1.4 Primary or Secondary Immune Deficiencies Flashcards
Primary Immune Deficiency
- Primary cause of immune deficiency
- Rare, inherited genetic disorders
Secondary Immune Deficiencies
- Caused by a condition outside the immune system
Primary Immune Deficiency Diseases (PIDD)
- Results from a defect in the immune system
- Rare and genetic
- Increased risk of having chronic debilitating infections such as Epstein-Barr Virus (EBV) that increase risk of cancer.
- HALLMARK SIGN IS RECURRENT INFECTIONS
- Many patients with PIDD also have autoimmune disorders (Rheumatoid Arthritis, Thyroid Disease, Inflammatory Bowel Disease)
MOST FREQUENT TYPE OF INFECTIONS
- Sinopulmonary Infections (Sinusitis, bronchitis, pneumonia) and otitis media (ear infection)
SEVERE COMBINED IMMUNODEFICIENCY (SCID)
- Group of disorders with defective T and B cell numbers and function
- Predisposes patients to infection with any pathogen
Secondary Immunodeficiency Diseases
- Most commonly caused by aging, malnutrition, medications, or HIV
SCREENING TO RULE OUT PRIMARY IMMUNODEFICIENCY (PID)
- CBC
- Serum Immunoglobin Quantification
- Biochemistry Panel (Basic Liver and Kidney Function, Total Protein and Albumin)
Transplantation and Immunosuppression
Patients must take the correct dosage of immunosuppressants when they receive a transplant
- Insufficient dose can cause organ rejection
- Excessive dose can cause organ failure (due to immunologic compromise)
- Excessive doses also allow opportunistic infections (cytomegalovirus, varicella-zoster) to invade and impede organ function
- Usually starts with a loading dose and then they change it to the smallest effective dose.
Tissue and Organ Transplant
- Inadequate immunosuppressants (especially with solid organs) can cause graft vs host disease with lymphoid-rich organs (produces a lot of lymphocytes) like bone marrow or stem cells.
- Liver transplant can also cause GVHD because it is a lymphoid rich tissue.
Immune Response
- Third line of defense (specific)
- When organs get transplanted into a body, the body recognizes it as foreign and tries to reject it or kill it. Immunosuppression is designed to stop this from happening.
Organ Rejection Medications
- imus - Immunosuppressant (Tacrolimus and Sirolimus)
- cept - Receptor modules that reduce strength of bodies immune system (Cellcept, Belatacept)
- mab - Monoclonal antibodies target and attach to cells (antigens) created by rejection activity of leukocytes (rituximab, adalimumab)
Immunosuppressants
Induction Phase - Period of time between when the organ is transplanted until the second week of transplantation.
- Immunosuppressants are usually started in the OR. After the medication has been started, they level out dosage to a stable dose, then implement a maintenance dose
Maintenance Regime - Starts around 3 months after transplant and lasts for a lifetime
- Maintenance dose is the lowest effective dose of medication
- THIS CAN ALSO BE USED TO TREAT ORGAN REJETION
Triple Therapy
- THE MOST EFFECTIVE IMMUNOSUPPRESSANT REGIME
This is the usage of 3 different immunosuppressant classes to promote optimal function of transplanted organ
- Corticosteroids
- Antimetabolites
- Calcineurin Inhibitors (CNIs)
Corticosteroids
- Maintenance therapy standard
- Suppresses immune system and inflammation
- Blocks Interleukin-1 which suppresses activation/growth of T-cells and decreases formation of antibodies by B-cells
Acute Phases - IV Methylprednisolone
Oral Route - Prednisone
- They are metabolized in the liver and excreted in the kidneys
- CAUTION FOR PATIENTS WITH LIVER TRANSPLANTS
Antimetabolites
- Antiproliferative Drugs (Used for Maintenance)
- Inhibit proliferation of B-cells and T-cells
- When cells ingest these they are unable to divide. They attack cells at specific phases in the cycle and are classified by when in the cycle they interfere.
Azathioprine
Mycophenolic Acid
Cyclophosphamide
- Metabolized in Liver, Excreted by Kidneys
Calcineurin Inhibitors (CNIs)
- Inhibit proliferation of Helper T-cells and how cytokines express themselves
TWO MOST COMMON TYPES (REVIEW THESE MEDICATIONS)
- Cyclosporine (nephrotoxic)
- Tacrolimus (nephrotoxic)
- Dosage depends on when patient was transplanted, history of rejection, present infections.
BIGGEST ISSUE IS THEY CAN RESULT IN CHRONIC NEPHROTOXICITY
- GRAPEFRUIT JUICE INCREASES ABSORPTION OF CYCLOSPORINE AND TACROLIMUS
Mammalian Target of Rapamycin (mTOR) Inhibitor
- Sirolimus (Rapamycin)
- Suppresses T-cell Activation/Proliferation
- Used with low-dose CNIs for organ rejection
- Lowers risk of nephrotoxicity, viral infections and malignancies of CNIs
- Triple shift is aiming at getting rid of antimetabolites and adding mTOR
Acute Organ Rejection
Acute Reaction
- Occurs 10 days to few months post-transplant OR if immunosuppressant medication are stopped.
CHARACTERISTICS
- Signs of organ failure
- Vasculitis lesions (lesions of small vessels) which leads to arterial narrowing/obliteration. They narrow to the point where there is no more blood flow going through them.
EXAMPLES
Kidney Transplant - Look at GFR and creatinine to check for organ failure
Liver Transplant - Look at liver function tests.
