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Immunodeficiency:
Secondary
Secondary article
Article Contents
. Introduction
Sudhir Gupta, University of California, Irvine, California, USA
Gabriel Fernandes, University of Texas, San Antonio, Texas, USA
. Malnutrition
. Malignancy
. Infections
Immune deficiencies that develop in previously immunologically intact individuals are
called secondary immunodeficiencies; they are a result of diverse external factors
(infections, surgery and trauma, malnutrition, drugs) and a number of human diseases,
including malignancy, nephrotic syndrome and protein-losing enteropathy.
Immunodeficiencies render the host markedly susceptible to viral and bacterial infections.
Introduction
Immune deficiencies that develop in previously immunologically intact individuals are called secondary immunodeficiencies; they are a result of diverse external factors
(infections, surgery and trauma, malnutrition, drugs) and a
number of human diseases, including malignancy, nephrotic syndrome and protein-losing enteropathy. Immunodeficiencies render the host markedly susceptible to viral
and bacterial infections.
Malnutrition
Malnutrition is the most common cause of secondary
immunodeficiency in the world. It is a serious problem,
particularly among young children in most developing
nations.
In malnutrition, inadequacy of essential nutrients results
in alterations in immune functions. The nutritional
deficiencies usually involve varying degrees of protein
and calorie deprivation (protein–calorie malnutrition).
Based on the predominant deficiency, protein–calorie
malnutrition has been divided into marasmus (caloric
deficiency due to decreased intake of all food) and
kwashiorkor (a deficiency of protein in a diet usually high
in calories). Marasmus usually occurs early in infancy. The
patients are grossly underweight and wasted; however, the
oedema and skin changes observed in kwashiorkor are
absent in marasmus. Kwashiorkor is more common during
the second year of life and is characterized by the presence
of growth retardation, dermatitis, oedema, moon facies,
hepatomegaly and abnormal hair. There is an overlap
between the two syndromes. Therefore, immunological
changes in both syndromes will be discussed together as
changes in protein–calorie malnutrition.
In protein–calorie malnutrition, the thymus is atrophic
and fibrotic. Changes are preferentially in the cortex; the
number of thymocytes is markedly reduced, as is thymic
. Drugs and Other Treatments
. Nephrotic Syndrome
. Protein-losing Enteropathy
hormone production. Varying degrees of germinal centre
depletion and depletion of paracortical cells in peripheral
lymphoid tissue are observed. Other T cell-mediated
changes include impaired delayed-type hypersensitivity
(DTH) reaction; reduced lymphocyte proliferation in
response to mitogens and antigens; decreased proportions
and numbers of cluster of differentiation (CD) 41 T cells;
and significantly increased levels of CD11 T cells.
Serum immunoglobulin levels are normal or raised.
Although serum immunoglobulin (Ig) A levels are often
increased, there is a significant decrease in secretory IgA
concentration. Raised levels of serum IgE have been
reported; however, involvement of parasitic infestation has
not been excluded. The numbers of CD201 B cells are
reduced and the affinity of antibodies, especially for Tdependent antigens, is impaired. Antibodies to pneumococcal polysaccharide are normal. Type 1 T-helper (TH)
cell cytokine (especially interferon g; IFNg) production is
reduced. Macrophage-derived and lipopolysaccharidestimulated interleukin (IL)-1 production is reduced, but
recovers after nutritional supplementation. Similarly,
tumour necrosis factor a (TNFa) production increases
after nutritional rehabilitation.
Polymorphonuclear leucocyte (PMN) functional defects
in protein–calorie malnutrition include impaired phagocytosis and intracellular killing, and altered mobility and
chemotaxis. In experimental animals, protein deprivation
is associated with decreased production of myeloid cells in
the bone marrow and the mobilization of PMNs into
inflammatory sites. This could be due to decreased
production of granulocyte colony-stimulating factor.
Natural killer (NK) cell activity is reduced even in
the presence of exogenous IFNg. Following nutritional
repletion, NK cell activity is normalized in the presence of
IFNg. Therefore, in protein–calorie malnutrition, abnormalities of T cells, B cells, monocytes–macrophages
and PMNs are present; however, T-cell deficiency is
usually predominant.
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1
Immunodeficiency: Secondary
Malignancy
Although some form of immunodeficiency can be observed
in the advanced stages of all types of malignancy,
secondary immunodeficiency is commonly observed in
lymphoid malignancies (leukaemia, lymphomas and plasma cell dyscrasias). Infections are common in lymphoid
malignancies and the most common cause of death in
lymphoid malignancy is infection.
Lymphoma
Antibody deficiency is observed in the advanced stages of
nonHodgkin lymphoma; however, significant immune
deficiency is a characteristic of Hodgkin disease. Hodgkin
disease was the first lymphoma to be associated with
abnormalities of the immune system. Immunological
defects may be related to the clinical stage of the disease
and the histological type (most severe defects are observed
in stages III and IV, and in lymphocyte depletion
histology). However, immune deficiency is observed even
in asymptomatic subjects. Hodgkin disease is a classic
example of T-cell deficiency in lymphoreticular malignancies. Lymphocyte depletion of lymphoid tissues, especially
of T-cell areas, is well recognized and may be associated
with peripheral blood lymphopenia. Both the proportion
and absolute number of T cells are reduced. There appears
to be an abnormal distribution of T-cell subsets between
peripheral blood and the spleen. Lymphocyte locomotion
is also abnormal, and this may be responsible for the
abnormal distribution of T-cell subsets in the blood and
spleen. Functional cell-mediated immune deficiency is
characterized by impaired or absent DTH to recall
antigens, and depressed proliferative response to mitogens,
antigens and alloantigens. Prolonged allograft survival is
observed in more than 50% of patients with Hodgkin
disease. Impaired synthesis of cytokines has also been
observed.
Although the precise mechanism of immunosuppression
in Hodgkin disease is not known, monocyte-mediated
suppression appears to be one of the important mechanisms. In addition, certain plasma factors have been
suggested to suppress the immune response. Levels of
serum immunoglobulins are usually normal; however, in
approximately 10% of patients either hyperimmunoglobulinaemia or hypogammaglobulinaemia may be observed. Secondary (IgG) antibody responses to specific
antigens are usually normal, but in some patients primary
antibody response (IgM) may be impaired. Specific antibody response to pneumococcal polysaccharide is normal.
Total serum complement concentration is normal or
raised. Phagocytic functions are usually intact, even in
the late stages of the disease. Phagocytosis, chemotaxis and
PMN mobilization are normal.
2
In summary, Hodgkin disease is associated with T-cell
deficiency without significant changes in other components
of the immune system.
Leukaemia
In contrast to patients with lymphoma, patients with acute
leukaemia generally have normal T cell- and B cellmediated immunity until they have advanced to the
terminal stage of the disease or have received chemotherapy. However, immune deficiency is commonly observed
in patients with chronic lymphocytic leukaemia (CLL).
Infections are the leading cause of death in CLL and in
multiple myeloma (see below). There appears to be a block
in the differentiation of B cells to plasma cells, resulting in
hypogammaglobulinaemia and specific antibody defects.
The incidence of hypogammaglobulinaemia in CLL varies
among various reports, ranging from 34% to 70%. The
levels of immunoglobulins vary with the duration of
disease. Patients with CLL also have a generalized defect in
specific antibody response to both protein and polysaccharide antigens (typhoid, diphtheria, tetanus, mumps,
influenza, pneumococcal polysaccharide, Vibrio vaccine).
There appears to be a correlation between levels of serum
IgG and increased infection rate in CLL; no such
correlation is observed with serum IgM levels. The
frequency of infection is markedly reduced with intravenous immune globulin treatment. The malignant B cells
express CD5 antigens on their surface. Although the
proportion of T cells is reduced, absolute numbers are
normal. When T cells are purified, on a cell per cell basis, Tcell functions in CLL are normal. Therefore, CLL
represents a classical example of secondary immunodeficiency of B cells with essentially normal T-cell functions.
Plasma cell dyscrasias
Multiple myeloma and Waldenström macroglobulinaemia
are the two most common plasma cell dyscrasias associated
with immunodeficiency. Both disorders are associated with
an increased incidence of infection. Immune deficiency is
more common and more severe in multiple myeloma than
in Waldenström macroglobulinaemia. Normal immunoglobulins appear to be decreased. There appears to be an
inverse correlation between the levels of monoclonal
immunoglobulin and normal immunoglobulins. Hypogammaglobulinaemia associated with multiple myeloma
appears to be due to increased catabolism (which correlates
with the levels of monoclonal immunoglobulin) and
increased suppressor activity of monocytes. Specific antibody response to antigens is also impaired. T cell-mediated
immunity is generally intact; however, decreased numbers
of CD41 T cells and increased CD81 T cells have been
observed in patients with multiple myeloma.
Immunodeficiency: Secondary
Infections
A variety of infectious agents are known to induce
immunosuppression. Therefore, immune deficiency is
observed in a variety of bacterial, fungal, protozoal and
viral infections, the latter being the most common clinical
condition associated with secondary immunodeficiency.
Some of the immunodeficiencies depend on the stage of
infection and are transient; others are permanent (e.g.
human immunodeficiency virus (HIV) infection).
(e.g. pneumococcal and meningococcal vaccine). This
abnormality of B-cell function appears to be due to
dysregulation of T-cell function. The CD41 /CD81 Tcell ratio is decreased and levels of gd T cells are
significantly increased. Although the mechanism of
malaria-induced immunosuppression is unclear, deficiency
of both IL-2 production and IL-2 receptor expression has
been observed. In addition, patients with acute malaria
have circulating IL-2 receptors, thereby potentially downregulating the response by binding secreted IL-2.
Bacterial infections
Viral infection
The most common bacterium associated with immunodeficiency is Mycobacterium leprae. Tuberculoid leprosy
displays pronounced T-cell immunity with low levels of
antibodies, whereas lepromatous leprosy is characterized
by severe T-cell deficiency with high antibody levels to M.
leprae. T-cell deficiency in lepromatous leprosy is demonstrable by cutaneous anergy and in vitro failure to induce
lymphocyte proliferation to soluble extract from M. leprae.
CD41 T cells predominate in tuberculoid lesions, whereas
CD81 T cells predominate in lepromatous lesions.
However, no such alterations are observed in peripheral
blood. T lymphocytes in lepromatous lesions are deficient
in IL-2 production but express IL-2 receptor (CD25) and
respond to IL-2. CD81 T cells from lepromatous lesions,
but not from tuberculoid lesions, show suppressor activity,
suggesting involvement of suppressor T cells in cutaneous
anergy in lepromatous leprosy. Interestingly, the DTH
response to other antigens may be intact, suggesting an
antigen-specific suppression of T-cell response.
A number of viruses can induce immunosuppression,
including measles, influenza, adenoviruses, herpesviruses
and HIV. Significant immunosuppression is observed with
measles, herpesvirus and HIV infection, and therefore
these are discussed in some detail.
Measles
Historically, measles provides the first evidence of viralinduced suppression of immune function. Measles virus
can infect both T and B cells; however, for its replication, T
and B cells have to be activated. Following a phase of
viraemia, virus is present in both lymphocytes and
macrophages, and is associated with lymphopenia and
suppression of T-cell responses both in vitro and in vivo.
Measles virus can suppress T-cell, NK-cell and B-cell
functions. Suppression associated with measles infection is
usually transient, although it can persist in some individuals.
Herpes infections
Fungal infections
Certain fungal infections have been implicated in the
pathogenesis of immune suppression. In vitro, Candida
albicans is known to suppress the lymphocyte proliferative
response to mitogens. Patients with chronic mucocutaneous candidiasis appear to have impaired DTH, lymphocyte proliferative response to mitogens and antigens, and
defective PMN chemotaxis. Immunosuppression has also
been observed in disseminated histoplasmosis. It is unclear
whether the immunosuppression in severe fungal infection
is due to general phenomena of immunological tolerance
secondary to high antigen load or to certain fungal antigens
that are truly immunosuppressive.
Protozoal infections
Acute malaria (Plasmodium falciparum infection) is
associated with polyclonal hyperimmunoglobulinaemia,
multiple autoantibodies and suppression of specific antibody response to both protein antigens (e.g. tetanus
toxoid, Salmonella typhi) and polysaccharide antigens
Infections by a group of herpes virus (e.g. Epstein–Barr
virus, cytomegalovirus (CMV) and herpes simplex virus
(HSV)) can be associated with immune suppression.
Generally, immunosuppression occurs during the acute
stage of infection and is transient. However, in some cases
persistence of infection may be associated with clinical
sequelae.
Epstein–Barr virus
The most common syndrome associated with acute
Epstein–Barr virus infection is infectious mononucleosis.
Immunological changes are characterized by T-cell immunosuppression, which could be due to T-cell receptorspecific impairment. Acute infectious mononucleosis is
associated with impaired DTH, decreased proliferative
response to mitogens and antigens, decreased NK cell
activity, increased IL-10 production, and increased B-cell
proliferation and differentiation to produce polyclonal
immunoglobulin. Atypical T cells in infectious mononucleosis are CD81 cytotoxic T cells. These immune
alterations are transient, but they can lead to long-term
immune dysregulation and clinical complications such as
3
Immunodeficiency: Secondary
X-linked lymphoproliferative syndrome, Burkitt lymphoma and nasopharyngeal carcinoma.
Cytomegalovirus
CMV is one of the most powerful immunosuppressive
viruses in the herpesvirus family. Immunosuppression
appears to be mediated by infected macrophages. CMVinfected macrophages are impaired in their capacity to
present antigens to autologous lymphocytes. The macrophage defect may be due to production of IL-1 inhibitor by
CMV. Carriers of CMV have an increased number of NK
cells with suppressive activity. Prolonged impairment of
lymphocyte proliferation to mitogens is observed in
children with congenital CMV infection.
Herpes simplex virus
Acute HSV-1 or HSV-2 infection is associated with
immune suppression resulting in depressed lymphocyte
transformation and production of specific antibodies. It
has been suggested that this is due to increased suppressor
T-cell activity; however, HSV glycoprotein can bind to Fc
receptor and inhibit phagocytosis, and can also inhibit
complement-mediated cytotoxicity. Patients with recurrent HSV infections also have immunological abnormalities characterized by lymphopenia and impaired
phagocytosis.
Influenza virus
Acute influenza infection is associated with T lymphopenia
and decreased lymphocyte proliferation to mitogens,
increased NK-cell activity, and production of IL-1 and
TNFa. In contrast to T-cell lymphopenia, acute influenza
is associated with expansion of gd T cells. Immunosuppression appears to be due to increased suppressor T-cell
activity and decreased IL-2 production. Increased NK-cell
activity appears to be secondary to increased interferon
production.
Human immunodeficiency virus
HIV infection is associated with almost every immunological abnormality, and it is not possible to discuss these in
detail here. There is a generalized lymphopenia, shared by
all subsets of lymphocytes, that is dependent upon the stage
of infection. During the acute stage of infection, there is an
expansion of CD81 cytotoxic T cells; however, as the
diseases progresses, several T-cell abnormalities are
observed, including selective depletion of CD41 T cells
resulting in an abnormally low ratio of CD41 /CD81 T
cells; decreased proliferative response to mitogens, soluble
antigens, autoantigens and alloantigens; decreased production of TH1 cytokines, and increased production of TH2
cytokines; and impaired cytotoxic T-cell function. Blymphocyte abnormalities include impaired specific antibody response to neoantigens; poor primary specific (IgM)
antibody response; polyclonal hyperimmunoglobulinae4
mia; increased proportion of circulating B cells; and
increased circulating immune complexes. NK-cell activity
is markedly impaired. Macrophages are defective in
presenting antigens and in the production of various
cytokines. Levels of complement components are normal
or increased (as acute-phase reactants). In HIV infection,
almost every component of the immune system is involved;
however, impaired T-cell abnormalities are mostly predominant.
Drugs and Other Treatments
The recognition and discovery of diseases associated with
abnormal immune response have resulted in the discovery
of drugs or agents that are capable of inhibiting undesirable immune responses. This group of agents, which are
nonspecific inhibitors of immune response (immunosuppressive agents), can be classified as physical, chemical or
biological agents.
Physical agents
Irradiation and depletion of lymphocytes by thoracic duct
drainage are two physical means of immunosuppression.
Because thoracic duct drainage is no longer used in clinical
settings, the immunosuppressive effects of irradiation are
discussed. Specific immune responses are predominantly
affected. Although phagocytosis is relatively resistant to
irradiation, low-dose irradiation suppresses antigen processing by macrophages. The effect on antibody response is
dependent on the dose of radiation. In contrast, T cellmediated immunity is significantly suppressed by irradiation. Studies of fractionated total lymphoid irradiation in
intractable rheumatoid arthritis and craniospinal radiation in children with acute lymphocytic leukaemia
demonstrated that radiation produces a significant effect
on T cell-mediated immunity, evident by pronounced
lymphocytopenia (predominantly of CD41 T cells),
impaired lymphocyte proliferation to mitogens and antigens, and decreased IgM and IgG production in response
to pokeweed mitogen (a T cell-dependent function). Levels
of CD81 T cells and NK cells are relatively normal or
increased.
Chemical agents
Immunosuppressive drugs can be divided into corticosteroids, cytotoxic drugs, and cyclosporin and allied drugs.
Corticosteroids
Corticosteroids are widely used as antiinflammatory and
immunosuppressive agents. Glucocorticoids are the most
effective steroids used for immunosuppression. The effects
of steroids are mediated by binding to specific receptors in
Immunodeficiency: Secondary
the cytoplasm. These translocate to the nucleus when
coupled with steroids and interact with chromatin to
regulate gene expression. More recently, it has been shown
that the major mechanism of corticosteroid-mediated
immunosuppression is its inhibition of the activation of
nuclear transcription factor NF-kB. The immunosuppressive effects of corticosteroids can be grouped into two
categories: effect on leucocyte traffic and effect on
leucocyte functions.
After a single injection of glucocorticoid there is a rapid
decrease in the total number of lymphocytes (that is
predominantly shared by CD41 T cells) due to sequestration of T lymphocytes in the lymphoid compartment. The
total number of lymphocytes as well as CD41 T cells
returns to normal levels 48 h after administration of
glucocorticoid. The B cell number is slightly reduced and
the NK cell number is unaffected, but the monocytopenia
remains significant.
In general, corticosteroids preferentially inhibit T-cell
functions. They inhibit the entry of cells into the G1 phase
and arrest the progression of activated lymphocytes from
the G1 to the S phase of the cell cycle. Corticosteroids
inhibit the lymphocyte proliferative response to mitogens,
antigens, alloantigens and autoantigens. Prolonged treatment also results in impaired DTH. Corticosteroids inhibit
production of IL-1, IL-2, TNFa, IL-4 and IL-6. Prolonged
treatment with corticosteroids may result in a modest
decrease in the serum level of IgG and possibly of IgA, but
not IgM. Specific antibody response is generally unaffected. Steroids have no effect on NK cells and antibodydependent cellular cytotoxicity (ADCC).
Steroids have a striking effect on monocyte–macrophage functions. They suppress bactericidal activity,
interfere with antigen presentation, impair chemotaxis,
decrease response to migration inhibition factor, and
suppress expression of Fc and complement receptor.
Corticosteroids do not alter PMN chemotaxis or lysosomal enzymes; however, steroids decrease the release of
nonlysosomal enzymes (e.g. collagenase and plasminogen
activator).
Cytotoxic agents
Cytotoxic agents are a group of chemicals with the
pharmacological property of killing self-replicating cells,
including lymphocytes. Immunosuppressive activity of
these agents is not limited to any single lymphocyte subset;
rather, they affect, to a varying extent, all immunocompetent cells, thereby producing generalized immunosuppression. These agents can produce differential cytotoxicity for
T and B cells. They are also cytotoxic to nonlymphoid
proliferating cells, resulting in their toxicity.
Cytotoxic agents can be classified into three major
groups. Group I agents exert their maximum immunosuppressive effect when administered just before antigen
challenge (e.g. nitrogen mustards). Group II agents
suppress immune response if administered following
antigenic challenge (e.g. azathioprine and methotrexate).
Group III drugs show inhibitory effects if administered
either before or after antigenic stimulation (e.g. cyclophosphamide).
Azathioprine
Azathioprine is a purine analogue that is rapidly converted
in vivo to 6-mercaptopurine. Azathioprine is cytostatic for
cells when they enter the S phase (deoxyribonucleic acid
(DNA) synthesis) of the cell cycle. 6-Mercaptopurine
exerts its effect after metabolism to thioinosinic acid, by
competitive inhibition of purine metabolism and by
incorporation into DNA as fraudulent base. Therefore,
the major effect of azathioprine is to inhibit DNA
synthesis, resulting in a decreased rate of cell replication.
It preferentially inhibits T-cell responses (response to
pokeweed mitogen is greater than that to phytohaemagglutinin) as compared to B-cell responses. However, both
T- and B-cell responses are inhibited. Primary antibody
response (IgM) is inhibited more easily than secondary
(IgG) antibody response. Azathioprine significantly reduces the numbers of NK cells and both NK and ADCC
activity. Azathioprine has no effect on monocyte chemotaxis, phagocytosis or microbial killing.
Cyclophosphamide
Cyclophosphamide is an alkylating agent that is toxic for
cells at all stages of the mitotic cycle, including the
intermitotic (G0) phase. However, it is more toxic for
cycling than for resting cells (G0). The cytotoxic effects are
due to azathioprine’s ability to crosslink DNA chains and
interfere with DNA replication. Although both T and B
cells are susceptible to the immunosuppressive effects of
cyclophosphamide, it is more cytotoxic for B cells than for
T cells. Suppressor T cells are more susceptible than helper
T cells to the inhibitory effect of azathioprine. Administration of azathioprine is associated with lymphopenia
(CD41 4 CD81 ), depressed DTH response to mumps
and Candida, impaired lymphocyte transformation to
mitogens (phytohaemagglutinin, pokeweed mitogen), decreased levels of immunoglobulins, and suppressed primary antibody response.
Cyclosporin A and related drugs
The immunosuppressive property of cyclosporin A (CsA)
was discovered in 1976; since then, FK-506 and rapamycin
have been shown to have similar properties and analogous
mechanisms of action. CsA has been used extensively in a
variety of disorders; FK-506 has just started to be used in
clinical research trials; and rapamycin has not yet been
used in clinical trials. Therefore, CsA alone will be
discussed. Cyclosporin is a noncytotoxic immunosuppressive agent, which has a powerful inhibitory effect on T cells,
on antigen presentation by macrophages, and on baso5
Immunodeficiency: Secondary
phils. It has a preferential effect on CD41 T cells. CsA
inhibits lymphocyte proliferation in response to mitogens,
antigens, alloantigens and autoantigens. It inhibits IL-2
messenger ribonucleic acid (mRNA) and protein synthesis
but not IL-2 receptor expression or the proliferative
response of T cells to exogenous IL-2. CsA also inhibits
IL-3, IL-4, IFNg, TNFa and granulocyte–macrophage
colony-stimulating factor mRNA. B cells are relatively
resistant to CsA; however, specific antibody response to Tdependent antigens is inhibited by CsA. CsA inhibits major
histocompatibility complex II expression on monocytes
and the antigen-presenting property of monocytes–macrophages and Langerhans cells. The molecular mechanisms
involved in CsA-mediated immunosuppression include
binding of CsA to intracellular cyclophilin; the CsA–
cyclophilin complex then binds to calcineurin (a calcium–
calmodulin-dependent phosphatase B), and finally inhibition of calcineurin results in inhibition of nuclear
transcription factor, NF-AT, and gene expression of
certain cytokines, including IL-2. FK-506 has the same
mechanism, except that it binds to a different immunophilin, FK-binding protein (FKBP). However, the effects of
rapamycin are different, even though it binds to FKBP.
Rapamycin does not inhibit early genes by activated T
cells. In contrast, it inhibits the effect of IL-2 binding to IL2 receptor.
Biological agents
Antilymphocyte globulin
Antilymphocyte globulin (ALG) is used to prevent
allograft rejection and in the treatment of aplastic anaemia.
Administration of ALG leads to lymphoid depletion from
both the peripheral blood and lymphoid tissues. DTH and
lymphocyte transformation to mitogens and antigens are
impaired. Primary antibody response to neoantigens is
impaired, but secondary antibody response is unaffected.
ALG poses a slight risk of lymphoproliferative malignancy
in posttransplant patients.
Nephrotic Syndrome
Serum electrophoresis from patients with idiopathic
nephrotic syndrome shows decreased albumin and gglobulin levels but an increased a2-globulin concentration.
Of the immunoglobulins, the greatest depletion occurs in
IgG. Serum IgG and IgA levels may remain low during
remission, although IgM concentration is increased. In
idiopathic nephrotic syndrome the antibody response to
bacterial antigen (pneumococcus polysaccharide) is impaired, whereas response to viral antigen (influenza
vaccine) is normal. T-cell number and functions are
generally normal except during uraemia. Complement
levels are increased. Neutrophil chemotaxis is impaired.
Protein-losing Enteropathy
Although a number of disease conditions are associated
with protein loss via the gut, protein loss occurs most
commonly in patients with gastrointestinal surface abnormalities (e.g. regional enteritis, ulcerative colitis, sprue
and coeliac disease). Reduction in the levels of all
immunoglobulins is associated with a normal or increased
synthetic rate and increased fractional catabolic rates.
Albumin and IgG concentrations are markedly decreased,
IgM level is mildly depressed, and a2-macroglobulin level is
normal. However, the specific antibody response is normal
and increased susceptibility to infection is unusual. In
addition, lymphopenia is observed in protein-losing
enteropathy associated with regional enteritis and intestinal lymphangiectasia. DTH is impaired, as is lymphocyte
response to mitogens. The CD41 /CD81 T-cell ratio is
decreased.
In summary, a number of external factors and certain
chemical and biological agents induce a wide spectrum of
secondary immunodeficiencies; many of them are transient, but others have long-lasting effects on the immune
system.
Anti-T cell monoclonal antibodies
A number of monoclonal antibodies against T-cell surface
antigens have been used in allogeneic organ transplantation, to deplete T cells from the donor marrow before
allogeneic bone marrow transplantation, and for the
treatment of acute graft-versus-host disease in patients
undergoing allogeneic bone marrow transplantation. The
most common monoclonal antibody used is against CD3
antigen. This antibody causes marked lymphocytopenia
associated with severe impairment of T-cell functions. It
should be noted that treatment with anti-CD3 monoclonal
antibody is associated with an increased incidence of
malignancy.
6
Further Reading
Craig L and Hecker AL (eds) (1996) Nutritional Immunomodulation in
Disease and Health Promotion. Ohio: Ross Production Division
Columbus.
Fernandes G (1991) Nutrition and immunity. Encyclopedia of Human
Biology, vol. 5, pp. 503–516. New York: Academic Press.
Gupta S (1992) Malnutrition and lymphocyte response in humans. In:
Cunningham-Rundles S (ed.) Nutritional Modulation of Immune
Responses, pp. 441–454. New York: Marcel Dekker.
Lachmann PJ, Peters DK, Rosen FS and Walport MJ (eds) (1993)
Clinical Aspects of Immunology. Oxford: Blackwell Scientific.
Steihm ER (ed). (1996) Immunologic Disorders in Infants and Children,
4th edn. Philadelphia, Pennsylvania: WB Saunders.