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)