Immunology and Rheumatology Cases Summary

Definitions

• Immunology: The branch of biomedical science that focuses on the study of the immune system, which consists of various cells, tissues, and organs that play crucial roles in defending the body against infection and disease. This field also encompasses the investigation of immune responses and dysfunctions that can lead to allergies, autoimmune diseases, and immunodeficiency.

• Rheumatology: A medical specialty dedicated to diagnosing, treating, and managing disorders characterized by inflammation, affecting not only bones, joints, and connective tissues but also internal organs. Many rheumatologic diseases, such as rheumatoid arthritis and systemic lupus erythematosus, are autoimmune in nature where the body's immune system mistakenly attacks its own tissues.

Immunity and Immunoglobulin Classes

Immune Response Systems

• Hypersensitivity Reactions: An inappropriate or exaggerated immune response to an antigen (Ag), which can be derived from environmental sources, self-tissues, or uniquely identified entities. These reactions can manifest in various forms, leading to allergies or autoimmune diseases depending on the type and severity of the response.

Immunoglobulins

• IgG: Comprising approximately 80% of all serum antibodies, IgG is crucial for long-term immunity as it protects against a wide range of pathogens. IgG is unique because it can cross the placenta, offering passive immunity to the fetus during pregnancy. This immunoglobulin also plays an essential role in opsonization and neutralization of toxins.

• IgM: The first antibody that the body produces in response to an infection, IgM is highly effective in agglutinating pathogens, thereby facilitating their removal. It exists mainly in a pentameric form and does not cross the placenta, making it crucial for early immune responses during initial exposure to antigens.

• IgA: Predominantly found in mucosal areas, saliva, tears, and breast milk, IgA serves as a first line of defense by preventing pathogens from adhering to and penetrating epithelial cells. In infants, maternal IgA in breast milk provides important protection against infections during early development.

• IgD: Mainly acts as a receptor on B cells, facilitating the activation process that leads to the differentiation of B cells into plasma cells. While its exact function remains less understood, it is believed to play a role in the initiation of immune responses.

• IgE: Involved in allergic reactions, IgE is responsible for the development of hypersensitivity responses and triggers the release of histamine and other chemicals from mast cells and basophils. Elevated IgE levels are commonly associated with asthma, hay fever, and allergic responses to foods and medications.

Types of Hypersensitivity

Type I (Immediate) Hypersensitivity

• Mechanism: This form involves the cross-linking of IgE antibodies bound to mast cells by free antigens, resulting in the rapid release of histamine and other mediators.

• Timing: Symptoms typically appear within 5 to 30 minutes after re-exposure to the allergen, although a late-phase reaction can occur hours later, leading to prolonged symptoms.

• Clinical Example: Anaphylaxis, a severe and potentially life-threatening allergic reaction characterized by widespread histamine release, resulting in hives, difficulty breathing, and hypotension.

Type II (Antibody-Mediated) Hypersensitivity

• Mechanism: In this response, the immune system erroneously identifies its own cells as foreign due to antibody binding (IgM and IgG) to specific host cell antigens, leading to cell destruction or dysfunction.

• Clinical Example: Blood transfusion reactions occur when an individual receives blood containing antigens that their immune system recognizes as foreign, resulting in fever, chills, hemolysis, and potential kidney failure.

Type III (Immune Complex-Mediated) Hypersensitivity

• Mechanism: This type involves the formation and deposition of immune complexes within tissues, which triggers inflammatory responses and tissue damage.

• Clinical Example: Systemic lupus erythematosus (SLE) is a classic example where immune complexes deposit in multiple organs, leading to a diverse range of symptoms such as rashes, joint pain, and renal dysfunction.

Type IV (Cell-Mediated) Hypersensitivity

• Mechanism: Characterized by the activation of sensitized T cells that respond to antigenic exposure, releasing cytokines or directly inducing cell death in infected or altered cells.

• Timing: Typically manifests as a delayed response, taking hours to days post-exposure.

• Clinical Example: Contact dermatitis is a common reaction to allergens like poison ivy, where T cell mediated inflammation develops in response to allergenic substances.

Anaphylaxis Management

• Symptoms: Patients may present with hives, respiratory distress, gastrointestinal symptoms (such as nausea and vomiting), and cardiovascular instability, including tachycardia and hypotension.

• Treatment: Rapid recognition of symptoms is critical; epinephrine is the first-line medication, effectively counteracting severe allergic reactions by constricting blood vessels and opening airways. Dosage should be administered intramuscularly at the outer thigh.

• Observation: Following treatment, patients should be monitored for 4-8 hours to detect possible biphasic reactions, allowing for timely intervention if symptoms recur.

Autoimmune Disorders

Common Autoimmune Conditions

• Rheumatoid Arthritis: A chronic inflammatory disorder primarily affecting joints, leading to pain, stiffness, swelling, and potential loss of function. Over time, it can result in joint deformities and systemic effects due to inflammation.

• Systemic Lupus Erythematosus: A multi-system autoimmune disease characterized by the production of autoantibodies that can affect various organs, including skin (butterfly rash), joints, kidneys (lupus nephritis), and the nervous system.

Infectious Disease Overview

Infectious Mononucleosis

• Caused by the Epstein-Barr Virus (EBV), Usually asymptomatic → some get mono

• Incubation period: 4-8 weeks

• Signs/Symptoms: Sore throat, cervical lymphenopathy, fatigue

• Diagnosis: Monospot and EBV Panel

• Treatment:

  • Symptomatic

  • Steroids to decrease sore throat within 12 hours

  • Don’t use amoxicillin

• Risk of Splenic Rupture:

  • Avoid all exercise for 21-28 days after illness onset

  • Then slowly increase activity starting and walking and progressing

  • 2-3 month recovery → may take longer

Lyme Disease

• Transmitted by infected ticks (notably Borrelia burgdorferi), it presents with erythema migrans (bull's-eye rash) at the site of the tick bite. If not treated promptly, it can progress to include arthritis, neurological complications, and cardiac issues.

HIV/AIDS

• A chronic immunodeficiency condition caused by the Human Immunodeficiency Virus (HIV), destruction of T cells, leading to immune system failure.

• Treatment:

  • Goal: achieve suppression of HIV replication 

  • Lifelong medication: has to be exactly followed 

    • Drug regimen 

    • Side effects

    • Rebound effects  

• Transmission:

  • Sexual contact

  • Exposure to blood or blood containing body fluids 

  • Materno fetal transmission 

• HIV/AIDS: Clinical Implication: 

  • Side Effects: Peripheral neuropathy, myalgia, HTN, Hyperglycemia 

  • Rehab Interventions: 

    • ADL’s, Heart Health, Reduce Pain, Improve balance, maintain body weight

• HIV/AIDS: Exercise 

  • Moderate exercise beneficial 

  • Strenuous exercise may be detrimental: may impair ability to mobilize neutrophils and NK cells 

  • For healthy, asymptomatic patients who are HIV+, unrestricted exercise is acceptable 

    • Avoid overtraining  

  • Mild to moderate symptoms

    • No competition or exhaustive exercise 

  • Most experts recommend against participation in professional sports due to demands 

Shingles

Shingles → Lives in the Dorsal Horn 

Signs and Symptoms:

• Follows a detrimental pattern 

• Rash 

• Can become chronic 

Predisposing Factors:

• Same virus that causes chickenpox 

• Contagious!

• High stress 

• Age 

Treatment:

• Vaccine → cant have if immunocompromised or over the age of 50 

Functional Somatic Syndromes

Chronic Fatigue Syndrome (CFS)

• Characterized by persistent, unexplained fatigue lasting more than six months, worsened by physical or mental exertion. Additional symptoms include unrefreshing sleep and cognitive impairments, such as memory and concentration issues.

Fibromyalgia

• A syndrome characterized by widespread musculoskeletal pain that often coexists with fatigue, sleep disturbances, and cognitive difficulties. It may be exacerbated by stress, hormonal changes, and viral infections, leading to a significant impact on quality of life.

Treatment and Management Strategies

• Autoimmune Diseases: Management strategies include the use of DMARDs (Disease-Modifying Anti-Rheumatic Drugs) to slow disease progression, NSAIDs for pain relief, and a comprehensive lifestyle approach focusing on exercise, nutrition, and self-management techniques.

• Infectious Diseases: Treatment for infectious mononucleosis typically focuses on symptomatic management, such as analgesics for pain relief and hydration, while Lyme disease requires timely antibiotic therapy for effective resolution.

• HIV: Management approaches include the initiation of antiretroviral therapy (ART) to control viral load, improve immune function, and enhance overall health and quality of life. Behavioral health support may also be necessary.

Summary of Key Hypersensitivity Reactions

• Type I: Immediate allergic reactions, such as anaphylaxis and asthma, involving IgE-mediated responses.

• Type II: Antibody-mediated autoimmune conditions, including Graves' disease and rheumatic fever, characterized by the destruction of target cells.

• Type III: Immune complex-mediated diseases, such as SLE and rheumatoid arthritis, involving localized tissue damage from deposited complexes.

• Type IV: Cell-mediated responses involving contact dermatitis and transplant rejection, highlighting the importance of T cells in these processes.

Factors that increase Exposure to Pathogens:

• Urinary catheter, IV*

• Traveling 

• Hygiene 

Factors that Alter the Immune System:

• Sleep

• Diet

• Stress

• Aging 

• High Intensity exercise

Hypersensitivity Reactions:

Type 1: Allergies → IgE-Mediated 

• Rapid reaction because antibody is performed 

  • 5-30 min after exposure 

  • Usually resolves in 60 min, but a second, late-phase reaction may start 2-24 hrs later and last several days 

  • Blood vessel dilation and fluid 

• Widespread histamine release = anaphylaxis

• Atopy: genetic predisposition to produce IgE antibodies against common antigens

Type II: Antibody Mediated Hypersensitivity 

• The body recognizes its own cells as foreign and attacks 

• Blood transfusion reaction → red blood cells destroyed by complement and antibody during a transfusion of mismatched blood type

  • fever/chills, flank or back pain, bloody urine, lightheadedness, flushing, kidney failure, anemia, lung problems, shock 

Type 3: Immune Complex Mediated Hypersensitivity 

• Exposure to Ag causes IgG formation 

• Antibody complexes are deposited in tissue → cause activation of complement → attracts neutrophils 

• Common forms of immune complex disease: glomerulonephritis, RA, and Lupus 

Type 4: Cell Mediated Hypersensitivity 

• Delayed response

• Sensitized T cells encounter Ag and release cytokines that lead to macrophage activation OR directly kill Ag-bearing cells 

• Common forms: contact dermatitis, poison ivy OR autoimmune → type I diabetes, MS, and RA