-
B-Primary deficiencies of the adaptive immune system
1-Primary T-lymphocyte deficiencies
These are characterised by recurrent viral, protozoal and fungal
infections . In addition, many T-cell deficiencies are associated with
defective antibody production because of the importance of T cells in
providing help for B cells.
2-Combined B- and T-lymphocyte immune deficiencies
causes recurrent bacterial, fungal and viral infections soon after birth.
Bone marrow transplantation is the only current treatment option,
although specific gene therapy is under investigation.
3-Primary antibody deficienciesMORE IN ADULT
characterised
by recurrent bacterial infections
, particularly of the
respiratory and gastrointestinal tract
,:
A-
SELECTIVE IMMUNOGLOBULIN A DEFICIENCY
Selective IgA deficiency is the most common primary
immunodeficiency disorder and is characterized by serum
IgA levels
15 mg/dL with normal levels of IgG and IgM;
its prevalence is about 1:500 individuals.
CL.F
1-
Most persons areasymptomatic
because of compensatory increases
in secretedIgG and IgM.
2-
frequent andrecurrent infections
, such as sinusitis, otitis, and
bronchitis.
3-Individuals with selective IgA deficiency may have high
titers of anti-IgA antibodies and are at
risk for anaphylactic
reactions
following exposure to IgA through infusions of
plasma (or blood transfusions). These anti-IgA antibodies
develop in the absence of prior exposure to human plasma or
blood, possibly due to crossreactivity to bovine IgA in cow’s
milk or prior sensitization to maternal IgA in breast milk.
TREATMENT
Some cases of IgA deficiency may spontaneously remit. Treatment
with commercial immune globulin isineffective, since IgA and IgM
are present only in trace quantitiesin these preparations
B-Common variable immune deficiency (CVID
)
#.
intrinsic B cell defects that prevent terminal maturationinto
antibody-secreting plasma cells.
#The absolute B cellcount in the peripheral blood is normal
#It is characterised by low serumIgG levels but over time all antibody
classes (IgG, IgA, and IgM)may be affected .
and failure to make antibody responses to exogenous pathogens.
CLINICAL FEATURES
by1- an increased incidence of
recurrent infections
,
2-
autoimmune phenomena
, Paradoxically, antibody-mediated
autoimmune diseases such as idiopathic thrombocytopenic purpura and
autoimmune haemolyticanaemia are common autoimmune
endocrinopathies, seronegativerheumatic disease, and gastrointestinal
disorders arealso commonly seen
3-
and neoplastic diseases
There is an increased propensity for the
development of B cell neoplasms
(increaserisk of lymphoma), gastric carcinomas, and skin cancers
INVESTIGATION
1-, specific antibody responses to known pathogens should be assessed
by measuring IgG antibodies against tetanus, H. influenzae and Strep.
pneumoniae.
(most patients will have been exposed to some of these antigens
through either infection or immunisation). If specific antibody levels
are low, immunisation with the appropriate killed vaccine should be
followed by repeat antibody measurement 6-8 weeks later; failure to
mount a response indicates a significant defect in antibody production.
Management
1-All patients with antibody deficiencies require aggressive treatment
of infections and prophylactic antibiotics may be indicated.
2- The mainstay of treatment is immunoglobulin replacement
(intravenous immunoglobulin, IVIgGcontains IgG antibodies to a wide
variety of common organisms. IVIgG is usually administered every 3-
4 weeks with the aim of maintaining trough IgG levels within the
normal adult range. Treatment may be self-administered and is life-
long.
With the exception of selective IgA deficiency, immunisation is
generally not effective because of the defect in IgG antibody
production. As with all primary immune deficiencies, live vaccines
should be avoided.
2-Secondary immune deficiencies
Secondary immune deficiencies are much more common than primary
immune deficiencies).
Causes of secondary immune deficiency
Physiological
Ageing
Prematurity
Pregnancy
Infection
HIV
Measles
Mycobacterial infection
Iatrogenic
Immunosuppressive therapy
Antineoplastic agents
Corticosteroids
Stem cell transplantation
Radiation injury
Anti-epileptic agents
Malignancy
B-cell malignancies including leukaemia, lymphoma
and myeloma
Solid tumours
Thymoma
Biochemical and nutritional disorders
Malnutrition
Renal insufficiency/dialysis
Diabetes mellitus
Specific mineral deficiencies, e.g. iron, zinc
Other conditions
Burns
Asplenia/hyposplenism
T-CELL IMMUNODEFICIENCIES
Acquired immunodeficiency syndrome (AIDS)
By far the most common immunodeficiency worldwide is that due to
infection with the human immunodeficiency virus (HIV), the cause of
AIDS. Although the most profound deficiency is in CD4 T-cells, B cells
are also affected to give a mixed pattern.
. Mechanisms of CD4 loss/dysfunction in HIV
infection
1-Direct cytopathic effects of HIV
2-Lysis of infected cells by HIV-specific cytotoxic
Tcells
The central and most characteristic is the progressive and severe
depletion of CD4
+
'helper' lymphocytes. As described earlier, these cells
orchestrate the immune response, responding to antigen presented to
them via antigen-presenting cells in the context of class II MHC. They
(CD4)proliferate and release cytokines, particularly
1-IL-2. This leads to proliferation of other reactive T-cell clones,
including cytotoxic T cells, (which eradicate viral infections),
2- gamma-interferon (which activates NK cells to cytotoxicity) and
macrophages (microbicidal activity against intracellular pathogens).
Loss of this single cell type can therefore explain nearly all the
immunological abnormalities of AIDS
HYPERSENSITIVITY DISEASES
'is reactivity of an host to an agent on a second or subsequent
occasion'.
Hypersensitivity reactions include a number of
1-
autoimmune and -2-allergic conditions
1-AUTOIMMUNE DISEASE
Autoimmunity can be defined as the presence of immune responses
against self-tissue
CHARACTERISED BY present of auto antibody and auto reactive T cells
The spectrum of autoimmune disease
Type Disease
A-Organ-specific
Immune response directed against localised antigens Graves' disease
Hashimoto's thyroiditis
Addison's disease
Pernicious anaemia
Type 1 diabetes
Idiopathic thrombocytopenic purpura
Autoimmune haemolyticanaemia
Myasthenia gravis
Rheumatoid arthritis
Dermatomyositis
B-Multisystem
Immune response directed to widespread target antigens
Systemic sclerosis,
Mixed connective tissue disease
SLE
Physiology and pathology of autoimmunity (PATHOPHYSIOLOGY)
1-Immunological tolerance
Failure of immune system distinguishes self from foreign tissue,
. Here, T and B lymphocytes that recognize self antigens are eliminated
before they develop into fully immune competent cells..
2-Factors predisposing to autoimmune disease
1-Both A- genetic and B-environmental factors contribute.
. The most important genetic determinants of autoimmune
susceptibility are the HLA genes,
HLA associations in autoimmune disease
Disease
HLA association Relative risk
Ankylosing spondylitis B27 ∼90:1
Type 1 diabetes DR3/DR4 ∼20:1
Rheumatoid arthritis DR4 ∼5:1
Graves' disease DR3 ∼5:1
Myasthenia gravis
DR3 ∼3:1
Several environmental factors can trigger autoimmunity in genetically
predisposed individuals. 1-infection, as occurs in acute rheumatic fever
following streptococcal infection or reactive arthritis following bacterial
infection. A number of mechanisms have been responsible , such as a-
cross-reactivity between the infectious pathogen and self determinants
(molecular mimicry),
2-a side-effect of drug treatment. For example, the metabolic products
of the anaesthetic agent halothane bind to liver enzymes, resulting in a
structurally novel protein. This is recognised as a new (foreign) antigen
by the immune system, and the autoantibodies and activated T cells
directed against it may cause hepatic necrosis.