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