immunodeficiency

Dr. Ahmed Adil Immunology 3rd class-college of Medicine
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Immunodeficiency
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. Clinically, recurrent or opportunistic infections are commonly
seen. Recurrent infections with pyogenic bacteria, e.g., staphylococci, indicate a B-cell
deficiency, whereas recurrent infections with certain fungi, viruses, or protozoa indicate a Tcell
deficiency.
I- Congenital Immunodeficiency
1- 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. Cell-mediated immunity is relatively
normal. Clinically, recurrent pyogenic bacterial infections, e.g., otitis media, sinusitis, and
pneumonia caused by Streptococcus pneumoniae and Haemophilus influenzae, occur in infants
at about 6 months of age, when maternal antibody is no longer present in sufficient amount to
be protective. Treatment with pooled gamma globulin reduces the number of infections.
B- Selective Immunoglobulin Deficiencies
IgA deficiency is the most common of these; IgG and IgM deficiencies are rarer. Patients with
a deficiency of IgA typically have recurrent sinus and lung infections. (However, some
individuals with IgA deficiency do not have frequent infections, possibly because their IgG and
IgM levels confer protection). Patients with a deficiency of IgA should not be treated with
gamma globulin preparations, because these patients may form antibodies against the foreign
IgA.
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
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2- T-Cell Deficiencies
A- Thymic Aplasia (DiGeorge s Syndrome)
Both the thymus and the parathyroids fail to develop properly. The most common presenting
symptom is tetany due to hypocalcemia caused by hypoparathyroidism.
Severe viral, fungal, or protozoal infections occur in affected infants early in life as a result of a
profound deficit of T cells. Pneumonia caused by Pneumocystis Jiroveci and thrush caused by
Candida albicans are two common infections in these patients.
B- X-linked Hyper-IgM Syndrome
Severe, recurrent pyogenic bacterial infections resembling those seen in X-linked
hypogammaglobulinemia begin early in life. Patients have a high concentration of IgM but
very little IgG, IgA, and IgE. They have normal numbers of T cells and B cells. The main
manifestations is inability of the B cell to switch from the production of IgM to the other
classes of antibodies. This is due to a mutation in the gene encoding the CD40 ligand in the
CD4-positive helper T cells that interacts with CD40 on the B-cell surface .Treatment with
pooled gamma globulin results in fewer infections.
3- Combined B-Cell & T-Cell Deficiencies
Severe Combined Immunodeficiency Disease (SCID)
This is a group of inherited diseases, all of which are due to a defect in the differentiation of an
early stem cell. There are two types: X-linked and autosomal; the X-linked form constitutes
about 75% of cases. 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. In some
children, the B and T cells are absent; in others, the number of cells is normal but they do not
function properly. Immunoglobulin levels are very low and tonsils and lymph nodes are absent.
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
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Pneumocystis pneumonia is the most common presenting infection in these infants. Infections
caused by C. albicans and viruses such as varicella-zoster virus, cytomegalovirus, and
respiratory syncytial virus are common and often fatal.
4- Complement Deficiencies
A-Recurrent Infections
Patients with deficiencies in C1, 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. Those with reduced levels of
C6, C7, or C8 are especially prone to bacteremia with Neisseria meningitidis or Neisseria
gonorrhoeae.
B- Paroxysmal Nocturnal Hemoglobinuria(PNH)
This disease is characterized by episodes of brownish urine (hemoglobinuria), particularly
upon arising. The hemoglobinuria is due to complement-mediated hemolysis. This occurs
especially at night because the lower oxygen concentration in the blood during sleep increases
the susceptibility of the red cells to lyse. Hemolysis occurs because there is a deficiency of
decay-accelerating factor (DAF) on the surface of blood cell precursors, leading to an
increased activation of complement. Iron can be given for the anemia.
5- Phagocyte Deficiencies
A-Chronic Granulomatous Disease (CGD)
Patients with this disease are very susceptible to opportunistic infections with certain bacteria
and fungi, e.g., S. aureus, enteric gram-negative rods, especially Serratia and Burkholderia,
and Aspergillus fumigatus. Recurrent infections with catalase-positive bacteria, such as
staphylococci, are common in these patients; whereas infections with catalase-negative
bacteria, such as streptococci, are rare. In 60–80% of cases, this is an X-linked disease that
appears by the age of 2 years. (In the remaining patients, the disease is autosomal.)
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
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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). As a result, no hydrogen peroxide or
superoxides are produced (i.e., no oxidative burst occurs), and the organisms, although
ingested, are not killed.
B- Chédiak-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 neutrophils
to fuse with phagosomes. The degradative enzymes in the lysosomes are, therefore, not
available to kill the ingested organisms. In addition, the neutrophils do not function correctly
during chemotaxis. Peroxide and superoxide formation is normal, as are B-cell and T-cell
functions. Treatment involves antimicrobial drugs.
II- Acquired Immunodeficiencies
1- B-Cell Deficiencies
-Common Variable Hypogammaglobulinemia
Patients present with recurrent infections caused by pyogenic bacteria caused by pyogenic
bacteria such as S. pneumoniae and H. influenzae. The number of B cells is usually normal, but
the ability to synthesize IgG (and other immunoglobulins) is greatly reduced. Cell-mediated
immunity is usually normal. Intravenous gamma globulin given monthly reduces the number of
infections.
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
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2- T-Cell Deficiencies
-Acquired Immunodeficiency Syndrome
Patients with acquired immunodeficiency syndrome (AIDS) present with opportunistic
infections caused by certain bacteria, viruses, fungi, and protozoa (e.g., Mycobacterium aviumintracellulare
, herpesviruses, C. albicans, and P. jirovice).
This is due to greatly reduced helper T-cell numbers caused by infection with the retrovirus
human immunodeficiency virus. This virus specifically infects and kills cells bearing the CD4
protein as a surface receptor. AIDS patients also have a high incidence of tumors such as
lymphomas.
3- Complement Deficiencies
-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.
4- Phagocyte Deficiencies
-Neutropenia
Patients with neutropenia present with severe infections caused by pyogenic bacteria such as S.
aureus and S. pneumoniae and enteric gram-negative rods. Neutrophil counts below 500/?L
predispose to these infections. Common causes of neutropenia include cytotoxic drugs, such as
those used in cancer chemotherapy; leukemia, in which the bone marrow is "crowded out" by
leukemic cells; and autoimmune destruction of the neutrophils. Ciprofloxacin is used to try to
prevent infections in neutropenic patients.
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
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