Chapter 13: Immunodeficiency

Question 1

How does Immunodeficiency occur? What are the two types of immunodeficiencies?

Answer 1

• Occurs when one or more component of the immune system is impaired

Primary:
- Cause recurrent infections early in life
- 6 million people are affected world wide
Secondary (aquired):
- Result of disease, medical interventions(drugs), and nutritional deficiency

• Recurrent infections by pyogenic, or pus forming, bact suggests a defect in antibody, compliment, or phagocyte function
• Persistent fungal skin infection or recurrent viral infections suggest a defect in host defense mediated by specific functions of T lymphocytes
  
  • Global T cell dysfunction impairs both B cell responses and aspect of innate immunity, giving rise to broad defects in host defense
    (IMAGE 3,4,5)

Question 2

What is SCID? What are the signs and symptoms?

Answer 2

Severe combined immune deficiency
- Group of genetic disorders
- Cannot make T cell dependent antibody responses nor cells mediated immune response. This results in NO IMMUNOLOGICAL MEMORY
- Diagnosed in early childhood

Signs and symptoms
- Infections that do not resolve after 2 months of treatment
- infections that require intravenous antibiotic treatment
- Persistent ear infections
- Persistent thrush in mouth or throat
- Repeated cases of pneumonia or bronchitis
- Repeated bouts of diarrhea

Question 3

What is X-linked SCID and what are its features?

Answer 3

• Most common SCID
• Mutations in the gene IL2RG on the X chromosome
  
  • Encodes IL2 receptor common gamma chain Yc
  • Gamma chain is required for all IL2 Cytokine family receptors
    
    • IL2, IL4, IL7, IL9, IL15, IL21
  • T cells and NK cells fail to develop normally
    
    • Low T cells and NK count
  • B cells develop normally but without T cells they do not function normally

Question 4

How common is X-linked SCID? What are the treatment options?

Answer 4

• 1/50-60K births
• Males overwhelmingly affected
• Without treatment, infant dies within 2 years
• Gene therapy and bone marrow transplant

Question 5

What is XLA and what are possible treatments?

Answer 5

• X linked agammaglobulinemia
• 1/200K births
• Mutation of BTK on the X chromosome disturbs BCR signal transduction
• Fail to develop and mature B cells
  
  • B cell development is halted with Pro B stage
  • Very low levels of antibodies and low B cell count
• Treatment is weekly infusion of antibodies
  (IMAGE 9 10)

Question 6

What is Job syndrome?

Answer 6

• Hyper-IgE syndrome
• Mutation in STAT3
• STAT3 is involved in broad spectrum of adaptive and innate immune functions such as Th17 differentiation and epithelial regeneration
• Cold abscess abscess without heat, redness, fever, significant pain, or inflammation
  (IMAGE 11)

Question 7

What is GATA2 deficiency and what treatment is availible?

Answer 7

• Mutation of GATA2 gene
  
  • GATA 2 transcription factor is important for hematopoiesis
• Affects varrious blood cells
  
  • Mainly affected cells are monocytes and dendritic cells
• Most common initial symptom is infections with NTM and viral infections
  Treatment: Bone marrow transplant

Question 8

What type of offspring would result if an affected parent had children with a unaffected mother? What are some features of GATA2 deficiency?

Answer 8

Question 9

What is HIV?

Answer 9

• Aquired autoimmune disease
• HIV is a retrovirus that establishes a chronic infection that slowly progresses to AIDS
• HIV infects and replicates within cells of immune system
  
  • Requires CD4 receptor and a chemokine coreceptor
• Initial infection begins with R5 variants
  
  • Use CCR5 coreceptor
• X4 variant emerges after initial infection
  
  • Uses CXCR4 coreceptor
  • Activated CD4 T cells are the major source of HIV replication

Question 10

How does HIV bypass the epithelium and replicates?

Answer 10

1. Enter via DC-SIGN binding on DC
2. HIV internalized into early endosomes
3. Transported to lymph nodes to transfer HIV to CD4 T cells

Question 11

What is the immune response to HIV like?

Answer 11

Question 12

What are the stages of HIV? What is the CD4 lymphocyte count for each stage?

Answer 12

Stage 1 - 500 or more leukocytes, 26% or more are CD4
Stage 2 - 400-299 leukocytes, 14-25% CD4 lymphocytes
Stage 3 - less than 200 leukocytes, CD4 is less than 14 percept categorized as AIDS

Question 13

What is the graph that compares the time after onset of HIV infection and CD4 cell concentrations?

Answer 13

Question 14

What is immune amnesia?

Answer 14

• Immune system loses its ability to fight infections that a patient was previously immune to
  
  • Loss of memory lymphocytes
• Measles virus infects B and T cells