• chronic infection
• recurrent infection
• unusual microbial agents
• incomplete clearing of infection
• incomplete response to treatment

• diarrhea (chronic)
• growth failure
• recurrent abscesses
• recurrent osteomyelitis

- telangiectasia

- partial albinism

Cells do not differentiate during hematopoiesis

- no lymphocytes and no phagocytes

1. antibody deficiency
2. cellular deficiency
3. phagocytic disorders
4. complement deficiencies

1. protein electrophoresis
2. quantitative of IgA, IgG, IgM and IgD
3. isohemagglutinin
4. specific ab response
5. b cell quantitation
6. b cell markers (CD19)

1. cross linked agammaglobulinemia
2. selective IgA deficiency
3. IgG subclasses deficiency
4. Hyper -IgM
5. CVID

a) What is XLA?

b) where is the defect and on what gene?

c) what is the result?

a) first immunodeficiency described which is considered prototypical antibody deficiency

b) x chromosome on the btk gene

c) absent or severe reduction in b lymphocytes along with Ig of all types.

a) Where is the site of infection of XLA?

b) when do symptoms appear?

a) mucuous membranes, ear, lungs, blood, gut

b) symptoms appear 6-9 months

Extracelular pyogenic organisms

- hemophilus

- penumococcus

- streptococcus

a) Where is BTK, the XLA gene, mapped at on the chromosome?

b) BTK is expressed at what stages during B cell lineage?

c) What cells is BTK found in and definitely not in?

d) how many mutations can there be via analysis?

a) X21.2-22.2

b) expressed at all b cell lineage stages except for plasma cell

c) macrophage, megacyte and platelet mast but not in T and NK cells

d) more than 600

a) What is pathogenesis of selective IgA defiency?

b) How prevalent is it?

a) block in B cell differentiation is due to intrinsic b cell defect or abnormal t cell help such as production of cytokine (TGF beta and IL 5) or in B cell responses to these cytokines

b) 1:700, most common identified disorder.

a) What is selective IgG subclass deficiency?

b) Which class is the most common in adults?

c) Which class is the most common in children?

a) normal levels of IgG, but subclasses are below normal levels

b) IgG3 adult

c) IgG2 children

a) What characterizes CVID?

b) What does CVID have a tendency of?

a) hypogammaglobulinemia

b) formation of autoantibody

• DTH
• total lymphocyte count
• lymphocyte response
• total t cell using ANTI-cd3
• CD4 and CD8 subset
• cytokine production

1. DiGeorge Syndrome
2. Defect in CD3/TCR
3. defect in signaling, defect in ZAP-70
4. defect in cytokine production as IL-2 and IFN gamma
5. defect in cytokine response

• Decreased T cells
• normal b cells
• normal or decreased sIg

What are other features of DiGeorge Syndrome?

• characteristic faces
• deletion in 22q11 in > 80%
• abnormal calcium homeostasis

• severe combined immunodeficiency (SCID)
• omenn syndrome
• Adenosine Deaminase deficiency (ADA)
• Ataxia-Telangiectasia syndrome (AT)
• Wiskoss-Aldrich syndrome (WAS)

• failure to thrive
• usually fatal in early year
• onset of infections in the neonatal period
• opporunistic infection
• chronic or recurrent thrush
• chronic rashes
• chronic or recurrent bacteria
• paucity of lymphoid tissue.

a) What causes Crossed linked SCID?

b) what cells are absent to synthesize?

c) There is a mutation on common gamma gene shared by what cytokines that play a role in signal tranduction through activation of Jak 3.

a) gamma c deficiency

b) NK, T and Ig

c) IL-2,4,7,9,15

1. JaK-3 deficiency: T/B/NK -SCID

2. RAG 1 or 2 deficiency: T/B/NK

How was SCID Treated in the past and currently?

How is it planned to be treated in the future?

a) infection can be limited to sterlie confinement. Currently, patients can undergo bone marrow transplant

b) Gene therapy to repair leukocytes

• cross linked
• Eczema, thrombocytopenia, bacterial infection (polysaccharide antigen)
• defective gene encode a cytoplasmic protein expressed in BM derived cells interact with adaptor molecules (Grb2) and G protein regulate actin cytoskeleton
• cell surface glycoproteins reduced; cd43 (or sialophorin) normally on lymphocytes, neutrocytes, macrophages and platelet
• these alteration interfere w/ migration of leukocytes to inflammation sites.

• abnormal recessive
• abnormal gait (ataxia)
• vascular malformations (telagiectasia), neurologic defects, tumors and ID
• ID may affect T and B cells
• IgA and IgG2 deficiency
• T cell fn is variably depressed
• gene responsible on chromosome 11
• Gene product may play a role in DNA repair.

Defective class II MHC Expression

What is bare lymphocyte syndrome?

• Autosomal recessive
• fail to express HLA-DP,DQ,DR on APC and in response to IFN gamma
• mutation in genes encoding proteins regulate class II MHC transcription
• transcription factor RFX5 or CIITA
• may result in defective positive selection of T cell in thymus and reduction of T CD4+
• Affected individual are deficient in DTH response and in antibody response to T dependent antigens

• chronic granulomatous disease (CGD)
• leukocyte adhesion deficiency (LAD I)
• Chediak-Higashi syndrome
• IL-12/IFN gamma pathway deficiencies
• chronic or cyclic neutropenia

a) How do people get secondary immunodeficiencies?

b) What is the most common form?

a) results from injury or infection

 acquired hypogammaglobulinemia

    - immunosuppresion

     - agent-induced immunodeficiency

b) HIV/AIDS caused by HIV-1 retrovirus

1. HIV GP120 binds to CD4 on target cell
2. fusogenic domain in gp41 and cxcr4, a g protein-linked receptor in the target-cell membrane, mediate fusion.
3. nucelocapsid containing viral genome and enzyme enter cells.
4. viral genome and enzymes are released following removal of core proteins
5. viral reverse transcriptase catalyzes reverese transcription of ssRNA, forming RNA-DNA hybrids
6. Original RNA template is partially degraded by ribonuclease H, followed by synthesis of second DNA strand to yiel HID dsDNA.
7. the viral dsDNA is then translocated to the nucleus and integrated into the hose chromosomal DNA by the viral integrase enzyme

1. Transcription factors stimulate transcription of proviral DNA into genomic ssRNA and, after procesing, several mRNAs.
2. viral RNA is exported to cytoplasm
3. a) host-cell ribosomes catalyze synthesis of viral precursor proteins
   b) viral protease cleaves precursors into viral proteins
4. HIV ssRNA and proteins assemble beneath the host-cell membrane, into which gp41 and gp120 are inserted.
5. a) the membrane buds out, forming the viral envelope
   b) released viral particles complete maturation; incorporated precursor proteins are cleaved by viral protease present in viral particles

a) During HIV-1 infection, what cells are depleting?

b) People typically don't die from HIV, but die from what?

c) what is the average time from infection to death?

a) Cd4+ t cells

b) opportunistic infections such as tuberculosis, pneumonia, severe wasting diarrhea

c) 9-12 years

• anti-retroviral drugs (only therapeutic); basically lowering viral load and relief from infection
• target aspects of the viral replication
  - prevent virus from fusing or entering a cell
  - interfere w/ reverse transcriptase
  - block viral protease needed for construction of new virions