Disorders of the Immune System

Disorders of the Immune System

Disorders of the Immune System

Normal Immune System Structure and Function

  • Function of immune system is to protect the host from invasion of foreign organisms by distinguishing “self” from “non-self.”
  • Necessary for survival
  • Prevents and repels attacks from external factors and endogenous factors
  • Normal immune response relies on careful coordination of complex network or biological factors, specialized cells, tissue, and organs necessary for recognition of pathogens and subsequent elimination of foreign antigens

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Anatomy of the Cells of the Immune System

  • Consists of both antigen-specific and nonspecific components
  • Major cellular components of the immune system consist of monocytes and macrophages, lymphocytes, and the family of granulocytic cells (including neutrophils, eosinophils, and basophils).
  • Mononuclear phagocytes participate in antigen processing, tissue repair, and secretion of mediators vital to initiation of specific immune responses
  • Lymphocytes are responsible for the initial specific recognition of antigen
  • Cytotoxic or “killer” T cells (CTLs) are responsible for defense against intracellular pathogens
  • Neutrophils phagocytose and destroy foreign antigens and microbial organisms
  • Eosinophils play a crucial role in the host’s defense against parasites; considerably less efficient than neutrophils at phagocytosis
  • Basophils play an important role in both immediate- and late-phase allergic responses
  • Mast cells are basophilic straining cells; source of many mediators of immediate hypersensitivity

Organs of the Immune System

  • Bone marrow is where all cells of the immune system are originally derived
  • Thymus functions to produce T lymphocytes and is the site of initial T-lymphocyte differentiation
  • In mammals, the lymph nodes, spleen, and gut-associated lymphoid tissue are secondary lymphoid organs connected by blood and lymphatic vessels

Inflammatory Mediators

  • Preformed mediators include histamine, eosinophil and neutrophil chemoattractants, proteoglycans (heparin, chondroitin sulfate) and various proteolytic enzymes.
  • Histamine is a bioactive amine; important in the pathogensis of allergic rhinitis, allergic asthma, and anaphylaxis

Physiology

  • Innate and adaptive immunity
  • Living organisms exhibit two levels of response: innate system of natural immunity and an adaptive system that is acquired
  • Antigens (or immunogens)
  • Foreign substances that can induce an immune response
  • Immune Response
  • A complex network of specialized cells, organs, and biologic factors is necessary for the recognition and subsequent elimination of foreign antigens
  • Antigen Processing & Presentation
  • Most foreign immunogens are not recognized by the immune system in their native form and require capture and processing by professional APCs
  • T-Lymphocyte Recognition & Activation
  • The recognition of processed antigen by specialized T lymphocytes known as helper T (CD4) lymphocytes and the subsequent activation of these cells constitute the critical events in the immune response.
  • CD8 Effector Cells (Cellular Immune Response)
  • CTLs eliminate target cells thus constituting the cellular immune response
  • Activation of B Lymphocytes (Humoral Immune Response)
  • Primary function of mature B lymphocytes is to synthesize antibodies
  • Antibody Structure & Function
  • Five classes (isotypes) of immunoglobulins are IgG, IgA, IgM, IgD, and IgE
  • Humoral Mechanisms of Antigen Elimination
  • Antibodies induce elimination of foreign antigen through a number of different mechanisms.
  • Mechanisms of Inflammation
  • Cytokines and antibodies trigger the recruitment of additional cells and the release of endogenous vasoactive and proinflammatory enzymatic substances.
  • Hypersensitivity Immunes Responses
  • Classified into four distinct types of reactions
  • Synthesis of IgE in Allergic Reactivity
  • Allergic hypersensitivity results from the inappropriate and sustained production of IgE in response to allergen.

Pathophysiology of Allergic Rhinitis

  • Characterized by local tissue damage and organ dysfunction in the upper and lower respiratory tract arising from an abnormal hypersensitivity immune response to normally harmless and ubiquitous environmental allergens
  • Allergens that cause airway disease are predominantly seasonal tree, grass, and weed pollens or perennial inhalants (house dust mite antigen, cockroach, mold, animal dander)
  • Implies the existence of type I (IgE-mediated) immediate hypersensitivity to environmental allergens that impact the upper respiratory mucosa directly

Allergic Rhinitis

  • The interaction of mediators with various target organs and cells of the airway can induce a biphasic allergic response.
  • The early-phase response occurs within minutes after exposure to an antigen; after intranasal challenge or ambient exposure to relevant allergen, the allergic patient begins sneezing and develops an increase in nasal secretions.
  • The late-phase allergic response may follow the early-phase response or may occur as an isolated event; late-phase response is characterized by erythema, induration, heat, burning, and itching.
  • Symptoms appear immediately after exposure to a relevant allergen (early-phase response), although many patients experience chronic and recurrent symptoms on the basis of the late-phase inflammatory response.
  • Complications of severe or untreated allergic rhinitis include sinusitis, auditory tube dysfunction, hyposmia, sleep disturbances, asthma exacerbations, and chronic mouth breathing.

Disorders of the Immune System