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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
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)