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The immune system functional compartments

The B-lymphocyte system The T-lymphocyte system The Phagocytic system The Complement system

Frequency of the Primary Immunodeficiency Diseases

The primary immunodeficiency diseases were originally thought to be quite rare. some of the primary immunodeficiency diseases are relatively common. For example, Selective IgA deficiency occurs in as many as 1/5001/1000 individuals. Other primary immunodeficiency diseases are much less common and occur with a frequency of between 1/10,000 and 1/100,000. Because there are so many primary immunodeficiency diseases, when taken together as a group of disorders, they become a significant health problem, occurring with a frequency comparable to leukemia and lymphoma in children and four times as frequently as cystic fibrosis

Causes of the Primary Immunodeficiency Diseases

Many of the primary immunodeficiency diseases are genetically determined. Some of these are inherited as autosomal recessive traits, some as X-linked recessive traits, and at least one is inherited as an autosomal dominant trait. Others are not inherited as single gene defects. In fact, two of the most common primary immunodeficiency diseases, Common Variable Immunodeficiency (CVID) and Selective IgA Deficiency, usually occur sporadically and do not appear to be due to single gene defects in most cases. However, there are even some rare cases of Common Variable Immunodeficiency Disease and Selective IgA Deficiency that occur in a familial setting.

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 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 Lyphoid Immunodeficiences

Severe Combined Immunodeficiency (SCID)

Low # of circulating lymphocytes Non-proliferating T cells Thymus doesnt develop Usually fatal early years of life
- Infant will have viral and fungal infections - Bacterial dont show up until later because of placental transfer of Abs from mother - Chronic diarrhea, pneumonia, lesions

Many genetic defects can contribute to SCID

Primary Immunodeficiences Lymphoid Immunodeficiences

Wiskott-Aldrich Syndrom (WAS)

X-linked disorder Initially B and T cell numbers are normal but will decrease with age Will result in fatal infection or lymphoid malignancy

Primary Immunodeficiences Lymphoid Immunodeficiences

Interferon-Gamma-Receptor Defect
Autosomal recessive trait results from inbreeding Defect in receptor for IFN-
Patients suffer from infection with mycobaterium, showing importance of this receptor in fighting mycobacterium

Primary Immunodeficiences Lymphoid 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 Lymphoid 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 Lymphoid Immunodeficiences

Common Variable Immunodeficiency (CVI)

Low levels of immunoglobulin hypogammaglobulinemia Manifests later in life

Primary Immunodeficiences Lymphoid Immunodeficiences

Hyper-IgE Syndrome (job syndrome)

Autosomal dominant Skin abscesses, pneumonia, eczema, facial abnormalities High # of eosinophils and IgE

Primary Immunodeficiences Lymphoid 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 Lymphoid Immunodeficiencies

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

Inherited disorder General failure to thrive

Primary Immunodeficiencies Myeloid 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 Myeloid Immunodeficiencies

Chediak-Higashi Syndrome
Autosomal recessive disease Phagocytes dont have ability to kill bacteria

Primary Immunodeficiencies Lymphoid Immunodeficiencies

Leukocyte Adhesion Deficiency (LAD)

Integrin proteins needed for adhesion and cellular interaction
Defect limits recruitment of cells into areas of inflammation

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