2. Objectives
• Describe the immune system.
• Mention the ways of activating B lymphocytes.
• Recognize the types of antibodies.
• Describe the Isotype switching.
• Define Immunodeficiency.
• Define the common variable immunodeficiency.
• Mention causes, pathophysiology, Signs &
Symptoms, Complications, Diagnosis, Differential
diagnosis, Management and Prevention.
3. The immune system
• Immunity is defined as resistance to disease,
specifically infectious disease.
• The collection of cells, tissues, and molecules that
mediate resistance to infections is called the
immune system, and the coordinated reaction of
these cells and molecules to infectious microbes is
the immune response.
• Immunology is the study of the immune system and
its responses to invading pathogens.
• The physiologic function of the immune system is to
prevent infections and to eradicate established
infections.
12. Immunodeficiency
Defects in the development and functions of
the immune system result in
Increased susceptibility to infections
reactivation of latent infections
increased incidence of certain cancers
13. Immunodeficiency
• Disorders caused by defective immunity are called
immunodeficiency diseases.
• Some may result from genetic abnormalities in one
or more components of the immune system; these
are called congenital (or primary)
immunodeficiencies.
• Other defects may result from infections, nutritional
abnormalities, or medical treatments; these are
called acquired (or secondary)
immunodeficiencies.
14. The Common variable
Immunodeficiency
• Common variable immunodeficiency is a
heterogeneous group of disorders that
represent a common form of primary
immunodeficiency.
• These disorders are characterized by poor
antibody responses to infections and
reduced serum levels of IgG, IgA, and often
IgM.
15. Genetic Causes
• Due to the unclear genetic nature of CVID, a clear
pattern of inheritance has not been defined.
• In some instances, more than one family members
are deficient in one or more types of
immunoglobulins
• CVID is autosomal recessive.
Gene Mutations in CVID
inducible co- Mutations in a
protein on B-
stimulatory cell receptor
cells (CD19)
(ICOS) (TACI)
16. Causes
• The underlying causes of common variable disease
are poorly understood but include defects in B call
maturation and activation.
• Some patients have mutations in genes encoding
receptors for B cell growth factors or co-stimulators
involved in T cell-B cell interactions.
17. Pathophysiology
Changes in the
humoral response
mediated response
Changes in the cell-
• Failed B cell • T cell
differentiation abnormalities
with impaired present as well,
secretion of therefore, this is a
immunoglobulins global immune
dysfunction
disease
18. Signs & Symptoms
• frequent and chronic bacterial, viral or fungal
infections (bronchitis, pneumonia, ear or skin
infections etc.)
• chronic sinusitis or upper respiratory damage,
bronchiectasis
• fatigue
• lymph gland enlargement
• joint pain or arthritis (may be due to infection)
• hair loss
• infections or disorders of the digestive tract,
diarrhea
• anemia
• spleen enlargement
20. Diagnosis
• Testing is done by measuring immune globulin levels
in the blood. Supportive tests such as antibody
response tests and CT scan of sinus or lungs may
also be utilized.
• CVID often goes undiagnosed until symptoms are
more profound, in the second to fourth decade of
life.
21. Differential Diagnosis
Primary hypogammaglobulinemia:
• X-linked agammaglobulinemia
• SCID: atypical infections, T cell defects, or dysmorphic features
• Hyper-IgM syndrome: neutropenia, with normal or elevated IgM
and absent IgG
Secondary hypogammaglobulinemia:
• Decreased production
o Malignancy: thymoma, CLL, lymphoma
o Drugs: immunosuppresants, antiepileptics
o Viral infections: EBV, HIV, CMV, parvovirus B19
o Systemic illnesses causing bone marrow suppression
• Increased loss
o Protein-losing enteropathies
o Nephrotic syndrome
o Burn victims
22. Management
• IVIG is the mainstay
of treatment.
• Treatment of
infections.
• Surveillance for
autoimmunity &
malignancy.
23. Prevention
• Inheritance patterns vary among
patients and are not present in
most patients, making this disorder
impossible to prevent.
In the past few years, mutations in several different genes have been found to be associated with CVID. These include inducible co-stimulatory (ICOS) in one family and a protein on B-cells (CD19) in several families as causes of autosomal recessive CVID. Mutations in a cell receptor (TACI) for two factors (BAFF or APRIL) needed for normal growth and regulation of B-cells have also been found in about 10% of patients with CVID. A causative role of these mutations in the immune defect is not yet clear since some of these mutations can be found in people with normal immunoglobulins
