Human Immune deficiency Virus

Introduction.
Components of the immune system.
Human Immunodeficiency Virus (HIV).
HIV invasion and host response to viral entry.
Conclusion.
References.

Introduction:

Our Immune System is often exposed to dangers represented by bacteria, fungi, viral infections and so forth.  Some of which are negligible and others may be fatal.  This essay will briefly outline the effects of Human Immune deficiency Virus on the immune system in the following scheme:

An introduction will include general information about the immune system.
The mechanism of HIV invasion into the host cells and the immune response to it.
Finally, the major immune cells affected by the virus will be mentioned.

Components of the Immune System:

The immune system is composed of many organs, such as, bone marrow, thymus, spleen, lymphatic system and peripheral blood and the cells it contains.  Examples:  lymphocytes including B cells and T cells, phagocytes, such as, mononuclear phagocytes, and auxillary cells like basophisl, mast cells and platelets. (1)(2).

Lymphocytes include:
1. T cells that are grouped into Th cells (CD4+) & Tc cells (CD8+).

- Inducer helper cells (Th) play a vital rule in immune defense mechanisms. Th cells are  subdivided into two more groups:
     - Th1 cells help the humoral immunity by inducing the production of opsonizing antibodies.  They also take a part      in cell mediated immunity by activating infected macrophage through releasing the cytokin INF gama.
    - Th2 cells activate naïve B cells to secrete IgM and induce the production of neutralizing Abs isotypes including weakly opsonizing Abs. i.e. contribute to humoral immunity, this is accomplished by releasing IL4, IL5.

 - (Tc) functions as cytotoxic cells and as suppressor cells.  They destroy host cells that have been infected by viruses or other intracellular pathogens. i.e. play a role in cell mediated immunity (2)

2.B cells: make about 10 - 20 % of circulating pool of lymphocytes.  When they are stimulated, antibodies are produced. (2)

Monocytes, which are white blood cells, play a vital role in defense mechanisms.  Their actions include phagocytosis and killing certain microorganisms, clearing antigens bound to antibodies.  Moreover, they also act as antigen presenting cells (APCs) i.e. presenting antigens to lymphocytes.(1)
In addition to what has been mentioned previously, other components of the immune system are: auxiliary cells like basophils,  mast cells, and soluble mediators, such as, antibodies and cytokines. (1)(2)

The Human Immune deficiency Virus (HIV)

The Human Immune deficiency Virus is an RNA enveloped virus.  Moreover, it is a retrovirus i.e.: capable of propagating itself.   The membrane envelope of the virus contains two linked glycoproteins, gp 120 and gp 41. (1)(2). 

HIV invasion and host response to viral entry:

HIV invades host cells that are CD4+ like Th cells and cells of monocytes/ macrophages lineage, such as, dendrites cells of lymphoid tissues and skin.  This process happens by binding of gp 120 to CD4 molecules and then entering these cells carrying this marker.  After that, HIV coat opens, RNA virus enters the cells and DNA is created from RNA by the enzyme reverse transcriptase.  Viral DNA, then, is integrated into cellular DNA of the host cells.  Consequently, cell products will include new virus structural components (1)(2).    HIV contains a number of proteins that can be recognized by the Th cells as epitopes.  Some of these epitopes are immunodominant i.e. frequently recognized by T cells of infected subjects.  T1 and T2 are the two  immunodominant epitopes on gp 120.( identified by Cease & colleagues).  In vitro, IL2 is recognized and secreted by T cells of 85% of HIV infected subjects in response to one of the two epitopes.  More over,  asymptomatic sereo-positive subjects show high proliferative response to HIV gp120, which decreases with the onset of AIDS.  The MHC class I-restricted CTL rise and proliferate in response to HIV protein.  However, it decreases as HIV progresses to AIDS.  Monocytes take a part in mediating ADCC against HIV-coated target cells in  asymptomatic sero-poositive subjects .(4)
  However,  the immune cells response to HIV decreases by time and several immunologic abnormalities can be detected.
The major immune cells affected by the virus are T4 (CD4+).  As has been mentioned previously, the CD4+ molecule is the cellular receptor for the virus.  This will not only lead to a quantitative defect in Th  (Decrease in T4 number resulting in lymphopenia, the cytotoxic (CD8+) usually are normal or slightly elevated in amount.  CD4: CD8 ratio decrease from 2 to less than 1), but the function of infected cells is also defected.  The functional defect in T4 cells is summarized in four points:
 

B cell are also affected by HIV.  In addition to inadequate regulation by  T cells, B cells are polyclonally activated resulting in increased level of circulating immunoglobulins.  However, B cells will lose the ability to produce antibodies in response to a new antigen. (1) (3)

Monocytes/macrophages are the third type of cells affected by HIV.  The ability of these cells for intracellular killing following phagocytosis is decreased.  Beside that, monocytes/phagocytes become unable to respond to a variety of chemotactic stimuli, such as, EMLP and LDCF.  Decreased expression of class II HLA antigens (HLA-DR) on circulating monocytes have been found.  Two possible reasons for the reduced expression of HLA antigens ,this can be due to either the lack of gamma interferon and other monocytes stimulating lymphokins or direct infection of monocytes/macrophages with HIV.(1)(3)

Conclusion:

To sum up, the Human Immune deficiency Virus (HIV) is one of the most dangerous immuno- pathies that threat the normal function of the immune system, especially the part of it assigned to CD4+ cells because the cellular receptor for the virus is the CD4 molecule itself.  The essay listed the normal functions for CD4+ & CD8+ cells in immune defense.
Finally, the major cells affected by the virus were mentioned.

Here is a summary of the immunologic abnormalities resulting from HIV infection of the helper /inducer T cells (CD4+).

B cells

Monocytes/macrophages

RBCs & platelet.

Natural Killer cells

(CD4+ ) T cells  ? Lymphopenia

(CD8+) T cells

Reference:

(1) Flaskerud, Jacquelyn. AIDS/HIV INFECTION A REFERENCE GUIDE FOR NURSING PROFESSIONALS. Phikadelphia, W.B SAUNDERS COMPANY. 1989. PP 37-44.
(2) Roitt, Ivan. Ed. Brostoff, Jonthan, etal. IMMUNOLOGY.4th ed. London,MOSPY.1998.   P1.4,  21.6-7
(3) Harawi,  Samij.  Ed, O'hara,Carl.  Pathology and Pathophysiology of AIDS and HIV Related diseases. St. Louis, THE C.V MOSPY COMPANY. 1989. PP 25,  28-32.
(4)  De Vita, Vincent T, Hellman, Samuel. etal.  AIDS, Etiology, Diagnosis, Treatment, and Prevention. 3rd ed. Philadelphia, JB. Lippincott Company. 1992. PP 79,80.