Assessment of immune function Management of patients with immunodeficiency disorders

Disorders of Immune System Defenses against infection Immune system disorders Autoimmune diseases Immunodeficiency

Defenses Against Infection Barriers (non-specific) Skin Mechanical removal (coughing, vomiting, diarrhea, skin sloughing) Normal flora Antimicrobial secretions Inflammation (non-specific) Immunity (specific)

Immune Response Natural vs. Acquired Active vs. Passive Primary vs. Secondary Humoral vs. Cell-Mediated

Humoral Immunity B Lymphocytes (Plasma Cells) Produced in bone marrow Make antibodies (immunoglobulins)

Antibodies Protein molecules produced by B-cells Specific shapes allow binding to specific molecules (antigens) Allow body to respond defensively to presence of specific potential threats

Antibody Types IgG IgM IgA IgD IgE

IgG Most common antibody type Only antibody that crosses placenta Prime mediator of secondary immune response Principal defender against bacteria, viruses, and toxins

IgM Macroglobulin Confined to bloodstream First antibody to appear in response to presence of antigen Agent of primary immune response

IgA Secretory antibody Found in saliva, tears, respiratory secretions, GI tract secretions Frontline bacterial, viral defense

IgD Role not fully understood Low serum levels High concentrations on B-cells May act as receptors that trigger production of other antibodies

IgE Very low serum levels Primarily bound to mast cells in tissues Controls allergic response Prevents parasitic infections

Antigen-antibody binding initiates reactions that: Neutralize bacterial toxins Neutralize viruses Promote phagocytosis Activate components of inflammatory response

Cell-Mediated Immunity T Lymphocytes Originate in bone marrow Altered by passage through thymus Responsible for mediation of cellular immunity

T Lymphocyte Types Helper cells (T4 cells) Cytotoxic cells (Killer T cells) Suppressor cells Memory cells

Helper T-Cells Master “on-switch” of immune system Recognize antigens Secrete lymphokines that activate all other immune system cells Stimulate B-cells to begin antibody production

Cytotoxic (Killer) T-Cells Respond to presence of antigens and lymphokines produced by T-4 cells Seek out, bind to, and destroy: Cells infected by viruses Some tumor cells Cells of tissue transplants Can deliver lethal hits on multiple cells in sequence

Suppressor T-Cells Produce lymphokines that inhibit proliferation of B and T cells Downregulate or dampen immune response

Memory T-Cells Have previously encountered specific antigens Respond in enhanced fashion on subsequent exposures Induce secondary immune response

Inflammation Occurs in vascularized tissue Nonspecific response to injury Response is same regardless of agent that initiates it

Inflammation: Physiology Triggered by cellular injury Injury activates mast cells Mast cells release chemical mediators: Histamine Heparin Leukotrienes (SRS-A) Eosinophil chemotactic factor

Inflammation: Pathology Mediators cause: Vasodilation (redness, heat) Vascular permeability (swelling) White cell movement to and infiltration of affected area (pus) Nerve ending stimulation (pain) “Dolor, Calor, Tumor, Rubor”

Inflammation: Purposes Confines injurious agents Increases blood cell, plasma movement to injured areas Enhances immune response Destroys injurious agents Promotes healing

Inflammation: Cellular Components Neutrophils Phagocytic cells Engulf foreign material/organisms Arrive early Short-lived

Inflammation: Cellular Components Macrophages Phagocytic cells Engulf foreign material/organisms Arrive later Long-lived Transfer antigens back to T4 cells Help initiate immune response to specific agents

Inflammation: Cellular Components Eosinophils Secrete caustic proteins Dissolve surface membranes of parasites

Disorders of Immunity

Autoimmune Disease Clinical disorder produced by an immune response to a normal tissue component of a patient’s body

Autoimmune Diseases Hyperthyroidism Primary myxedema Type I diabetes Addison’s disease Multiple sclerosis Myasthenia gravis

Autoimmune Diseases Rheumatic fever Crohn’s disease Ulcerative colitis Rheumatoid arthritis Systemic lupus erythematosis

Systemic Lupus Erythematosis Primarily occurs in 20- to 40-year old females Also in children and older adults 90% of patients are female Autoimmune reaction to host DNA Mortality after diagnosis averages 5% per year

Systemic Lupus Erythematosis Signs/Symptoms Facial rash/skin rash triggered by sunlight exposure Oral/nasopharyngeal ulcers Fever Arthritis

Systemic Lupus Erythematosis Signs/Symptoms Serositis (pleurisy, pericarditis) Renal injury/failure CNS involvement with seizures/psychosis Peripheral vasculitis/gangrene Hemolytic anemia

Systemic Lupus Erythematosis Chronic management Anti-inflammatory drugs Aspirin Ibuprofen Corticosteroids Avoidance of emotional stress, physical fatigue, excessive sun exposure

Immunodeficiency Diseases Disorders of Immunity Immunodeficiency Diseases

Immunodeficiency Diseases Congenital Acquired

Immunodeficiency Diseases: Congenital B cell deficiency Agammaglobulinemia Hypogammaglobulinemia

Immunodeficiency Diseases: Congenital T cell deficiency IgA deficiency Severe combined immune deficiency syndrome (B and T cell deficiency)

Immunodeficiency Diseases: Acquired Nutritional deficiency Iatrogenic (drugs, radiation) Trauma (prolonged hypoperfusion) Stress Infection (AIDS)