Immunity and Altered Immune Response

Immunity

• Definition: The body’s ability to resist disease.
• Three core functions:
  • Defense: identifies and destroys pathogens.
  • Homeostasis: removes damaged cellular substances to keep internal environment stable.
  • Surveillance: identifies mutations or abnormal cells (e.g., early cancer) and eliminates them.

Antigens

• Any substance that elicits an immune response (chemicals, bacteria, viruses, pollen, etc.).
• Most antigens are proteins.
• All body cells display unique “self” antigens; immune system is normally non-responsive to these.
• “Non-self” antigens trigger reactions.
• Human Leukocyte Antigen (HLA):
  • Surface proteins that help immune cells recognize each other and differentiate self from foreign.
  • NOT the same as antibodies.

Types of Immunity

• Innate (natural):
  • Present at birth; first-line nonspecific defense (skin, mucous membranes, phagocytes, NK cells, etc.).
• Acquired (specific): develops after birth.
  • Active:
  • Natural: infection → body produces antibodies.
  • Artificial: vaccination.
  • Passive:
  • Natural: transfer of antibodies (e.g., maternal IgG via placenta, IgA via breast milk).
  • Artificial: injection of antibodies (e.g., immune globulin therapy).

Lymphoid Organs

• Central (primary): bone marrow & thymus gland.
  • Lymphocytes produced in bone marrow.
  • T-cells mature in thymus.
• Peripheral: lymph nodes, tonsils, spleen, gut/bronchial/skin-associated lymphoid tissue.
• Lymphocytes migrate from central → peripheral sites where immune responses are initiated.

Cells of the Immune System

• Mononuclear phagocytes (monocytes ➔ macrophages):
  • Phagocytose, process, & present antigens to lymphocytes.
• Lymphocytes (adaptive):
  • B cells ➔ plasma cells ➔ antibodies.
  • T cells:
  • T cytotoxic (CD8): kill infected/abnormal cells.
  • T helper (CD4): coordinate immune activity.
• Natural Killer (NK) cells (innate): destroy virally-infected & early malignant cells.
• Dendritic cells: antigen capture at skin & mucous membranes ➔ present to T cells.

Cytokines and Interferons

• Cytokines: >100 small signalling proteins; act as inter-cell messengers; regulate growth, differentiation & activity of immune & blood cells.
• Can be beneficial (host defense) or detrimental (chronic inflammation, autoimmunity, sepsis).
• Interferons (IFNs):
  • Sub-group of cytokines.
  • Secreted mainly in response to viral entry; inhibit viral replication inside host cells.

Immunoglobulins (Antibodies)

• Glycoproteins produced by plasma cells; highly specific for antigens.
• Classes:
  • IgM – first produced on initial exposure.
  • IgG – most abundant, crosses placenta.
  • IgA – body secretions (tears, saliva, breast milk).
  • IgE – allergic & parasitic responses.
  • IgD – B-cell receptor.

Immune Response to a Virus (Fig 16.2 synopsis)

1. Virus invades body (A).
2. Macrophage engulfs virus, presents antigen (B).
3. Cytokines (e.g., IL-1, TNF) recruit/activate:
   • Natural Killer cells.
   • T helper (CD4) cells (C).
4. IL-2 & γ-IFN stimulate clonal expansion →
   • T cytotoxic cells kill infected cells.
   • B cells mature ➔ plasma cells ➔ antibodies (F).
5. Memory T & B cells formed (E, G) → quicker secondary response.

Humoral vs Cell-Mediated Immunity

• Humoral (antibody-mediated):
  • B-cell → plasma cell → antibodies.
  • Targets extracellular organisms; rapid.
• Cell-mediated:
  • T cells ± macrophages & NK cells.
  • Targets intracellular pathogens & cancer cells; slower (delayed-type).

Primary vs Secondary Immune Responses

• Primary exposure: IgM peaks first, IgG follows; overall lower titre.
• Secondary (anamnestic): rapid, larger IgG surge; basis for vaccination.

Age-Related Changes

• ↓ Immune effectiveness; ↑ susceptibility to infection & autoimmune disease.
• ↓ Antibody response to immunizations.
• Thymic involution; ↓ T-cell function.

Altered Immune Responses

• Immunocompetence = ability to identify & destroy foreign substances.
• Under-responsive immune system ➔ severe infections, immunodeficiency, malignancy.
• Over-responsive ➔ hypersensitivity & autoimmune disorders.

Hypersensitivity Reactions (Table 16.7)

• Type I (Antibody-mediated, IgE): Anaphylaxis & Atopy (asthma, rhinitis, dermatitis, urticaria, angioedema).
• Type II (Cytotoxic): hemolytic transfusion reaction, Goodpasture’s syndrome.
• Type III (Immune-complex): systemic lupus erythematosus, rheumatoid arthritis.
• Type IV (Delayed, cell-mediated): contact dermatitis, transplant rejection.

Type I Details

• Occur in susceptible, highly-sensitized individuals.
• Anaphylaxis: systemic mediator release within minutes; life-threatening. Medications = leading cause of fatalities.
• Atopic disorders:
  • Allergic rhinitis (hay fever): airborne allergens; sneezing, nasal discharge, pruritus.
  • Atopic dermatitis: chronic relapsing eczema.
  • Urticaria: transient wheals, intense pruritus; histamine-mediated.
  • Angioedema: deeper dermal/submucosal swelling (lids, lips, tongue, larynx, extremities, GI, genitalia); onset minutes → hours.
• Systemic Anaphylaxis S/S (multi-system):
  • Neurologic: headache, dizziness, paresthesia, "impending doom".
  • Skin: pruritus, erythema, urticaria, angioedema.
  • Respiratory: hoarseness, wheeze, stridor, dyspnea ➔ arrest.
  • Cardiovascular: hypotension, tachycardia, dysrhythmias, arrest.
  • GI: cramp, nausea, vomiting, diarrhea.

Type II: Hemolytic Transfusion Reaction

• ABO-incompatible blood ➔ antibodies coat donor RBCs ➔ agglutination.
• Micro-vascular blockage & consumptive coagulopathy ➔ bleeding; life-threatening.
• Nursing: strict pre-transfusion checks, close monitoring, stop transfusion & treat immediately if reaction.

Type III: Immune-Complex

• Small Ag-Ab complexes deposit in tissues (kidneys, skin, joints, vessels, lungs).
• Activate complement/inflammation ➔ tissue destruction; can be local/systemic, immediate/delayed.

Type IV: Delayed (Contact Dermatitis)

• T-cell mediated; rash confined to contact site; appears $24–48\,\text{h}$ after exposure.

Allergic Disorders – Assessment & Collaborative Care

• Health history; focused physical (skin, ENT, respiratory).
• Diagnostics: serum IgE & eosinophils, skin tests.
• Care priorities:
  • Recognize & control allergen exposure.
  • Medication (antihistamines, corticosteroids, decongestants, leukotriene antagonists, epinephrine for anaphylaxis).
  • Immunotherapy (allergen desensitization) when avoidance & meds fail; monitor for anaphylaxis during injections.

Latex Allergy

• Growing concern for patients & HCPs.
• Type IV contact dermatitis or Type I IgE reaction.
• Latex-food syndrome: cross-reaction with foods (banana, kiwi, avocado, etc.).
• Nursing: identify risk, implement latex-free environments.

Autoimmunity

• Immune reaction against self-proteins; etiology unknown (genetic + triggers).
• Can cluster; organ-specific or systemic (see Table 16.13).

Immunodeficiency Disorders

• Inadequate protection due to impaired mechanisms:
  • Phagocytosis, humoral, cell-mediated, complement, combined.
• Primary: congenital (rare, severe) – Table 16.14.
• Secondary: acquired; more common, less severe (malnutrition, chemo, radiation, splenectomy, chronic stress, AIDS, etc.) – Table 16.15.

Nursing Support for Immunocompromised Clients

• Reduce infection risk: strict hand hygiene, asepsis, masks, limit exposure, hygiene & nutrition promotion.
• Vigilant assessment: blunted inflammatory signs; monitor labs; inspect for oral thrush, etc.
• Psychosocial support (anxiety, coping).

Infection Overview

• Infection = invasion by pathogenic microorganism & host response.
• Localized vs systemic.

Causes

• Bacteria: reproduce intracellularly or via toxins (e.g., $C.\ difficile$, $Bordetella\ pertussis$, TB, UTIs).
• Viruses: RNA/DNA + protein coat; replicate only in host cells (e.g., SARS-CoV-2, influenza, HIV).
• Fungi: plant-like; usually localized (Candida, ringworm).
• Protozoa: single-cell animal-like (malaria, giardiasis).

Health-Care Associated Infection (HCAI)

• Acquired from health-care exposure; surgical & immunocompromised patients at highest risk; prevention strategies imperative.

Emerging/Re-Emerging & Resistant Infections

• Emerging: Lyme, H1N1, West Nile, Zika.
• Re-emerging: pertussis, measles, TB.
• Resistant: MRSA, VRE, CPE.

Human Immunodeficiency Virus (HIV)

• HIV: RNA retrovirus; AIDS = most advanced stage.
• Global stats 2020: $37.7\,\text{million}$ living with HIV; $1.5\,\text{million}$ new infections.
• Canada: $75\,500$ living with HIV; $21\%$ unaware of status.

Pathophysiology

• HIV integrates into host DNA; daughter cells inherit infection.
• Targets cells with CD4 receptors: CD4+ T helper lymphocytes, monocytes, glial cells.
• Destroyed at rate ≈ $1\times10^{9}$ CD4 cells/day.
• Immune problems begin when CD4 < $500\,\text{cells}/\mu L$ (normal $800–1\,200/\mu L$).
• High viral load first $2–3$ wk ➔ prolonged low level until AIDS.

Transmission

• Blood, semen, vaginal secretions, breast milk.
• Modes: sexual, perinatal, blood exposure.
• NOT via casual contact, tears, urine, saliva, sweat.
• Occupational risk low; report all needle sticks.

Natural History (untreated)

• Acute: flu-like within $1–3\,\text{wk}$; lasts $1–2\,\text{wk}$; high viral load.
• Early chronic: asymptomatic or mild fatigue, headache, night sweats; may last years; contagion persists.
• Intermediate: CD4 $200–500/\mu L$; persistent fever, night sweats, chronic diarrhea, thrush, shingles, oral hairy leukoplakia, KS, bacterial & vaginal infections.
• Late (AIDS): meets WHO criteria; severe immunosuppression; multiple opportunistic infections/malignancies (PCP pneumonia, CMV, cryptococcal meningitis, lymphoma, wasting, dementia).

Diagnostics

• Pre-diagnosis rapid tests: INSTI POC or self-test (capillary blood, minutes).
  • Reactive result ➔ confirmatory public-health testing.
• Post-diagnosis monitoring: CD4 count/fraction, viral load, CBC (neutropenia, anemia), LFTs, resistance assays.

Interprofessional Care

• Monitor disease & immune status.
• Initiate & manage ART.
• Prevent/detect/treat opportunistic infections.
• Manage symptoms & treatment complications.
• Psychosocial/spiritual support & transmission prevention.

Antiretroviral Therapy (ART)

• Goals: ↓ viral load $90–99\%$, ↑/maintain CD4, delay symptoms/OIs, prevent transmission.
• Start ASAP regardless of CD4/viral load/pregnancy (assess readiness).
• Use ≥3 drugs from ≥2 classes to curb resistance.
• Pregnant women: full ART.
• Adherence critical; missed doses → resistance.
  • Individualized strategies: education, pillboxes, reminders, simplified regimens.

Additional Therapies

• Pre-Exposure Prophylaxis (PrEP).
• OI prophylaxis/treatment.
• Vaccination research ongoing.

Nursing Management

• Assessment: detailed risk history, physical, labs.
• Diagnoses: individualized (Table 17.16) – e.g., infection risk, coping, knowledge deficit.
• Planning goals: low viral load, strong immunity, prevent transmission & OIs, maintain QOL.
• Interventions: med adherence support, healthy lifestyle, safe sex/needle practices, psychosocial support, case management, legal & end-of-life planning as needed.

Health Promotion & Prevention

• Primary prevention: education, safer sex, needle programs, routine testing & counseling.
• Perinatal: prevent HIV in women; treat HIV-positive pregnancies.

Stigma & Social Constructs

• HIV associated with moral judgments (sex, drugs) ➔ stigma & discrimination.
• Impacts mental health, social integration, economics.
• Canadian Human Rights Commission: right to equality & dignity regardless of status.

Summary

• The immune system uses innate & adaptive mechanisms for defense, homeostasis, and surveillance.
• Dysregulation produces hypersensitivity, autoimmunity, or immunodeficiency.
• Hypersensitivity Types I–IV differ by mechanism & timing; Type I (anaphylaxis) most urgent.
• HIV exemplifies chronic immune compromise; early detection, combination ART, adherence, & comprehensive nursing care markedly improve outcomes.