LEUKOCYTE/ IMMUNE SYSTEM DISORDERS

VARIATIONS IN IMMUNE FUNCTION

Fetal and Neonatal Immune Function Antibody, phagocytic and complement

functions deficient at birth. Maternal antibodies are protective 5- 6 months

Immune Function in Elderly Diminished T cell and antibody response Increased auto antibodies

Factors Affecting System

Stress Nutrition Drugs Other diseases

• renal failure

• malignancy

• diabetes mellitus

• systemic infections

HYPERSENSITIVITY DISORDERS

Type I Immediate—IgE mediated Type II Sub-Acute—IgG or IgM Type III Sub-Acute—IgG or IgM Type IV—Delayed –T Cell mediated

Type I Hypersensitivity

Allergies, anaphylaxis, anaphylactic shock anaphylactoid reactions

Occurs in seconds to minutes IgE normally binds to surface of basophils

and mast cells Concentrates in lining of respiratory and GI

tracts, skin

Fig 8-1

Fig 8-1 continued

Type I Hypersensitivity

Offending antigen enters body—ingestion, injection, inhalation

• Peanuts, walnuts, latex

• Any insect venom (bee stings)

When appropriate antigen binds to 2 IgE molecules, they cross link

• Histamine, leukotrienes, interleukins, kinins released

Type I Hypersensitivity

Get contraction smooth muscle, increased permeability of vessel walls

Fluid leaks into interstitial space, smooth muscle in respiratory and GI tracts spasms

Angioedema, esp of face, hands, feet Vessels not damaged

If this is local, irritating but not likely to be fatal

Signs of Anaphylaxis begin within seconds to minutes

Body wide reaction to ingested, inhaled, injected ag Acute systemic reaction due to IgE release

Urticaria Itching, laryngeal edema, angioedema Bronchospasm—may die from anoxia Hypotension—may die from hypotensive shock GI and UG cramping (least common)

Administer epinephrine, establish airway, give antihistamines and glucocorticoids

Atopy-chronic, inherited disorder

IgE at mucosal surfaces reacts with normally innocuous compounds

• Pollen, animal dander, certain types of foods

Reaction is localized to surface stimulated Multiple manifestations

Associated with increased incidence of allergic rhinitis and asthma

Atopic eczema (atopic dermatitis)

Associated with allergic rhinitis or asthma T helper 2 cells overproduce IL 31

(believed to be underlying problem) Weeping, eroded, red, scaly patches of skin

• scalp, face, and diaper area most often affected

• exacerbated by weather changes, drying from XS soap and water

• severe itching2º bacterial infection

Atopic eczema

Atopic eczema (atopic dermatitis)

May spontaneously disappear as child ages Other allergies commonly appear Areas of knee, elbow, neck, etc. involved if continues Points of flexion/extension

May spread over entire body in adults—remission rare

Treat with dietary restrictions (infants), moisturizers, antihistamines

Antibiotics for skin infections Topical steroids/T cell modulators as needed

Allergic rhinitis—nasal allergy

Seen more in developed nations with high standards of cleanliness

less exposure to pathogens and more exposure to chronic irritants

Less development of the suppressor (regulatory)) T cells

May predispose person to developing asthma

Allergic Rhinitis--S&S

Stuffy, runny nose; red, weepy eyes; itching of eyes and nose

Dark circles under eyes, chronic sinusitis may develop

May report ringing in ears or sensation of pressure in ear

Eosinophils in nasal secretion distinguishes from infection

Subsets of allergies

Seasonal form (hay fever)—pollen, mold Perennial allergies—more likely dust mites,

animal dander

Cytotoxic (Type II) and Immune Complex (Type III) Diseases

Type II involves antibodies binding cells—tissue specific reaction—rapid

Type III involves antibodies binding soluble proteins—serum sickness

• Develops 7-10 days after antigen is introduced• Urticaria, angioedema, fever, generalized

lymphadenopathy• Activation of complement as complexes precipitate in

capillaries• Joint pain, renal dysfunction, GI problems

Fig 8.4

Type III Figure 8-5

Type IV Hypersensitivity—48-72 hours

Allergic Contact Eczema—delayed hypersensitivity T lymphocytes Poison ivy, nickel allergies

Weeping, red, puritic vesicles at site of contact

Localized edema initially, thickening of skin if contact continues avoid offender, steroids as needed

Contact dermatitis Fig 8-7

Type IV

Fig 8-6

AUTOIMMUNE DISORDERS

#3 cause of death in the US

AI Disorders -- general

Immune system must tolerate normal antigens by removing all T and B cells that would react with self proteins

AI diseases occur when the immune system starts to attack the cell of the body—break in tolerance

• Occur more frequently in females than males• Precise cause unknown—believe that foreign antigen

resembles a self antigen• Several are associated with HLA antigens--see T 8-5• Presence of one increases risk of others

Relapse and remission common• Seem to get worse when stressed

Immune system removes foreign compound first• Continued surveillance sees normal cell proteins presented by

MHC I molecules as foreign, and attacks those cells

• System eventually turns on to normal proteins

Some suggestion that may start if inflammation accompanies apoptosis reaction

AI diseases be cytotoxic T cell mediated or antigen-antibody reaction or both

Organ specific AI diseases

Damage is limited to one organ/tissue

Rest of the body suffers as a result of damage done to that organ/tissue

Examples

Idiopathic thrombocytopenic purpura Autoimmune hemolytic anemia Type I Diabetes Mellitus Autoimmune thyroiditis Addison’s Disease Celiac Disease

Multiple organ system AI diseases

Most of these involve antibodies that react with the body’s connective

tissue

Examples

Rheumatoid arthritis Systemic Lupus Erythematosis (SLE) Scleroderma

Rheumatoid arthritis

In women 2.5X as often as in men, peak incidence 40-60 years; 1% all adults

Seems to have some association with HLA-DR4 (Minor HC) antigens (varies with ethnic group)

Production of multiple destructive enzymes: collagenase, protease

Attacks synovial membranes Produces granulation tissue that extends into joints-

pannus Destruction of cartilage, ligaments, tendons, bones

Signs & Symptoms

Fever, fatigue, malaise Swollen, painful joints; often bilateral

Hands, knees, feet

Morning stiffness that lasts > 1 hour Deformed joints as cartilage is destroyed

Juvenile rheumatoid arthritis

Systemic onset—boys and girls equally—20% poorest prognosis Multiple organs, any age

Polyarticular onset—girls 2X as often as boys—40% 5 or more joints, and age Little involvement outside joints

Pauciarticular onset—girls 6X as often as boys—40% best prognosis Max of 4 joints, typically < 6 yrs old

Signs and symptoms of JRA

Fatigue, anorexia, weight loss, fever Shifting, symmetrical polyarthritis; any

diarthrotic joint is possible Morning stiffness of joints > 1 hour Erosive arthritis seen on X rays, followed

by deformity

Both age groups

Rheumatoid nodules, usually indicates active or severe disease

Damage to other organs—heart, lungs, eyes, blood vessels

Normocytic, normochromic anemia if bone marrow is involved

Turbid, non-viscous synovial fluid with high WBC count

Increased T cell activity causes increased TNF, which causes increased osteoclast activity

Rheumatoid factor in 85 % of pts

IgM that reacts with altered human IgG Anti-gamma globulin factor Complexes ppt onto joint tissue, stim immune

reaction May show up in other AI connective tissue

diseases Seen in 5-20% of normal people

Increased incidence as get older

Systemic lupus erythematosis

Signs and symptoms are diverse, easily missed in early stages

Butterfly rash across face is classic sign (40% of cases) AB form vs nucleic acids (anti-nuclear

antibodies) RBC, WBC, platelets, coagulation proteins, etc, Mild to rapidly fatal

In US: incidence in Fe 10x M Incidence in Black Fe 8x White Fe

Signs and symptoms of SLE

Symmetric arthritis or joint pain (90%)—not erosive or deforming

Fever, fatigue, weakness (50% have mild anemia), weight loss, possibly severe hair loss

Vasculitis (80%) with butterfly rash that gets worse if exposed to sunlight

Pleurisy chest pain; myocarditis, pericarditis Anemia or other marrow deficiencies

Renal complications

Antinuclear antibodies attach to DNA, deposit in glomerulus

Complement attaches to immune complex, renal inflammation begins

65% of SLE pts develop glomerulonephritis 40% have clinical renal disease 25% have severe renal damage (renal failure)

CNS complications usually fatal Diagnose with + antinuclear antibody test

Scleroderma

Now called Progressive Systemic Sclerosis Usually starts in 20‘s-40’s, least common of

diseases mentioned here Disease is overproduction of collagen, may be

localized or systemic Slow, progressive fibrosis of skin and other organs Proliferation of collagen in walls of blood vessels—lose

elasticity

Localized scleroderma—restricted to skin

May occur as result of repeated exposure to some chemicals

Milder, better prognosis

Generalized scleroderma

Limited cutaneous systemic sclerosis (Raynaud’s phenomenon)

• Vasospasm when extremities are exposed to cold

• Digits become white, then blue, then red in each attack

• Thickening and tightening of skinsausage appearance

Diffuse cutaneous—CT of skin and viscera, rapid progression

Progression of Scleroderma

Gradually spreads up limbs, involves trunk, face Very taut face, wrinkled mouth, smooth forehead Arthritis, joint pain and stiffness common Esophageal dysfunction, GI dysfunction Decreased pulmonary volumes Renal vessels damaged—proteinuria, hematuria,

hypertension Renal failure is leading cause of death for

generalized scleroderma