IMMUNODEFICIENCY

SYNDROMES
T CELL DEFICIENCIES, COMBINED BAND T-CELL IMMUNODEFICIENCY,
ACQUIRED IMMUNODEFICIENCY
DISEASE AND DISEASES OF IMMUNE
DYSREGULATION

OBJECTIVES
Understand aspects of the immune system affected in
severe combined immunodeficiency disease
Identify some of the features of Hemophagocytic
Lymphohistiocytosis (HLH)
Describe how retroviruses replicate in HIV disease

OBJECTIVES
Primary T-cell defect
DiGeorge syndrome
X-linked hyperIgM syndrome

T and B cell defect SCID

Disorders of Immune Dysregulation
HLH
X-linked lymphoproliferative syndrome

HIV

DIGEORGE SYNDROME
Clinical Presentation

Newborn period
Heart defect
Abnormal facies
Cleft palate
Seizures
3rd and 4th pharyngeal pouches

DIGEORGE SYNDROME

DIGEORGE SYNDROME

DIGEORGE SYNDROME
Laboratory

Hypocalcemia
Hypoparathyroidism
Absent thymus on CXR
Decreased circulating T-cells
Decreased T-cell response
Deletion long arm chromosome 22
Primarily a T-cell defect

X-LINKED HYPER IGM

SYNDROME
Males 2 per million
CD40L deficiency
CD40L is on surface of activated T-cells
Activated T-cells use CD40L to interact with B cells to
switch from IgM production to IgG production
Increased IgM, decreased IgG

SEVERE COMBINED
IMMUNODEFICIENCY DISEASE (SCID)
Clinical

Most severe form of primary immunodeficiency

1/80,000 births
Failure to thrive, chronic diarrhea
Recurrent infections, pneumocystis pneumonia

SCID
Newborn screening
Genetic mutations affect both T and B cells in adaptive
immune system

X-linked (most common)

Autosomal recessive
De novo mutations
Adenosine deaminase deficiency
Omenn syndrome (RAG genes)

NEWBORN SCREENING
FOR SCID

IMMUNODEFICIENCY

12

SCID

SCIDS DEFECT

SCID
Treatment

BONE MARROW TRANSPLANT

Gene therapy
Enzyme replacement therapy
In utero stem cell replacement

SCID

HEMOPHAGOCYTIC
LYMPHOHISTIOCYTOSIS
(HLH)
Clinical

Fever
Hepatosplenomegaly
Lymphadenopathy
Jaundice
Rash

HEMOPHAGOCYTIC
LYMPHOHISTIOCYTOSIS
(HLH)
Laboratory

1.2 cases/million (rare)

All age groups: younger more likely genetic (primary)
Pancytopenia
Elevated ferritin levels
Elevated sIL-2r
Histopathology: activated macrophages ingest RBCs, WBCs and
platelets

DISTRIBUTION OF PRIMARY
IMMUNODEFICIENCY DISEASES

19

HEMOPHAGOCYTIC
LYMPHOHISTIOCYTOSIS
(HLH)

HLH
Primary HLH
Five gene mutations
FHL1-5

Secondary HLH
Infections
Lymphoma
Metabolic disease

OUTCOME FOR HLH

Without treatment, patients with familial HLH survived
two months
In 1994, reported survival was 55% with median followup at 3.1 years
Before 2000, survival after bone marrow
transplantation was 50 to 65%
Outcome may now be better with improved treatment
regimens

X-LINKED
LYMPHOPLOLIFERATIVE
SYNDROME
Long arm X chromosome
SH2D1A gene, XIAP gene (X-linked recessive)
1 male per million
Epstein-Barr Virus (EBV) triggers hemophagocytic
lymphohistiocytosis
Lymphoma
Treatment: stem cell transplant

HIV/AIDS
Human immunodeficiency virus
Acquired immunodeficiency syndrome

HIV
Single stranded RNA virus
Viral encoded reverse transcriptase makes double
stranded DNA
Viral integrase allows viral DNA to be spliced into
human DNA
May remain dormant or code for new viruses to be
made
HIV-1, HIV-2

TRANSMISSION
Blood transfusion
Sexual contact
Vertical transmission mother to baby
IV drug abuse
Body fluid exposure only if contaminated with blood
Breast milk
Organ transplantation
Needle stick

PATHOPHYSIOLOGY
Enters the body and get viral replication
Virus attaches to T lymphocytes, macrophages
CD4+ cells (helper) depleted at expense of CD8+
(suppressor) cell activation
Eventually majority of CD4+ cells are lost and immune
system partially disabled leading to oppurtunistic
infections and cancer

ACUTE CLINICAL
PRESENTATION

PATHOGENESIS

KAPOSIS SARCOMA

CLINICAL
Acquired Immunodeficiency Syndrome
Defined as CD4+ counts<200 or intercurrent diseases associated
with HIV infection (pneumocystis pneumonia, Kaposis sarcoma)
Occurs in 50% of HIV + individuals within 10 years of infection if
not treated

TREATMENT
HAART- highly active antiretroviral therapy
DNA analogs: reverse transcriptase inhibitors
Non DNA analogs: bind to enzyme (reverse transcriptase) and
cause conformational change so cannot make DNA

TREATMENT

CONCLUSION
Outcomes for children with immunodeficiency
dependent depends on the following:
Timely recognition
Adequate therapy and surveillance
The nature of the underlying disease

THANK YOU FOR

ATTENDING
Immunodeficiency
Syndromes
T cell Deficiencies
Combined B- and T-cell Immunodeficiency
Acquired Immunodeficiency Disease Diseases of Immune Dysregulation

QUESTIONS?