Introduction to the Immune System

• Immunology is the study of the immune system, which defends the body against disease.
• The immune system recognizes and responds to a variety of threats, including pathogens (bacteria, viruses, fungi, and parasites) and altered host cells (e.g., tumor cells).

Cells of the Immune System

• Lymphocytes (T cells, B cells, and NK cells) are central to adaptive immunity.
• Antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells are essential for initiating T cell responses.
• The myeloid lineage includes granulocytes (neutrophils, eosinophils, basophils), mast cells, and monocytes/macrophages.

Innate Immunity

• Represents the first line of defense against pathogens.
• Includes physical barriers (skin, mucous membranes), chemical barriers (antimicrobial peptides, low pH), and cellular defenses (phagocytes, NK cells).
• Pattern recognition receptors (PRRs) recognize conserved microbial structures called pathogen-associated molecular patterns (PAMPs).
• Inflammation is a key feature of innate immunity, characterized by redness, heat, swelling, and pain.
• Cytokines like TNF-α, IL-1, and IL-6 mediate inflammation and systemic effects.
• The complement system is part of innate immunity, enhancing phagocytosis, inflammation, and direct lysis of pathogens.

Adaptive Immunity

• Characterized by specificity and memory.
• Mediated by lymphocytes (T cells and B cells) that recognize specific antigens.
• T cells mature in the thymus and are responsible for cell-mediated immunity.
• B cells mature in the bone marrow and produce antibodies (humoral immunity).
• Antigens are molecules recognized by the adaptive immune system.
• T cell receptors (TCRs) recognize antigens presented on MHC molecules.
• Antibodies bind to antigens with high affinity and mediate effector functions like neutralization, opsonization, and complement activation.

Antigen Presentation

• MHC class I presents intracellular antigens to cytotoxic T cells (CD8+ T cells).
• MHC class II presents extracellular antigens to helper T cells (CD4+ T cells).
• Dendritic cells are professional APCs that initiate T cell responses in lymph nodes.
• Antigen processing involves breaking down proteins into peptides that can bind to MHC molecules.

T Cell Activation and Differentiation

• T cell activation requires two signals: TCR recognition of antigen/MHC and co-stimulation (e.g., CD28-B7 interaction).
• Helper T cells (CD4+ T cells) differentiate into various subsets (e.g., Th1, Th2, Th17, T regulatory cells) that secrete different cytokines and mediate different effector functions.
• Cytotoxic T cells (CD8+ T cells) kill infected or cancerous cells by releasing cytotoxic granules.
• T regulatory cells (Tregs) suppress immune responses and maintain self-tolerance.

B Cell Activation and Antibody Production

• B cell activation requires crosslinking of the B cell receptor (BCR) by antigen and co-stimulation from helper T cells.
• Activated B cells differentiate into plasma cells that secrete antibodies.
• Antibodies have a characteristic Y-shaped structure with antigen-binding sites (Fab region) and an effector region (Fc region).
• Antibody classes (IgG, IgM, IgA, IgE, IgD) have different structures and effector functions.
• Affinity maturation is the process by which B cells produce antibodies with increasing affinity for antigen during a T-dependent immune response.
• Isotype switching is the process by which B cells change the class of antibody they produce while maintaining the same antigen specificity.

Immunological Memory

• Adaptive immune responses generate memory T cells and memory B cells that provide long-lasting protection against reinfection.
• Upon re-exposure to antigen, memory cells mount a faster and stronger response than naive cells.
• Vaccination exploits immunological memory to provide protection against infectious diseases.

Hypersensitivity

• Hypersensitivity reactions are exaggerated or inappropriate immune responses that cause tissue damage.
• Type I hypersensitivity (immediate hypersensitivity) is mediated by IgE antibodies and mast cell activation (e.g., allergies, anaphylaxis).
• Type II hypersensitivity is mediated by IgG or IgM antibodies that bind to cell surface antigens and activate complement or ADCC (e.g., transfusion reactions, hemolytic disease of the newborn).
• Type III hypersensitivity is mediated by immune complexes that deposit in tissues and activate complement (e.g., serum sickness, Arthus reaction).
• Type IV hypersensitivity (delayed-type hypersensitivity) is mediated by T cells (e.g., contact dermatitis, tuberculin reaction).

Autoimmunity

• Autoimmunity is the immune system attacking the body's own tissues.
• Autoimmune diseases can be organ-specific (e.g., type 1 diabetes, Hashimoto's thyroiditis) or systemic (e.g., rheumatoid arthritis, systemic lupus erythematosus).
• Genetic and environmental factors contribute to the development of autoimmunity.
• Mechanisms of autoimmunity include molecular mimicry, bystander activation, and defects in immune regulation.

Immunodeficiency

• Immunodeficiency is a condition in which the immune system is unable to adequately protect the body against infection.
• Primary immunodeficiencies are genetic disorders that affect the development or function of immune cells.
• Secondary immunodeficiencies are caused by external factors such as infection (e.g., HIV/AIDS), malnutrition, or immunosuppressive drugs.

Transplantation Immunology

• Transplantation involves the transfer of cells, tissues, or organs from a donor to a recipient.
• The immune system recognizes transplanted tissues as foreign, leading to rejection.
• MHC molecules (HLA in humans) are the major targets of rejection.
• Immunosuppressive drugs are used to prevent or treat rejection.
• Graft-versus-host disease (GVHD) can occur in bone marrow transplantation when donor T cells attack recipient tissues.

Tumor Immunology

• The immune system can recognize and destroy tumor cells.
• Tumor antigens are molecules expressed by tumor cells that can be recognized by the immune system.
• Immune evasion mechanisms allow tumors to escape immune surveillance.
• Immunotherapies aim to enhance the immune response against tumors.
• Examples of immunotherapies include checkpoint inhibitors, adoptive cell therapy, and cancer vaccines.

Cytokines

• Cytokines are signaling molecules that mediate communication between immune cells.
• Interleukins (ILs), interferons (IFNs), tumor necrosis factor (TNF), and chemokines are major classes of cytokines.
• Cytokines regulate immune cell development, activation, differentiation, and effector functions.
• Cytokine storms are excessive and dysregulated production of cytokines that can lead to severe tissue damage and systemic inflammation.

Complement System

• The complement system is a group of serum proteins that enhance the ability of antibodies and phagocytic cells to clear microbes and damaged cells, promote inflammation, and attack the pathogen's plasma membrane.
• The complement system can be activated by three pathways: the classical pathway, the alternative pathway, and the lectin pathway.
• Complement activation leads to the formation of the membrane attack complex (MAC), which lyses pathogens.
• Complement proteins also act as opsonins, promoting phagocytosis, and as anaphylatoxins, promoting inflammation.

Regulation of the Immune System

• The immune system is tightly regulated to prevent excessive or inappropriate immune responses.
• Regulatory T cells (Tregs) suppress immune responses and maintain self-tolerance.
• Checkpoint molecules (e.g., CTLA-4, PD-1) inhibit T cell activation.
• Cytokines like IL-10 and TGF-β suppress immune responses.
• Defects in immune regulation can lead to autoimmunity or immunodeficiency.

Immunological Techniques

• ELISA (enzyme-linked immunosorbent assay) is used to detect and quantify antibodies or antigens.
• Flow cytometry is used to identify and count cells with specific surface markers.
• Western blotting is used to detect and quantify proteins.
• PCR (polymerase chain reaction) is used to amplify DNA or RNA.
• Immunohistochemistry is used to detect antigens in tissue sections.

An introduction to the immune system, its cells, and innate immunity. The immune system defends the body against disease by recognizing and responding to pathogens and altered host cells. Includes lymphocytes, antigen-presenting cells, and myeloid lineage.