Definitions

1.     immunodeficiency disorders- diverse group of illnesses which, as a result of one or more abnormalities of the immune system, predispose an individual to infection.

1. can involve malfunction of blood cells (lymphs, granulo., monos)
2. soluble molecules- (Ab, complement)

CAUSES

1. inherited genetic trait (PRIMARY)
2. unrelated illness or agent (SECONDARY)

Incidence 1: 10,000, except for certain IgA deficiencies (1:500). The most common are SCID & X-linked agammaglobulemia- 1:100,000.

“Arrest point” – point where B or T cell maturation stops or ceases.

Principle manisfestation- increased susceptibility to infection shown by:

a.     increased frequency of infection

b.     increased severity

c.      prolonged duration

d.     unexpected complications or unusual manisfestation

e.     infection w/ org. of low pathogenicity

Disorders of the B-Cell system

X-Linked (Brutons) Agammaglobulemia

• lack all classes of Igs and circ. B cells
• no plasma cells thus no Ab response
• recurrent bacterial and pyogenic (pus producing) infections between 6-9 mths (remember maternal IgG)
• DO NOT GIVE LIVE VACCINES
• due to lack of cytoplasmic tyrosine kinase which prevents B cell maturation and production of Igs
• maturation is interrupted between the pre-B and B cell stage

Selective IgA deficiency

• MOST common form of immunodeficiency (1:500)
• strong familial association
• GI symptoms of infection and malabsorption (IgA coats mucosal surfaces)
• unknown cause: maybe since under T cell control, maybe through down-regulation of T cell circuits (they don’t produce the right cytokines); some patients have an allergic shock when receiving blood tranfusions due to Ab against IgA
• chance for developing CVID (next)

Common Variable Immunodeficiency (CVID)

• sometime after infancy (15-35 yoa) develop recurrent bacterial infections, ß Ig levels, and impaired Ab responses
• cellular immunity is usually normal
• persistent lung infections and GI giardiasis
• IgG fraction is missing
• Cancers (T-cell attrition)

Immunodeficiency with elevated IgM

• CD40 ligand on T cells in defective
• decreased IgG and IgA; increased IgM
• no IgM- IgG class switch
• recurrent pulmonary infections
• lymph nodes have no follicles

T cell Abnormalities

DiGeorge Syndrome (Cellular Immunodeficiency with Hypoparathyroidism)

• NO thymus—-no T cells
• failure of 3^rd and 4^th pharyngeal pouches to develop at about week 10 (when other organs are developing i.e. heart)
• sporadic with some familial patterns
• Seizures on the first day of life due to low calcium in the blood
• diaper dermatitis (Candida) and Pneumocystis carinii (like AIDS patients)
• DO NOT GIVE LIVE VIRAL VACCINES
• there are partial syndromes also.
• normal serum Igs and circ B lymphs
• chest x-ray

Severe Combined Immunodeficiency (SCID)

• many forms: most common X-linked
• mutation in the gene that codes for the gamma chain of the IL-2 receptor.
• NO IL-2 receptor—-NO T cell maturation and proliferation—— No T cell function
• most infants don’t make any serum Igs also (due to the fact that the defective gamma chain gene also renders the IL-4, IL-7, and IL-15 receptors dysfunctional also)
• serious infection with Pneumocystis carinii
• In about 15% of cases, there is an Adenosine deaminase deficiency.
• autosomal recessive
• recurrent bacterial, viral, and fungal infections
• lack of ADA—-high serum deoxyadenosine metabolites which are toxic in T cells

Phagocytic Deficiency

Chronic Granulomatous Disease

• CGD granulocytes can ingest bacteria but cannot kill them
• CGD leukocytes have no O₂ uptake, therefore no H₂O₂ production
• X-Linked
• Nitroblue tetrazolium dye (NBT) test and chemiluminescence assay to diagnose.
• no dye reduction or enhanced energy release

Leukocyte Adhesion deficiency

• rare autosomal recessive
• recurrent bacterial and fungal infections and impaired wound healing
• delayed separation of the umbilical stump
• deficient expression of the b₂ integrins or the CD11 or CD18 glycoproteins —- (LFA-1, CD11, CD18)
• these proteins participate in the adhesion of leukocytes to other cells and also in the phagosytosis of complement-coated particles
• high leukocyte counts
• present with herpes symptoms (not herpes) like cold sores, swollen gums, gum bleeding

Disorders of the Complement System

• C3 deficiency/ disorders have many infections (very rare)
• infections occur from birth (Not like Bruton’s)
• if no C3, no C3a and C5a, so no chemotaxis of phagocytic cells
• if have classical or alternate only, still do ok
• primordial protection system
• KNOW PATHWAY

DIAGNOSIS

Birth to 3 mths-

• DiGeorges syndrome
• Neutrophil defects
• Chemotaxis defects
• complement defects
• CMI defect

Three to Six mths

• SCID

After 6

• Agammaglobulemia
• Hypogammaglobulemia

Entire 3-18 mth period

• Wiskott-Aldrich syndrome
• Neutrophil assoc. defects

>5 years

• CVID

LABS

Ø  White blood cell function

• NBT test

Ø  Complement function

Ø  Ab function

Ø  Lymphocyte function

Tags: Agammaglobulemia, autosomal recessive, b-cell system, chemotaxis, chronic Granulomatous Disease, CMI, complement defects, Complement System, DiGeorge Syndrome, elevated IgM, Hypogammaglobulemia, IgA deficiency, immunodeficiency disorders, infections, low pathogenicity, lung infections, Neutrophil, Neutrophil defects, plasma cells, SCID, Severe Combined Immunodeficiency, T cell abnormalities, Wiskott-Aldrich syndrome

This entry was posted on Thursday, March 5th, 2009 at 5:09 am and is filed under Immunology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.