Inappropriate Immune Responses, Hypersensitivity & Autoimmune Diseases

Inappropriate Immune Responses

• Immunity is a complex system that protects the body.
• The immune system usually combats pathogens and restores homeostasis.
• Inappropriate immune responses occur when the immune system doesn't respond correctly, leading to:
  • Exaggerated reactions to environmental antigens (allergies).
  • Reactions against transplanted foreign tissues.
  • Misdirection against the body’s own cells (autoimmune diseases).
  • Insufficient protection (immune deficiency diseases).

Learning Objectives

• Describe inappropriate immune responses.
• Explain how an individual becomes sensitized to an allergen in type I hypersensitivity reactions.
• Describe common clinical manifestations of allergic reactions and their processes.
• Discuss and differentiate between the four types of hypersensitivity reactions.
• Differentiate between immediate and delayed hypersensitivities with examples.
• Discuss blood group antigens and compatibility issues for transfusions.
• Define autoimmune disease and give an example.
• Discuss risk factors and treatment plans for autoimmune diseases.

Hypersensitivity Reactions

• Hypersensitivity reactions are exaggerated or inappropriate immune responses causing disease or damage.

Type I Hypersensitivity

• Most common type.
• Mediated by IgE and mast cells.
• Occurs against environmental antigens (allergens).
• Histamine is the most potent mediator, causing:
  • Bronchial smooth muscle contraction.
  • Increased vascular permeability.
  • Vasodilation.
  • Increased gastric acid secretion.
• Histamine effects are seen in tissues with many mast cells (GI, respiratory tracts, skin).

Anaphylaxis

• A severe, life-threatening type I hypersensitivity reaction.
• Occurs within minutes of exposure to an antigen.
• People are highly sensitized to specific allergens.
• IgE antibodies attach to mast cells and basophils.
• Granules in these cells contain chemical mediators (histamine, serotonin, leukotrienes, etc.).
• These mediators trigger systemic inflammation.

Pathophysiology of Anaphylaxis

• First Exposure: Body produces IgE to bind to mast cells and basophils.
• Subsequent Exposures: Allergen triggers adaptive immune response; bound IgE on mast cells recognizes the allergen, causing degranulation and release of chemical mediators, leading to a systemic allergic reaction.

Treatment of Anaphylaxis

• Administer adrenaline intramuscularly to reverse airway swelling and cardiovascular effects.
• Systemic glucocorticoids to lessen the inflammatory reaction.
• Antihistamines to prevent the action of widespread histamine release.
• Avoid the allergen in the future; carry a pre-loaded adrenaline pen (Epi-pen).

Therapeutic Effect of Adrenaline

• Adrenaline causes vasoconstriction of blood vessels, increasing blood pressure and cardiac output.

Type II Hypersensitivity

• Specific cell or tissue is the target of an immune response.
• Antibodies bind to tissue-specific antigens.
• Examples: blood transfusion reaction, Rh incompatibility, Graves' disease (hyperthyroidism).
• Involves the complement system.

Type III Hypersensitivity

• Immune complex-mediated.
• Antigen-antibody complexes are formed in the circulation and deposited in blood vessel walls or other tissues, causing inflammation and tissue damage.
• Not organ-specific.
• Examples: Post-streptococcal glomerulonephritis, rheumatoid arthritis, Systemic lupus erythematosus (SLE).

Type IV Hypersensitivity

• Does not involve antibody (delayed reaction).
• Mediated by T lymphocytes.
• Cytotoxic T lymphocytes or lymphokine producing TH1 cells.
• Direct killing by TC or recruitment of phagocytic cells by TH1 cells.
• Tissue damage results from these actions.
• Examples: Acute graft rejection, Mantoux test for TB, contact dermatitis, type 1 diabetes mellitus.

ABO Blood Group System

• Important for blood transfusions.

Autoimmune Disease

• Autoimmune diseases occur when individuals produce autoantibodies that react to self-antigens in sufficient volume to damage their tissues.
• Development involves genetic predisposition and environmental exposures, leading to loss of self-tolerance.
• Sometimes, antibodies against bacterial antigens cross-react with the individual’s tissues (e.g., rheumatic heart disease).

The breakdown of tolerance

• Individuals are usually tolerant to their own antigens.
• Self-tolerance is a state of immunological control, so that the individual does not make a detrimental immune response against their own cells and tissues.
• Autoimmune disease results from a breakdown of this tolerance.
• In individuals with group A streptococcal sore throats, proteins in the bacterial capsule mimic normal heart antigens and induce antibodie
  s that also react with proteins in the heart valve, damaging the mitral valve in particular. Thus, rheumatic fever is a type II autoimmune hypersensitivity.
• Additionally, some streptococcal skin or throat infections release bacterial antigens into the blood that form circulating immune complexes. The complexes may deposit in the kidneys and initiate an immune complex glomerulonephritis. Thus, streptococcal antigens (an environmental antigen) may also cause a type III allergic hypersensitivity.

Risk Factors for Autoimmune Diseases

• Sex, genetics, obesity, smoking, certain medications, infection, and having existing autoimmune disease.

Autoimmune disease & family history

• Autoimmune diseases can occur in families, however affected family members may not all develop the same disease, several members may have different disorders characterised by a variety of hypersensitivity reactions, including autoimmune and allergic reactions.

Autoimmune disease & Stress

• Stress response contributes to the development of autoimmune disease?

Organ Systems Affected by Autoimmune Diseases

Management of Autoimmune Diseases

• Certain pharmacological agents helps relieving symptoms of autoimmune disease (e.g., relapse into remission). However for some autoimmune diseases, there are no cure.
• Knowing individual's trigger for disease relapse is important to maintain good quality of life when living with long term illnesses (e.g., stress, physical strain, obesity, infection, fatigue, smoking etc).

Treatment options for autoimmune disease.

Inflammatory Bowel Disease (IBD)

• Involves chronic inflammation of the gastrointestinal tract.
  • Crohn’s disease
  • Ulcerative colitis

Crohn’s disease vs. Ulcerative colitis

• Crohn’s disease can affect any part of your digestive system from the mouth to the anus whereas, Ulcerative colitis only affects the large intestine (large bowel or colon).

Risks factors links to IBD

• Family history of IBD, smoking, certain medications such as NSAIDS and antibiotics.

Irritable Bowel Syndrome (IBS)

• Not the same as IBD.
• Symptoms include abdominal cramping, bloating, diarrhea, and constipation.
• Treated with lifestyle changes.

LOW-FODMAP diet

• A temporary eating plan designed to help individuals with irritable bowel syndrome (IBS) and/or small intestinal bacterial overgrowth (SIBO) identify problematic foods. It involves restricting foods high in FODMAPs, which are fermentable short-chain carbohydrates that are poorly absorbed in the small intestine. This restriction can help reduce gut symptoms like bloating, gas, and abdominal pain.

Complications of chronic autoimmune disorders (IBD & IBS)

• Fistulas, abscesses, colorectal cancer risk, malnutrition, reduced quality of life.

Altered Immune Function

• Enhanced immunity (exaggerated or inappropriate responses).
• Immune deficiencies (insufficient immunity) occur when the immune system or inflammatory responses fail to function normally, resulting in increased susceptibility to pathogenic microorganisms and cancers.
• The affected individual can be referred to as being immunocompromised, or immunosuppressed.
  • Primary immune deficiencies: congenital
  • Secondary immune deficiencies: acquired by another condition, i.e.g, cancer, infection or ageing.
• Acquired forms of immune deficiency are far more prevalent than the rare primary immune deficiencies.

Altered immune function in paediatrics

Common conditions seen in paediatrics resulted from the altered immune function

• Food allergy, eczema, asthma, allergic rhinitis.

Altered immune function in ageing

• Immunosenescence: Decline in immune function with age. More susceptible to infections and cancers. Slower healing. Lower response to vaccines. Thymus gland atrophy and decline in haematopoiesis.

Primary Immune Deficiencies

• Most are the result of a single gene defect, sporadic, not inherited.
• Five groups:
  • B lymphocyte deficiencies
  • T lymphocyte deficiencies
  • Combined immune deficiencies
  • Complement deficiencies
  • Phagocyte deficiencies

Secondary Immune Deficiencies

• Not related to genetic defects, are complications of other conditions, e.g.
  • Normal physiological conditions (e.g., pregnancy, infancy or aging), psychological stress.
  • Dietary insufficiencies, malignancies.
  • Physical trauma, infections, medical treatments.

Conditions associated with secondary immunodeficiencies

• A high level of cortisol is secreted in the body as a result of the endocrine regulation during stress response. Cortisol suppresses the immune response by decreasing the immune cell activities.

Acquired Immunodeficiency Syndrome (AIDS)

• Caused by Human Immunodeficiency Virus (HIV).

Epidemiology

• Overall the rates of HIV infection in New Zealand are low compared to other Western countries and reflect the effectiveness of public health campaigns instituted since 1987.

• Due to a combination of pre-exposure prophylaxis and early treatment of those who are diagnosed positive. Effective funded antiretroviral therapy is available for anyone living with HIV in NZ, regardless of residency status.

Health inequities in STIs

• Sexually transmitted infections (STIs) in Aotearoa New Zealand disproportionately affect young people, men who have sex with men (MSM) and Māori and Pacific people.

How to address health inequities during nursing practice?

• Focus on providing culturally safe care; addressing individual needs, offer patient education and additional supports.

Transmission of HIV

• HIV is a blood-borne pathogen
  • Blood or blood products
  • Intravenous drug abuse
  • Heterosexual activity and maternal-child transmission before or during birth

Effective measure in reducing the risk of HIV transmission from an infected mother to her infant during childbirth?

• Administering azidothymidine (AZT, a type of antiretroviral medication) to the pregnant woman

NOT a documented mode of HIV transmission

• Casual contact, such as hugging, shaking hands or kissing an infected person

John's journey

• Clinical findings suggest he is in phase 3 - Acute - AIDS - Immunodeficiency.
  Patient symptoms:
• Persistent fever and night sweats for the past 3 months.
• Unexplained weight loss (15 kg over 6 months).
• Chronic diarrhea for the past 2 months.
• Persistent dry cough and shortness of breath.
• Fatigue and generalized weakness.
• John's severely low CD4 count of 120 cells/mm3 indicates a severely compromised immune system.

The progression from HIV infection to AIDS immunodeficiency

• The psychological distress associated with the diagnosis can disrupt the body's natural stress response, leading to changes in immune cell function. Specifically, stress can increase cortisol levels and decrease CD4 cell counts, which are crucial for fighting off infections.

Clinical Manifestations of HIV

• First phase: mild, generalized flu-like symptoms (low fever, fatigue, arthralgia, sore throat).
• Prolonged second/latent phase: often no clinical signs, some have generalized lymphadenopathy.
• Final acute stage: immune deficiency is evident, marked by serious complications.
  • General manifestations of HIV infection.
  • Gastrointestinal effects.
  • Neurologic effects.
  • Secondary infections.
  • Malignancies (caused by immunodeficiency).

Pneumocystis jirovecii

• classified as a fungus, explain how does it cause pneumocystis pneumonia in immunocompromised patients like Mr. Mwangi? In immunocompromised individuals, the fungus proliferates uncontrollably in the lungs, leading to lung inflammation, impaired gas exchange, and potentially respiratory failure.

Treatment and Prevention of HIV

• Antiviral drugs reduce viral replication but don't cure the virus.
• Current treatment: highly active antiretroviral therapy (HAART).
  • Reverse transcriptase inhibitors
  • Integrase inhibitors
  • Protease inhibitors

When would a pre-exposure prophylaxis (known as PrEP) be indicated for individual to reduce the risk of deveoping HIV infection?

• Mother-baby delivery.

Challenges in HIV Vaccine Development

• HIV is genetically variable; a vaccine against one variant may not protect against another.
• Circulating antibodies against HIV are not always protective.