A Brief Look at Immunity - Pharmacology

The immune system is the body’s way of combating the invasion of microscopic organisms such as bacteria, viruses, molds, spores, pollens, protozoa, and cells from transplant donors (human or animal). The immune system prevents an invasion from attacking internal organs and, if that fails, the immune system neutralizes, destroys, and eliminates any non-self proteins and cells, including microorganisms.

Non-self proteins and cells also include self cells (the body’s own cells) that have become infected or debilitated. One example is malignant transformation that changes healthy cells into cancer cells. The ability of the immune system to differentiate between the body’s own cells and non-self cells is called self-tolerance.

The immune system is able to recognize self-cells by using unique proteins that are on the surface of all self-cells. Think of these proteins as an identification code. Foreign cells have a different identification code. These are called antigens and stimulate the immune response of a host.

When bacteria invade your body, your immune system detects the bacteria’s surface protein as not being a self-cell. This triggers your immune system to launch an attack against the bacteria.

The immune system originates in the bone marrow. Mature immune system cells are released from the bone marrow into the bloodstream where they circulate throughout the body looking for invaders.

There are three processes necessary for immunity: inflammation, antibody-mediated immunity (humoral immunity), and cell-mediated immunity (CMI).


This is discussed in detail in Chapter(INFLAMMATION).


Antibody-mediated immunity occurs when the immune system produces antibodies that neutralize, eliminate, or destroy an antigen (foreign protein). Antibodies are produced by B lymphocytes. The body must be exposed to sufficient amounts of an antigen before the immune system produces an antibody to combat the antigen. Patients can be given vaccinations that stimulate the immune system to generate antibodies before the microorganism actually invades the body. In this way, the antibodies already exist and can attack at the first sign of the microorganism.


Cell-mediated immunity, also known as cellular immunity, uses T-leukocytes (referred to as natural killer cells or NK cells) to attack non-self cells. Cell-mediated immunity also causes the body to release cytokines, which regulate the activities of antibody-mediated immunity and inflammation.

Cell-mediated immunity is especially useful in identifying and ridding the body of self-cells that are infected by organisms that live within host cells and self-cells that mutate at the DNA level transforming them into abnormal and potentially harmful cells. Cell-mediated immunity is critically important in preventing development of cancer and metastasis after exposure to carcinogens.

HIV and the immune system

Human immunodeficiency virus (HIV) is a retrovirus that gradually destroys the immune system’s function. When the retrovirus becomes active, the patient develops acquired immunodeficiency syndrome (AIDS), which is characterized by profound immunological deficits, opportunistic infection, secondary infections, and malignant neoplasms.

HIV disables and kills CD4+ T cells, which lowers the immune system’s capability to fight infection. The number of CD4+ T cells triggers other cells in the immune system to attack invading organisms. HIV lowers the CD4+ T cell count and thereby inhibits other immune system cells to go on the attack.

A healthy person who is not HIV positive, has between 800 and 1200 CD4+ T cells per cubic millimeter (mm3) of blood. HIV reduces this count to 200 mm3. This is equal to or less than 14%. Infected patients are particularly vulnerable to opportunistic infections and cancers.

In addition to the T-cell count, the viral load (VL) is a test used to evaluate the status of the patient’s immune system. The higher the number, the higher the viral load. HIV is transmitted in three ways: injection of infected blood or blood products, sexual contact, and maternal-fetal transmission. Occupational exposure to HIV accounts for a small number of transmissions usually from a needle-stick.

HIV uses three enzymes to genetically encode, replicate, and assemble a new HI virus within a host cell. HIV can replicate only inside cells. These enzymes are reverse transcriptase, integrase, and protease.

The HI virus enters the cell through the CD4 molecule on the cell surface. Once inside the cell, the virus is uncoated with the help of the reverse transcriptase enzyme enabling the virus’ single stranded RNA to be converted into DNA.

The viral DNA migrates to the nucleus of the cell where it is spliced into the host DNA with the help of the integrase enzyme. Once combined, the HIV DNA is called the provirus and is duplicated each time the cell divides. The protease enzyme assists in the assembly of a new form of the viral particles.

Patients with HIV undergo Highly Active Antiretroviral Therapy (HAART) that uses antiretroviral medications designed to slow or inhibit reverse transcriptase and protease enzymes. The Food and Drug Administration approved the first reverse transcriptase (RT) inhibitor in 1987. The first protease inhibitor was approved in 1995. No integrase inhibitors have been approved as yet.

HAART decreases the viral load to undetectable levels, thereby preserving and increasing the number of CD4+ T cells. HAART also prevents resistance to disease and keeps the patient in good clinical condition and prevents secondary infections and cancer.

The patient must adhere to HAART therapy as the virus becomes resistant and the antiretroviral agents lose their therapeutic effect. In addition, patients must avoid opportunistic infections and aggressive prophylaxis and treatment of opportunistic infections that do occur is recommended. Nutritional therapy, complementary therapy, and supportive care are also necessary.

Antiretroviral therapy is offered to patients who have less than 500 CD4+ T cells mm3 or whose plasma HIV RNA levels are greater than 10,000 copies/mL (B-DNA assay) or 20,000 copies/mL (R-PCR assay). Therapy should be considered for all HIV-infected patients who have detectable HIV RNA in plasma. There are risks and benefits to early initiation of antiretroviral therapy in the asymptomatic HIV-infected patient.

Potential Benefits

  • Control of viral replication and mutation
  • Reduction of viral burden
  • Prevention of progressive immunodeficiency
  • Maintenance of the normal immune system
  • Reconstruction of the normal immune system
  • Delay in the progression to acquired immunodeficiency syndrome and prolongation of life
  • Decreased risk of selection of resistant virus
  • Decreased risk of drug toxicity
  • Possible decreased risk of viral transmission

Potential Risks

  • Reduction in quality of life from adverse drug effects
  • Inconvenience of taking the regimen of medications
  • Earlier development of drug resistance
  • Transmission of drug-resistant virus
  • Limitation in future choices of antiretroviral agents as a result of develop-ment of resistance
  • Unknown longterm toxicity of antiretroviral drugs
  • Unknown duration of effectiveness of current antiretroviral therapies

HIV medication

There are four classes of medication approved by the FDA for treatment of HIV (see Charts). These are:

Nonnucleoside Reverse Transcriptase Inhibitors(NNRTIs)

NNRTIs bind to reverse transcriptase, a protein HIV needs to make more copies of itself. In doing so, reverse transcriptase becomes disabled. Drugs within this category include Delavirdine (Rescriptor, DLV), Efavirenz (Sustiva, EFV), and Neviapine (Viramune, NVP).

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

NRTIs are faulty version reverse transcriptase. Reproduction of HIV is stalled when HIV uses NRTI instead of the normal reverse transcriptase. Drugs within this category include Abacavir (Ziagen, ABC), Abacavir, Lamivudine (Epzicom), Abacavir, Lamivudine, Zidovudine (Trizivir), Didanosine (Videx, ddI, Videx EC), Emtricitabine (Emtriva, FTC, Coviracil), Emtricitabine, Tenofovir DF (Truvada), Lamivudine (Epivir, 3TC), Lamivudine, Zidovudine (Combivir), Stavudine (Zerit, d4T), Tenofovir DF (Viread, TDF), Zalcitabine (Hivid, ddC), and Zidovudine (Retrovir, AZT, AZV).

Protease Inhibitors (PIs)

PI disables protease, a protein that HIV needs to make more copies of itself. Drugs within this category include Amprenavir (Agenerase, APV), Atazanavir (Reyataz, ATV), Fosamprenavir (Lexiva, FPV), Indinavir (Crixivan, IDV), Lopinavir, Ritonavir (Kaletra, LPV/r), Nelvinavir (Viracept, NFV), Ritonavir, (Norvir, RTV), and Saquinavir (Fortovase, SQV; Invirase).

Fusion Inhibitors

Fusion Inhibitors prevent HIV from entry into cells. They include Enfuviritide(Fuzeon, T-20).

HIV therapy and pregnancy

Special care must be taken when an HIV patient is pregnant. The objective is to reduce the risk of transmission of HIV to the fetus. Before the onset of labor, the patient is given 100 mg of ZDV five times daily, initiated at 14 to 34 weeks of gestation and continued throughout the pregnancy.

The patient is given ZDV intravenously in a 10-hour loading dose of 2 mg per kg of body weight, followed by a continuous infusion of 1 mg per kg of body weight per hour at beginning of labor and until delivery.

The newborn is then given PO ZDV at 2 mg/kg/per dose every 6 hours for the first 6 weeks of life, beginning 8 to 12 hours after birth.

Postexposure prophylaxis

Postexposure prophylaxis is administered to all healthcare workers according to the Public Health Service Statement on the Management of Occupational Exposures to HIV and Recommendations. The policy for postexposure prophylaxis is institution specific and should be available to all employees.

Basic and Expanded Postexposure Prophylaxis Regimens

Basic and Expanded Postexposure Prophylaxis Regimens

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