Transcript Body
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
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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
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 jointspannus
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