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Immune deficiency diseases may be caused by

:
1. inherited defects affecting immune system

development, 2. or they may result from secondary effects of other diseases (e.g., infection, malnutrition, aging, immunosuppression, autoimmunity, or chemotherapy).

Clinically
increased susceptibility to infections  as well as to certain forms of cancer. The type of infections in a given patient

depends largely on the component of the immune system that is affected.

Patients with defects in Ig, complement, or

phagocytic cells typically suffer from recurrent infections with pyogenic bacteria  whereas those with defects in cell-mediated immunity are prone to infections caused by viruses, fungi, and intracellular bacteria.

Primary Immune Deficiencies
Most primary immune deficiency diseases are

genetically determined and affect either: 1. adaptive immunity (i.e., humoral or cellular) or 2.innate host defense mechanisms, including complement proteins and cells such as phagocytes and NK cells.

Defects in adaptive immunity are often

subclassified on the basis of the primary component involved (i.e., B cells or T cells, or both) Most primary immune deficiencies come to attention early in life (between 6 months and 2 years of age), usually because the affected infants are susceptible to recurrent infections

X-Linked Agammaglobulinemia (XLA, Bruton Disease)
It is characterized by the failure of pre-B cells to

differentiate into B cells; there is a resultant absence of gamma globulin in the blood XLA does not become apparent until approximately 6 months of age, when maternal immunoglobulins are depleted. recurrent bacterial infections such as acute and chronic pharyngitis, sinusitis, otitis media, bronchitis, and pneumonia suggest an underlying immune defect

Because antibodies are important for

neutralizing viruses, these patients are also susceptible to certain viral infections, especially those caused by enteroviruses. Similarly, Giardia lamblia, an intestinal protozoan usually neutralized by secreted IgA, cannot be efficiently cleared and causes persistent infections

Isolated IgA Deficiency
IgA is the major Ig in mucosal secretions and is

thus involved in airway and gastrointestinal defense. Although most individuals with this condition are asymptomatic, weakened mucosal defenses predispose patients to recurrent sinopulmonary infections and diarrhea. There is also a significant (but unexplained) association with autoimmune diseases. IgM and IgG subclasses of antibodies are present in normal or even supranormal levels

Thymic Hypoplasia: DiGeorge Syndrome
DiGeorge syndrome results from a congenital

defect in thymic development with deficient Tcell maturation. T cells are absent in the lymph nodes, spleen, and peripheral blood, and infants with this defect are extremely vulnerable to viral, fungal, and protozoal infections. Patients are also susceptible to infection with intracellular bacteria, because of defective T-cell-mediated immunity. B cells and serum immunoglobulins are generally unaffected.

The disorder is a consequence of a

developmental malformation affecting the third and fourth pharyngeal pouchesstructures that give rise to the thymus, parathyroid glands, and portions of the face and aortic arch. Thus, in addition to the thymic and T-cell defects, there may be parathyroid gland hypoplasia resulting in hypocalcemic tetany, as well as additional midline developmental abnormalities

Severe Combined Immunodeficiency
Severe combined immunodeficiency (SCID)

represents a constellation of genetically distinct syndromes with the common feature of defects in both humoral and cell-mediated immune responses. Affected infants are susceptible to severe recurrent infections by a wide array of pathogens, including bacteria, viruses, fungi, and protozoans; opportunistic infections by Candida, Pneumocystis, CMV, and Pseudomonas also cause serious (and occasionally lethal) disease.

the thymus is hypoplastic. Lymph nodes and

lymphoid tissues (e.g., in the tonsils, gut, and appendix) are atrophic and lack B-cell germinal centers as well as paracortical T cells. Affected patients may have marked lymphopenia, with both T- and B-cell deficiency; others may have increased numbers of immature T cells and/or large numbers of B cells that are nonfunctional because of a lack of T-cell help

Genetic Deficiencies of Components of Innate Immunity
 Complement Proteins  complement components play important roles in inflammatory and

immunologic responses. Consequently, hereditary deficiency of complement components, especially C3 (critical for both the classical and alternative pathways), results in an increased susceptibility to infection with pyogenic bacteria. Inherited deficiencies of C1q, C2, and C4 do not make individuals susceptible to infections, but they do increase the risk of immune complex-mediated disease (e.g., SLE), possibly by impairing the clearance of apoptotic cells or of antigen-antibody complexes from the circulation. Deficiencies of the late components of the classical complement pathway (C5-C8) result in recurrent infections by Neisseria (gonococci, meningococci) but, curiously, not by other microbes. Lack of the regulatory protein C1 inhibitor allows unfettered C1 activation, with the generation of down-stream vasoactive complement mediators; the result is hereditary angioedema, characterized by recurrent episodes of localized edema affecting the skin and/or mucous membranes.  0 Phagocytes Body_ID: HC005087 Several congenital defects in phagocytes are known. These include defects in the phagocyte oxidase enzyme, the cause of chronic granulomatous disease, and defects in integrins and selectin ligands, causing the leukocyte adhesion deficiencies. These disorders were described in Chapter 2.

Secondary Immune Deficiencies
Immune deficiencies secondary to other

diseases or therapies are much more common than the primary (inherited) disorders. Secondary immune deficiencies may be encountered in patients with malnutrition, infection, cancer, renal disease, or sarcoidosis. However, the most common cases of immune deficiency are therapy-induced suppression of the bone marrow and of lymphocyte function

AIDS
• Acquired immune deficiency syndrome

secondary to infection with human immunodeficiency virus HIV.

Characterized by :
1. Marked suppression in T-lymphocyte. 2. Secondary neoplasm. 3. Opportunistic infections. 4. Neurologic disease.

Modes of transmission
1. Sexual contact. 2. Parental inoculation. 3. Passage from the infected mother to fetus.

Virus structure
Retrovirus. Lipid envelop derived from infected host

membrane. Two viral gp120,gp41 & the former important in binding to CD4 lymphocyte.

Pathogenesis
 Binding 0f the virus to target cells (CD4 LC,

lower level of monocyte & macrophage) & virus internalized.  Reverse transcription & viral DNA integrated to host genome.  Virus replications depend on T-cell activation.  Greater proportion of CD4 (+HIV) in LN mostly in the latent phase.

 Infected monocyte & macrophage refractory    

to cytopathic effect of the virus act as: reservoirs for HIV Vehicles for transport (CNS) These cells continuously infect T-cells as they pass through LN. Continuous depletion T-cells lead to immunodeficiency.

 Infected monocyte & macrophage refractory    

to cytopathic effect of the virus act as: reservoirs for HIV Vehicles for transport (CNS) These cells continuously infect T-cells as they pass through LN. Continuous depletion T-cells lead to immunodeficiency.

Abnormalities of the immune system
1. Lymphopenia 2. Decreased T-cell function. • Opportunistic infections •

Neoplasm 3. Abnormal B-cell activation 4. Altered monocyte & macrophage function • Decreased chemotaxis • Diminished ability to present Ag to T-cell

History of HIV infection
1. Acute phase • Transient viremia, seeding of lymphoid • •

tissue temporary fall in CD4-Tcells. Followed by seroconversion & control of viral replication by CD8 antiviral cells. Acute illness sore throat, mylagia, clinical recovery & near normal T-cells occur in 6-12 wk.

2. Chronic phase Clinical latency Low level of viral replication mainly in LN Slow decrease in in CD4-Tcells. Patient develop generalized LN enlargement. 7-10 years.

3. Crisis phase Sharp decline in in CD4-Tcells. Weight loss. Diarrhea. Opportunistic infections Secondary neoplasm.

Clinical features of AIDS
1. Variety of opportunistic infections due to

defect in CMI .(pneumocyctis carini )occur in 50% of patients. 2. Wide spectrum of pyogenic infections. Due to defect in humeral immunity. 3. Malignant neoplasm. Kaposi sarcoma 25% more in homosexual. NHL 60 fold more than general populations. 4. Neurological involovment 30%-50%