Immunodeficient Disorders Flashcards
States of immune deficiency
- Primary immunodeficiency
2. Secondary (acquire) immunodeficiency
Primary immunodeficiency
Results form genetic or developmental defect in the immune system
Affect either adaptive or innate immune functions
Categorized by type of cell involvement or developmental stage defect occurs
Affect cells of lymphoid or myeloid lineages and involve specific genes
Depending on affected component, varying levels of susceptibility to infection
Reticular dysgenesis
Stem cells fail to differentiate, causing total lack of leukocytes
Lymphoid immunodeficiencies
Involve B cells, T cells or both (sometimes NK cells)
Effect is mainly adaptive immune response
Lymphoid immunodeficiencies: B cell defects
Range from complete absence of B cells, plasma cells and Ig to selective loss of certain Ig
Result in frequent bacterial infections due to the absence of humoral immunity, especially encapsulated bacteria
Immunity to most viral and fungal infections is normal
Lymphoid immunodeficiencies: T cell defects
Result in frequent viral and fungal infections due to absence of cell-mediated immunity
Humoral immunity to T-dependent antigens is also affected
Some decrease in antibody levels
Severe combined immunodeficiency (SCID)
Family of disorders that effects either T cells, or both T and B cells
Common cause is defects in cell interaction and signaling molecules
Deficiency in gamma chain of IL2R and JAK-3 kinase impedes critical signaling
CD3 zeta chain deficiency only affects T cells
Defect in RAG-1 and RAG-2 causes T and B cells not to differentiate
Severe and recurrent infections that usually lead to death in early life
Live or attentuated vaccines can kill
Life can be prolonged by confinement to a sterile environment
Treatment by bone marrow transplant
Gene therapy is possible treatment but can cause cancer due to use to retroviral vectors
DiGeorge Syndrome (congenital thymic aplasia)
Developmental defect in which children are born without thymus or parathyroid (sometimes thyroid is not completely absent)
Few functional T cells so cell-mediated immunity is absent
B cells are present but cannot make specific antibody in response to infection or vaccination because of lack of T helper cells
Transplantation of fetal thymus can help
BC Immunodeficiency: X-linked agammaglobulinemia
1 in 1000-1000000 males
Pre-B cells in bone marrow do not differentiate
Defect in Brunton’s tyrosine kinase required to couple pre-BCR to nuclear events causing light chain rearrangement and BC maturation
Little or no circulating antibody
Can be treated with injections of purified pooled IgG
Sinopulmonary infections persist due to lack of secretory IgA
BC Immunodeficiency: X-linked hyper-IgM syndrome
Defect in gene coding for CD40 ligand
CD40 on B cells must interact with CD40 ligand on T cells for B cell activation to occur
Response to T-independent antigens is normal, leading to heightened IgM production
IgG, IgA and IgE are absent as there is no class switching
BC Immunodeficiency: Selective immunoglobulin deficiencies
One antibody class or subclass is missing Most common is IgA, due to failure of IgA-committed B cells to differentiate into plasma cells (increased allergies with IgE production, treatment is with broadspectrum antibiotics)
Myeliod cell immunodeficiencies
Affect innate immunte function, especially phagocytosis
- Congenital neutropenia
- Chronic granulomatous disease
- Leukocyte adhesion deficiency (LAD)
Myeliod cell immunodeficiencies: congenital neutropenia
Decreased production of granulocyte-colony stimulating factor (G-CSF)
Myeloid stem cels fail to differentiate into neutrophils
Frequent bacterial infections are common as neutrophil-mediated phagocytosis is absent
Myeliod cell immunodeficiencies: chronic granulomatous disease
Defect in oxidative pathway that phatocytes use to generate hydrogen peroxide
Phagocytes unable to kill many types of phagocytosed bacteria
Excessive inflammatory response and susceptibility to bacterial and fungal infections
Antigen processing and presentation to macrophages is impaired
Myeliod cell immunodeficiencies: leukocyte adhesion deficiency (LAD)
Failure to express the beta subunit of adhesion molecules LFA-1, MAC-1(CR3), and gf150,90(CR4)
Required for cell interactions, nearly absent from membrane
Impaired extravasation of neutrophils, monocytes and lymphocytes
Impaired ability of CTL and NK to adhere to target cells
Failure of T helped cells and B cells to form conjugates
Frequent bacterial infections and impaired wound healing
Defects in the complement system
- In early components of classical
- C3 deficiencies
- C5-C9 deficiencies
- In Factor D or properdin
Defects in the complement system: deficiencies in early components of classical complement
CIq, Clr, C1s, C2, C4
Prevents generation of C3 convertase
Absence of C3b (opsonin) causes frequent bacterial infections and immune complex disease due to failure to cleare immune complexes by phagocytosis
Defects in the complement system: C3 deficiencies
Most severe
Cause frequent bacterial infections
No opsonization by C3b and failure to form MAC
Results in autoimmune complex disease
Impairs immune complex clearance by phagocytosis
Defects in the complement system: C5-C9 deficiencies
Cause few health problems
Increased incidence of infections by Neisseria species that are normally susceptible to lysis by MAC
Immune complex disease is rate (enough C3b produced for clearance)
Defects in the complement system: Factor D or properdin
Required for proper function of alternative pathway
Result in susceptibility to infection by Neisseria species
Acquired immunodeficiencies
AIDS
Can be caused by immunosuppressive drugs
Chemotherapeutic agents
Acquired Immunodeficiency Syndrome (AIDS)
Progressive loss of immune responsiveness due to infection and death of CD4+ T helper cells by HIV-1 retrovirus
Macrophages and dendritic cells are infected
Death due to pulmonary infections, cancer, CNS complications
Spreads by sexual contact, infected blood, mother to infant
Infect via CD4 chemokine receptors that act as coreceptors
Chemotherapeutic agents
Ie. cisplatin
Toxic to proliferating bone marrow stem cells, T cells and B cells
Loss of immune function
Immunosuppressive drugs
ie. Cyclosporin A and rapamycin To prevent organ graft rejection Interfere with normal T cell responses T cells are present but not responsive Can result in overwhelming infections and can increase the incidence of certain cancers, especially lymphomas
