Porth Chapter 15 Flashcards
Classification of Immunodeficiency States: Primary
(congenital or inherited)
Classification of Immunodeficiency States: Secondary
(acquired later in life)
Malnutrition
Infection (e.g., acquired immunodeficiency syndrome [AIDS])
Neoplastic disease (e.g., lymphoma)
Immunosuppressive therapy (e.g., corticosteroids or transplant rejection medications)
Results of Alterations of the Immune System
Immunodeficiency states
Allergic or hypersensitivity reactions
Transplantation rejection
Autoimmune disorders
Four Major Categories of Immune Mechanisms
Humoral or antibody-mediated immunity (B lymphocytes)
Cell-mediated immunity (T lymphocytes)
The complement system
Phagocytosis (neutrophils and macrophages)
Humoral Immunodeficiencies
B-cell function and immunoglobulin or antibody production are involved.
Defects in humoral immunity increase the risk of recurrent pyrogenic infections.
Humoral immunity usually is not as important in defending against intracellular bacteria (mycobacteria), fungi, and protozoa.
Viruses are usually handled normally, except for the enteroviruses that cause gastrointestinal infections.
Primary Humoral Immunodeficiency Disorders
Genetic disorders of the B lymphocytes
Approximately 70% of primary immunodeficiencies
Immunoglobulin production depends on the following:
The differentiation of stem cells to mature B lymphocytes
The generation of immunoglobulin-producing plasma cells
Can interrupt the production of one or all of the immunoglobulins
Combined T-Cell and B-Cell Immunodeficiencies
Severe combined immunodeficiency
X-linked SCIDs
Ataxia–telangiectasia
Wiskott-Aldrich syndrome
Disorders of the Complement System
Primary
Most inherited as autosomal recessive traits and can involve one or more complement components
Secondary
Can occur in persons with functionally normal complement systems because of rapid activation and turnover or reduced synthesis of complement components
Hereditary angioneurotic edema and loss of regulation
The Phagocytic System
Definition: composed primarily of polymorphonuclear leukocytes and mononuclear phagocytes
Action of these cells:
Migrate to the site of infection
Aggregate around the affected tissue
Envelope the invading microorganisms
Generate microbicidal substances to kill the ingested pathogens
Dysfunction of the Phagocytic System
A defect in phagocytic functions or a reduction in the absolute number of available cells disrupts the system.
Susceptible to
Candida species.
filamentous fungi.
Chronic granulomatous disease (CGD)
Adaptive Immunity
Development of response to the antigen
Specific humoral and cellular recognition
Memory cells
Hypersensitivity Disorders
Definition
Excessive or inappropriate activation of the immune system
Types
Type I, IgE-mediated disorders
Type II, antibody-mediated disorders
Type III, complement-mediated immune disorders
Type IV, T-cell–mediated disorders
Types of IgE-Mediated Allergic Reactions
Atopic Disorders
Heredity predisposition and production of a local reaction to IgE antibodies produced in response to common environmental agents
Urticaria (hives), allergic rhinitis (hay fever), atopic dermatitis, food allergies, some forms of asthma
Nonatopic Disorders
Lack the genetic component and organ specificity of the atopic disorders
Phases of Type I Hypersensitivity Reactions
Primary or Initial-phase Response
Vasodilation
Vascular leakage
Smooth muscle contraction
Secondary or Late-phase Response
More intense infiltration of tissues with eosinophils and other acute and chronic inflammatory cells
Tissue destruction in the form of epithelial cell damage
Type II (Cytotoxic) Hypersensitivity Reactions
Action
Mediated by IgG or IgM antibodies directed against target antigens on the surface of cells or other tissue components
Endogenous antigens: present on the membranes of body cells
Exogenous antigens: absorbed on the membrane surface
Examples
Mismatched blood transfusion reactions
Hemolytic disease of the newborn
Certain drug reactions
Type III, Immune Complex Allergic Disorders
Mediated by the formation of insoluble antigen–antibody complexes that activate the complement pathway
Activation of the complement pathway by the immune complex generates chemotactic and vasoactive mediators that cause tissue damage by
alterations in blood flow.
increased vascular permeability.
destructive action of inflammatory cells.
Immune complexes formed in the circulation produce damage when in contact with the vessel lining or are deposited in tissues.
They elicit an inflammatory response by activating the complement pathway.
Leading to chemotactic recruitment of neutrophils and other inflammatory cells
Responsible for the vasculitis seen in certain autoimmune diseases
Systemic immune complex disorders
Serum sickness
Localized immune complex reactions
Arthus reaction
Type IV Hypersensitivity Reactions
Cell-Mediated Immune Response
The principal mechanism of response to a variety of microorganisms, including intracellular pathogens and extracellular agents
Can lead to cell death and tissue injury in response to chemical antigens or self-antigens
Basic Types
Direct cell-mediated cytoxicity
Hepatitis
Delayed-type hypersensitivity
Allergic contact dermatitis
Hypersensitivity pneumonitis
Routes of Exposure to Latex
Cutaneous
Mucous membrane
Most severe reactions resulted from contact with the mouth, vagina, urethra, or rectum
Inhalation
Internal tissue
Intravascular routes
Reaction types
Type I versus type IV
Histocompatibility Complex
Major histocompatibility complex
Set of molecules displayed on cell surfaces
Lymphocyte recognition
Antigen presentation
Controls the immune response through recognition of “self” and “nonself”
Allogeneic
The donor and recipient are related or unrelated but share similar HLA types.
Syngeneic
The donor and recipient are identical twins.
Autologous
The donor and recipient are the same person.
Stem Cell Transplantation
Many primary immunodeficiency disorders traced to deficiency in stem cells can be cured with allogeneic stem cell transplantation from an unaffected donor.
SCIDs, Wiskott-Aldrich syndrome, and chronic granulomatous disease
Stem cells can repopulate the bone marrow and reestablish hematopoiesis.
To be effective, the bone marrow cells of the host are destroyed by myeloablative doses of chemotherapy.
Mechanisms Postulated to Explain the Tolerant State
Self-tolerance
Central tolerance
The elimination of self-reactive T cells and B cells in the central lymphoid organs (i.e., the thymus for T cells and the bone marrow for B cells)
Peripheral tolerance
Derives from the deletion or inactivation of autoreactive T cells or B cells that escaped elimination in the central lymphoid organs
Hyperacute Reaction
Occurs almost immediately after transplantation.
Produced by existing recipient antibodies to graft antigens initiating a type III, Arthus-type hypersensitivity reaction
Acute Rejection
Occurs within first few months after transplantation with signs of organ failure; may occur months or years after immunosuppression has been terminated
T lymphocytes respond to antigens in the graft tissue
Chronic Host-Versus-Graft Rejection
Occurs over a prolonged period
Manifests with dense intimal fibrosis of blood vessels of the transplanted organ
The actual mechanism is unclear but may include release of cytokines that stimulate fibrosis.
Basic Requirements Necessary for GVHD
The transplant must have a functional cellular immune component.
The recipient tissue must bear antigens foreign to the donor tissue.
The recipient immunity must be compromised to the point that it cannot destroy the transplanted cells.
Autoimmune Diseases
Systemic lupus erythematosus (SLE)
Autoimmune hemolytic anemia (AIHA)
Pemphigus vulgaris
Hashimoto thyroiditis
Mechanisms of Autoimmune Disease
Heredity and gender
Failure of self-tolerance
Disorders in MHC–antigen complex/receptor interactions
Molecular mimicry
Superantigens
Criteria for Determining an Autoimmune Disorder
Evidence of an autoimmune reaction
Determination that the immunologic findings are not secondary to another condition
The lack of other identified causes for the disorder
