Coupon Accepted Successfully!


Immunodeficiency Syndromes

  • The two major targets of HIV infection are the immune system and the CNS. The profound immunodeficiency is the hallmark of AIDS. The viral envelope gp120 interacts with CD 4 molecule. The commonly affected CD4 cells in the human body include helper T cells ( worst affected), monocyte – macrophages and dendritic cells.
  • Defective CCR5 receptors lead to protective effect of providing resistance to the development of AIDS.
Major abnormalities of immune function in AIDS
Lymphopenia Decreased T cell function in Vivo Altered T-cell function in vitro Polyclonal B-cell Activation Altered monocyte functions
Predominantly due to selective loss of the CD4+ helper inducer T-cell subset; inversion of CD4: CD8 ratio Preferential loss of memory T cells and Decreased delayed-type hypersensitivity Decreased proliferative response to mitogens, alloantigens, and soluble antigens Hyper gamma globulinemia and circulating immune complexes Decreased chemotaxis and phagocytosis
  Susceptibility to neoplasms and opportunistic infections Decreased helper function for pokeweed mitogen induced B-cell immunoglobulin production Inability to mount de novo antibody response to a new antigen or vaccine Decreased HLA class II antigen expression and reduced antigen presentation to T cells

The opportunistic infections seen are: 
Bacterial infections Viral infections Fungal infections Protozoal infection
  • M. tuberculosis
  • Salmonella
  • Nocardiosis
  • Atypical mycobacterial infection
  • Cytomegalovirus
  • Herpes simplex virus
  • Varicella zoster virus
  • JC virus causing progressive multifocal leukoencephalopathy
  • Candidiasis
  • Pneumocystis jiroveci
  • Cryptococcosis
  • Histoplasmosis
  • Coccidiomycosis
  • Cryptosporidium
  • Isosporidium
  • Toxoplasmosis

Neoplasms in AIDS
Kaposi’s sarcom It is caused due to infection with Kaposi sarcoma herpesvirus (KSHV) or human herpes virus-8 (HHV8).
It is characterized by the proliferation of spindle-shaped cells that express markers of both endothelial (vascular or lymphatic) and smooth muscle cells.
KSHV infection is related to rare B cell lymphomas in AIDS patients known as body cavity based primary effusion lymphomas and to a multicentric B-cell lymphoproliferative disorder called as Castleman disease.  
  1. Lymphomas: AIDS related lymphomas include
    1. Systemic lymphomas having the CNS as the most common extranodal site for development of lymphom
    2. Primary CNS lymphoma found more commonly in AIDS than in general population.
    3. Body cavity lymphomas present as pleural, peritoneal or pericardial effusions.
These tumors are more frequently seen in patients with CD4+ T cell count <50 per microliter.
  1. Genital cancer including cancer of the cervix and the anal cancers due to infection with human papilloma virus (HPV)

Wiskott - Aldrich Syndrome

  • Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease".
  • It is caused by mutations in the WASP gene located on short arm of chromosome X. The WASP  protein is expressed in cells of all hematopoietic lineages. It is required for cytoskeletal integrity and signal transduction that are particularly important in platelets and T cells.
  • The disorder is seen in male patients and becomes symptomatic in children. It is characterized by bruising caused by thrombocytopenia", eczema (itchy rash), recurrent infection so, bloody diarrhea (due to thrombocytopenia) and a propensity for autoimmune disorders and malignancies (mainly lymphoma and leukemia).
  • In Wiskott-Aldrich syndrome, the platelets are small, have a shortened half life and do not function properly. They are removed by the spleen, which leads to low platelet counts. Splenomegaly may be seen.
The diagnosis is made on the basis of clinical parameters, the blood film and low immunoglobulin levels.
It is done with bone marrow transplantation. The alternatives include intravenous immunoglobulin infusions or splenectomy. 

Common Variable Immunodeficiency

Most patients with common variable immunodeficiency have normal or near-normal numbers of B cells in the blood and lymphoid tissues which are not able to differentiate into plasma cells.
Patients have intrinsic B-cell defects (defective cytokine receptor called BAFF which normally promotes B cell differentiation and survival) as well as abnormalities of T cell-mediated regulation of B cells.

The clinical manifestations include recurrent sinopulmonary pyogenic infections, recurrent herpesvirus infections and persistent diarrhea caused by G. lambli It affects both sexes equally, and the onset of symptoms is relatively late (in childhood or adolescence).
 These patients have a high frequency of autoimmune diseases like rheumatoid arthritis and increased risk of lymphoid malignancy (particularly in women). 

Digeorge Syndrome Or Velocardiofacial Syndrome

It is a T-cell deficiency due to deletion of chromosome 22qll.2.
The patients have a loss of  T cell-mediated immunity (owing to hypoplasia or lack of the thymus), tetany (owing to lack of the parathyroids), and congenital defects of the heart and great vessels. They may also have abnormal facies with defects in the mouth and ears.
The absence of cell-mediated immunity results in the development of recurrent fungal and viral infections.
Mnemonic: (CATCH 22)
        C      Cardiac abnormalities (especially tetralogy of Fallot)
        A     Abnormal facies
        T      Thymic aplasia
        C      Cleft palate
        H     Hypocalcemia (due to hypoplasia or lack of parathyroids)
        22   22q 11 deletion

Test Your Skills Now!
Take a Quiz now
Reviewer Name