ACQUIRED

Environmental

• (viruses) HIV/AIDS
• Malnutrition
• Induced (e.g., medication)
  
  

Multifactorial

• Common variable immunodeficiency (CVID)

Job's Syndrome (AD-HIES)
Classic triad

• recurrent skin boils (pockets of infection; "cold")
• cyst-forming pneumonias
• extreme IgE elevations
  
  • should be below 120
  • in JS, significantly higher than this
    
    

Facial phenotype emerges in teens

• broad nose
  

• coarse facial features
  

• high palate
  

• deep set eyes
  

• facial asymmetry
  

  • retain their baby teeth
  • osteopenia
  • fractures with minimal trauma
  • chronic yeast-like skin infections
    
    

STAT3 mutations
Rare
Treatment: Antibiotics

Other Immunodeficiency Syndromes

DNA repair defects

• Nijmegen breakage
• Bloom syndrome
• ICF
• homozygous PMS2
• Riddle syndrome
  
  

Immune-osseus dysplasia

• cartilage hair hypoplasia
• Schimke syndrome
  
  

Hyper-IgE syndromes

• Job's syndrome
  
  

Dyskeratosis Congenita
Comel-Netherton s.
VODI
IKAROS deficiency
IPEX syndrome

X-Linked Agammoglobulinemia

• aka Bruton's agammaglobulinemia
• occurs in 3 to 6 million males, panethnic
• Mutations in Btk
• Blocks B cell development
  
  • they recognize the antigen
  • cannot produce the antibody
• Recurrent, severe or unusual infections in first 2 years of life
• Treated by regular infusions of IVIG
  
  • intravenous immunoglobulin
  • basically a shot of antibodies

Wiskott-Aldrich syndrome

• X-linked disorder
• Textbook triad
  
  • Low platelet counts (easy bruising, easy bleeding)
  • Eczema (80%)
  • Recurrent infections (esp. ear)
• 1 to 4 per million males, panethnic
• rare
• WAS mutations
• can develop autoimmunity
  
  • against blood cells; hemolytic anemia; similar to SCD
  • destroy their own platelets
• individuals exposed to MONO may develop lymphoma (13%)
• Treatment: transplant

Ataxia Telangiectasia

• Autosomal recessive
• will develop either bone marrow failure or lymphoma/leukemia (up to 38%)
• 60-80% will have immunodeficiency
• can present with low IgA
• 1 in 40000 to 100000 births in USA
• symptoms appear between 1-4 yrs
• ataxia appears around age 2
• Oculocutaneous telangiecstasia by age 6
• recurrent infections
• ATM mutations
• Treatment: antioxidants, IVIG

Selective IgA Deficiency

• *MOST COMMON IMMUNODEFICIENCY
• You don't make IgA
• Affects up to 1 in 500 people
• More common in males
• range from asymptomatic to recurrent infections
  
  • many people don't know
  • therefore, infections can be mild
• associated with autoimmune diseases
• moderately increases risk of GI cancer
• No specific treatment

Hyper-IgM

• Low serum IgG and IgA which leads to a lot of IgM
• T cells don't appropriately signal the B cells
  
  • so you don't get that recombination and hypermutation in the B cells
• Recurrent infections, chronic diarrhea
• May be anemic and low platelets, PMNs
• Autoimmune disorders, liver disease
• May be X-Linked, recessive, or (rarely) dominant
  
  • males have higher chance for lymphoma
• Can accompany ectodermal dysplasia (IKBKG)
• ~1 in 500000 males (XL)
• Treatment: IVIG, transplant

Chronic Granulomatous Disease

• disorder that occurs if the phagocytes don't work
  
  • phagocytes surround antigen, but they can't destroy it
• 2/3 of cases are X-linked, the remainder are recessive
• 1 in 200000 in the USA
• Caused by inability to kill engulfed pathogens
• recurrent infections, atypical organisms
• arthritis, bone infections, blood infections
• Most diagnosed in childhood
• When x-linked, caused by CYBB mutations
• Treatment: Antibiotics/antifungals, interferon, transplant, gene therapy sometimes works, sometimes not

Severe Combined Immune Deficiency

• t cells are absent, or low, or nonfunctioning
• severe disorder, can be syndromic

• no dominant forms

  
  

• 1 in 50000 births

• Multiple genetic etiologies
  
  • single gene (ADA deficiency)
  • syndromic (22q, CHARGE)
• Uniformly fatal by year 1 if not treated
• Most do NOT have fmhx
• Transplant < 3 months has best outcome
  
  • gene therapy trials on-going
• ALL have low or absent T cells
• MA offers NBS for SCID
  
  • DNA testing, usually it's a protein assay
  • How to detect SCID
  • look for evidence of T cells
  • uses marker of T cell development
  • TRECs
  • t-cell receptor excision circles
  • which is a DNA product

Type 1 Diabetes

• Was called 'juvenile onset'
• Follows development of antibodies to pancreas
• Symptoms occur after more than 80% of the insulin-making cells are destroyed
• May be due to cross-reactivity after viral infection

Celiac Disease

• 1 in 100 people of european ancestry
• Due to immune response within the gut lining
• Associated with HLA-DQ2 type
• Requires exposure to gluten
  
  • wheat, barley, rye
• Symptoms include
  
  • diarrhea
  • abdominal pain
  • weight loss
  • anemia
• Can progress to malnutrition, iron deficiency
• Increased in Down syndrome, Turner syndrome, selective IgA deficiency and autoimmune disorders

Ankylosis Spondylitis

• chronic inflammatory arthritis of the spine
• typically appears in adolescents/early adults
• results in fusion of the vertebrae +/- joints
• acute iritis associated in up to 40%
• multigenic and multifactorial
• Associated wtih HLA-B27
• Worse in men
• 0.2% to 1% of europeans

MECHANISMS

• Direct cell-cell interaction

  
  
  • phagocytosis
  • antigen-presenting cells
    

• Release of chemicals to induce reaction

  
  
  • Complement
  • Cytokines
  • Antibodies

Determination of Self

• development of tolerance
• selection occurs in thymus or lymph nodes
• Self-reactive lymphocytes are culled

T and B Cells

B = Bone
the 'infantry'
antibodies are their weapon

T = Thymus
the 'generals'
give orders