Download Kuby Immunology 6/e - Dr. Jennifer Capers

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