provides inflammatory mediators and recruits neutrophils. Enzymes released from neutrophils damage tissue. Ex: Post streptococcal glomerulonephritis, Rheumatoid arthritis, systemic lupus erythematosus. Type IV hypersensitivity : T-cell–mediated reactions that cause tissue damage through activated macrophages and cytotoxic T cells. Soluble or cell bound antigen. TH1 cells secrete cytokines which activate macrophages and cytotoxic T cells. Ex: Contact dermatitis, Type 1 diabetes, and multiple sclerosis. Type I hypersensitivity: occur when a presensitized individual is exposed to an allergen, leading to a rapid immune response called an allergy. Allergens can be harmless substances like animal dander, molds, or pollen, or hazardous substances like insect venom or therapeutic drugs. Food intolerances can also trigger allergic reactions, such as to peanuts or shellfish. The first exposure activates a primary IgE antibody response, sensitizing the individual to a type I hypersensitivity reaction upon subsequent exposure. For susceptible individuals, TH2 cells play a key role by releasing interleukin (IL)-4 and IL-13, activating B cells specific to the allergen. This leads to clonal proliferation, plasma cell differentiation, and an antibody-class switch from IgM to IgE. The Fc regions of IgE bind to receptors on mast cells, which can hold up to 500,000 IgE molecules. Although the allergen is often no longer present, mast cells remain primed, making the individual sensitized. On subsequent exposure, allergens cross-link IgE molecules, activating mast cells and triggering degranulation (a reaction in which the contents of the granules in the mast cell are released into the extracellular environment.), releasing histamine ( Causes smooth-muscle contraction, increases vascular permeability, increases mucus and tear formation), serotonin (Increases vascular permeability, causes vasodilation and smooth- muscle contraction), bradykinin, leukotrienes (Causes smooth-muscle contraction and mucus secretion, increases vascular Permeability), prostaglandins (Causes smooth-muscle contraction and vasodilation), and cytokines like Tumor Necrosis Factor (Causes inflammation and stimulates cytokine production by other cell types). These chemical mediators cause inflammation and symptoms of type I hypersensitivity reactions, such as mucus secretion, runny nose, watery eyes, itching, sneezing, hives, headaches, angioedema, and hypotension. Bronchiole constriction can lead to wheezing, dyspnea, coughing, and cyanosis, while histamine effects in
the gastrointestinal tract can cause vomiting, intestinal relaxation, and diarrhea. It can be localized (hay fever, hives, asthma) or systemic (anaphylaxis, anaphylactic shock). Anaphylaxis is life-threatening due to airway blockage, swelling, low blood pressure, and shock, potentially causing death within minutes. Late-phase reactions occur 4–12 hours later, involving eosinophils, neutrophils, and lymphocytes, leading to swelling, redness, coughing, and wheezing. Evolutionary perspective: IgE may have evolved to fight helminth infections , as helminths have proteins targeted by IgE. Helminth infections in early life may reduce the likelihood of allergies later. Type II (Cytotoxic) Hypersensitivities Type II hypersensitivities are immune reactions mediated by IgG and IgM antibodies binding to cell-surface antigens or matrix-associated antigens on basement membranes. These antibodies can: - Activate complement , leading to inflammation and cell lysis. - Trigger antibody-dependent cell-mediated cytotoxicity (ADCC) with cytotoxic T cells Immunohematology is the study of blood and blood-forming tissue in relation to the immune response. Antibody- initiated responses against blood cells are type II hypersensitivities, thus falling into the field of immunohematology. Some antigens may be self-antigens, causing autoimmune diseases, while others may be naturally occurring but exogenous, such as blood group antigens on RBCs. This leads to antibody binding, complement activation, complement- mediated lysis of RBCs, and opsonization for phagocytosis. Two examples of type II hypersensitivity reactions involving RBCs are hemolytic transfusion reaction (HTR, IgG and IgM bind to antigens on transfused RBCs, targeting donor RBCs for destruction. S&S: Fever, jaundice, hypotension, disseminated intravascular coagulation, possibly leading to kidney failure and death) and hemolytic disease of the newborn (HDN IgG from mother crosses the placenta, targeting the fetus’ RBCs for destruction. S&S: Anemia, edema, enlarged liver or spleen, hydrops (fluid in body cavity), leading to death of newborn in severe cases). ABO Blood Group System Identified by Karl Landsteiner (1900s) , based on A and B surface carbohydrates Blood type inheritance follows dominant and codominant patterns : AA or AO = Type A (A antigen present) BB or BO = Type B (B antigen present) AB = Type AB (both A and B antigens present) OO = Type O (no A or B antigens) All RBCs share a common protein receptor, with enzymes adding specific carbohydrates. IgM antibodies in plasma that cross-react with blood group antigens do not present on an individual’s own RBCs are called isohemagglutinins. They are produced within the first few weeks after birth and persist throughout life. These antibodies are produced in response to exposure to environmental antigens from food and microorganisms. A transfusion with an incompatible ABO blood type may lead to a strong, potentially lethal type II hypersensitivity cytotoxic response called hemolytic transfusion reaction (HTR) leading to agglutination, complement activation, and RBC destruction. In addition, activation of the classical complement cascade will lead to a strong inflammatory response, and the complement membrane attack complex (MAC) will mediate massive hemolysis of the transfused RBCs. The debris from damaged and destroyed RBCs can occlude blood vessels in the alveoli of the lungs and the
like systemic lupus erythematosus (SLE) and rheumatoid arthritis also involve type III hypersensitivity when autoantibodies form immune complexes with self-antigens. Type IV hypersensitivities are T-cell mediated, not antibody-driven, and involve effector cells. They are categorized into three subtypes based on T-cell subtype, antigen type, and effector mechanism.
- CD4 TH1-Mediated (Delayed-Type Hypersensitivity - DTH): Antigen is introduced into the skin, phagocytosed by antigen-presenting cells (APCs), and presented to helper T cells. Memory TH1 cells release cytokines upon re-exposure, activating macrophages, which cause tissue damage. Examples include the Mantoux tuberculin skin test and contact dermatitis (e.g., latex allergy).
- CD4 TH2-Mediated: Inhaled soluble antigens lead to eosinophil recruitment, cytokine release, and chronic inflammation, seen in chronic asthma and allergic rhinitis.
- CD8 Cytotoxic T Lymphocyte (CTL)-Mediated: APCs present antigens with MHC I to CD8 T cells, which differentiate into CTLs. CTLs induce apoptosis in target cells, involved in transplant rejection and contact dermatitis (e.g., poison ivy). TH1 cells can enhance CTL activation. 15.2 Autoimmune Disorders: Autoimmune diseases occur when the immune system mistakenly attacks the body’s own cells due to a loss of immune tolerance. They involve type II, III, and IV hypersensitivity reactions and present with symptoms that can flare up and subside, making diagnosis challenging. The causes of autoimmunity are a mix of genetic and environmental factors, such as sunlight, infections, medications, and chemicals, though the exact triggers are not well understood. Regulatory T and B cells help maintain tolerance, but failures in these mechanisms can lead to autoimmunity. Antigen mimicry, hidden self-antigens exposed by trauma or disease, and cross-reactivity can also contribute. Tissue and organ damage result from inappropriate inflammatory responses, so treatments often include immunosuppressive drugs and corticosteroids. Organ-Specific Autoimmune Diseases : target specific tissues or organs, such as celiac disease, Graves' disease, Hashimoto thyroiditis, type 1 diabetes mellitus, and Addison disease. Celiac disease primarily affects the small intestine but can involve other organs. It results from an immune reaction to gluten proteins in wheat, barley, and rye. This triggers autoantibodies and inflammation, leading to villous atrophy, malabsorption, diarrhea, abdominal pain, weight loss, and anemia. Diagnosis involves serological tests for the presence of primarily IgA antibodies to components of gluten, the transglutinaminase enzyme, and autoantibodies to endomysium, a connective tissue surrounding muscle fibers. Serological tests are typically followed up with endoscopy and biopsy of the duodenal mucosa. Treatment requires strict gluten avoidance. Other theoretical approaches include breeding grains that do not contain the immunologically reactive components or developing dietary supplements that contain enzymes that break down the protein components that cause the immune response. Type 1 Diabetes : (juvenile diabetes) is a T-cell-dependent autoimmune disease that destroys pancreatic β cells, leading to insulin deficiency. It involves CD4 TH1-mediated CD8 T cells,
anti-β-cell antibodies, and macrophage activity. Symptoms include sudden onset of hyperglycemia, excessive thirst, frequent urination, weight loss, and fatigue. Viral infections may influence disease development. Autoimmune Addison Disease ( also called primary adrenal insufficiency (PAI ) : results from immune-mediated destruction of the adrenal glands, leading to impaired steroid hormone production. Symptoms include fatigue, weakness, nausea, weight loss, hyperpigmentation, electrolyte imbalances (hyperkalemia, hyponatremia), hypoglycemia, hypotension, anemia, and lymphocytosis. In extreme stress, adrenal crisis can cause vomiting, severe pain, and shock. Systemic Autoimmune Diseases: Unlike organ-specific autoimmune diseases, systemic autoimmune diseases affect multiple organs or tissues. Examples include multiple sclerosis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. Multiple Sclerosis (MS): MS is an autoimmune disease that affects the central nervous system (CNS), causing inflammation, demyelination, and neuron degeneration. Immune cells, including T cells, cross the blood-brain barrier, disrupting nerve signaling. Symptoms include vision problems, muscle weakness, balance issues, numbness, and cognitive impairment. Psoriasis: is a skin disease that causes red, scaly patches due to an accelerated cell turnover process. This is triggered by interactions between keratinocytes, dendritic cells, T cells, and cytokines. In psoriatic arthritis, joints also become inflamed. Rheumatoid Arthritis (RA) : is a chronic inflammatory joint disease caused by immune complex formation involving rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti- CCP) antibodies. CD4 T cells and inflammatory cytokines (IL-1, IL-6, TNF-α) contribute to joint damage. Diagnosis involves detecting RF, anti-CCP, C-reactive protein (CRP), and imaging studies to assess joint damage. Systemic Lupus Erythematosus (SLE): SLE is a type III hypersensitivity disorder characterized by widespread autoimmune activity against nuclear and cytoplasmic proteins. Autoantibodies, including anti-nuclear antibodies (ANAs), anti-dsDNA, and anti-Sm, cause immune complex deposition and inflammation. Symptoms vary but include fatigue, fever, joint pain, a characteristic butterfly-shaped rash, neurological issues, and kidney damage. Diagnosis requires identifying multiple symptoms and confirming autoantibody presence. 15.3 Organ Transplantation and Rejection: Cancer involves a loss of the ability of cells to control their cell cycle, the stages each eukaryotic cell goes through as it grows and then divides. These cells also lose the ability to differentiate into the correct cell type and may start growing on top of each other, forming tumors. Tumors can be benign (non-cancerous) or malignant (cancerous). Traditional cancer treatments, such as radiation and chemotherapy , destroy cancer cells but can also harm healthy cells. Cell-Mediated Response to Tumors: targets cancer cells, which often lack normal self- proteins , making them recognizable by the immune system. Some cancer cells present tumor
