Immunopathology IV (Immunodeficiency Syndromes)

Question 1

Define what is meant by “immunodeficiency” and name the two categories into which it is divided.

Answer 1

Primary: Genetic disorders
Secondary: Acquired disorders

Question 2

List 4 X-linked and 2 autosome-linked diseases that cause immunodeficiency.

Answer 2

X-Linked
    •	X-linked Agammaglobulinemia (Bruton’s)
    •	Hyper IgM Syndrome
    •	Severe Combines Immunodeficiency (SCIDS)
    •	Wiskott-Aldrich Syndrome
Autosomal
    •	Dominant
        -	C1 inhibitor Deficiency
    •	Recessive
        -	DiGeorge Syndrome
        -	SCIDS

Question 3

List three causes of acquired immunodeficiencies.

Answer 3

• AIDS
• Chemotherapy
• Immunosuppressive therapy (steroids)

Question 4

Discuss the cause of Bruton’s X-linked agammaglobulinemia.

Answer 4

B cells cannot differentiate past lymph cell
- Mutation in Bruton tyrosine kinase (Bkt) gene on X chromosome
- Bkt involved in light chain rearrangement and B-cell maturation
Common Infections
- Recurrent bacterial infections of the RT
o Haemophilus influenzae
o Streptococcus pneumoniae
o Staphylococcus aureus
- Enteroviral encephalitis
o Echovirus
o Poliovirus
o Coxsackievirus

Question 5

Identify the anatomic abnormalities associated with DiGeorge Syndrome.

Answer 5

• Inability to produce mature T-Cells
• Deformity in 3rd and 4th pharyngeal pouch results in
• Tetany & congenital heart defects are also associated
• 22q11 deletion
• Common Infections
o Bacterial sepsis
o CV, severe varicella, chronic respiratory & intestinal infection
o Fungi & parasites

Question 6

Name the life-threatening condition associated with IgA deficiency.

Answer 6

• Anaphylactic shock when receiving a transfusion that contain IgA

Question 7

Describe severe combined immunodeficiency syndrome (SCID) and name two molecular etiologies for it.

Answer 7

• Lymphopenia
o Low or absent T & B cells
•Hypogammaglobulinemia
• Etiologies
o Cytokine Receptor Deficiency (X-linked)
o ADA Deficiency (autosomal deficiency)

Question 8

Describe the disease hereditary angioneurotic edema and discuss its etiology.

Answer 8

• C1 inhibitor Deficiency
• Peri-oral edema and swelling (episodic)
• Dangerous based on location i.e. pharynx and GI
• Give prophylaxis C1 inhibitor or plasma if going into surgery

Question 9

Diagram the HIV genome and name the functions of the genes encoded therein.

Answer 9

In Order

1. LTR: Long Terminal Repeat (transcription initiation)
2. Gag: Capsid protein
3. Pol: Polymerase
4. Vif: Viral Infectivity Factor (promotes replication)
5. Vpr: Viral Protein R (Replication & infection of macrophages)
6. Vpu: Viral Protein U (degradation of CD4)
7. Env: gp 160 envelope protein
8. Nef: Negetive Effector down regulation of CD4 and MHC I expression (no Nef = slower progression to disease)
9. LTR

Question 10

Discuss the natural evolution of HIV-1 infection in an untreated host.

Answer 10

• Virus infects CD 4+ or dendritic cell
• Cells migrate into lymph node
• Viremia detectable via nucleic acid testing in less than 1 week
• Infects cells by binding to gp120, CCr5 & chemokine receptor
• G941 undergoes conformational change so that the virus can fuse with host cell membrane
• Integration with host genome
• Budding (covered by host membrane) and release of mature virus

Immunodeficiency

 - Direct Cytopathic effect of replicating virus
 - Colonization of lymphoid tissue

Natural History
     -	Viremia
        o	Flu like illness
    -  Partial control
       o	Lower viral lode
    -	Latent infection
       o	CD34+ cells decrease in time
       o	Constitutional symptoms appear when very low
      o	Death