Alterations in Immune Function

Alterations in Immune Function

Immune System

• Defends the body against invasion or infection by antigens.
• Patrols for and destroys abnormal or damaged cells.

Immune System Disorders

• Excessive immune responses.
• Deficient immune responses.

Overview of the Immune System

The immune system consists of various organs, tissues, and cells located throughout the body, including:

• Tonsils
• Lymph Nodes
• Thymus
• Spleen
• Peyer's Patches
• Lymph Vessels
• Bone Marrow

White Blood Cells (WBCs)

• Made inside bone marrow.
• Travel through the body inside lymph vessels, which are in close contact with the bloodstream.

Types of WBCs:

• Neutrophils: Engulf and destroy.
• Monocytes (Macrophages): Engulf and destroy.
• Eosinophils: Fight parasitic infections.
• Basophils: Release histamine.
• Lymphocytes: Attack specific pathogens. Plasma cells produce antibodies.

Levels of Defense

Barriers

• Prevent entry.
• Examples:
  • Skin and mucous membranes.
  • Stomach acid and digestive enzymes.
  • Beneficial bacteria that live in the colon (the gut microbiota).

Innate Immunity

• General defense.
• WBCs (neutrophils and macrophages) engulf and destroy foreign invaders and damaged cells.

Acquired Immunity

• Specific defense.
• T lymphocytes (T cells): Target and destroy infected or cancerous cells.
• B lymphocytes (B cells) and plasma cells: Produce antibodies that target and destroy infected or cancerous cells.

Excessive Immune Responses

• Increase in immune system activity.

Types:

• Autoimmunity: Immune system attacks own tissues; failure of self-tolerance.
• Hypersensitivity: Describes the mechanism of injury; may or may not involve autoimmunity.

Autoimmunity

• Autoimmune disorders occur when the immune system erroneously reacts with “self” tissues.
• Thought to be polygenic and multifactorial, but the exact etiologic process is unknown.

Theories

• Antigenic mimicry.
• Sequestered antigens.
• Abnormal production of subclasses of T lymphocytes.
• Development of abnormal B cells that do not respond to suppressor T-cell signals.

Factors

• Genetic factors: Female gender, Major histocompatibility complex (MHC) genes.
• Environmental triggers: Chronic or multiple viral or bacterial infections.
• A variety of noninfectious environmental factors have been associated with autoimmunity; environmental stress and occupational stress.
• Autoantibodies injure body tissues through the mechanisms described for type II and type III hypersensitivity reactions.

Pharmacotherapies

• Immunosuppressive therapy:
  • Immunosuppressive agents: corticosteroids, biological agents, immunomodulators, and cytotoxins.
  • Purine analogs.
  • Therapeutic plasmapheresis.
  • Intravenous immunoglobulin (IVIg).

Hypersensitivity

• Normal immune response that is either inappropriately triggered or excessive, producing undesirable effects on the body.

Four Types

• Types I, II, and III are mediated by antibodies.
• Type IV is T cell–mediated.
• Hypersensitivity reactions are specific to a particular antigen.

Type I

• IgE-Mediated Hypersensitivity
• IgE is bound to mast cells via its Fc portion. When an allergen binds to these antibodies, crosslinking of IgE induces degranulation.
• Causes localized and systemic anaphylaxis, seasonal allergies including hay fever, food allergies such as those to shellfish and peanuts, hives, and eczema

Type II

• IgG-Mediated Cytotoxic Hypersensitivity
• Cells are destroyed by bound antibody, either by activation of complement or by a cytotoxic T cell with an Fc receptor for the antibody (ADCC)
• Red blood cells destroyed by complement and antibody during a transfusion of mismatched blood type or during erythroblastosis fetalis

Type III

• Immune Complex-Mediated Hypersensitivity
• Antigen-antibody complexes are deposited in tissues, causing activation of complement, which attracts neutrophils to the site
• Most common forms of immune complex disease are seen in glomerulonephritis, rheumatoid arthritis, and systemic lupus erythematosus

Type IV

• Cell-Mediated Hypersensitivity
• Th1 cells secrete cytokines, which activate macrophages and cytotoxic T cells and can cause macrophage accumulation at the site
• Most common forms are contact dermatitis, tuberculin reaction, autoimmune diseases such as diabetes mellitus type I, multiple sclerosis, and rheumatoid arthritis

Type I hypersensitivity

• Mediated by IgE
• Etiology, Pathophysiology, Clinical Manifestations: Massive histamine release from mast cells (primary effector cell) leads to vasodilation = dramatic hypotension.
• Treatment, Prevention, Pharmacotherapeutic prevention

Type II hypersensitivity

• Etiology and pathogenesis
• Transfusion reaction: RBC destruction due to recipient antibodies.
• Hemolytic disease of the newborn: Rh Negative Mother.
• Myasthenia gravis: Autoimmune of the NMJ.
• Hyperacute graft rejection: Due to cytotoxic T cells present in recipient.

Type IIb hypersensitivity

• Myasthenia Gravis (MG)

Type III hypersensitivity

• Etiology and Pathogenesis
• Tissue deposition
• Immune complex glomerulonephritis, Systemic lupus erythematosus

Type IV hypersensitivity

• Type IVa—Ggranulomatous hypersensitivity
• Type IVa—Tuberculin-type hypersensitivity (no antibody production)
• Type IVa—Allergic contact dermatitis
• Type IVb—Persistent asthma
• Type IVc—Stevens–Johnson syndrome and toxic epidermal necrolysis
• Type IVd—Pustular psoriasis

Deficient Immune Responses

• Result from a functional decrease in one or more components of the immune system.

Two Types

• Primary: Congenital; predisposed to multiple deficiencies.
• Secondary: Non-immune system disorders; treatments that secondarily affect immune function.

Primary Immunodeficiency Disorders

B- and T-cell combined disorders

• Severe Combined immunodeficiency disorders
  • First identified due to recurrent infections
  • Etiology and pathogenesis, Clinical manifestations and treatment
• Wiskott–Aldrich Syndrome
  • Etiology and pathogenesis, Clinical manifestations and treatment

T-cell disorders

• 22q11.2 Deletion syndrome (DiGeorge syndrome)
  • Etiology and pathogenesis, Clinical manifestations and treatment
• Chronic mucocutaneous candidiasis disease
  • Etiology and pathogenesis, Clinical manifestations and treatment

B-cell disorders

• IgA Deficiency
  • Etiology and pathogenesis, Clinical manifestations and treatment
• X-Linked Agammaglobulinemia
  • Etiology and pathogenesis, Clinical manifestations and treatment
• Transient hypogammaglobulinemia, Common variable immunodeficiency disease
  • Clinical manifestations and treatment

Secondary Immunodeficiency Disorders

• Cause: problems in neuroendocrine and immune system interactions
• Excessive neuroendocrine response to stress with increased corticosteroid production increases susceptibility to infection.
• Medications: Cytotoxins and other cancer pharmacotherapeutic drugs
• Anesthetics, alcohol, antibiotics, and steroids, also affect the immune response