🛡️Immunobiology Unit 2 – Cells and Tissues of the Immune System

Key Players in the Immune System

• Immune system consists of a complex network of cells, tissues, and organs that work together to protect the body from pathogens and other harmful substances
• White blood cells (leukocytes) are the primary cells involved in the immune response and can be broadly categorized into innate immune cells and adaptive immune cells
• Innate immune cells include neutrophils, monocytes/macrophages, dendritic cells, natural killer cells, and granulocytes (basophils, eosinophils, and mast cells)
  • These cells provide the first line of defense against pathogens and respond quickly to infections
• Adaptive immune cells include T lymphocytes (T cells) and B lymphocytes (B cells)
  • T cells are involved in cell-mediated immunity and help to destroy infected or cancerous cells
  • B cells are responsible for humoral immunity and produce antibodies that neutralize pathogens
• Lymphoid organs (thymus, spleen, lymph nodes) provide a microenvironment for immune cell development, maturation, and activation
• Cytokines are small proteins secreted by immune cells that facilitate communication and coordinate the immune response

Immune Cell Origins and Development

• Hematopoietic stem cells (HSCs) in the bone marrow give rise to all blood cells, including immune cells
• HSCs differentiate into two main lineages: myeloid and lymphoid
  • Myeloid lineage gives rise to innate immune cells such as neutrophils, monocytes/macrophages, and dendritic cells
  • Lymphoid lineage gives rise to adaptive immune cells, including T cells, B cells, and natural killer cells
• T cell precursors migrate from the bone marrow to the thymus for maturation and selection
  • Positive selection ensures T cells can recognize self-MHC molecules
  • Negative selection eliminates T cells that react too strongly to self-antigens, preventing autoimmunity
• B cells undergo maturation and selection in the bone marrow
  • Positive selection ensures B cells can recognize foreign antigens
  • Negative selection eliminates B cells that react too strongly to self-antigens
• Mature immune cells circulate in the blood and lymphatic system, patrolling for pathogens and other threats

Structure and Function of Immune Tissues

• Lymphoid organs are critical for immune cell development, maturation, and activation
• Thymus is the site of T cell maturation and selection
  • Cortex and medulla provide distinct microenvironments for positive and negative selection
• Spleen filters blood and serves as a site for immune cell activation and antibody production
  • Red pulp filters blood and removes old or damaged red blood cells
  • White pulp contains T cell and B cell zones for adaptive immune responses
• Lymph nodes are located throughout the body and filter lymph fluid
  • Afferent lymphatic vessels bring antigen-presenting cells and foreign antigens to the lymph nodes
  • Efferent lymphatic vessels carry activated immune cells and antibodies back into circulation
• Mucosa-associated lymphoid tissues (MALT) are found in mucosal surfaces (gut, respiratory tract) and provide local immune protection
  • Peyer's patches in the small intestine and tonsils in the throat are examples of MALT

Cell Communication in Immunity

• Immune cells communicate through direct cell-cell interactions and soluble mediators (cytokines, chemokines)
• Antigen-presenting cells (APCs) such as dendritic cells and macrophages process and present antigens to T cells via MHC molecules
  • MHC class I presents intracellular antigens to CD8+ T cells
  • MHC class II presents extracellular antigens to CD4+ T cells
• T cell receptor (TCR) on T cells recognizes specific antigen-MHC complexes on APCs
• B cell receptor (BCR) on B cells recognizes specific antigens in their native form
• Cytokines are small proteins secreted by immune cells that regulate immune responses
  • Pro-inflammatory cytokines (IL-1, IL-6, TNF-α) promote inflammation and immune cell activation
  • Anti-inflammatory cytokines (IL-10, TGF-β) suppress immune responses and promote tissue repair
• Chemokines are chemotactic cytokines that guide immune cell migration to sites of infection or inflammation

Innate vs. Adaptive Immune Cells

• Innate immune cells provide rapid, non-specific responses to pathogens and do not confer long-lasting immunity
  • Neutrophils are the most abundant innate immune cells and quickly migrate to sites of infection to engulf and destroy pathogens
  • Monocytes/macrophages are phagocytic cells that engulf and digest pathogens and cellular debris
  • Dendritic cells are professional APCs that link innate and adaptive immunity by presenting antigens to T cells
  • Natural killer cells recognize and kill virus-infected or cancerous cells without prior sensitization
• Adaptive immune cells provide specific, long-lasting immunity through the generation of memory cells
  • T cells are involved in cell-mediated immunity and can be divided into CD4+ helper T cells and CD8+ cytotoxic T cells
    • CD4+ T cells orchestrate immune responses by secreting cytokines and activating other immune cells
    • CD8+ T cells directly kill infected or cancerous cells
  • B cells are responsible for humoral immunity and produce antibodies that neutralize pathogens and mark them for destruction
  • Memory T and B cells provide rapid, specific responses upon re-exposure to the same antigen

Immune Cell Activation and Regulation

• Immune cell activation requires two signals: antigen recognition and co-stimulation
  • Signal 1: TCR or BCR engagement with specific antigen
  • Signal 2: Co-stimulatory molecules (CD28, CD80/86) provide additional activation signals
• Absence of co-stimulation can lead to T cell anergy or tolerance
• Regulatory T cells (Tregs) suppress immune responses and maintain self-tolerance
  • Tregs express high levels of CD25 (IL-2 receptor α-chain) and the transcription factor Foxp3
  • Tregs secrete anti-inflammatory cytokines (IL-10, TGF-β) and directly inhibit effector T cells
• Immune checkpoints (CTLA-4, PD-1) are inhibitory receptors that regulate T cell activation and prevent autoimmunity
  • Checkpoint inhibitors (anti-CTLA-4, anti-PD-1) are used in cancer immunotherapy to enhance anti-tumor T cell responses

Clinical Relevance and Disorders

• Immunodeficiencies are disorders characterized by impaired immune function, leading to increased susceptibility to infections
  • Primary immunodeficiencies are genetic disorders (SCID, X-linked agammaglobulinemia)
  • Secondary immunodeficiencies are acquired due to infections (HIV), medications, or other factors
• Autoimmune diseases occur when the immune system mistakenly attacks self-tissues
  • Examples include rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus
  • Treatments aim to suppress immune responses (corticosteroids, immunosuppressants)
• Allergies are hypersensitivity reactions to normally harmless substances (allergens)
  • Type I hypersensitivity (immediate) is mediated by IgE antibodies and mast cell degranulation
  • Symptoms can range from mild (hay fever) to severe (anaphylaxis)
• Vaccines exploit adaptive immunity to confer long-lasting protection against specific pathogens
  • Vaccines contain inactivated or attenuated pathogens, or pathogen-derived antigens, to stimulate an immune response without causing disease

Cutting-Edge Research and Future Directions

• Cancer immunotherapy harnesses the immune system to fight cancer
  • Checkpoint inhibitors (anti-CTLA-4, anti-PD-1) release the brakes on anti-tumor T cell responses
  • Chimeric antigen receptor (CAR) T cell therapy engineers patient-derived T cells to target specific tumor antigens
• Personalized medicine tailors immunotherapies to an individual's unique genetic and immunological profile
• Microbiome research investigates the role of commensal bacteria in shaping immune responses
  • Dysbiosis (imbalance) of the gut microbiome has been linked to various immune-related disorders (inflammatory bowel disease, allergies)
  • Probiotics and fecal microbiota transplantation are being explored as potential therapies
• Single-cell technologies (scRNA-seq, CyTOF) enable high-resolution analysis of immune cell heterogeneity and function
  • These technologies can identify rare immune cell subsets and characterize their roles in health and disease
• Immunoengineering combines immunology with engineering principles to design novel therapies and diagnostic tools
  • Examples include nanoparticle-based vaccines, engineered cytokines, and microfluidic devices for immune cell analysis