Immunodeficiency Flashcards
What histopathology and laboratory abnormalities are seen in B cell deficiencies?
- Absent or reduced follicles and germinal centers in lymphoid organs
- Reduced serum Ig levels
What histopathology and laboratory abnormalities are seen in T cell deficiencies?
- Reduced T cell zones in lymphoid organs
- Reduced DTH reactions to common antigens
- Defective T cell proliferative responses to mitogens in vitro
What are common infectious consequences of B cell deficiencies?
- Pyogenic bacterial infections
- Enteric bacterial and viral infections
What are common infectious consequences of T cell deficiencies?
- Viral and other intracellular microbial infections
- Pneumocystis jiroveci
- Virus-associated malignancies
- EBV associated lymphomas
Which area of the lymph node is B cell rich?
Germinal Center
Which area of the lymph node is T cell rich?
Paracortex
What can happen in any type of immunodeficiency?
- Increased susceptibility to newly acquired infections
- Reactivation of latent infections
- Increased incidence of cancers
X-linked SCID
- T cells -
- B cells +
- Serum Ig -
- NK cells -
- Mutation in common gamma chain receptor for cytokine
- No T cell maturation
- No Il-7 or Il-15 signals
AR SCID (ADA)
- T cells -
- B cells -
- Serum Ig -
- Accumulation of toxic metabolites in lymphs
AR SCID (PNP)
- T cells -
- B cells +
- Serum Ig +
- Accumulation of toxic metabolites in lymphs
What type of SCID is missing JAK3?
Autosomal recessive
What type of SCID is caused by missing common gamma chain?
X-linked
Bruton’s agammaglobulinememia X-linked
- Mother is carrier, manifested in male offspring
- Mutation of Bruton tyrosine kinase (BTK)
- Inability of pre-B cells to develop into mature B cells
- Diagnosed 5-6 mo old
- Repeated bacterial infections
- Lacking all Ig
- No CD19 B cells
- T cells +
- Tx gamma globulin injections
DiGeorge Syndrome
- T cell defect
- Dysmorphogenesis of the 3rd and 4th pharyngeal pouches
- Thymus and parathyroid
- Aortic arch, lip and ears
- Neonatal tetany
- Absent thymic shadow
- Decreased T cells
- 22q11.2 deletion
Hyper IgM syndrome
- X-linked
- Mutation in CD40L gene
- Lack of class switching
- Susceptibility with intracellular microbe, pneumocystis jiroveci
IgA deficiency
- Most common primary deficiency
- No IgA secreting plasma cells
- Asymptomatic -> recurrent sinopulmonary infections and diarrhea
Common Variable Immunodeficiency
- Failure in maturation of B cells into plasma cells
- Low serum levels IgG and IgA
- Normal to low IgM
- Major problems are respiratory and GI infections with pyogenic bacteria
Wiskott-Aldrich Syndrome
- X-linked
- Triad of problems:
- Lowered platelet count
- Skin rashes (decreased IgM)
- Recurrent bacterial infections
- Unable to respond to bacterial polysaccharides
Ataxia Telangiectasia
- Multisystem disorder:
- Neurologic: staggering gate
- Vascular: abnormal dilation
- Immunologic: both T and B cell
- Low levels of IgA and IgG
- Inability to respond to skin tests
- Reduction in T cells
Leukocyte adhesion deficiency
- Defect in adhesion of leukocytes to vascular endothelium
- Defect on leukocyte
- Selectin ligand
- Beta chain of integrin
- Limits recruitment of cells to sites of inflammation
- Bacterial infections without pus formation
Chediak-Higashi Syndrome
- Phagocytes from pts have giant cytoplasmic granules
- Granules dysfunctional
- Do not have ability to kill bacteria
Chronic Granulomatous Disease
- Defective production of reactive oxygen intermediates
- Intracellular survival of microbes leads to granuloma formation
- NBT test for measuring respiratory burst
Hereditary angiodema
- Deficiency in C1 inhibitor
- Results in excessive C4 and C2 activation
- Leads to localized edema