🦠Microbiology Unit 19 – Diseases of the Immune System

Key Concepts and Terminology

• Immune system protects the body against infectious agents and other harmful substances
• Innate immunity provides immediate, non-specific defense mechanisms (physical barriers, inflammatory response)
• Adaptive immunity develops specific responses to pathogens through T cells and B cells
  • T cells directly attack infected cells and coordinate the immune response
  • B cells produce antibodies that neutralize pathogens and mark them for destruction
• Autoimmunity occurs when the immune system mistakenly attacks the body's own tissues
• Immunodeficiency results from a weakened or absent immune response, increasing susceptibility to infections
• Hypersensitivity refers to an exaggerated immune response to typically harmless substances (allergens)
• Cytokines are signaling molecules that regulate the immune response (interleukins, interferons)
• Major histocompatibility complex (MHC) molecules present antigens to T cells for recognition

Immune System Overview

• The immune system consists of organs, tissues, and cells that work together to defend the body
• Lymphoid organs include the thymus, spleen, lymph nodes, and bone marrow
  • Thymus is the site of T cell maturation
  • Spleen filters blood and stores platelets and white blood cells
• Innate immune response is rapid and non-specific, acting as the first line of defense
• Adaptive immune response is slower but highly specific, providing long-lasting protection
• White blood cells (leukocytes) play a central role in the immune response
  • Neutrophils, macrophages, and dendritic cells are part of the innate immune system
  • Lymphocytes (T cells and B cells) are the main components of the adaptive immune system
• Complement system enhances the immune response through a cascade of protein interactions
• Cytokines mediate communication between immune cells and regulate the immune response

Types of Immune Disorders

• Autoimmune diseases result from the immune system attacking the body's own tissues
  • Examples include rheumatoid arthritis, systemic lupus erythematosus (SLE), and multiple sclerosis
• Immunodeficiency disorders impair the immune system's ability to fight infections
  • Primary immunodeficiencies are genetic disorders (severe combined immunodeficiency, X-linked agammaglobulinemia)
  • Secondary immunodeficiencies are acquired conditions (AIDS, immunosuppressive therapy)
• Allergies and hypersensitivities involve an overreaction of the immune system to harmless substances
  • Type I hypersensitivity is mediated by IgE antibodies (hay fever, asthma)
  • Type II hypersensitivity involves antibodies targeting cell surface antigens (autoimmune hemolytic anemia)
• Autoinflammatory diseases are characterized by recurrent episodes of inflammation without autoantibodies or T cell involvement (familial Mediterranean fever)
• Cancers of the immune system, such as leukemia and lymphoma, can disrupt normal immune function

Autoimmune Diseases

• Autoimmune diseases occur when the immune system mistakenly attacks the body's own tissues
• Genetic, environmental, and hormonal factors contribute to the development of autoimmune diseases
• Rheumatoid arthritis causes inflammation and damage to joints, leading to pain and stiffness
• Systemic lupus erythematosus (SLE) can affect multiple organs, causing skin rashes, joint pain, and kidney damage
  • SLE is characterized by the production of autoantibodies, particularly antinuclear antibodies (ANA)
• Multiple sclerosis involves immune-mediated damage to the myelin sheath surrounding nerve fibers
• Type 1 diabetes results from autoimmune destruction of insulin-producing beta cells in the pancreas
• Inflammatory bowel diseases (Crohn's disease and ulcerative colitis) involve chronic inflammation of the digestive tract
• Diagnosis of autoimmune diseases often involves detecting specific autoantibodies and assessing organ damage
• Treatment typically includes immunosuppressive medications to control the overactive immune response

Immunodeficiency Disorders

• Immunodeficiency disorders impair the immune system's ability to fight infections effectively
• Primary immunodeficiencies are genetic disorders that affect immune system development or function
  • Severe combined immunodeficiency (SCID) is characterized by a lack of functional T cells and B cells
  • X-linked agammaglobulinemia (XLA) results in the absence of B cells and antibody production
• Secondary immunodeficiencies are acquired conditions that weaken the immune system
  • Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) infection
  • Immunosuppressive medications used to treat autoimmune diseases or prevent transplant rejection can increase the risk of infections
• Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low antibody levels
• Chronic granulomatous disease (CGD) impairs the ability of phagocytic cells to kill ingested pathogens
• Diagnosis of immunodeficiencies involves assessing immune cell counts, antibody levels, and response to vaccines
• Treatment may include immunoglobulin replacement therapy, stem cell transplantation, or gene therapy

Allergies and Hypersensitivities

• Allergies and hypersensitivities involve an exaggerated immune response to typically harmless substances (allergens)
• Type I hypersensitivity is mediated by IgE antibodies and mast cell degranulation
  • Symptoms include hay fever, asthma, and anaphylaxis
  • Allergen-specific IgE binds to mast cells, leading to the release of histamine and other mediators
• Type II hypersensitivity involves antibodies targeting cell surface antigens
  • Examples include autoimmune hemolytic anemia and Graves' disease
• Type III hypersensitivity is caused by immune complex deposition and inflammation
  • Serum sickness and systemic lupus erythematosus (SLE) are examples of type III hypersensitivity
• Type IV hypersensitivity is mediated by T cells and delayed-type reactions
  • Contact dermatitis and tuberculosis skin tests are examples of type IV hypersensitivity
• Diagnosis of allergies often involves skin prick tests, specific IgE measurements, and oral food challenges
• Treatment options include allergen avoidance, antihistamines, corticosteroids, and immunotherapy (allergy shots)

Diagnostic Techniques

• Diagnostic techniques for immune disorders help identify the specific condition and guide treatment decisions
• Complete blood count (CBC) assesses the number and types of white blood cells, red blood cells, and platelets
• Flow cytometry analyzes the expression of cell surface markers to identify specific immune cell populations
• Enzyme-linked immunosorbent assay (ELISA) detects and quantifies antibodies or antigens in blood samples
  • Used to diagnose autoimmune diseases, allergies, and infectious diseases
• Immunofluorescence techniques (direct and indirect) visualize the presence and location of antibodies in tissues
• Polymerase chain reaction (PCR) amplifies specific DNA sequences to detect genetic mutations or infectious agents
• Lymphocyte proliferation assays assess the functional response of T cells to specific antigens
• Complement assays evaluate the activity and levels of complement proteins in the blood
• Imaging techniques (CT scans, MRI) can reveal inflammation, organ damage, or lymph node enlargement

Treatment Approaches and Emerging Therapies

• Treatment for immune disorders depends on the specific condition and severity of symptoms
• Immunosuppressive medications are used to control overactive immune responses in autoimmune diseases and transplant recipients
  • Corticosteroids (prednisone) have broad anti-inflammatory effects
  • Disease-modifying antirheumatic drugs (DMARDs) slow the progression of autoimmune diseases (methotrexate, hydroxychloroquine)
• Biologic therapies target specific components of the immune system
  • Monoclonal antibodies (adalimumab, rituximab) block inflammatory cytokines or deplete specific immune cell populations
  • Fusion proteins (etanercept) inhibit the action of inflammatory mediators
• Immunoglobulin replacement therapy provides antibodies to patients with primary immunodeficiencies
• Stem cell transplantation can reconstitute the immune system in severe immunodeficiencies or autoimmune diseases
• Gene therapy aims to correct genetic defects in primary immunodeficiencies by introducing functional copies of the defective gene
• Allergen immunotherapy (allergy shots) gradually desensitizes the immune system to specific allergens
• Checkpoint inhibitors (nivolumab, pembrolizumab) enhance the immune response against cancer cells
• Personalized medicine approaches tailor treatment based on an individual's genetic and immunological profile