5.2.1 Immunity Notes

Pharmacology: Cyclosporine (Gengraf, Neoral)

Drug Class: Immunosuppressant

Mechanism of Action

• Inhibits normal immune responses (both cellular and humoral).

• Specifically inhibits interleukin-2 ($IL-2$), which is responsible for initiating T-cells.

• Target: Calcineurin.

Therapeutic Uses

• Prevention of organ rejection in renal, hepatic, and cardiac transplants.

• Treatment of severe Rheumatoid Arthritis ($RA$).

• Treatment of severe recalcitrant psoriasis.

Contraindications & Specific Warnings

• Hypersensitivity to castor oil or alcohol.

• Concurrent radiation therapy.

• Use with other immunosuppressants.

Side Effects

• Common: Hypertension ($HTN$), hirsutism (increased hair growth), acne, nausea, vomiting, diarrhea ($N/V/D$), and gingival hyperplasia.

• Specific/Life-Threatening:     * Nephrotoxicity and Hepatotoxicity.     * Pancreatitis.     * Malignancy.     * PML (Progressive Multifocal Leukoencephalopathy): Signs include hemiparesis, apathy, confusion, and cognitive deficits.     * PRES (Posterior Reversible Encephalopathy Syndrome): Signs include altered level of consciousness ($LOC$), convulsions, vision changes, and psychiatric symptoms.

Nursing Considerations & Patient Education

• Monitoring: Monitor blood pressure ($BP$) every $2$ weeks, daily weight ($Wt$), and labs including Creatinine ($Cr$), $BUN$, $AST$, $ALT$, and Glomerular Filtration Rate ($GFR$).

• Administration: Typically given $4-12$ hours pre-transplant. Dosage is adjusted based on serum levels.

• Dietary: Strictly avoid grapefruit juice.

• Longevity: This is often lifelong therapy for transplant patients.

• Reporting: Patients must report diarrhea and shortness of breath ($SOB$).

• Dental Care: Dental exams are required every $3$ months due to the risk of gingival hyperplasia.

• Onset: Onset for $RA$ is approximately $4-4.8$ weeks.

Pharmacology: Sulfasalazine (Azulfidine)

Drug Class: Disease-Modifying Antirheumatic Drug ($DMARD$); Anti-inflammatory.

Mechanism of Action

• Provides immunosuppression by decreasing B-cell and T-cell activity.

Therapeutic Uses

• Rheumatoid Arthritis ($RA$).

Contraindications

• Liver or renal disease.

• Active infection.

• Lactation (risk of causing infant jaundice).

Side Effects

• Dizziness and headache.

• Gastrointestinal: $N/V$, GI ulcers.

• Life-Threatening/Serious: Bone marrow suppression, hepatotoxicity, and pulmonary fibrosis.

Nursing Considerations & Patient Education

• Monitoring: Monitor $CBC$ and liver function tests.

• Assessment: Screen for signs of infection or unusual bleeding.

• Hydration: Ensure adequate hydration.

• Avoid: Alcohol consumption.

• Reporting: Patients must report signs of infection, bleeding, or jaundice.

Pharmacology: Biologic DMARDs (Etanercept & Adalimumab)

Generic Names (Brand):

1. Etanercept (Enbrel)

2. Adalimumab (Humira)

Drug Class: Biologic Target Therapy; Immunosuppressant.

Mechanism of Action

• Inactivates Tumor Necrosis Factor ($TNF$), which prevents the inflammatory response in the joints.

Contraindications

• Active infection.

• Malignancy.

• Demyelinating disorders.

Side Effects

• Common: Injection site reactions, dizziness, pharyngitis, and Upper Respiratory Infection ($URI$).

• Serious: Serious infection, $TB$ reactivation, pancytopenia, Heart Failure ($HF$), and liver dysfunction.

Nursing Considerations & Patient Education

• Pre-administration: Mandatory screening for Tuberculosis ($TB$) before starting therapy.

• Monitoring: Perform regular $CBC$ and liver lab tests; monitor for signs and symptoms of Heart Failure ($HF$) and abdominal pain.

• Vaccinations: Patients must get all necessary vaccines before starting therapy; avoid live vaccines while on the medication.

• Storage: Medications should be refrigerated.

• Dosing: Often administered weekly.

• Reporting: Report infection, fever, or adverse reactions immediately.

Pharmacology: Hydroxychloroquine (Plaquenil)

Drug Class: Antimalarial; Non-biologic $DMARD$.

Mechanism of Action

• Suppresses immune response by interfering with lymphocyte activity, thereby decreasing inflammation.

Therapeutic Uses

• Rheumatoid Arthritis ($RA$) - primarily to slow the progression of the disease.

Contraindications

• Active infection.

• Liver or renal impairment.

Side Effects

• Dizziness, headache, blurred vision, and $N/V$.

• Serious: Hepatotoxicity, bone marrow suppression (increased infection risk), GI ulcers, and pulmonary fibrosis.

Nursing Considerations & Patient Education

• Monitoring: Monitor $CBC$ (including $RBC$, $WBC$, and Platelets) and liver function.

• Assessment: Assess for signs of infection and monitor respiratory status.

• Education: Report infection, unusual bleeding, jaundice, shortness of breath ($SOB$), or mouth sores. Avoid alcohol and maintain hydration.

Pharmacology: Corticosteroids (Prednisone)

Brand Names: Deltasone, Rayos. Drug Class: Glucocorticoid; Anti-inflammatory; Immunosuppressant.

Mechanism of Action

• Suppresses inflammation and immune response by inhibiting leukocyte infiltration and cytokine production.

Therapeutic Uses

• Rheumatoid Arthritis ($RA$).

• Autoimmune disorders.

• Severe allergic reactions.

• Asthma / $COPD$ exacerbations.

Contraindications

• Systemic fungal infections.

Side Effects

• Metabolic/Endocrine: Weight gain, hyperglycemia, increased appetite, and adrenal suppression.

• Cardiovascular: Hypertension ($HTN$) and fluid retention.

• Musculoskeletal: Osteoporosis (long-term use).

• Other: Dizziness, insomnia, mood changes, Peptic Ulcer Disease ($PUD$), and cataracts/glaucoma.

Nursing Considerations & Patient Education

• Monitoring: Monitor Blood Pressure ($BP$), fluid levels, and bone density for long-term users. Monitor for infection.

• Dosing: Specifically mentioned range of $3-10\,mg/day$. Take with food to minimize GI upset.

• Critical Warning: Do NOT stop therapy abruptly; must be tapered to avoid adrenal crisis.

• Dietary: Supplement with Calcium and Vitamin D.

• Reporting: Report black stools (indicative of GI bleed), swelling, or vision changes. Avoid exposure to infections.

Immunity Function and Inflammatory Response

Inflammatory Response

• Purpose: Prevent damage, remove debris, and prepare the body for healing.

• Function: Mast cells release histamine, leading to vasodilation (bringing cells to the area) and increased permeability (bringing leukocytes to the area).

• Process: Fibrinogen clots the area; phagocytosis occurs; cytokines (histamine, leukotrienes, prostaglandins, bradykinins) act as signals.

• Signs/Response: Redness, heat, swelling (edema), pain, loss of function, fever, chills, and malaise.

Stages of Wound Healing

1. Hemostasis.

2. Inflammation.

3. Proliferation.

4. Remodeling.

Types of Immunity

• Innate System: Nonspecific and natural.     * Physical barriers: Skin, mucous membranes.     * Initial inflammatory response.

• Adaptive System: Specific and adaptive. Recognizes self vs. non-self.     * Cellular Response: T-cells.     * Humoral Response: B-cells.     * Includes a memory component (antibodies).

Lymphatic System Components

• Marrow, Thymus, Leukocytes, Nodes, Spleen.

• Peyer's patch.

• Function: Transports excess interstitial fluid (not reabsorbed by capillaries) back to the blood and provides drainage and fluid balance.

Immunity Assessment

• History: Age, medications, allergies ($ALGY$), existing problems, and nutrition.

• Physical: Vital signs ($VS$), skin, membranes, lymph nodes, and system-specific checks.

• Diagnostics: Blood tests, skin tests, bone marrow aspiration, and imaging.

• Labs: $CBC$, $CRP$, and $WBC$ differential.

Clinical Laboratories for Inflammation

C-Reactive Protein (CRP)

• Purpose: Detects presence of inflammation or tissue damage. Created in the liver in response to acute inflammation.

• Normal Range: Good is < 0.3\,mg/dL; Bad (High) is > 10\,mg/dL.

• High Causes: Infection, autoimmune disease ($RA$), tissue injury, cancer.

• Low Causes: Severe liver disease.

• Signs of High CRP: Fever, pain, fatigue, symptoms of infection.

• Nursing Actions: Assess for infection/inflammation, monitor vital signs, and trend values.

Rheumatoid Factor (RF)

• Normal Range: < 20\,IU/mL.

• Purpose: Tests for antibodies that attack healthy tissue; used for Rheumatoid Arthritis diagnosis ($RA\,dx$).

Erythrocyte Sedimentation Rate (ESR)

• Purpose: Screens for the presence of an inflammatory process. Measures how fast RBCs settle in $1\,hour$.

• Pathophysiology: Inflammation causes increased fibrinogen, making RBCs clump and settle faster.

• Normal Ranges:     * Female ($F$) > 50: < 30\,mm/hr.     * Male ($M$) > 50: < 20\,mm/hr.     * Female ($F$) < 50: < 20\,mm/hr.     * Male ($M$) < 50: < 15\,mm/hr.

• High Causes: Chronic inflammation, autoimmune (Lupus), infection, cancer, pregnancy, anemia.

• Low Causes: Polycythemia, sickle cell anemia, severe leukocytosis.

• Signs of High ESR: Joint pain, fatigue, fever.

• Nursing Actions: Assess for chronic conditions, trend values, and correlate with $CRP$.

Arthritis Overview: JIA, RA, and OA

Juvenile Idiopathic Arthritis (JIA)

• Onset: Occurs in children < 16 years old.

• Symptoms: Similar to $RA$; involves immunity disorders.

• Risk: High risk of uveitis (eye damage), which can lead to blindness.

Rheumatoid Arthritis (RA)

• Definition: Chronic, systemic autoimmune inflammatory disease affecting diarthrodial joints.

• Pathophysiology: Immune response targets the synovial membrane. The membrane thickens (synovial proliferation), forming a pannus which destroys cartilage and bone. Collagenase is released, breaking down collagen.

• Risk Factors: Female, Native American (Pima/Chippewa), genetics, air pollution, history of inflammatory disease.

• Signs & Symptoms:     * Symmetrical inflammatory polyarthritis.     * Joint pain and boggy swelling.     * Morning stiffness (> 60\,minutes).     * Deformities: Swan neck, Boutonniere, ulnar deviation.     * Systemic: Rheumatoid nodules, fatigue, weight loss/decreased appetite, pleuritis, episcleritis/scleritis, and osteopenia.

• Testing: Labs (Antibodies/anti-CCP, RF, CRP, ESR); Ultrasound/X-ray.

• Treatment: NSAIDs, Glucocorticoids, $DMARDs$, balance of rest and aerobic exercise, heat/cold therapy, and Mediterrenean diet (Omega-3, antioxidants, honey; avoid sugar, alcohol, caffeine).

Osteoarthritis (OA)

• Definition: Most common form of arthritis; local breakdown of cartilage and loss.

• Pathophysiology: Cartilage is damaged leading to osteophytes (projections of new cartilage and bone) on the joint line. The joint becomes unprotected.

• Risk Factors: Age (> 40), obesity, female, occupation (repetitive use), sports injury, trauma.

• Signs & Symptoms:     * Asymmetrical progressive joint pain.     * Functional loss and unsteady gait.     * Tender bony prominences.     * Crepitus.     * Nodes: Bouchard (PIP) and Heberden (DIP) nodes.

• Treatment: Acetaminophen, NSAIDs, corticosteroids; Surgery (irrigation, debridement), PT/OT, aerobic exercise.

Hypersensitivity and Anaphylaxis

Reaction Types

• Type 1 (Immediate/Rapid): IgE mediated. Rapid release of histamine.     * Examples: Asthma, allergies, anaphylaxis.     * Effects: Smooth muscle contraction, vasodilation, increased vascular permeability, bronchoconstriction, edema.

• Type 2 (Cytotoxic): IgG reaction with membranes leading to cell lysis.     * Examples: Transfusion reactions, Rh incompatibility, hemolytic anemia.

• Type 3 (Immune Complex): Antigen-antibody complexes deposit in walls, releasing neutrophils (IgG/IgM).     * Examples: Rheumatoid arthritis, Lupus.

• Type 4 (Delayed/Cell-Mediated): Autoantibodies stimulate continued overreaction. Very slow onset.     * Examples: Grave's disease, transplant rejection, TB skin test, Type 1 Diabetes ($T1DM$).

Anaphylaxis

• Extreme hypersensitivity. Sudden onset and severe.

• Signs: Wheeze/crackles, rash/urticaria, $N/V/D$, anxiety, flushed skin, angioedema, bronchospasm, hypotension, dyspnea, tachycardia.

• Treatment:     1. Epinephrine IM (Repeat doses as needed).     2. Glucagon.     3. Antihistamines.     4. Corticosteroids.

• Nursing Actions: Give oxygen ($100\%$ non-rebreather), elevate Head of Bed ($HOB$), keep emergency resuscitation equipment nearby, apply cold pack to injection site.

Immunosuppression vs. Overactive Immunity

Immunosuppression

• Definition: Reduced or absent immune response; impaired function of B-cells, T-cells, or neutrophils.

• Etiology: Primary (genetic) or Secondary (Chemo, radiation, HIV/AIDS, CKD, malnutrition, long-term corticosteroids).

• Signs: Frequent/recurrent infections, opportunistic infections (fungal, viral), delayed healing, fever, exhaustion.

• Labs: Low $WBC$ (Neutropenia defined as ANC < 500), low lymphocytes, pancytopenia (bone marrow suppression).

• Treatment: Growth factors, immunoglobulin therapy, avoid live vaccines, infection prevention.

Overactive Immunity

• Definition: Immune system attacks self or harmless substances; includes autoimmunity and hypersensitivity.

• Risk Factors: Female, genetics, environment (smoke, infection), stress.

• Signs: Inflammation, fatigue, joint pain, rash.

• Labs: Elevated $ESR$, elevated $CRP$, presence of autoantibodies.

• Complications: Chronic tissue damage, organ failure, disability.

• Treatment: Anti-inflammatories, Corticosteroids, $DMARDs$, biologic agents, immunosuppressants.

Neutrophil Shifts

• Left Shift: Indicates active bacterial infection (increased immature neutrophils).

• Right Shift: Indicates deficiency, chronic infection, or age-related changes (mature neutrophils).