Immunodeficiency

Question 1

Children have recurrent infections

Answer 1

• toddlers have ~6 respiratory per year
• daycare attendees average 9
• children exposed to second hand smoke average 12
• symptoms from a common cold last for 4-12 days (mean 6.8 days)

Question 2

When should an immune evaluation be considered

Answer 2

• two or more invasive bacterial infections is unusual
• persistent or recurrent sinopulmonary infections warrant further evaluation
• unusual etiologic agents or unsual severity of an otherwise common infection may be a red flag

Question 3

Evaluation for immunodeficiency

Answer 3

• history
• physical exam
• Labs

Question 4

History of children with immunodeficiency

Answer 4

• growth and development
• types and sites of infections
• severity of infections, complications
• specific organisms
• HIV risk factors
• diarrhea, malabsorption
• autoimmune or allergic phenomenon
• family history- any unexplained earl infant deaths

Question 5

Physical Exam with immunodeficiency

Answer 5

• physical and anatomic barriers
• growth and development
• tonsils, nodes, liver and spleen
• thrush
• rash: eczyma, seborrhea, petechiae, others

Question 6

Nonimmunologic lines of defense

Answer 6

• skin and mucous membranes- eczyma, burns, open fractures, sinus tracts
• adequate drainage of body fluids- eustation tube dysfunction, ciliary immotility, cystic fibrosis, ureteral reflux
• foreign bodies- medical, accidental

Question 7

Four limbs of the immune system

Answer 7

• Cellular immunity- T-cells, NK-cells, cytokines-7%
• Humoral immunity- B- cells, immunologlobulins-46%
• complement-2%
• phagocytes-20%
• Combined- 25%

Question 8

Severe Combined Immunodeficiency: SCID

Answer 8

• 6 week old, failure to thrive, oral thrush, skin rash, diarrhea
• 75% patients are male
• X linked and autosomal recessive
• early death without bone marrow transplant
• IL-2 gamma chain defect
• Adenosine deaminase (ADA) deficency)
• Purine nucleotide phosphorylase deficiency
• T Cell signal transduction defects

Question 9

Beta chain

Answer 9

• this is often the defect with SCIDS
• problems with IL-21 (B cell maturation_
• Il-15- NK cell development
• IL-9- hematopoiesis
• IL-7- T cell development
• IL-4- class switch recombination
• IL-2 peripheral T cell homeostasis

Question 10

SCIDs Labs

Answer 10

-lymphopenia
-enumeration of specific lymphocytes subsets assists in diagnosis
-analysis of lymphocyte proliferation in response to
1- Mitogens (PHA, concanavalin A, pokeweed)
2- Non-self HLA antigens in a mixed lymphocyte culture
3- Specific antigens

Question 11

Treatment for SCIDs

Answer 11

• immediate bone marrow transplant
• risks include invasive, life threatening viral, fingal, and bacterial infections
• thrush is commno
• aggressive treatment with antibiotics, replacement immunoglobulin, and often antivirals and antifungals while awaiting transplant

Question 12

Humoral Immunodeficiency

Answer 12

• present with pneumonia, bronchiectasis (thickening and scarring), chronic problems with sinusitis
• have to rule out cystic fibrosis, immotile cilia syndrome and HIV
• B cell enumeration (C19 and/or CD20)
• Quantitative immunoglobins- IgG, A and M, consider IgG subclasses, pre and post vaccine titers, isohemmagglutins

Question 13

Types of Humoral Immunodeficiency

Answer 13

• X-linked Agammaglobulinemia- absence of B cells due to mutation in Bruton’s tyrosine kinase (BTK)
• CD40 ligand deficiency- hypogammaglobulinema with hyper-IgM
• common variable immunodefiency
• selective defect in anti-polysaccharide antibody production
• TH1 cell -> opportunistic infections because macrophages aren’t properly being active
• infectious risk include encapsulated bacterial pathogens, especially Strep pneumoniae
• unique susceptibility to chronic enterovirus meningoencephalitis
• autoimmune disease common
• lifelong risk of lymphoma

Question 14

Medical Management of Humoral Immunodeficiency

Answer 14

• immunoglobulin replacement, usually monthly
• early identification and treatment of infections,including enteroviral disease
• aggressive pulmonary follow-up

Question 15

Selective IgA deficiency

Answer 15

• incidence 1:600
• 2/3 are asymptomatic
• can be associated with IgG subclass 2 deficiency
• recurrent sinopulmonary infections
• defect in producing antibodies to polysaccharide antigens

Question 16

Complement Deficiency

Answer 16

• Neisseria like meningococcemia or gonorrhea
• IV antibiotics
• receive meningococcal vaccine and antibiotic prophylaxis

Question 17

Phagocyte deficiency

Answer 17

• present with liver abscess from Staph aureus, past history of pulmonary aspergillous (weird stuff)
• common neutrophil defect= chronic granulomatous disease
• low activity of NADPH oxidase
• highest risk with catalase positive bacteria
• develop fungal infections- aspergillus or pseudallescheria
• treatment: antibiotic prophylaxis, early identification and treatment of infections, interferon gamma
• Other disorders- B integrin CD11/CD18 or selectin deficiency, Chediak-Higashi or Job’s syndrome

Question 18

Cellular Immunodeficiency

Answer 18

DiGeorge syndrome- abnormal embryonic development of the 3rd and 4th pharyngeal pouches

• congenital thymic hypoplasia/aplasia-variable T cell numbers and function
• congenital heart disease (LV outflow tract)
• hypoparathyoidism
• infection risks include invasive and severe viral and fungal disease
• thymic transplants for severe immunodeficiency
• irradiated blood products only
• many patients have gradual improvement in cellular immune function over time

Question 19

HIV/AIDS

Answer 19

• caused by a virus HIV
• loss of CD4+ T cells
• opportunistic infections
• associated with certain malignancies- Kaposi’s sarcoma, lymphoma and squamous cell carcinoma

Question 20

Opportunistic infections from HIV

Answer 20

• Bacterial-Tuberculosis, Mycobacterium Avian Complex
• Fungal- PCP, candidiasis, cryptococcosis and penicilliosis
• Protozoal-toxoplasmosis, microsporidiosis, cryptosporidiosis, isopsoriases, and leishmaniasis
• Viral- CMV, herpes simplex, herpes zoster virus