CLASE TEÓRICA 7 - INMUNOPATOLOGÍA PARTE 1

Introduction to Immunopathology

Overview of Immunity

• The immune system is the body's defense mechanism against physical, chemical, and microbiological aggressions from the environment.

• Immunity can be categorized into two types: innate and acquired. Innate immunity is present at birth.

Components of Innate Immunity

• Innate immunity includes biological barriers such as various epithelial types, like ciliated respiratory epithelium that protects against specific noxious agents through cilia action.

• Mucous secretions in the digestive and respiratory tracts also provide protection against harmful agents.

• Phagocytosis is performed by specific blood and tissue cells, including macrophages and neutrophils, which utilize lytic enzymes for defense.

Acquired Immunity

Mechanisms of Acquired Immunity

• Acquired immunity relies on lymphoid cells produced in bone marrow that circulate to sites needing defense via B and T lymphocytes.

• Humoral immunity involves B lymphocytes differentiating into plasma cells that produce antibodies (immunoglobulins) in response to antigenic stimuli.

• Cellular immunity is primarily represented by T lymphocytes (CD4, CD8), natural killer cells, and monocytes transforming into macrophages at tissue levels.

Physical and Chemical Barriers

Role of Secretions in Defense

• Various glandular secretions contribute to non-specific natural immunity; examples include lysozymes from lacrimal glands and saliva from salivary glands.

• The skin acts as a keratinized stratified barrier preventing desiccation while protecting against external aggressors. Additionally, internal organ epithelia serve as chemical barriers through enzymatic actions (e.g., gastric enzymes).

Lymphoid Organs

Primary Lymphoid Organs

• Primary lymphoid organs include the thymus and bone marrow; these are crucial for humoral and cellular immunity development during childhood but undergo atrophy with age.

Secondary Lymphoid Organs

• Secondary organs consist of regional lymph nodes located throughout the body that facilitate immune responses through drainage systems for lymphatic fluid. Examples include tonsils in oropharyngeal regions and Peyer's patches in the intestines.

Histological Structure of Lymph Nodes

Composition of Lymph Nodes

• Histologically, lymph nodes are encapsulated structures containing arterial blood vessels, venous channels, afferent/efferent lymphatics facilitating drainage functions within their parenchyma regions consisting of cortical areas rich in B cell follicles (primary/secondary).

Functional Zones within Lymph Nodes

• The cortex contains germinal centers where B cells proliferate; surrounding areas host T cells along with dendritic reticular cells aiding phagocytic activity within medullary zones rich in vascular structures essential for immune function support.

This structured summary provides a comprehensive overview of key concepts discussed regarding immunopathology while ensuring easy navigation through timestamps linked directly to relevant sections for further exploration.

Immune Response Mechanisms

Role of Lymphocytes in Immune Response

• Lymphocyte functions differentiate through antigen-presenting cells, utilizing chemical mediators to activate B lymphocytes that produce antibodies (immunoglobulins) via plasma cells.

• Immunoglobulins (IgG, IgA, IgM, IgD, IgE) have specific molecular structures; for instance, secretory immunoglobulin has a J chain and IgG consists of heavy and light chains arranged in a pentameric form.

Antibody Production and Memory

• Initial contact with an antigen leads to increased serum levels of immunoglobulin antibodies, indicating acute infection or inflammation while the body develops immune defenses.

• Immunoglobulin E (IgE) is primarily elevated during allergic reactions and certain parasitic infestations; it is associated with respiratory and digestive epithelial tissues.

T Cell Activation in Hypersensitivity Reactions

• T cells participate in type 4 hypersensitivity reactions by being activated through antigen presentation by antigen-presenting cells, releasing interleukins that stimulate T cell proliferation.

• Activated T lymphocytes migrate to areas needing intervention against pathogens or allergens.

Classification of Hypersensitivity Reactions

• Kuns and Gel classify hypersensitivity into four types:

• Type 1: Anaphylactic

• Type 2: Cytotoxic

• Type 3: Immune complex-mediated

• Type 4: Delayed-type cellular response.

Mechanisms of Type I Hypersensitivity

• In type I hypersensitivity, rapid reactions occur in sensitized individuals when antigens bind to IgE antibodies on mast cells or basophils, leading to the release of histamine and other mediators.

• This can result in severe allergic responses such as bronchial asthma, allergic rhinitis, urticaria (hives), eczema, and potentially life-threatening anaphylaxis characterized by multi-organ failure.

Cytotoxic Reactions in Type II Hypersensitivity

• In type II hypersensitivity reactions, antibodies target antigens on cell surfaces leading to complement activation; this can cause tissue damage seen in conditions like hemolytic anemia or transfusion reactions.

Immune Complex-Mediated Damage in Type III Hypersensitivity

• In type III hypersensitivity reactions involving circulating immune complexes that activate complement pathways lead to increased phagocytosis by neutrophils causing tissue damage such as vasculitis or glomerulonephritis.

Cellular Responses in Type IV Hypersensitivity

• The delayed-type hypersensitivity reaction involves CD4+ and CD8+ T lymphocytes which release lymphokines stimulating macrophage migration for chronic inflammatory responses seen in diseases like tuberculosis.

Understanding Hypersensitivity Reactions and Autoimmunity

Types of Hypersensitivity Reactions

• Overview of Hypersensitivity: Discusses various types of hypersensitivity reactions, including allergic rhinitis, angioedema, and anaphylactic shock. Highlights the significance of type 2 hypersensitivity with examples like erythroblastosis fetalis.

• Mechanism in Erythroblastosis Fetalis: Explains how maternal antibodies against Rh-positive fetal red blood cells can lead to hemolysis and potential fetal death after a spontaneous abortion.

• Preventive Measures: Emphasizes the importance of serology in pregnant women to monitor antibody levels and administer gamma globulin to prevent adverse reactions between maternal and fetal blood.

• Type 3 Hypersensitivity Mechanism: Describes how immune complexes formed by antigens and antibodies activate complement systems, leading to vasculitis and organ damage due to increased vascular permeability.

• Type 4 Hypersensitivity Overview: Introduces delayed-type hypersensitivity mediated by T-cells, where antigen-presenting cells activate T-helper cells that release cytokines, promoting chronic inflammation.

Autoimmune Diseases

• Chronic Inflammation in Autoimmunity: Details how autoimmune diseases arise from the immune system's failure to recognize self-tissues as non-threatening, leading to chronic granulomatous inflammation characterized by modified macrophages.

• Loss of Self-Tolerance: Discusses factors contributing to autoimmunity such as genetic predisposition, environmental triggers (like drugs or infections), and cross-reactivity with foreign antigens.

• Role of B Cells in Autoimmunity: Highlights the activation of B cells resulting in excessive production of autoantibodies that target the body's own tissues.

• Types of Autoimmune Disorders: Differentiates between organ-specific autoimmune diseases (e.g., Hashimoto's thyroiditis) versus systemic conditions (e.g., systemic lupus erythematosus).

Systemic Lupus Erythematosus (SLE)

• Characteristics of SLE: Identifies SLE as a prototype systemic autoimmune disease affecting multiple organs such as kidneys, skin, joints, and heart.

• Impact on Quality of Life: Notes that SLE predominantly affects women during reproductive years, significantly impacting their quality of life and increasing mortality risk at younger ages.

• Autoantibody Production in SLE: Describes the formation of autoantibodies against DNA, RNA, histones which contribute to tissue damage through immune complex deposition.

• Clinical Manifestations Related to SLE: Discusses complications like anemia due to red blood cell destruction (hemolytic anemia), leukopenia increasing infection risk, and thrombocytopenia affecting coagulation processes.

Pathophysiology of Lupus and Associated Complications

Vascular and Tissue Damage

• The transcript discusses the injury to capillary walls, characterized by rigid thickening due to immune complex deposits, leading to thrombus formation that occludes capillary lumens, resulting in ischemic phenomena and necrosis.

Inflammatory Responses

• Lymphocytes mediate inflammatory responses at various tissue levels, including skin degeneration with hydropic changes in the epidermal basal layer, lymphocyte accumulation, and vasculitis with fibrinoid necrosis observed in joints.

Cardiac Implications

• Endocarditis is highlighted as a significant concern, marked by small vegetations attached to heart valves (particularly the aorta and mitral valve), alongside splenomegaly and associated vasculitis phenomena affecting multiple organs.

Pulmonary Complications

• The presence of diffuse alveolitis leads to chronic restrictive pulmonary disease and pulmonary hypertension; severe cases may result in diffuse intrapulmonary hemorrhage.

Diagnostic Criteria for Lupus