Understanding the Immune System

• Immunology studies the immune system, which defends the body against foreign invaders.
• The immune system distinguishes between self and non-self antigens to selectively target and eliminate threats, including pathogens like bacteria, viruses, parasites, and fungi, as well as cancerous cells.
• Dysregulation of the immune system can result in various diseases, such as autoimmune disorders, immunodeficiencies, and hypersensitivities.

Cells of the Immune System

• Leukocytes, or white blood cells, constitute the immune system's primary cells.
• Leukocytes are divided into myeloid and lymphoid cells.

Myeloid Cells

• Myeloid cells include monocytes/macrophages, granulocytes (neutrophils, eosinophils, and basophils), and dendritic cells.
• Monocytes differentiate into macrophages in tissues, acting as phagocytic cells that engulf and digest pathogens and debris, also presenting antigens to T cells.
• Neutrophils, the most abundant granulocyte, are crucial for acute inflammatory responses against bacterial and fungal infections through phagocytosis and release of antimicrobial substances.
• Eosinophils target parasites and participate in allergic reactions, releasing toxic granules containing enzymes and proteins.
• Basophils release histamine and other mediators that promote inflammation and are involved in allergic responses.
• Dendritic cells, as antigen-presenting cells (APCs), capture and process antigens, migrating to lymph nodes to activate T cells.

Lymphoid Cells

• Lymphoid cells include T cells, B cells, and natural killer (NK) cells.
• T cells mature in the thymus and mediate cellular immunity.
• T cells include helper T cells (CD4+), cytotoxic T cells (CD8+), and regulatory T cells.
• Helper T cells (CD4+) secrete cytokines that activate other immune cells, including B cells, macrophages, and cytotoxic T cells.
• Cytotoxic T cells (CD8+) recognize and kill infected or cancerous cells by releasing cytotoxic granules.
• Regulatory T cells suppress immune responses to maintain self-tolerance and prevent autoimmune diseases.
• B cells mature in the bone marrow, mediating humoral immunity via antibody production.
• When activated, B cells differentiate into plasma cells that secrete large quantities of antibodies specific to a particular antigen.
• Antibodies neutralize pathogens, promote phagocytosis (opsonization), and activate the complement system.
• Natural killer (NK) cells, part of the innate immune system, recognize and kill infected or cancerous cells without prior sensitization by detecting alterations on the cell surface.

Organs of the Immune System

• Primary lymphoid organs include the bone marrow and thymus, where lymphocytes develop and mature.
• The bone marrow is the site of hematopoiesis, where all blood cells, including immune cells, are produced.
• The thymus is where T cells mature and undergo selection to ensure self-tolerance.
• Secondary lymphoid organs, including lymph nodes, the spleen, and mucosa-associated lymphoid tissue (MALT), are where immune responses are initiated.
• Lymph nodes filter lymph and are sites where lymphocytes interact with antigens and initiate adaptive immune responses.
• The spleen filters blood, removing damaged or aged red blood cells, and it is also a site where lymphocytes can encounter antigens and initiate immune responses.
• MALT includes tonsils, adenoids, Peyer's patches in the small intestine, and the appendix, which initiates immune responses to antigens encountered at mucosal surfaces.

Innate Immunity

• Innate immunity serves as the first line of defense against pathogens, providing rapid, non-specific responses.
• Components include physical barriers like skin and mucous membranes.
• Cellular components include phagocytes (neutrophils and macrophages), NK cells, and dendritic cells.
• Pattern recognition receptors (PRRs) recognize conserved microbial structures called pathogen-associated molecular patterns (PAMPs).
• Toll-like receptors (TLRs) are a major class of PRRs on immune cells that recognize different PAMPs and trigger intracellular signaling pathways, leading to cytokine production and immune response activation.
• The complement system comprises serum proteins activated by pathogens or antibodies, leading to opsonization, inflammation, and direct pathogen killing.
• Cytokines are signaling molecules mediating communication between immune cells and regulating immune responses.

Adaptive Immunity

• Adaptive immunity is a slower, more specific response developing after exposure to antigens.
• It involves T cells and B cells.
• Key characteristics include specificity, diversity, memory, and self-tolerance.
• Antigens are molecules recognized by the adaptive immune system.
• Antibodies are produced by B cells, with each antibody specific for a particular antigen.
• T cells recognize antigens presented by antigen-presenting cells (APCs) in the context of major histocompatibility complex (MHC) molecules.
• MHC class I molecules present antigens to CD8+ T cells (cytotoxic T cells).
• MHC class II molecules present antigens to CD4+ T cells (helper T cells).
• T cell activation requires two signals: recognition of the antigen-MHC complex and co-stimulatory signals.
• B cell activation requires antigen recognition by the B cell receptor and help from T helper cells.
• Following activation, B cells undergo clonal expansion and differentiate into plasma cells, which produce antibodies, and memory B cells, which provide long-lasting immunity.
• T cells also undergo clonal expansion, differentiating into effector T cells and memory T cells.

Humoral Immunity

• Humoral immunity is mediated by antibodies produced by B cells.
• Antibodies neutralize pathogens by blocking their ability to infect cells.
• Opsonization enhances phagocytosis by coating pathogens with antibodies or complement proteins.
• The complement system can be activated by antibodies bound to antigens, leading to the formation of the membrane attack complex (MAC) and lysis of pathogens.
• Antibody-dependent cell-mediated cytotoxicity (ADCC) is a process by which NK cells and other immune cells kill antibody-coated target cells.

Cell-Mediated Immunity

• Cell-mediated immunity is mediated by T cells.
• Cytotoxic T cells (CD8+) kill infected or cancerous cells by recognizing antigens presented on MHC class I molecules.
• Helper T cells (CD4+) secrete cytokines that activate other immune cells, including B cells, macrophages, and cytotoxic T cells.
• T helper 1 (Th1) cells promote cell-mediated immunity against intracellular pathogens.
• T helper 2 (Th2) cells promote humoral immunity against extracellular parasites and allergens.
• Regulatory T cells (Tregs) suppress immune responses and maintain self-tolerance.

Immunological Tolerance

• Immunological tolerance is the immune system's ability to distinguish between self and non-self antigens and not attack the body's own tissues.
• Central tolerance occurs in the thymus and bone marrow, where T cells and B cells that recognize self-antigens are eliminated or inactivated.
• Peripheral tolerance occurs in peripheral tissues and involves mechanisms such as anergy, T cell suppression by regulatory T cells, and clonal deletion.
• Failure of immunological tolerance can lead to autoimmune diseases.

Hypersensitivity Reactions

• Hypersensitivity reactions are exaggerated or inappropriate immune responses that can cause tissue damage and disease.
• Type I hypersensitivity is an immediate reaction mediated by IgE antibodies and mast cells, such as allergic rhinitis, asthma, and anaphylaxis.
• Type II hypersensitivity is mediated by IgG or IgM antibodies that bind to cell surface antigens, leading to complement activation and cell destruction, such as autoimmune hemolytic anemia.
• Type III hypersensitivity is mediated by immune complexes that deposit in tissues, leading to complement activation and inflammation, such as serum sickness and rheumatoid arthritis.
• Type IV hypersensitivity is a delayed-type hypersensitivity mediated by T cells, such as contact dermatitis and tuberculin skin test.

Immunodeficiency Disorders

• Immunodeficiency disorders are conditions in which the immune system is weakened or absent, increasing susceptibility to infections.
• Primary immunodeficiencies are genetic disorders affecting the development or function of immune cells or components.
• Secondary immunodeficiencies are acquired due to factors such as infections (e.g., HIV), malnutrition, immunosuppressive drugs, or cancer.
• Severe combined immunodeficiency (SCID) is a primary immunodeficiency characterized by a lack of functional T and B cells.
• Acquired immunodeficiency syndrome (AIDS) results from HIV infection, which destroys CD4+ T cells and impairs immune function.

Autoimmune Diseases

• Autoimmune diseases are conditions in which the immune system attacks the body's own tissues and organs.
• Genetic factors and environmental triggers contribute to the development of autoimmune diseases.
• Examples include rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis (MS), and type 1 diabetes.
• Autoantibodies are often present in autoimmune diseases, targeting various self-antigens.
• Treatment involves immunosuppressive drugs to reduce immune system activity and inflammation.

Transplantation Immunology

• Transplantation immunology studies the immune responses involved in organ and tissue transplantation.
• Graft rejection occurs when the recipient's immune system recognizes the donor's tissues as foreign and attacks them.
• MHC molecules (HLA in humans) are the major targets of graft rejection.
• Immunosuppressive drugs are used to prevent or treat graft rejection.
• Graft-versus-host disease (GVHD) can occur in bone marrow transplantation when donor T cells attack the recipient's tissues.

Tumor Immunology

• Tumor immunology studies the interactions between the immune system and cancer cells.
• Cancer cells evade immune detection by downregulating MHC expression, expressing immunosuppressive molecules, or inducing immune tolerance.
• Tumor-associated antigens (TAAs) are molecules expressed by cancer cells that can be recognized by the immune system.
• Immunotherapy aims to enhance the immune system's ability to recognize and kill cancer cells.
• Examples include immune checkpoint inhibitors, adoptive T cell therapy, and cancer vaccines.

Immunization

• Immunization induces immunity to infectious diseases by administering vaccines.
• Vaccines contain weakened or inactivated pathogens, or components of pathogens, stimulating an immune response without causing disease.
• Active immunity develops when the body produces its own antibodies or T cells in response to a vaccine or infection.
• Passive immunity is acquired by receiving antibodies from another source, such as maternal antibodies or intravenous immunoglobulin.
• Herd immunity occurs when a large proportion of the population is immune to a disease, providing protection to susceptible individuals.