This document summarizes immunodeficiency disorders, including deficiencies of the innate immune system and other well-defined syndromes. It discusses clinical presentations and treatments for disorders like chronic granulomatous disease, hyper IgE syndrome, complement deficiencies, selective IgA deficiency, common variable immunodeficiency, Wiskott-Aldrich syndrome, ataxia telangiectasia, and IRAK-4 deficiency. The conclusion emphasizes that immunodeficiency disorders have a variety of genetic causes and treatments including antibiotics, immunoglobulin therapies, stem cell transplantation, and gene therapy.
3. Conclusions – Part One
• The immune system developed for your protection
• Involves complex interactions between antigens,
immune cells, and cytokines
• Responsible for killing bacteria, viruses, fungi, and
parasites
• Deficits within the immune system may be
congenital or acquired and lead to
immunodeficiency
• Relative to transplantation and tumor immunology
• Imbalances in the regulatory mechanisms of the
immune system may lead to organ-specific or
nonorgan-specific autoimmune diseases
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5. Objectives
• Identify the most common
immunodeficiency disorders
• Recognize the clinical presentation for
patients with immunodeficiency disorders
• Understand treatment options for patients
with immunodeficiency disorders
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7. Clinical Presentation
• Medical History
– Recurrent bacterial infections
– 2 or more severe infections (pneumonia,
sepsis, meningitis, osteomyelitis)
– Atypical presentation
– Unusually severe course, impaired response
to treatment
– Opportunistic pathogen
– Recurrent infection same pathogen
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8. Clinical Presentation
• Medical History
– Recurrent abscesses in internal organs or skin
– Failure to thrive with chronic diarrhea
– Prolonged candidiasis (oral/skin)
– Delayed umbilical cord separation >4 weeks
– Delayed shedding primary teeth
– Family history
– Unexplained bronchiectasis
– Autoimmune disease
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9. Clinical Presentation
• Physical Exam
– Dysmorphic features, face, microcephaly
– Albinism, abnormal hair, eczema, dermatitis
– Telangiectasia, ataxia
– Gingivitis, oral ulcers
– Abnormal wound healing
– Absence of lymph tissue (nodes, tonsils) or no
thymus on CXR
– Lymphadenopathy, organomegaly, digital clubbing
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11. Phagocytic Cell Defects
Continued
• Chronic Granulomatous Disease
– Phagocytes(monocytes and neutrophils) fail to
produce reactive oxygen intermediates (superoxides)
and hydrogen peroxide that kill bacteria
– 75% inherited X-linked recessive, remainder
autosomal recessive (15% are girls)
– 20 new cases a year; 1/200,000 births
– Diagnosis by fluorescent chemical after exposure to
hydrogen peroxide in phagocytes
– Prophylactic and early treatment to prevent infections
– Gamma interferon treatment may reduce infections by
70%
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18. Leukocyte Adhesion Deficiency
• Rare 1/100,000
• Autosomal recessive
• Cannot migrate (chemotaxis) out of the
blood vessel
• Diagnosis (high neutrophil levels)
• Absent CR3 protein
• Do not form abscesses
• Treatment bone marrow transplant
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20. Complement System
• Complex series of 20 proteins in plasma
• Enzyme activation of cascade
• Complement facilitates phagocytosis
• Complement (C3b) binds to bacteria and allows recognition
by phagocytes to engulf
• May stimulate (C3a and C5a) phagocytes make reactive
oxygen intermediates and enhance expression of cell
surface receptors
• Trigger degranulation of mast cells and granulocytes
• Attract other inflammatory cells
• Part of anaphylaxis
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22. Distribution of Primary
Immunodeficiency Diseases
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28. IgG Subclasses
• IgG1- most common IgG (60-70%), antibodies to
proteins; diptheria, tetanus, viruses
• IgG2-polysaccharide antigens;
hemophilus, pneumococcus
• IgG3-antibodies to proteins; diptheria, tetanus, viruses
• IgG4
• Natural history- IgG subclass deficiency associated with
recurrent ear, sinus and lung infections, usually resolves
by adulthood
• Treatment prophylactic antibiotics and gammaglobulin
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29. Selective IgA Deficiency
• Relatively common
• 1/333 births
• Generally asymptomatic
• May be associated with recurrent
respiratory and urinary tract infections
• May be associated with other disorders
(e.g., celiac disease)
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30. Hyper IgM Syndrome
• Genetic disorder (x linked, some AR)
• B cells cannot switch from IgM production
to IgG production
• Normal or elevated IgM production, other
Ig low
• Low neutrophils and platlets
• Increased risk for infections
• Prophylactic antibiotics, IV IgG
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31. Predominantly Antibody
Deficiencies
• X-linked (Bruton-type)
agammaglobulinemia
– X chromosome
– Arrest in early B-cell maturation
– Males
– Pyogenic infections (staph, strep
A, Neisseria, Haemophilus, pneumocystis
– Treatment gammaglobulin infusions
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33. Common Variable
Immunodeficiency (CVID)
• Defined by decrease of 2 out of 3
immunoglobulins (B cell defect)
• Decreased response to immunization in
children > 2 years
• Recurrent ENT and airway infections
• 1:50,000
• Genetic basis
• Treatment: gammaglobulin
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41. IRAK 4 Deficiency
Lung Abscess
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42. Conclusion
• Immunodeficiency disorders are fairly
infrequent
• Some are transient with improvement over
time
• More severe forms of immunodeficiency
are associated with shortened life span
without bone marrow transplantation
• A genetic cause has been identified for a
substantial portion of these disorders
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43. Conclusion
• Treatment options incude:
– Prophylactic antibiotics
– SQ gammaglobulin
– IV gammaglobulin
– Stem cell or bone marrow transplantation
– New biologicals
– Gene therapy
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44. Thanks for Attending
• Next presentation will include:
– Diseases of immune dysregulation
– Severe combined immunodeficiency
– Predominantly T-cell disorders
– Autoinflammatory disorders
• Watch for notification – the next lecture will
occur in April.
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