Immune System Diseases Overview

Immune System Diseases

• The immune system is vital for survival, protecting against infections and cancers. Immune deficiencies make individuals vulnerable to infections and increase cancer risk. Immune responses can cause tissue damage and disease (allergies and autoimmunity).
• Innate immunity provides rapid, immediate defense, recognizing microbial products. Key components include epithelial barriers (e.g., skin), phagocytic cells (neutrophils, macrophages), dendritic cells, natural killer cells, and complement proteins.
• Adaptive immunity develops more slowly, responding specifically to microbes and foreign substances, displaying memory. This involves lymphocytes (B and T cells) with highly diverse receptors (antibodies and T cell receptors) to recognize a vast array of antigens.
• Class I MHC molecules are displayed on all nucleated cells and platelets, recognizing peptides from cytoplasmic proteins (normal or pathogen-associated). CD8+ cells are responsible for recognizing these peptide-MHC complexes.
• Class II MHC molecules display peptides from extracellular antigens, recognized by CD4+ T cells, which play a crucial role as helper cells.
• Cytokines are messenger molecules crucial for activating various immune cells and mediating essential immune functions in both innate and adaptive immunity. Cytokines can activate cells, promote proliferation, and differentiation and activate various other functions.
• Cellular receptors for microbes, damaged cells, and foreign substances are crucial for innate immunity.
• Natural killer (NK) cells have activating and inhibitory receptors, recognizing healthy or stressed cells (like virus-infected or cancer cells) to destroy them. This is regulated through the interaction between these receptors and the recognized cells.
• Dendritic cells (DCs) are specialized cells residing in tissues and lymphoid organs that capture, process, and present antigens to T cells. They're responsible for initiating adaptive immune responses.
• Lymphocyte diversity enables the recognition of a vast range of antigens. Lymphocytes are crucial for adaptive immunity, and their high diversity helps in detecting a broad array of antigens and mounting an effective response.
• Lymphocyte recirculation maximizes the chances of antigen-specific lymphocytes encountering and responding to antigens in secondary lymphoid tissue through the lymphatic system, where antigen concentration is higher.
• T lymphocytes exist in different sub-types. Helper T cells assist B cells in antibody production and activate other leukocytes, cytotoxic T cells (CTLs) kill infected cells, and regulatory T cells prevent reactions against self-antigens.
• B lymphocytes produce antibodies (the mediators of humoral immunity) which neutralise threats, opsonise pathogens for phagocytosis, and activate the complement system.

Hypersensitivity

• Hypersensitivity reactions are excessive or harmful reactions to antigens (exogenous or endogenous).
• Type I hypersensitivity (immediate): rapid reaction involving IgE antibodies, mast cells, and inflammatory mediators, causing symptoms like allergies and anaphylaxis.
• Type II hypersensitivity (antibody-mediated): antibodies directly attack cells or tissues, leading to phagocytosis or lysis (e.g., autoimmune hemolytic anemia).
• Type III hypersensitivity (immune-complex-mediated): antigen-antibody complexes deposit in tissues and activate complement, triggering inflammation.
• Type IV hypersensitivity (cell-mediated): T cells cause tissue damage, typically by activating macrophages or directly killing cells (e.g., contact dermatitis).

Autoimmune Diseases

• Autoimmune diseases result from immune reactions against self-antigens.
• Systemic lupus erythematosus (SLE): a systemic autoimmune disease involving multiple organs, characterized by a broad range of autoantibodies and immune complexes (e.g., anti-dsDNA antibodies).
• Other notable systemic conditions include Rheumatoid arthritis, systemic sclerosis (scleroderma), and Sjögren Syndrome.

Immunodeficiency Diseases

• Immunodeficiency diseases result from defects in the innate and/or adaptive immune systems.
• Primary immunodeficiencies: inherited genetic defects in immune components, causing increased susceptibility to infections.
• Secondary immunodeficiencies: acquired immunodeficiencies resulting from conditions that impair the immune system (e.g., HIV infection).
• Severe combined immunodeficiency (SCID): a severe deficiency affecting both humoral and cellular immunity, leading to increased infections.
• Other conditions that may result in immunodeficiency include X-linked agammaglobulinemia, IgA deficiency, and digeorge syndrome.

Transplant Rejection

• Transplant rejection is immune-mediated responses against transplanted tissues. Rejection can result from pre-formed antibodies, and T cell mediated responses.
• Hyperacute rejection: caused by pre-formed antibodies against the graft.
• Acute rejection: primarily cell-mediated responses.
• Chronic rejection: a slow, progressive process, often involving vascular damage and fibrosis.

Acquired Immunodeficiency Syndrome (AIDS)

• AIDS is caused by HIV, leading to profound immune deficiency and severe conditions.
• A critical step in the progression of the disease involves loss of CD4+ T cells. This impacts several key components of the adaptive immune response (cell mediated and humoral). The loss of these critical immune cells leads to widespread infections and cancers.

Amyloidosis

• A group of diseases characterized by extracellular deposits of misfolded proteins forming fibrils. Amyloid accumulation damages tissues and compromises organ functions.
• Amyloid forms include AL (immunoglobulin light chains), AA (reactive systemic), ATTR (transthyretin), and Aβ (in Alzheimer's disease).