1. Chapter 18 AIDS and other Immunodeficiences Dr. Capers
Immunology

2. Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 20
AIDS and Other Immunodeficiencies
Copyright © 2007 by W. H. Freeman and Company

3. Autoimmunity – system attacks host cells and tissues
Immunodeficiency – system fails to protect
Primary immunodeficiency
Genetic or developmental defect
Secondary immunodeficiency - acquired

4. 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

7. 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

8. MHC defects Symptoms can resemble SCID
Lack of MHC II - Bare-lymphocyte syndrome

9. 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

10. 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

11. 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

12. Primary Immunodeficiences Combined Immunodeficiences
Hyper-IgE Syndrome (job syndrome)
Autosomal dominant
Skin abscesses, pneumonia, eczema, facial abnormalities
High # of eosinophils and IgE

13. 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

14. Primary Immunodeficiences B cell Immunodeficiences
Common Variable Immunodeficiency (CVI)
Low levels of immunoglobulin – hypogammaglobulinemia
Manifests later in life

15. 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

16. 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

17. Primary Immunodeficiencies Innate Immunodeficiencies
Chediak-Higashi Syndrome
Autosomal recessive disease
Phagocytes don’t have ability to kill bacteria

18. 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

19. Primary Immunodeficiencies Innate Immunodeficiencies
Myeloid Immunodeficiencies
Affect innate immune system
Impaired phagocytic process
Recurrent microbial infection

20. 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

21. Primary Immunodeficiencies Innate Immunodeficiencies
Complement deficiencies
Fairly common
Mostly associated with bacterial infections or immune-complex diseases

22. 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

23. 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

24. AIDS and other secondary acquired Immunodeficiences

25. Acquired Immunodeficencies
No a genetic component
Examples:
Hypogammaglobulinemia – unknown cause, different from genetic condition
AIDS

27. 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

29. Passage of HIV (green) between
T cell and dendritic cell

30. HIV Therapeutic agents inhibit retrovirus replication
Have to be specific for HIV so that they don’t interfere with cellular processes

33. Vaccine may be only
Way to stop HIV