chapter 18 aids and other immunodeficiences dr. capers
TRANSCRIPT
Chapter 18
AIDS and other Immunodeficiences
Dr. Capers
Kuby IMMUNOLOGYSixth Edition
Chapter 20AIDS and Other
Immunodeficiencies
Copyright © 2007 by W. H. Freeman and Company
Kindt • Goldsby • Osborne
Autoimmunity – system attacks host cells and tissues
Immunodeficiency – system fails to protectPrimary immunodeficiency
○ Genetic or developmental defectSecondary immunodeficiency - acquired
Primary ImmunodeficienciesLymphoid 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 ImmunodeficiencesCombined 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 ImmunodeficienciesCombined 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 ImmunodeficiencesCombined 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 ImmunodeficiencesCombined 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 ImmunodeficiencesCombined Immunodeficiences
Hyper-IgE Syndrome (job syndrome)○ Autosomal dominant○ Skin abscesses, pneumonia, eczema, facial
abnormalities○ High # of eosinophils and IgE
Primary ImmunodeficiencesB 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 ImmunodeficiencesB cell Immunodeficiences
Common Variable Immunodeficiency (CVI)
○ Low levels of immunoglobulin – hypogammaglobulinemia
○ Manifests later in life
Primary ImmunodeficiencesB cell Immunodeficiences
Selective Deficiences of Immunoglobulin Classes
○ IgA deficiency is most commonRecurrent respiratory and urinary tract infections,
intestinal problems
○ IgG deficiencies are rareCan often be treated by administering
immunoglobulin
Primary ImmunodeficienciesInnate Immunodeficiencies
Leukocyte Adhesion Deficiency (LAD)○ Integrin proteins needed for adhesion and
cellular interactionDefect limits recruitment of cells into areas of
inflammation
Primary ImmunodeficienciesInnate Immunodeficiencies
Chediak-Higashi Syndrome○ Autosomal recessive disease○ Phagocytes don’t have ability to kill bacteria
Primary ImmunodeficiencesInnate 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 ImmunodeficienciesInnate Immunodeficiencies
Myeloid Immunodeficiencies○ Affect innate immune system○ Impaired phagocytic process○ Recurrent microbial infection
Primary ImmunodeficienciesMyeloid Immunodeficiencies
Reduction in neutrophil count○ Low concentration – granulocytopenia or
neutropenia○ Congenital neutropenia
Frequent bacterial infections
○ Acquired neutropeniaCertain drugs or chemotherapy can cause thisAutoimmune disorder – destruction of neutrophils
Primary ImmunodeficienciesInnate 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 systemTests can then be done on the mouse to
see effects on that species’ immune systemExamples:
- 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) betweenT 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