Immunology and Immune System

Immunity 2025 Course Objectives

• Identify safe, effective nursing management of pharmacological interventions for individuals across the lifespan and their families dealing with chronic immune disorders.
• Select and prioritize nursing outcomes and interventions to develop a plan of care for individuals with chronic immune disorders.

Drug Classification

• Students must understand the following details for each drug class:
  • Generic name/trade names
  • Classification
  • Indications
  • Mechanism of action (pharmacokinetics, including absorption, distribution, metabolism, excretion, half-life, onset/peak/duration)
  • Contraindications/precautions
  • Adverse reactions/side effects (including toxicity and overdose management)
  • Drug-drug and food-drug interactions
  • Route/dosage
  • Nursing considerations (lab values/assessment and monitoring priorities, nursing interventions, and patient/family teaching)
• Additional self-study: Human Immunodeficiency Virus (HIV)

Immune System Defense

• Innate Immunity: Skin, mucous membranes, enzymes, natural microbial flora; Phagocytes (granulocytes, macrophages)
• Adaptive Immunity: Lymphocytes (T-cells, B-cells)

Immune System Key Players

• T cells: Central to immune activation and cytokine production
• B cells: Produce antibodies and contribute to autoimmune responses
• Antibodies: Bind to pathogens or self-antigens to neutralize or flag for destruction
• Macrophages: Process antigens, secrete cytokines, and initiate inflammation

Cytokines: Immune Regulation

• Cytokines are small proteins acting as messengers between immune cells
• Key role in coordinating and regulating immune responses (inflammation, immune activation, suppression)
• Types and functions of cytokines include pro-inflammatory, anti-inflammatory, growth/differentiation, interferons, and chemokines
• Examples and examples of drug classes for each cytokine type are provided in the notes.

Screening Prior to Immunosuppressant Medication

• Prior to administering medications that suppress the immune system, patients should be screened for:
  • Tuberculosis
  • Hepatitis C and B
  • Any acute or chronic infections (pneumonia, osteomyelitis)
  • Vaccination status
  • Pregnancy status and potential future reproduction considerations

Immune Modifying Therapy Nursing Implications

• Agency protocols should be reviewed for who is permitted to administer immunosuppressants and the requirements for a double-check.
• Units may have additional safeguards (e.g., Foothills Medical Centre Unit 37 does not allow student nurses to work with transplant patients).
• Safe handling and safe disposal of cytotoxic medications are essential.

Immune Modifying Therapies

• Immunosuppressants: Drugs that reduce immune system activity (e.g., corticosteroids, calcineurin inhibitors)
• Immunomodulators: Drugs that regulate or enhance immune responses without broadly suppressing them (e.g., interferons, IVIG)

Specific Drug Classes

• Various categories of immune-modifying therapies (e.g., broad immunosuppressants, targeted immunosuppressants, cytotoxic/antiproliferative agents, antibody-based therapy, immune modulators) are presented with their corresponding drug classes (e.g., corticosteroids, calcineurin inhibitors, mycophenolate, JAK inhibitors, monoclonal antibodies, interferons, interleukin inhibitors, IVIG).

Immune Modifying Therapy General Nursing Considerations

• Head-to-toe assessment considerations (allergies, infection, hypertension, bleeding, side effects associated with inhibiting cell division, including toxicity to liver, kidney, or lungs)
• Lab test considerations (CBC and differential, CRP, liver function, kidney function, CXR, serum drug levels)
• Confirming the last medication dose and preventing pharmacokinetic disruption

Corticosteroids: Review

• Examples: Prednisone, Dexamethasone, Methylprednisolone
• Indications: Short-term management of acute immune flares (e.g., lupus, RA), adjunct in preventing transplant rejection, used in combination with others for long term disease control
• Mechanism of action: Reduce inflammation by inhibiting phospholipase A2, decreasing prostaglandin and leukotriene synthesis; suppress immune response by reducing cytokine production and lymphocyte proliferation
• Adverse effects: Long-term use: Osteoporosis, hyperglycemia, hypertension, adrenal suppression, Cushing's syndrome; short-term use: Mood changes, fluid retention; glucocorticoids cannot be abruptly stopped

Calcineurin Inhibitors

• Examples: Cyclosporine, Tacrolimus
• Indications: Prevention of organ transplant rejection, treatment of autoimmune diseases (e.g., rheumatoid arthritis, psoriasis)
• Mechanism of Action: Block calcineurin, a protein needed for activating T cells and producing interleukin-2, essential for cellular proliferation, thereby suppressing the immune system.
• Adverse effects: Nephrotoxicity, hypertension, hyperkalemia, neurological effects (e.g., tremors, headaches), increased risk of infections
• Drug interactions: Grapefruit juice, NSAIDs (increased risk of kidney damage), phenytoin, rifampin (reduce drug efficacy by increasing metabolism)

mTOR Inhibitors

• Examples: Sirolimus (Rapamune), Everolimus (Zortress)
• Indications: Organ transplant rejection prevention, treatment of specific cancers (e.g., renal cell carcinoma)
• Mechanism of Action: Block mTOR, a protein that controls T-cell growth and division after being activated by interleukin-2, suppressing the immune system.
• Adverse effects: Hyperlipidemia, thrombocytopenia, delayed wound healing
• Drug interactions: CYP3A4 inhibitors (e.g., ketoconazole), increase drug levels, CYP3A4 inducers (e.g., rifampin) decrease efficacy.

Cytotoxic (Antiproliferative) Agents

• Examples: Methotrexate, Azathioprine, Mycophenolate mofetil
• Indications: Lupus nephritis, autoimmune hepatitis, rheumatoid arthritis, organ transplant maintenance therapy
• Mechanism of Action: Block DNA or RNA synthesis, preventing rapid division of immune cells (T and B lymphocytes), suppressing the immune system.
• Adverse effects: Bone marrow suppression (anemia, leukopenia, thrombocytopenia), GI disturbances (nausea, vomiting, diarrhea), hepatotoxicity, increased infection risk
• Drug interactions: allopurinol, antacids and cholestyramine (reduce absorption of mycophenolate)

Cytotoxic (Antiproliferative) Agents: Janus Kinase (JAK) Inhibitors

• Examples: Tofacitinib, Baricitinib
• Indications: Rheumatoid arthritis, psoriatic arthritis, ulcerative colitis
• Mechanism of Action: Block Janus kinase (JAK) pathways, which are crucial for cytokine signaling and immune activation, thereby reducing inflammation and immune overactivity.
• Adverse effects: Increased risk of infections, elevated liver enzymes, thrombosis
• Drug interactions: CYP3A4 inhibitors/inducers alter drug metabolism.

Monoclonal Antibodies

• Examples: Infliximab (Remicade), Rituximab (Rituxan), Adalimumab (Humira)
• Indications: Rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriatic arthritis, multiple sclerosis
• Mechanism of Action: Infliximab/Adalimumab: TNF-alpha inhibitors; Rituximab: targets CD20, a protein on B lymphocytes, marking them for destruction, reducing B cell-driven immune responses.
• Adverse effects: Infusion reactions, increased risk of infections
• Drug interactions: Live vaccines, concurrent immunosuppressive drugs.

Polyclonal Antibodies

• Example: Anti-thymocyte globulin (ATG)
• Indications: Prevention and treatment of acute organ transplant rejection, aplastic anemia unresponsive to other therapies.
• Mechanism of Action: Antibodies made from animals (rabbits or horses) immunized with human т-cells that target multiple T-cell antigens, binding to, and destroying T cells. Suppresses immune response.
• Adverse effects: Infusion reactions (fever, chills, hypotension), risk of infection, serum sickness.
• Drug interactions: Immunosuppressants (e.g., calcineurin inhibitors)

Interferons

• Examples: Interferon beta-1a (Avonex, Rebif), Interferon beta-1b (Betaseron)
• Indications: Multiple sclerosis (reduces relapse rates in relapsing-remitting MS)
• Mechanism of Action: Reduce inflammation by altering cytokine production, decreasing pro-inflammatory and increasing anti-inflammatory cytokines. This shifts the overactive immune system to balance
• Adverse effects: Flu-like symptoms, injection site reactions, depression, increased risk of infections
• Drug interactions: Immunosuppressants, hepatotoxic drugs.

Interleukin Inhibitors

• Examples: Tocilizumab (Actemra), Secukinumab (Cosentyx), Ustekinumab (Stelara)
• Indications: Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, psoriasis
• Mechanism of Action: Blocks specific interleukin pathways to reduce inflammation and immune activation
• Adverse effects: Increased infection risk, injection site reactions
• Drug interactions: Avoid live vaccines during therapy, immunosuppressants

Intravenous Immunoglobulin (IVIG) Review

• Examples: Gammagard, Privigen
• Indications: Immune thrombocytopenia (ITP), Kawasaki disease, primary immunodeficiencies
• Mechanism of Action: Provides passive immunity by neutralizing autoantibodies and inflammatory cytokines
• Adverse effects: Infusion reactions, headache, thromboembolism
• Drug Interactions: Avoid live vaccines within 6 months of IVIG therapy

Disease-Modifying Antirheumatic Drugs (DMARDs)

• Medications that slow the progression of autoimmune diseases, particularly rheumatic disorders, to reduce inflammation, prevent joint damage, and improve long-term outcomes
• Classifications
  • Non-biologic DMARDs: Synthetic compounds broadly suppressing the immune system (e.g., methotrexate, sulfasalazine, leflunomide, hydroxychloroquine)
  • Biologic DMARDs: Targeted therapies interfering with specific immune pathways (e.g., infliximab, adalimumab)

Specific Non-Biologic DMARDs

• Methotrexate: Inhibits dihydrofolate reductase, reducing DNA synthesis and T-cell activation
• Adverse effects: Bone marrow suppression, hepatotoxicity, stomatitis
• Drug interactions: NSAIDs, TMP-SMX, PPIs, Aspirin/Salicylates, Folic Acid/Folinic Acid, Penicillins, Alcohol, Leflunomide, Live Vaccines
• Sulfasalazine: Reduces inflammation by modulating immune pathways
• Adverse effects: GI disturbances, hypersensitivity reactions
• Drug interactions: Folic Acid, Methotrexate, Antibiotics, Warfarin
• Hydroxychloroquine: Interferes with how macrophages process antigens, reducing their ability to activate T-cells
• Adverse effects: Retinopathy
• Drug interactions: Tamoxifen, Digoxin, Antacids
• Leflunomide (Arava): Blocks pyrimidine synthesis
• Adverse effects: Hepatotoxicity, hypertension, gastrointestinal disturbances
• Drug Interactions: Warfarin, other hepatotoxic drugs

Specific Biologic DMARDs

• Infliximab (Remicade): TNF-alpha inhibitor
• Indications: Rheumatoid arthritis, Crohn's disease, psoriasis
• Adverse effects: Infusion reactions, infections
• Adalimumab (Humira): Indications: Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis
• Adverse effects: Infections, injection-site reactions, increased risk of malignancies
• Rituximab (Rituxan): Targets CD20 on B lymphocytes
• Indications: Rheumatoid arthritis (refractory), lupus, certain cancers
• Adverse effects: Infusion reactions, hepatitis B reactivation, hypogammaglobulinemia
• Etanercept (Enbrel): Indications: Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis

Chronic Immune Disorders

• General information is included about different types of chronic immune disorders (including rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, and immune deficiency)

Transplant

• Lifelong immunosuppressive therapy needed to prevent graft rejection
• Includes calcineurin inhibitors, mTOR Inhibitors, corticosteroids, and Polyclonal antibodies.
• Detailed notes are provided on managing side effects from medications such as nephrotoxicity, hyperlipidemia, infection risk, and therapeutic monitoring considerations for transplant patients.
• Additional information includes the importance of infection prevention education, and collaborative care with the multidisciplinary team for transplant patients.

Immune Deficiency

• SCID details and treatment are described, including HSCT and IVIG
• Nursing care considerations and the importance of preventing infections for patients with SCID are underscored.

References

• Resources for various conditions are available in the notes