Transcript Chapter 18
Chapter 18 AIDS and other Immunodeficiences Dr. Capers Kindt • Goldsby • Osborne Kuby IMMUNOLOGY Sixth Edition Chapter 20 AIDS and Other Immunodeficiencies Copyright © 2007 by W. H. Freeman and Company Autoimmunity – system attacks host cells and tissues Immunodeficiency – system fails to protect Primary immunodeficiency ○ Genetic or developmental defect Secondary immunodeficiency - acquired Primary Immunodeficiencies Lymphoid Immunodeficiences Combined – effects both B and T cells B-cell Immunodeficiency ○ Range from absence of B cells, plasma cells, immunoglobulins to absence of only certain classes of Abs ○ Subject to bacterial infections but do well against viral since T-cell branch is ok T-cell Immunodeficiency ○ Can effect both humoral and cell-mediated Primary Immunodeficiences Combined Immunodeficiences Severe Combined Immunodeficiency (SCID) ○ Low # of circulating lymphocytes ○ Non-proliferating T cells ○ Thymus doesn’t develop ○ Usually fatal early years of life - Infant will have viral and fungal infections - Bacterial don’t show up until later because of placental transfer of Abs from mother - Chronic diarrhea, pneumonia, lesions ○ Many genetic defects can contribute to SCID MHC defects ○ Symptoms can resemble SCID ○ Lack of MHC II - Bare-lymphocyte syndrome Primary Immunodeficiencies Combined Immunodeficiencies Thymus ○ DiGeorge Syndrome – decreased or absent thymus - Results from deletion of region on chromosome 22 in developing embryo, developmental anomaly - Lowered T cell numbers, results in B cells not producing sufficient Abs ○ Nezelof - Inherited disorder - General failure to thrive Primary Immunodeficiences Combined Immunodeficiences Wiskott-Aldrich Syndrom (WAS) ○ X-linked disorder ○ Initially B and T cell numbers are normal but will decrease with age ○ Treated with passive antibodies or stem cell transfer ○ can result in fatal infection or lymphoid malignancy Primary Immunodeficiences Combined Immunodeficiences X-linked Hyper-IgM Syndrome ○ Deficiency of IgG, IgE, IgA but elevated levels of IgM ○ Defect in T cell surface marker CD40L - This is needed for interaction between TH and B cell for class switching for T-dependent antigens - T independent antigens are not effected therefore there is production of IgM Primary Immunodeficiences Combined Immunodeficiences Hyper-IgE Syndrome (job syndrome) ○ Autosomal dominant ○ Skin abscesses, pneumonia, eczema, facial abnormalities ○ High # of eosinophils and IgE Primary Immunodeficiences B cell Immunodeficiences X-linked Agammaglobulinemia ○ B cell defect - Defect in kinase that keeps B cells in pre-B stage with H chains rearranged but L chains not ○ Low levels of IgG and absence of other classes ○ Recurrent bacterial infections Primary Immunodeficiences B cell Immunodeficiences Common Variable Immunodeficiency (CVI) ○ Low levels of immunoglobulin – hypogammaglobulinemia ○ Manifests later in life Primary Immunodeficiences B cell Immunodeficiences Selective Deficiences of Immunoglobulin Classes ○ IgA deficiency is most common Recurrent respiratory and urinary tract infections, intestinal problems ○ IgG deficiencies are rare Can often be treated by administering immunoglobulin Primary Immunodeficiencies Innate Immunodeficiencies Leukocyte Adhesion Deficiency (LAD) ○ Integrin proteins needed for adhesion and cellular interaction Defect limits recruitment of cells into areas of inflammation Primary Immunodeficiencies Innate Immunodeficiencies Chediak-Higashi Syndrome ○ Autosomal recessive disease ○ Phagocytes don’t have ability to kill bacteria Primary Immunodeficiences Innate Immunodeficiences Interferon-Gamma-Receptor Defect ○ Autosomal recessive trait – results from inbreeding ○ Defect in receptor for IFN-γ and subsequent pathways - Patients suffer from infection with mycobaterium, showing importance of this receptor in fighting mycobacterium Primary Immunodeficiencies Innate Immunodeficiencies Myeloid Immunodeficiencies ○ Affect innate immune system ○ Impaired phagocytic process ○ Recurrent microbial infection Primary Immunodeficiencies Myeloid Immunodeficiencies Reduction in neutrophil count ○ Low concentration – granulocytopenia or neutropenia ○ Congenital neutropenia Frequent bacterial infections ○ Acquired neutropenia Certain drugs or chemotherapy can cause this Autoimmune disorder – destruction of neutrophils Primary Immunodeficiencies Innate Immunodeficiencies Complement deficiencies ○ Fairly common ○ Mostly associated with bacterial infections or immune-complex diseases Treatments for Immunodeficiency Replacement of missing protein ○ Administering immunoglobulin ○ Express genes in vitro (in bacteria) for cytokines Replacement of missing cell type ○ Bone marrow transplantation Replacement of missing or defective gene ○ Gene therapy SCID mouse Since it virtually has no immune system, immune cells from other species can be used to reestablish the immune system Tests can then be done on the mouse to see effects on that species’ immune system Examples: - HIV research - Contaminant research AIDS and other secondary acquired Immunodeficiences Acquired Immunodeficencies ○ No a genetic component ○ Examples: - Hypogammaglobulinemia – unknown cause, different from genetic condition - AIDS HIV Retrovirus (Lentavirus genus) Viral envelope derives from host ○ Can have Class I and Class II MHC Recognizes CD4 antigen on T cell 2 copies of single stranded RNA Passage of HIV (green) between T cell and dendritic cell HIV Therapeutic agents inhibit retrovirus replication Have to be specific for HIV so that they don’t interfere with cellular processes Vaccine may be only Way to stop HIV