Lecture Notes for Med. Tech. Class

Lecture Notes for Med. Tech. Class

Immunodeficiency Oct. 2000

C.K.Shieh

Phagocyte Immunodeficiency

•Chronic granulomatous disease (CGD)

defects in leukocyte NADPH oxidase, no oxygen free radical production.

characterized by wide-spread granuloma formation.

•Lymphocyte adhesion deficiency (LAD)

defects in leukocyte adhesion molecules

characterized by leukocytosis and poor leukocyte trafficking, phagocytosis

B Cell Immunodeficiency

•X-linked agammaglobulinemia (Bruton’s agammaglobulinemia)

•Isotype or subclass deficiency

•Hyper IgM syndrome

CD40-CD40 Ligand Interaction is essential for isotype switching. Lack of CD40-CD40L interaction causes hyper IgM syndrome

•Common variable immunodeficiency

Late-onset defect in Ab production. Probably secondary to viral infection.

•Transient hypogammaglobulinemia of Infancy

Different Functions of Antibody Isotypes

Ig Levels in Fetal and Newborn Blood

Failure of newborn B cells to produced IgG may cause severe hypogammaglobulinemia in infants.

Complement Immunodeficiency

•Recurrent bacterial infection (late C’ components)

•Autoimmunity due to immune complex (early C’ components)

•Angioedema (C1 inhibitor)

T Cell Immunodeficiency

•Severe combined immunodeficiency (SCID)

•DiGeorge syndrome

•Wiskott-Aldrich syndrome

•Hereditary ataxia-telangiectasia

•MHC class II deficiency

DiGeorge Syndrome

•A defect in the development of the 3rd and 4th pharyngeal pouches

•Involved organs: thymus, parathyroid glands, heart

•Characteristic facial malformations: Low-set ears, wide-set eyes, shortened philtrum of upper lip

•Presenting with T cell immunodeficiency and hypocalcemic tetanus

•Variable severity

Hereditary Ataxia-Telangiectasia (AT)

•An autosomal recessive disease

•Presenting with wobbly gate (ataxia) at 18 months and dilated capillaries (telangiectasia) at 6 years of age.

•Involving both T cell development and B cell isotype switching (70% involve IgA, G2, G4 defects)

•A defect for repair of double strand breaks for DNA.

Wiscott-Aldrich Syndrome

•An X-linked disease

•Small platelets with thrombocytopenia

•Eczema

•Lack of microvilli in T cells

•A defect in cytoskeleton which results in faulty T cell-B cell collaboration

AIDS: Depletion of CD4+ T Cells by HIV Infection

HIV Struture: env: receptor binding LTR, vpr, tat: transcription regulationpol: reverse transcriptase

Treatment for HIV Infection

•NRTI

•NNRTI

•Proteinase inhibitor

Immunosuppressive drugs

Cyclosporin, FK506 (Tacrolimus), and Rapamycin (T cell specific immunosuppressants)

•Binding a class of cytoplasmic proteins (immunophilins) having peptidyl prolyl isomerase activity

•Cyclosprin binds to cyclophilin and then targets a serine threonine phosphotase named calcineurin

•FK506 and rapamycin bind FK binding protein

•Cyclosprin and FK506 inhibit T cell proliferation but have limited effect on other cells

•Rapamycin seems to affect T cell activation at a later stage, it may have a synergistic effects with other agents on T cell suppression