LEUKOCYTE/ IMMUNE SYSTEM
DISORDERS
VARIATIONS IN IMMUNE
FUNCTION
Fetal and Neonatal Immune Function
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Antibody, phagocytic and complement
functions deficient at birth.
Maternal antibodies are protective 5- 6 months
Immune Function in Elderly
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Diminished T cell and antibody response
Increased auto antibodies
Factors Affecting System
Stress
Nutrition
Drugs
Other diseases
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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
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anaphylactoid reactions
Occurs in seconds to minutes
 IgE normally binds to surface of basophils
and mast cells
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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
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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 itching2º bacterial infection
Atopic eczema
Atopic eczema (atopic dermatitis)
May spontaneously disappear as child ages
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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
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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
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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
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Attacks synovial membranes
Produces granulation tissue that extends into jointspannus
Destruction of cartilage, ligaments, tendons, bones
Signs & Symptoms
Fever, fatigue, malaise
Swollen, painful joints; often bilateral
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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
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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
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Increased incidence as get older
Systemic lupus erythematosis
Signs and symptoms are diverse, easily missed in
early stages
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Butterfly rash across face is classic sign (40% of cases)
AB form vs nucleic acids (anti-nuclear
antibodies)
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RBC, WBC, platelets, coagulation proteins, etc,
Mild to rapidly fatal
In US: incidence in Fe 10x M
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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
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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
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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 skinsausage 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