Chapter 11 & 12: Disorders of the Immune Response, Disorders of the Immune Response, Including HIV/AIDS

What is the immune system and what is the result of alterations to the immune system?

• Immune system is a large network of organs, white blood cells, proteins (antibodies) and chemicals. This system works together to protect the body from foreign invaders (bacteria, viruses, parasites, and fungi) that cause infection, illness and disease.

Results of Alterations of the Immune System:

• Hypersensitivity

• Autoimmune disorders

• Transplantation rejection

• Immunodeficiency states

What are immunodeficiency disorders and how are they classified?

• Immunodeficiency is defined as an abnormality in one or more parts of the immune system that results in an increased susceptibility to disease states normally eliminated by a properly functioning immune response.

Classification of Immunodeficiency State:

• Primary (congenital or inherited)

• Secondary (acquired later in life). It develops later in life because of other pathophysiologic states

  • Immunosuppressive therapy (transplant rejection medications)

  • Infection: HIV/AIDS (acquired immunodeficiency syndrome).

What is histocompatibility and why is it important?

• The major histocompatibility complex (MHC) is a group of genes that encode proteins on the cell surface that have an important role in immune response:

  • It is necessary for cell self-recognition and the prevention of the immune system from targeting its own cells.

  • Allorecognition which is the ability of an organism to distinguish its tissues from those of another organism within the same species and has important implications for transplantation.

  • The MHC is involved in the direct mechanism of allorecognition, where T cells recognize determinants on the donor MHC molecule- peptide complex displayed at the cell surface. This is because the MHC molecules display an antigenic determinant called an epitope, which is either self or non-self. Antigens from the transplanted cells are recognized as non-self

What is a human leukocyte antigen?

• Human leukocyte antigens (HLA) are a type of molecule found on the surface of most cells in the human body. HLA plays a crucial role in the body's immune response to foreign substances. *They make up a person’s tissue type, which varies from person to person. HLA tests are done before a donor stem cell or organ transplant to find out if tissues match between the donor and the person receiving the transplant.

What is bone marrow or stem cell transplat?

• A bone marrow transplant is a medical treatment that replaces your bone marrow with healthy cells. The replacement cells can either come from your own body or from a donor.

• A bone marrow transplant is also called a stem cell transplant or, more specifically, a hematopoietic stem cell transplant. Transplantation can be used to treat certain types of cancer, such as leukemia, myeloma, and lymphoma, and other blood and immune system diseases that affect the bone marrow.

What are the types of stem cell transplant?

• Allogeneic

  • The donor and recipient are related or unrelated but share similar human leukocyte antigens (HLA) types. HLA are markers on the surface of your white blood cells.

• Syngeneic

  • The donor and recipient are identical twins or triplet who can donate stem cells

• Autologous

  • The donor and recipient are the same person. The stem cells are remove and stored. Those cells are returned to the person after completion of treatments, such as high-dose chemotherapy or radiation. The transplant helps restore the body’s ability to make normal, blood-forming stem cells.

How are stem transplants used?

• Many primary immunodeficiency disorders traced to deficiencies in stem cells can be cured with allogeneic stem cell transplantation from an unaffected donor.

  • Immunodeficiency disorders like severe combined immunodeficiency (SCIDs), chronic granulomatous disease, and Wiskott-Aldrich syndrome.

  • Wiskott- Aldrich syndrome is a rare genetic disorder of the immune system that primarily affects boys. It is characterized by abnormal immune function and a reduced ability to form blood clots. Management: (short/long-term) management of bleeding; bone marrow transplant

• Stem cells can repopulate the bone marrow and reestablish hematopoiesis, the process by which blood cells are produced.

What are the basic patterns of transplant rejection? 2 Different types?

• Hyperacute Reaction

  • Occurs almost immediately after transplantation.

  • Produced by existing recipient antibodies to graft antigens initiating a type III, Arthus-type hypersensitivity reaction. Hyperacute rejection occurs because antibodies against human leukocyte antigens (HLA) antigens are deposited in vessels, causing necrosis.

• Acute Rejection

  • Occurs within first few months after transplantation with signs of organ failure; may occur months or years after immunosuppression has been terminated

  • T lymphocytes respond to antigens in the graft tissue

What is Graft versus host disease?

• Graft versus host disease (GvHD) is a complication that might occur after an allogeneic transplant.

• In GvHD, the donated stem cells (graft) view the recipient’s cells (host) as an unfamiliar threat. As a result, the donated cells attack the recipient’s cells. This is why the disease is referred to as “graft versus host.”

• Types: acute and chronic

What are the two types of GVHD and what are the treatments?

• Acute graft versus host disease (aGvHD): aGvHD occurs shortly after your transplant, usually within the first 100 days. But symptoms of aGvHD may also start later. aGvHD most often affects your skin rash on palms/soles, gastrointestinal (GI) tract pain/nausea or liver.

• Chronic graft versus host disease (cGvHD): cGvHD can appear any time after an allogenic transplant, but most cases start within two years. Chronic GvHD might affect your skin rash on palms/soles, mouth, liver, lungs, GI tract pain/nausea, muscles, joints or genitals.

• Treatment: Preventive (prophylactic) medicines to suppress clients immune system after the transplant. These immunosuppressive medicines decrease donor cells’ ability to start an immune response (attack) against your tissues. Acute GvHD)

What are immune suppressants?

• Immune suppressants often are used in conjunction with corticosteroids, which block the inflammatory reaction and decrease initial damage to cells. They are especially beneficial in cases of organ transplantation and in the treatment of autoimmune diseases.

• The immune suppressants include the immune modulators, T and B cell suppressors, an interleukin receptor antagonist, and monoclonal antibodies—

  antibodies produced by a single clone of B cells that react with specific antigens. There is a newer drug, belatacept (Nulojix) that was approved for the prevention of acute transplant rejection in adults with kidney transplants.

Immunosuppressive Medication- T & B cell suppressors (Indications, Actions, Pharmacokinetics, Adverse Effects)

• Prototype Summary: Cyclosporine (Sandimmune, Neoral)

• Indications: Prophylaxis for organ rejection in kidney, liver, and heart transplants (used with corticosteroids); treatment of chronic rejection in patients previously treated with other immune suppressants; treatment of rheumatoid arthritis and recalcitrant psoriasis.

• Actions: Reversibly inhibits immunocompetent lymphocytes; inhibits T helper cells and T suppressor cells, lymphokine production, and release of interleukin-2 and T-cell growth factor.

• Pharmacokinetics: T1/2: 8 to 19 hours (varies per formulation), metabolized in the liver and excreted in the bile and urine.

• Adverse Effects: Tremor, hypertension, gum hyperplasia, renal dysfunction, diarrhea, hirsutism, acne, bone marrow suppression, interleukin receptor antagonist.

What is the nursing management following a transplant?

• Protect your skin from sun exposure by wearing long-sleeved shirts and long pants and using sunscreen with a

  minimum SPF of 50. (Sun exposure can trigger or worsen GvHD.)

• Practice good dental hygiene to reduce your susceptibility to gum disease.

• Avoid foods that can upset your stomach or irritate your mouth, like spicy foods.

• Call the healthcare provider immediately for especially symptoms of infection and fevers of 100.4 degrees or higher

• Reverse isolation –teach family/friends about the patient risk of getting infection

• For out patient care, arrange for caregiver who can monitor patients health/psychosocial support

What is HIV?

• The human immunodeficiency virus (HIV) is a retrovirus belonging to the family of lentiviruses. Retroviruses can use their RNA (ribonucleic acid) and host DNA (deoxyribonucleic acid) to make viral DNA and are known for their long incubation periods

What are the methods of HIV transmission?

Common

• Unprotected sex with an infected partner

• Sharing needles with infected person

Almost eliminated

• Transmission from infected mother to fetus

• Infection from blood products

What is the life cycle of HIV?

• Binding and Entry

• Reverse Transcription

• Integration

• Replication

• Budding

• Maturation

What is important to keep in mind with HIV/AIDS testing? Support services, retesting?

• Counseling, consent, patient education and specific follow up plan *

• If high risk, negative confirmatory plan repeat the test in 4 weeks

  • Recommend testing every 3-6 months

  • Does not mean 100% the patient is negative, the body has not produced antibodies

What are the types of HIV/AIDS testing that can be done?

• Enzyme-linked immunosorbent assay (ELISA)

  • Usually first/initial test to detect infection with HIV

  • Detects presence of antibodies

  • Positive –repeat to confirm before Western blot assay

• Western Blot Assay

  • Detects antibodies

  • More difficult test

  • Done to confirm a POSITIVE ELISA tests

• Post test counseling, aware of reporting, privacy, partner notification

• Viral Load

  • Measures plasma HIV RNA

  • Used to track response to Tx with HIV meds

  • High viral load = active viral replication

• CD4 counts & T cell %

  • Extent of HIV damage to immune system

  • < 200 – high incidence of progression to AIDS

• CBC, Chem studies, LFT, STD screening

What occurs during the acute HIV phase?

• Primary (Acute/Recent Infection)

• Period between initial exposure to virus and appearance of HIV antibodies (window period)

• Test negative HIV antibody test (antibodies are not detected, can take weeks)

• Highly infectious (virus fast & furious)

• Elevated HIV viral load, decreased CD4 but not < 200. Normal CD4 is > 500

• Non-specific symptoms occur 2-4 weeks post infection

• Test immunoassay may be Negative/Positive, pending time of seroconversion

What occurs during the latent or chronic HIV phase?

• “clinically latent” period of years between HIV infection and clinical signs and symptoms of AIDS, evidence of HIV replication and host immune system destruction

• Without HIV treatment, this stage may last a decade or longer, or may progress faster

• Asymptomatic, patient feels well, and may not be sick during this phase

• Test immunoassay may be Positive

• At the end of this stage, the amount of HIV in the blood (viral load) goes up and the person may move into Stage 3 (AIDS).

When is the criteria for AIDS? Other factors?

• Need to meet criteria defined by CDC

  • CD4 levels < 200 or 14% of all lymphocytes

  • Positive antibodies to HIV

  • Diagnosed with one or more AIDS defining illnesses called opportunistic infections: candidiasis, pneumocystis carinii pneumonia, HIV encephalopathy, Lymphoma, Kaposi sarcoma....

• Other factors include:

  • High viral load and may easily transmit HIV to others.

  • Without HIV treatment, people with AIDS typically survive about three years.

What are opportunistic infections and when do they occur?

• This is when the CD4 continues to drop, infections use the “opportunity” of non - functioning immune system to infect the body.

&

• The immune system loses the ability to control infections that are in a dormant phase, allowing the infection to become reactivated.

What is candidiasis (candida albicans)? Where can it occur + symptoms associated with it?

• Oral candidiasis

• Vaginal –yeast

• Esophagus

• Thrush

• Dysphagia

• Vaginitis/Rectal lesions

• Inflammation Nails/ Skin Folds

What is mycobacterium avium complex (MAC)? Symptoms?

• Common in Soil/Water/Food (eggs/animals/raw dairy)

• Fever/Night Sweats/

• Diarrhea/Anorexia/

• Fatigue/Wt loss

• RX:Ciprofloxin

What is Pneumocystosis Carinii (PCP)? Symptoms?

• Exists in Lungs/Air Food/Water

• Fungus? Protozoa

• Fever/SOB/Cough/Wheeze/Fatigue

• Infections Spleen/Lymph nodes/Blood

• RX: Improve airway, Pentam 300/Septra

What is Oncologic Kaposi Sarcoma? Symptoms?

• Most common HIV malignancy involving endothelial layers of blood vessels and lymph nodes

• Course variable

• Localized cutaneous lesions dark violet in color– multiple organs

• Tx: Palliative Radiation, vincristine

• B cell lymphoma

  • Aggressive

  • Tx: Chemo

What is the general treatment to give support for opportunistic infections + AIDS/HIV?

• Patient Education and counseling is essential

• Follow up care

• Community resources and support systems

• Nursing Care

  • Accurate assessments, education

  • Assess and treat substance abuse

Nucleoside Reverse Transcriptase Inhibitors (NRTI) (MOA, S/E, education)

• Zidovudine (AZT, Retrovir)

• MOA: Inhibits the synthesis of DNA by reverse transcriptase. Zidovudine becomes incorporated into the strand of DNA being synthesized--- DNA strand is terminated

• S/E: most serious:

  • Bone marrow depression: anemia, granulocytopenia, thrombocytopenia

  • Other effects: n/v/d, abdominal pain, myopathy, headache, seizures, lethargy

• Teaching:

  • Adherence

  • It will not eradicate HIV, transmission to others is possible

  • Can be given with Lamivudine– Combivir

  • Monitor CBC

  • Monitor platelete count

  • GI side effects and h/a may resolve after one month of treatment

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) (MOA, S/E, education)

• Nevirapine (Viramune)

• MOA: Inhbits HIV reverse transcriptase. It binds directly to reverse transcriptase

• S/E: most serious

  • Hepatotoxicity

  • Other effects: fever, h/a, rash, n/v, abdominal pain

• NI/Teaching:

  • Adherence to drug therapy

  • Careful monitoring esp. first 4 months of treatment for hepatotoxicity

  • Monitor LFT

  • Assess skin rashes and report to MD

  • Small frequent meals to decrease GI distress

Protease Inhibitors (PI) (MOA, S/E, education)

• Saquinavir (Invirase)

• MOA: Competitive inhibitor of HIV protease. This enzyme is needed for HIV replication.

• S/E: most common:

  • n/d/ gi distress, h/a, insomnia, hyperglycemia

  • Other effects: deposits of fatty tissue at base of posterior neck and abdominal area.

    • It is associated with a syndrome of fat redistribution,increased cardiac and pancreatic issues

• NI/Teaching:

  • Adherence

  • GI and h/a may resolve after one month of treatment

  • Assess fat redistribution, if present: assess cholesterol and triglyceride levels

  • Best adm: two hours after eating high calorie, high fat meal for best absorption

What is ARTRIPLA?

• Known as “Triple Cocktail”

• Inclusive of all HIV medications

• 1 NNRTI (non nucleoside reverse transcriptase inhibitors) & 2 NRTI’s (nucleoside reverse transcriptase inhibitors)

• High rate of compliance