Immune and Inflammatory Altered Immune Responses

 # Fundamentals of the Immune System

• Conceptual Definition: The immune system serves three primary functions in maintaining health and responding to threats:
      * Defense: Provides protection against invasion by foreign substances or microorganisms.
      * Homeostasis: Ensures that internal cells remain uniform and regular; it involves "self-tolerance," where the body recognizes its own proteins versus foreign ones.
      * Surveillance: Actively identifies and destroys cellular mutations as they arise.

• Lymphoid Organs: The physical infrastructure of the immune system includes:
      * Thymus gland
      * Bone marrow
      * Lymph nodes (responsible for filtering lymph and lymphoid tissue to remove foreign particles)
      * Tonsils
      * Spleen

• Immune Capabilities Under Normal Conditions:
      * Neutralization, elimination, or destruction of "non-self" substances.
      * Recognition of unique proteins on cell surfaces; if they are not “self” (antigens), an immune response is activated.

Types of Immunity

• Innate Immunity: Specific to being present at birth. It is non-specific and acts as the body’s first line of defense.

• Acquired Immunity: The development of immunity over time, divided into active and passive forms:
      * Active Acquired Immunity:
          * Natural Active: Occurs after recovering from a disease (e.g., chickenpox). It is the most effective and longest-lasting form of immunity.
          * Artificial Active: Resulting from vaccinations (e.g., tetanus vaccine). This usually requires a booster shot to maintain effectiveness.
      * Passive Acquired Immunity: Provides immediate, short-term protection. Examples include the transfer of antibodies/globulin across the placental membrane or through injection.

Lymphocyte Function and Humoral vs. Cellular Immunity

• B Lymphocytes (Humoral/Antibody-Mediated Immunity):
      * Characterized by a rapid response.
      * Primary Immune Response: Takes $4$ to $8$ days following initial exposure to an antigen.
      * Secondary Immune Response: Mediated by Memory cells. Occurs in only $1$ to $3$ days; it is faster, stronger, and longer-lasting because the body "remembers" the antigen.

• T Lymphocytes (Cellular-Mediated Immunity):
      * Characterized by a slower response.
      * Helper T Cells: Stimulate the process of phagocytosis.
      * Cytotoxic T Cells: Release cytolytic substances to destroy infected cells.
      * Natural Killer (NK) Cells: Recognize and kill mutated or infected cells.

The Inflammatory Response

• Immunocompetence: Requires the interaction of three processes: Inflammation, Humoral immunity, and Cell-mediated immunity.

• Inflammatory Response Characteristics: A non-specific defense against tissue injury, invasion by microorganisms, or foreign proteins.

• Cellular Response Timeline:
      * Neutrophils: The first WBCs to arrive at the site of injury ($6$ to $12$ hours). They phagocytize bacteria and foreign material but have a short life span ($24$ to $48$ hours), leading to the formation of pus.
      * Monocytes (Macrophages): Arrive later ($3$ to $7$ days). They transform into macrophages with a long life span to assist in significant "clean up" of the infection site.
      * Lymphocytes: Arrive even later; their role is specifically related to humoral and cell-mediated immunity.

• "Shift to the Left": A clinical term indicating an increased number of "bands" (immature neutrophils). This occurs during acute infections when the bone marrow's production and release of neutrophils are accelerated to meet high demand.

• Cardinal Signs of Inflammation:
      * Local: Heat, loss of function, pain, redness, and swelling.
      * Systemic: Increased WBC count, fatigue, nausea/anorexia, increased pulse and respiratory rate, and fever.

Hypersensitivity Reactions

• Definition: An excessive immune response to an antigen to which the client has been previously exposed, resulting in potential tissue damage. Responses range from mild allergies to life-threatening anaphylaxis.

• Classification (4 Types):
      * Type I: Rapid IgE Mediated: Includes allergies and latex allergy. Can lead to anaphylaxis (emergency priority: ABCs—Airway, Breathing, Circulation). Associated with eosinophils and histamine release.
      * Type III: Immune Complex: Complexes deposit in small blood vessels, damaging organs. Examples: Rheumatoid arthritis and Systemic Lupus Erythematosus (SLE).
      * Type IV: Delayed Hypersensitivity: Mediated by sensitized T-lymphocytes. The response occurs hours to days after exposure. Examples: Positive PPD (TB test) or poison ivy.

Autoimmunity and Systemic Lupus Erythematosus (SLE)

• Autoimmunity: The immune system fails to recognize "self," directing antibodies against healthy tissues. The cause is often unknown but linked to genetics, sun exposure, and toxins.

• Systemic Lupus Erythematosus (SLE):
      * A chronic, progressive, inflammatory connective tissue disease that affects skin, joints, kidneys, and the neurologic system.
      * Demographics: Approximately $90\%$ of cases occur in women.
      * Pathophysiology: Circulation of immune complexes against DNA. These deposit in the basement membranes of capillaries in the heart, kidneys, skin, brain, and joints, triggering destructive inflammation.
      * Complications:
          * Renal involvement is the most common cause of death.
          * Butterfly rash (sun-exposed areas).
          * Arthritis and musculoskeletal pain.
          * Central nervous system issues (headaches to cerebrovascular disease).
      * Diagnostics: No specific test; diagnosed via History and Physical (H&P), ANA (Antinuclear Antibody), and ESR (Erythrocyte Sedimentation Rate).
      * Management: NSAIDs, steroids, and immune modulators. Patients should avoid stress and drying soaps and use sunscreen.

Gout and Related Conditions

• Gout: Inflammation caused by urate crystal deposits in joints.
      * Primary Gout: Genetic; caused by a lack of the enzyme uricase.
      * Secondary Gout: Caused by conditions or drugs (e.g., loop diuretics) that increase uric acid production or decrease excretion.
      * Triggers: High intake of purine-rich foods (red meat, organ meat, shellfish), excess alcohol, fasting, or fructose drinks.
      * Clinical Stages:
          * Initial: Excruciating pain, usually in the big toe.
          * Chronic: Formation of tophi (urate crystals) under the skin and inside organs (kidneys).
      * Management:
          * Acute: Oral colchicine and NSAIDs.
          * Long-term: Allopurinol or probenecid to lower serum uric acid.
          * Diagnosis: Synovial fluid aspiration to check for crystals.

Lyme Disease and Fibromyalgia

• Lyme Disease: Caused by a spirochete infection from a deer tick bite.
      * Symptoms: "Bulls-eye" rash, muscle/joint stiffness, flu-like symptoms, and fatigue.
      * Progression: If untreated, can spread to the heart, joints, and CNS (Lyme arthritis).
      * Treatment: Oral antibiotics like doxycycline.

• Fibromyalgia: A chronic central pain syndrome.
      * Characteristics: Widespread, non-articular musculoskeletal pain, multiple tender points, and fatigue.
      * Theory: Abnormal central processing of nociceptive pain input in the CNS (increased sensitivity).
      * Management: Lyrica for chronic pain, SSRIs for depression, gentle exercise, and stretching to maintain muscle tone.

HIV and AIDS

• Pathophysiology: HIV is a retrovirus that infects cells with CD4+ receptors. The virus forces the host cell to use viral RNA as a template to make complementary DNA, which is then incorporated into the host’s DNA to replicate.

• Transmission: Spread through infected blood, semen, vaginal secretions, or breast milk. It is not spread by tears, saliva, urine, feces, sweat, or respiratory droplets.

• Disease Progression:
      * Acute Infection: Mononucleosis-like symptoms (fever, swollen nodes, sore throat) occurring $2$ to $4$ weeks after infection.
      * Asymptomatic Chronic: Can last about $10$ years.
      * Symptomatic Chronic: Persistent fever, night sweats, chronic diarrhea, and severe fatigue.
      * AIDS: Defined by meeting CDC criteria, including opportunistic diseases (e.g., Candida/thrush, TB, Pneumocystis pneumonia, Hepatitis B/C).

• Management and Prevention:
      * Goal: Achieve an "undetectable" viral load.
      * Drug Therapy: Antiretrovirals.
      * Prevention: Biomedical prevention (PrEP - Pre-exposure Prophylaxis) and behavior modification.