Immunodeficiency Disorders Flashcards
(36 cards)
Recurrent vs. Chronic Immunodeficiency Causes
Antibody deficiency, Phagocyte deficiencies, or Complement protein deficiencies are associated with RECURRENT INFECTIONS with extracellular pyogenic bacteria (pneumonia, otitis media, skin infections)
Deficiency in Cell-mediated immunity is associated with RECURRENT OR CHRONIC viral, fungal, or protozoal diseases
Ig Heavy Chain Deletions
Ig Heavy Chain Deletions: IgG1, 2, and 4 absent from chromosomal deletions
Defects in T cell Receptor Complex
Defects in T cell Receptor Complex: decreased T cells/cell mediated immunity from mutations in genes encoding CD3 proteins
Defects in Th1 Responses
Defects in Th1 Responses: decreased T cell mediated macrophage activation from mutations in IL-12 receptors or IFN gamma
Defects in Th17 Responses
Defects in Th17 Responses: decreased T cell mediated inflammatory responses from mutations in STAT3, IL-17
X linked Lymphoproliferative Syndrome
X linked Lymphoproliferative Syndrome: uncontrolled EBV induced B cell proliferation from mutations in SAP
Transient Hypogammaglobulinemia of Infancy
B cell deficiency
Loss of maternal IgG and delayed onset of IgG synthesis by infant
Symptoms at 9 mo. to 2 yr of age
Treat with intravenous immunoglobulin (IVIG) every couple months because of half life of Ig’s
Pre-birth: IgG dominates from mother through the placenta and low levels of IgM are produced by fetus
At birth: immune system develops and develops own IgG, IgM predominates, and IgA is very slow and does not reach high levels until puberty
If delayed IgG production (their own) which will cause recurrent infections but resides over time
X-linked Hyper IgM syndrome
Defective CD-40L expression by T cells
B cells present, IgM but no IgG or IgA
Poorly organized germinal, centers, no B memory
absent DC-T cell interaction va CD40-CD40L reduces T cell activation thus promoting malignancies
Treat with IVIG or bone marrow transplantation
Selective IgA Deficiency
Occurs in 1:600-1:800 people presenting at any age
Undetectable or low IgA, normal IgG and IgM
Possible but not uniform connection with increased sinopulmonary and gastrointestinal infections and allergies
20% make adverse anti-IgA responses to transfusions or replacement therapy
Bruton’s X-linked Agammmaglobulinemia
Defective btk gene (Bruton’s tyrosine kinase)
B cell maturation arrested at pre-B-stage
Circulating mature B cells absent
T cells present
Infants have recurrent infections with pyogenic bacteria between ages 4 months and 2 years
Treat with replacement Ig
CVID (common variable immunodeficiency)
Most common primary Ab deficiency (heterogeneous group of disorders)
1/3 of patients have defects in CMI as well
Recurrent infection, autoimmunity, lymphomas
90% diagnosed in adulthood
Poor Ab response to infection with low IgG &IgA, normal or low IgM and B cell numbers
Defects in cytokine receptors & costimulators
Replacement Ig therapy
Complications of B cell Deficiency
Respiratory tract or GI tract sepsis
Common organisms (pyogenic bacteria): staphylococci, streptococci, Haemophilus
Less common organisms: enteroviruses (echovirus, poliovirus) or other bacteria (salmonella, campylobacter)
Rare incidence of malignancy
SCID
Primary defects in T cell differentiation or function result in combined loss of T and B cell function
Usually present in first few months of life
Other systems often affected
Severe Combined Immunodeficiency Disease (SCID) results from complete loss of B and T cell function
Present early with persistent infection and failure to thrive
Therapeutic and prophylactic antibiotics are appropriate.
Administration of live vaccines or transfusions must be avoided
Bone marrow transplantation is the treatment of choice
Gene therapy is promising
Defects in SCID Disorders
X-linked SCID: defect in IL-7 receptor (g chain)
Autosomally inherited SCIDs: adenosine deaminase deficiency or purine nucleotide phosphorylase deficiency
DNA recombinase deficiencies (RAG1 or RAG 2 deficiency) cause arrested lymphocyte development due to failure to rearrange antigen receptor genes
Defects in Thymus Functions
Bare Lymphocyte syndrome: absence of MHC II gene products in thymus stops positive selection of CD4 T cells in the thymus
MHC Class I deficiency in thymus causes lack of CD8 T cells
Congenital thymic aplasia (DiGeorge syndrome) eliminates T cell maturation
*All block T cell development
Chronic Granulomatous Disease
Chronic Granulomatous Disease: defective production of reactive O2 intermediates by phagocytes via mutations in genes encoding components of oxidase enzyme
Leukocyte Adhesion Deficiency 1
Leukocyte Adhesion Deficiency 1: absent or deficient expression of beta2 integrins so leukocytes cannot adhere to wall via mutation in beta chain of beta2 integrins
Leukocyte Adhesion Deficiency 2
Leukocyte Adhesion Deficiency 2: absent of deficient expression of leukocyte ligands for endothelial E and P selectins causing failure of migration via mutations of protein for synthesis of selectins
Complement C3, C2/4 Deficiencies
Complement C3 Deficiency: defect in complement cascade activation via mutation in the C3 gene
Complement C2, C4 Deficiency: deficient activation of classical pathway via mutations of C2 and C4; can cause lupus like disease development
Chediak Higashi Syndrome
Chediak Higashi Syndrome: defective lysosomal function in neutrophils, DC, macrophages, and NK cells via mutation of lysosomal regulatory proteins
HSV 1 Encephalitis
HSV 1 Encephalitis: defective antiviral immunity in the CNS via mutations in gene encoding TLR3
Recurrent Bacterial Pneumonia
Recurrent Bacterial Pneumonia: defective innate immune responses to pyogenic bacteria via mutations in gene encoding MyD88
Hereditary Angiodema and C5-C9 Deficiency
Hereditary Angioedema
C1 Inhibitor deficiency (most common inherited complement deficiency)
C5,C6,C7,C8, or C9 Deficiency
Recurrent bacterial meningitis due defective membrane attack complex
Common Causes of Secondary Immunodeficiency
Cancer (immunoproliferative diseases) Cytotoxic drugs or radiation Malnutrition Splenectomy Immunosuppressive therapies Stress/emotions (neuroendocrine effects) Aging (thymic atrophy, other) Infection (such as HIV/AIDS)
