Transcript Immune status. Immunodeficiency

Indication for an assessment of immune status.
1. Detailed examination of the human health.
2. Genetic defects of the immune system (primary immunodeficiency).
3. Acute and chronic bacterial, viral and protozoan disease (hepatitis,
sepsis, chronic pneumonia, leishmaniasis, AIDS etc.).
4. Autoimmune diseases (rheumatism, rheumatoid arthritis, systemic
lupus erythematous, etc).
5. Dermatoveneral diseases (contact dermatitis, pemphigus, mycosis
fungoides, syphilis, etc.).
6. Tuberculosis and leprosy.
7. Allergic diseases (bronchial asthma, atopy, etc.).
8. Malignant tumours (leukosis, lymphogranulomatosis, lymphosarcoma
etc.).
9. Psychical diseases (narcomania, schizophrenia, etc.).
10. Examination of the patients in gerontological and endocrinological
hospitals.
11. The control of cytostatic, immunosuppressive and immunostimulation
therapy.
12. Examination of the recipients before and after transplantations.
The first level tests for assessment of immune status (approximate):
1. Determination of total quantity of lymphocytes in periferal blood (absolute
and relative);
2. Determination of Т– and B–lymphocytes in peripheral blood;
3. Determination of the concentration of the main classes of
immunoglobulins;
4. Determination of phagocitic activity of leukocytes.
The second level tests for assessment of immune status (analytical):
1. Determination of subpopulations of T lymphocytes (CD4+ and CD8+);
2. Leukocyte migration inhibition test;
3. Examination of proliferative ability of T– and B–lymphocytes
(lymphocyte blast transformation test);
4. Cutaneous tests of hypersensitivity;
5. Determination of circulating immune complexes;
6. Determination of B-lymphocytes which carry superficial
immunoglobulins;
7. Assessment of immunoglobulins synthesis in B-lymphocytes culture;
8. Assessment of activity of K–cells and NK–cells;
9. Examination of the components of the complement system;
10. Assessment of different stages of phagocytosis.
Immunodeficiency diseases
• SCID: severe combined
immunodeficiency
• Thymic aplasia: DiGeorge anomaly
• XLA: Bruton’s agammaglobulinemia
• Common variable immunodeficiency
• Selective IgA deficiency
• Wiskott-Aldrich syndrome
• Ataxia-telangiectasia
• Chronic granulomatous disease
• Chédiak-Higashi syndrome
• Hyper-IgE syndrome (Job’s syndrome)
IMMUNODEFICIENCIES
Immunodeficiency can occur in any of the four major components of
the
immune system: (1) B cells (antibody), (2) T cells, (3) complement, and
(4) phagocytes. The deficiencies can be either congenital or acquired.
CONGENITAL IMUNODEFICIENCIES
B Cell Deficiencies
A. X-Linked Hypogammaglobulinemia (Bruton's Agammaglobulinemia): Very low levels of all immunoglobulins (IgG, IgA, IgM, IgD, and
IgE) and a virtual absence of B cells are found in young boys; female
carriers are immunologically normal. Pre-B cells are present, but they
fail to differentiate into B cells.
B. Selective Immunoglobulin Deficiencies: IgA deficiency is the most
common of these; IgG and IgM deficiencies are rarer. Patients with a defi
ciency of IgA typically have recurrent sinus and lung infections. The
cause of IgA deficiency may be a failure of heavy-chain gene switching.
Patients with selective IgM deficiency or deficiency of one or more of
the IgG subclasses also have recurrent sine-pulmonary infections caused
by pyogenic bacteria such as S. pneumoniae, H. influenzae, or S. aureus.
T Cell Deficiencies
A. Thymic Aplasia (DiGeorge's Syndrome). Severe viral, fungal, or protozoal
infections occur in affected infants early in life. a result of a profound deficit
of T cells. Both the thymus and the parathyroids fail to develop properly. The
most common presenting symptom is tetany due to hypocalcemia caused by
hypoparathyroidism. Other congenital abnormalities are common. A
transplant of fetal thymus may reconstitute T cell immunity.
Combined B Cell and T Cell Deficiencies
A. Severe Combined Immunodeficiency Disease (SCID): Recurrent
infections caused by bacteria, viruses, fungi, and protozoa occur in early
infancy (3 months of age), because both B cells and T cells are defective.
This is a group of inherited diseases, all of which are due to a defect in the
differentiation of an early stem cell.
B. Wiskott-Aldrich Syndrome: Recurrent pyogenic infections, eczema, and
bleeding caused by thrombocytopenia characterize this syndrome. These
symptoms typically appear during the first year of life. The defect appears to
be in the ability of T cells to provide help to B cells.
C. Ataxia-Telangiectasia: In this disease, ataxia, telangiectasia and
curerrent infections appear by 2 years of age. It is an autosomal recessive
disease caused by mutations in the genes that encode DNA repair enzymes.
Complement Deficiencies
Hereditary Angloedema: This is an uncommon autosomal dominant
disease caused by a deficiency of Cl inhibitor.
Recurrent Infections: Patients with deficiencies in Cl, C3 or C5 or the
later components C6, C7, or C8 have an increased susceptibility to
bacterial infections. Patients with C3 deficiency are particularly
susceptible to sepsis with pyogenic bacteria such as S aureus.
Autoimmune Diseases: Patients with C2 and C4 deficiencies have
diseases resembling systemic lupus erythematosus.
Phagocyte Deficiencies
A. Chronic Granulomatosis Disease (CGD): Patients with this
disease are very susceptible to opportunistic infections with
certain bacteria and fungi, eg, S aureus, enteric gram-negative
rods, especially Serratia and Burkholderia, and Aspergillus
fumigatus. CGD is due to a defect in the intracellular
microbicidal activity of neutrophils as a result of a lack of
NADPH oxidase activity (or similar enzymes).
B. Chediak-Higashi Syndrome: In this autosomal recessive
disease, recurrent pyogenic infections, caused primarily by
staphylococci and streptococci, occur. This is due to the failure
of the lysosomes of neitrophils to empty their contents.
ACQUIRED IMMUNODEFICIENCIES
B Cell Deficiencies
Common Variable Hypogammaglobulinemia:
T Cell Deficiencies
A. Acquired Immunodeficiency Syndrome:
B. Measles: Patients with measles have a transient suppression of delayed
hypersensttivity as manifested by a loss of PPD skin test reactivity.
Complement Deficiencies
A. Liver failure: Liver failure caused by alcoholic cirrhosis or by
chronic Hepatitis B or hepatitis C can reduce the synthesis of complement
proteins by the liver to a level that severe pyogenic infections can occur.
Neutropenia: Patients with neutropenia present with severe infections
caused by pyogenic bacteria such as S aureus and S pneumoniae.
Neutrophil counts below 500/μL predispose to these infections. Common
causes of neutropenia include cytotoxic drugs
Chronic Fatigue Syndrome (Chronic Fatigue Immune Dysfunction
Syndrome)