Immunologic Disorders: Immune Function and Types

Immunologic Disorders

• Discusses assessment of immune function and management of immune deficiency disorders
• Also addresses allergic disorders and rheumatic disorders

Assessment of Immune Function

• Focuses on anatomy and physiology review, physical assessment techniques, and transplant rejection

Anatomy & Physiology Review

• The immune system functions as the body's defense mechanism against invasion and allows a rapid response to foreign substances
• Inflammation and immunity must work with other defenses to protect from harmful microorganisms and cells
• Inflammation and immunity are critical for maintaining health and preventing disease
• Immunocompetence is when all parts of inflammation and immunity are working well, giving maximum protection against infection

Types of Immunity

• Two general types of immunity exist: natural (innate) and acquired (adaptive)
• Natural (innate) immunity is nonspecific, present at birth, and serves as the first line of defense
• Acquired (adaptive) immunity is specific and develops after birth
• Acquired immunity usually develops from prior antigen exposure through vaccination or disease

Natural Immunity

• Also called inflammation
• Provides immediate protection against tissue injury and foreign proteins
• Innate-native immunity features natural protection
• It is a barrier to prevent organisms from entering the body or an attacking force that eliminates organisms that have entered
• Includes skin, mucosa, cilia of the respiratory tract, acidic gastric secretions, and antimicrobial chemicals on the skin

Acquired (Adaptive) Immunity

• Internal protection results in long-term resistance to invading microorganisms
• Responses aren't automatic, the body learns to generate specific immune responses when infected or exposed
• Includes active acquired immunity: immunologic defenses developed by one's own body
• Passive acquired immunity is temporary immunity transmitted from a source outside the body, due to previous immunization or disease

Immunoglobulins

• IgG makes up 75% of total immunoglobulin
  • Appears in serum and tissues and assumes a major role in bloodborne and tissue infections
  • Activates complements system and enhances phagocytosis
  • Crosses the placenta
• IgA makes up 15% of total immunoglobulin
  • Appears in body fluids and protects against respiratory, gastrointestinal, and genitourinary infections
  • Prevents absorption of food antigens
  • Passes to neonates in breast milk for protection
• IgM makes up 10% of the total immunoglobulin
  • Appears mostly in intravascular serum and is the first immunoglobulin produced in response to bacterial and viral infections
  • Activates complement system
• IgD makes up 0.2% of the total immunoglobulin
  • Appears in small amounts in serum
  • Possibly influences B-lymphocyte differentiation, but role is unclear
• IgE makes up 0.004% of total immunoglobulin
  • Appears in serum and takes part in allergic and hypersensitivity reactions
  • Combats parasitic infections

Autoimmunity

• Inappropriate immunity where antibodies or lymphocytes are directed against healthy normal cells and tissues
• Antibodies directed against self tissues or cells are autoantibodies
• Management depends on the organ(s) affected, as there is no cure
• Anti-inflammatory and immunosuppressive drugs are often used with symptomatic treatment

Immunity Changes with Aging

• Inflammation: reduced neutrophil function, absence of leukocytosis during acute infection, and lack of fever during inflammatory episodes
• Antibody-mediated immunity involves diminished colony-forming B-lymphocytes and mature cells, decline in natural antibodies, decreased response to antigens, and reduced antibody response time
• Cell-mediated immunity involves decreased circulating T-lymphocytes

Physical Assessment Techniques

• Neurosensory: cognitive dysfunction, hearing loss, visual changes, headaches, ataxia, tetany
• Respiratory: changes in RR, cough, abnormal lung sounds, rhinitis, bronchospasm
• Cardiovascular: hypotension, tachycardia, dysrhythmia, vasculitis, anemia
• Gastrointestinal: hepatosplenomegaly, colitis, vomiting, diarrhea
• Genitourinary: frequency and burning, hematuria, discharge
• Musculoskeletal: joint mobility, edema, pain
• Integumentary: lesions, dermatitis, purpura, urticaria, inflammation, discharge
• Lymph: palpate lymph nodes for location, size, consistency, tenderness
• Vital signs: measure temperature and observe for chills/sweating

Immune Deficiency Disorders

• Focuses on human immune deficiency virus (HIV) and acquired (secondary) immune deficiencies (AIDS)

Human Immune Deficiency Virus (HIV)

• Retrovirus transmitted through direct contact with HIV-infected body fluids: blood, semen, genital secretions
• Can be transmitted from an HIV-infected mother to child during pregnancy, birth, or breastfeeding
• HIV attacks the body's immune system
• HIV enters a cell, takes it over, and forces it to make more copies of the virus particles, which are shed to infect additional cells

HIV Life Cycle

• Attachment and fusion
• Injection of core
• Uncoating
• Conversion to DNA
• Circular DNA
• Entrance into nucleus
• Integration
• Transcription
• Translation
• Protein modification
• Assembly of core
• Budding

Reducing the Spread of Human Immune Deficiency Virus

• Recommendations for "Standard Precautions"
  • Perform hand hygiene
  • Wear personal protective equipment
  • Handle soiled patient care equipment appropriately with gloves
  • Follow procedures for environmental control
  • Handle textiles and laundry in a manner that prevents transfer
  • Handle needles and other sharps appropriately
  • Use devices during patient resuscitation
  • Prioritize patient placement as needed
  • Educate on proper respiratory hygiene and cough etiquette

Protecting Against HIV Infection

• All patients should be advised to:
  • Abstain from exchanging sexual fluids (semen and vaginal fluid)
  • Reduce the number of sexual partners to one
  • Always use latex condoms
  • Not reuse condoms
  • Avoid using cervical caps or diaphragms without a condom
  • Always use dental dams for oral-genital or anal stimulation
  • Avoid anal intercourse, or use lubricant
  • Avoid manual-anal intercourse ("fisting")
  • Avoid sharing needles, razors, toothbrushes, sex toys, or blood-contaminated articles
  • Consider PrEP if regularly engage in high-risk behaviors
  • Use needle-exchange programs and don't share drug equipment
• HIV seropositive patients should also:
  • Take ART regularly to achieve viral suppression
  • Inform partners of their HIV-positive status
  • Avoid unprotected sex with another HIV-seropositive person, as cross-infection can worsen the infection
  • Not donate blood, plasma, body organs, sperm

Acute HIV Infection

• Signs & symptoms can include:
  • Fever, night sweats, chills, headache, muscle aches, sore throat, rash

Stages of HIV

• Stage 0: interval between detectable HIV RNA and first antibody detection, with 40-80% of patients developing symptoms of a nonspecific viral illness lasting 1-2 weeks
• Stage 1: CD4+ T-cell count greater than 500 cells/mm³ with no AIDS-defining illnesses
• Stage 2: CD4+ T-cell count between 200 and 499 cells/mm³ with no AIDS-defining illnesses
• Stage 3: CD4+ T-cell count less than 200 cells/mm³ with AIDS-defining illnesses, or higher CD4+ counts but has an AIDS-defining illness

Acquired Immune Deficiency Syndrome (AIDS)

• Diagnosis requires being HIV positive and having either:
  • CD4+ T-cell count of less than 200 cells/mm³
  • Opportunistic infection
• Once AIDS is diagnosed, it remains even if T-cell count increases or infection is successfully treated

AIDS Infections

• Bacterial infections, multiple or recurrent
• Candidiasis of bronchi, trachea, or lungs
• Candidiasis of esophagus
• Cervical cancer, invasive
• Coccidioidomycosis, disseminated or extrapulmonary
• Cryptococcosis, extrapulmonary
• Cryptosporidiosis, chronic intestinal (>1-month duration)
• Cytomegalovirus disease (other than liver, spleen, or nodes)
• Cytomegalovirus retinitis (with loss of vision)
• Encephalopathy, HIV-related
• Herpes simplex: chronic ulcers (>1-month duration) / bronchitis, pneumonitis, or esophagitis
• Histoplasmosis, disseminated or extrapulmonary
• Isosporiasis, chronic intestinal (>1-month duration)
• Kaposi's sarcoma
• Lymphoid interstitial pneumonia / pulmonary lymphoid hyperplasia complex
• Lymphoma, Burkitt's (or equivalent term)
• Lymphoma, immunoblastic (or equivalent term)
• Lymphoma, primary, of brain
• Mycobacterium avium complex/Mycobacterium kansasii, disseminated or extrapulmonary
• Mycobacterium tuberculosis (any site), pulmonary, disseminated, or extrapulmonary
• Mycobacterium (other/unidentified species), disseminated or extrapulmonary
• Pneumocystis jiroveci pneumonia
• Pneumonia, recurrent (2 instances within 12 months)
• Progressive multifocal leukoencephalopathy
• Salmonella septicemia, recurrent
• Toxoplasmosis of brain
• Wasting syndrome attributed to HIV

Symptoms of AIDS

• Immunologic manifestations of AIDS symptoms include lymphadenopathy and fatigue
• Integumentary manifestations include dry skin, poor wound healing, skin lesions, night sweats
• Respiratory manifestations include cough and shortness of breath
• Gastrointestinal manifestations include diarrhea, weight loss, nausea, vomiting
• Central nervous system manifestations include confusion, dementia, headache, fever, visual changes, memory loss, personality changes, pain, seizures

HIV/AIDS Diagnostics

• Diagnostic labs:
  • Antibody tests, antigen/antibody tests, nucleic acid (RNA) tests, viral load testing, CD4+ T-cell count
• Diagnostic tests:
  • None

HIV/AIDS Interventions

• Prevention is key - education!
• Pre-exposure prophylaxis, such as Truvada (emtricitabine and tenofovir) for HIV-negative sexual partners
• Highly active antiretroviral therapy (HAART) reduces viral load, improves CD4+ T-cell counts, restores immunologic function, slows disease progression, and reduces HIV-associated morbidity/mortality
• Every health care encounter should briefly review the treatment regimen, any new issues, and reinforce behaviors
• Lab tests evaluate ART effectiveness and viral load should be measured regularly to monitor the response to ART
• Pain management includes prescribed NSAIDs, Lyrica, TCAs, Neurontin, Dilantin, and opioids
• Nutrition enhancement: high-calorie and high-protein diet, good mouth care, 2-3L of fluids/day, and appetite stimulants
• Monitoring/treating opportunistic infections includes knowing the signs, symptoms, and educating on self-management

AIDS Manifestations

• Monitor for AIDS manifestations and opportunistic infections:
  • Respiratory: pneumocystis jiroveci pneumonia (PCP) symptoms include SOB, cough, chest pain, and fever; TB symptoms include cough, night sweats, weight loss, and hemoptysis
  • Gastrointestinal symptoms: candidiasis causes oropharyngeal and esophageal painless creamy white plaque-like lesions, HIV wasting syndrome causes loss of >10% of body weight with diarrhea/weakness & fever for more than 30 days
  • Oncological: Kaposi sarcoma has a variable course from brownish-pink to deep purple cutaneous lesions to multiple organ system involvement

Allergic Disorders

• Focuses on hypersensitivities, allergies, and autoimmunity

Hypersensitivities/Allergies

• Excessive inflammation occurs in response to an antigen (foreign protein or allergen)
• There are four types:
  • Type I: Immediate
  • Type II: Cytotoxic
  • Type III: Immune complex-mediated
  • Type IV: Delayed

Types of Hypersensitivity Reactions

• Type I (Rapid or Immediate Reaction): reaction of IgE antibody on mast cells with antigen; results in release of mediators (histamine); clinical examples are hay fever, anaphylaxis, and angioedema
• Type II (Cytotoxic): reaction of IgG with host cell membrane/antigen adsorbed by host cell membrane; clinical examples are autoimmune hemolytic anemia, Goodpasture's syndrome, and myasthenia gravis
• Type III (Immune Complex-Mediated): formation of immune complexes of antigen/antibody deposit in blood vessel walls and results in complement release/inflammation; clinical examples are serum sickness, vasculitis, and systemic lupus erythematosus
• Type IV (Delayed): the reaction of sensitized T-cells with antigen releasing lymphokines activates macrophages to induce inflammation; clinical examples are poison ivy, graft rejection, and positive TB skin test

Allergy Diagnostics

• Diagnostic labs include CBC, ELISA for serum IgE, and skin testing
• Diagnostic tests include none

Type I (Rapid) Hypersensitivity Reaction

• Also called atopic allergy; is the most common type of hypersensitivity from excess immunity
• Primary chemical mediators cause symptoms to the skin, lungs, and gastrointestinal tract
• Some reactions occur in areas exposed to the antigen
  • Symptoms can include rhinorrhea, sneezing, itchy, red, or watery eyes
• Other reactions may involve the bronchiolar smooth muscle and blood vessels
  • Can cause widespread blood vessel dilation, decreased cardiac output, and bronchoconstriction
• Examples include inhaled plant pollens, ingested food additives, injected bee venom, and contacted latex

Allergic Rhinitis

• Signs/symptoms include rhinorrhea, itchy, watery eyes, mouth breathing, headache/sinus pressure, and dry/scratchy throat
• Interventions include avoidance therapy, antihistamines, adrenergic agents, mast cell stabilizers, leukotriene modifiers, and desensitization therapy/immunotherapy

Anaphylaxis (Type I: Rapid)

• Life-threatening hypersensitivity reaction
• Occurs rapidly and systemically and affects many organs within minutes of exposure
• Common causes include drugs, dyes, food, and insect stings/bites
• Some patients must carry an emergency epinephrine injector

Anaphylaxis Symptoms

• Mild systemic reaction characterized by peripheral tingling, warmth sensation, mouth/throat fullness, nasal congestion, pruritus, sneezing, and tearing of eyes
• Moderate systemic reaction with mild symptoms, flushing, warmth, anxiety, itching, bronchospasm, and edema of airways or larynx with dyspnea, cough, and wheezing
• Severe systemic reaction characterized by abrupt onset with rapid bronchospasm, laryngeal edema, severe dyspnea, cyanosis, hypotension, dysphagia, abdominal cramping, vomiting, diarrhea, seizures, coma, and cardiac arrest

Anaphylaxis Interventions

• Assess ABCs and call Rapid Response Team (RRT)
• Apply oxygen via high-flow non-rebreather mask at 90-100% and remove allergen if possible
• Administer IV/IM epinephrine and NS and position patient with HOB elevated 10-45 degrees with legs raised
• Stay with the patient
• Give sympathetic-mimetic drugs such as epinephrine, Benadryl, corticosteroids, vasopressors, or IV fluids/volume expanders

Type II (Cytotoxic) Reactions

• The body makes autoantibodies directed against self cells that have some form of foreign protein attached
• Autoantibody binds to the self cell and forms an immune complex, then the self-cell is destroyed
• Examples include immune hemolytic anemias, hemolytic transfusion reactions, and drug-induced hemolytic anemia
• Interventions include discontinuing the offending drug/blood product, plasmapheresis, and symptomatic treatment
• Complications monitoring is also important

Type III (Immune Complex) Reactions

• Excess antigens cause immune complexes to form in the blood that lodge in small blood vessel walls of the kidneys, skin, and joints
• Complexes trigger inflammation, leading to tissue/vessel damage or permeability results
• Examples include rheumatoid arthritis and systemic lupus erythematosus (SLE)
• Symptoms include fever, arthralgia, rash, malaise, lymphadenopathy, polyarthritis, and nephritis
• Interventions include supportive care, antihistamines, aspirin for arthralgias, and prednisone if manifestations are severe

Type IV (Delayed) Reactions

• T-lymphocyte reactive cells respond to an antigen by triggering chemical mediators and macrophages
• Type IV response occurs 24-48 hours after exposure and consists of edema, induration, ischemia, and tissue damage at the site
• Examples include positive purified protein derivative (PPD) test, contact dermatitis, local response to insect stings, and tissue transplant rejections
• Interventions: removal of the offending antigen is priority and corticosteroids are used to reduce discomfort/help resolve the reaction quickly

Transplant Rejection

• Occurs due to cytotoxic T-cells and natural killer (NK) cells that targets cells from other people/animals
• Solid transplanted organs cause the recipient's immune system cells to recognize the newly transplanted organ as non-self due to minor HLA matches
• Recipient's immune system will begin destroying these cells without interventions for rejection
• Rejection can be hyperacute, acute, or chronic

Hyperacute Rejection

• Happens right after/immediately with transplantation and an antibody-mediated response
• Antigen-antibody complexes form in blood vessels of the transplanted organ and lead to ischemic necrosis, massive cellular destruction, and graft loss
• Symptoms occur within minutes of attachment, include mottled organ/cyanotic, and lead to complete organ failure

Acute Rejection

• The first mechanism, antibody mediated, results in vasculitis within the transplanted organ
• The second mechanism is cellular and involves the recipient's cytotoxic T-cells and NK cells that enter the transplanted organ triggering an inflammatory response
• Symptoms include pain/tenderness of the organ/site, general discomfort/uneasiness, flu-like symptoms, and organ dysfunction

Chronic Rejection

• Chronic inflammation and scarring, and donated organ tissues are replaced with fibrotic/scar tissue, reducing the organ's function
• Symptoms of infection can include pain/tenderness of the organ/site, general discomfort, uneasiness, and organ dysfunction
• Although its process can be delayed through good control over recipient's immune system

Transplant Rejection

• Maintenance therapy involves continuous immunosuppression: use drugs such as combinations of a calcineurin inhibitor, corticosteroid, and an antiproliferative agent
• Rescue therapy is used to treat acute rejection episodes: the drug categories for this purpose are the monoclonal and polyclonal antibodies
• Drugs used for maintenance are also used during rejection episodes at much higher dosages

Rheumatic Disorders

• Discusses rheumatoid arthritis, lupus erythematosus, Sjögren's syndrome, Gout, and fibromyalgia syndrome

Rheumatoid Arthritis (RA)

• Chronic, progressive, systemic autoimmune disease that affects primarily the synovial joints
• Transformed autoantibodies (rheumatoid factors [RFs]) attack healthy tissue, especially synovium, causing inflammation
• The disease then involves the articular cartilage, joint capsule, and surrounding ligaments and tendons
• Characterized by natural remissions and exacerbations

Rheumatoid Arthritis Symptoms

• Early manifestations are symmetric joint pain/stiffness and systemic issues, such as low-grade fever, fatigue, weakness, anorexia, paresthesias
• Late manifestations include joint deformities, systemic issues, such as fever, fatigue, anemia, lymph node enlargement, subcutaneous nodules, pericarditis, neuropathy and cardiovascular disease

Rheumatoid Arthritis Interventions

• Nonpharmacological treatment: ice, heat, proper positioning, adequate rest, proper diet, and a hot shower in the morning
• Pharmacological: anti-inflammatory/analgesics (NSAIDs, COX2 inhibitors, glucocorticoids) and immunosuppressives/DMARDs (methotrexate, hydroxychloroquine)
• Surgical: Synovectomy and/or total joint replacement

Differential Diagnosis: Rheumatoid vs Osteoarthritis

• The typical rheumatoid arthritis onset age is between 35-45 years old, while osteoarthritis develops in persons 60 years or older
• Rheumatoid arthritis is more common in females (3:1) and is driven by genetic, environmental and stress-induced, autoimmune causes
• Osteoarthritis affects fewer females (2:1), and is often aging-driven or caused by genetic factors, trauma or repetitive stress
• Rheumatoid arthritis manifests as inflammatory and affects several joints bilateral
• Osteoarthritis is a degenerative disease that is unilateral and affects the spine, hands, and weight-bearing joints
• Rheumatoid arthritis is a systemic condition, while osteoarthiritis is nonsystemic
• Rheumatoid arthritis creates elavated rheumatoid factor, antinuclear antibodies and ESR, whereas osteoarthritis creates normal or slightly elevated ESR
• Common drugs used for rheumatoid arthritis are NSAIDS, Methotrexate and Leflunomide, while common drugs used for osteoarthritis are Tylenol or NSAIDs

Systemic Lupus Erythematosus (SLE)

• Inflammatory, autoimmune disorder that affects nearly every organ in the body
• Examples of SLE are lupus nephritis and discoid lupus erythematosus
• The disease process involves chronic states where symptoms are minimal, but can flare up acutely

Systemic Lupus Erythematosus Symptoms

• Symptoms are inflamed, discoid lesions rash and oral ulcers
• Also accompanied by kidney failure/nephritis, hypertension, dysrhythmias, pericarditis, Raynaud's phenomenon, atherosclerosis and pleural effusions
• Also includes psychosis, cognitive impairment, GI issues, abdominal pain, joint inflammation arthralgias, fever, weight loss, fatigue and anorexia

Systemic Lupus Erythematosus Interventions

• Interventions are topical cortisone preparations, analgesics, hydroxychloroquine antimalarial agent, immunosuppressive agents and biologic/monoclonal antibodies

Sjögren's Syndrome (SS)

• Systemic autoimmune disease that progressively affects the lacrimal, vaginal and salivary glands
• Autoimmune destruction (excess immunity) causes problems, such as keratoconjunctivitis sicca, xerostomia, and a dry vagina
• This causes dry eyes, blurred vision, mattering in the conjunctiva, difficulty swallowing, changes in taste, and frequent respiratory infections
• Causes Nonpharmacological needs of artificial tears/saliva, avoidance of smoking/alcohol, small, frequent meals, and humidifers, while pharmacological needs are rituximab and interferon

Gout

• Type of inflammatory arthritis
• Systemic disease in which urate crystals deposit in the joints and tissues, causing inflammation
• Incidence increases with age, BMI, alcohol consumption, hypertension, and diuretics
• Uric acid, a byproduct of purine metabolism, are basic compounds found in meat
• Trauma, alcohol, medications, stress, or illness can trigger an acute attack
• Look for diagnostic Labs: serum uric acid, ESR and arthrocentesis, but no specific diagnostic test

Gout Symptoms

• Symptoms include joint inflammation, redness, warmth, pain, and renal calculi
• Symptoms also include swollen joints, painful even to touch

Gout Interventions

• Perform nonpharmacological measures, such as diet
• For acute attacks, use colchicine, Nsaids and corticosteroid
• For chronic attack use, Allopurinol and febuxostat

Fibromyalgia

• Chronic pain syndrome that is not inflammatory
• Cause is pain, stiffness, and tenderness occur at sites in the back of the neck, chest, trunk, low back, and extremities
• Trigger or tender points include also known and typically be palpated to elicit pain in a predictable, reproducible way
• Patients can have other rheumatic conditions from 25%-65%
• Risk factors of viral infection, depression, pain, stress, sleep disorder, physical trauma
• Check and evaluate chronic fatigue, forgetfulness and concentration, function impairment, stiffness Interventions: - perform physical therapy
• Interventions: give sleep pattern and supportive care, limited caffeine/alcohol
• Cognitive therapy, prescribed anticonvulsants, Tricyclic antidepressants(TCAs)