The Human Immune System

• The immune system defends the body against pathogens and abnormal cells through physical barriers, chemical defenses, cells, and tissues.

Anatomy of the Immune System

• Skin, mucous membranes, acid, enzymes, and mucus serve as physical and chemical barriers blocking pathogen entry.
• Lysozyme, HCl, and acidic secretions provide chemical defenses.
• Immune cells, also known as leukocytes, originate from hematopoietic stem cells in bone marrow.
• Granulocytes include neutrophils, eosinophils, and basophils, while agranulocytes include monocytes and lymphocytes.
• Phagocytes, such as neutrophils, eosinophils, macrophages, and dendritic cells, engulf pathogens and secrete cytokines.
• B cells secrete antibodies, T cells directly attack infected cells, and natural killer (NK) cells target virus-infected and cancer cells rapidly.
• Mast cells release histamine during inflammation.
• Central lymphoid tissues include bone marrow and the thymus, where B and T cells mature.
• Peripheral lymphoid tissues, such as lymph nodes, spleen, tonsils, and Peyer’s patches, trap pathogens and present them to immune cells.

Pathogens

• Viruses are the smallest pathogens, require a host to reproduce rapidly.
• Bacteria are prokaryotic organisms that release endotoxins or exotoxins.
• Fungi are eukaryotic organisms, like yeast and molds, that grow slowly.
• Parasites include protozoa, such as Trypanosoma, and worms.

Nonspecific (Innate) Defenses

• Inflammation occurs due to histamine release, which leads to vasodilation and increased permeability.
• Macrophages engulf and destroy pathogens through phagocytosis.
• Cytokines signal and activate immune cells.
• Interferons are anti-viral proteins that promote resistance.
• NK cells induce lysis of infected cells.
• The complement system is a cascade that forms a membrane attack complex (MAC) to lyse bacteria through classical, alternative, and lectin pathways. Classical needs antibodies. Alternative follows direct bacterial surface binding. Lectin binds to mannose.
• Steps of phagocytosis:
  • Attachment via opsonins
  • Internalization (phagosome + lysosome)
  • Degradation
  • Exocytosis

Humoral Immunity (B Cells)

• Exposure to an antigen activates B cells, leading to clonal selection.
• B cells differentiate into:
  • Plasma cells, which are short-lived and secrete 2000 antibodies per second.
  • Memory B cells, which are long-lived and antigen-specific.
• Antibody functions include neutralizing antigens, marking antigens for phagocytosis, and triggering complement lysis.
• T-dependent activation needs a helper T cell and IL-2.

Cell-Mediated Immunity (T Cells)

• Helper T cells secrete cytokines and activate B/T cells, macrophages, and NK cells.
• Cytotoxic T cells destroy infected or cancerous cells via MHC I.
• Suppressor T cells regulate and suppress the immune response.
• MHC I molecules are found on all nucleated cells and are recognized by cytotoxic T cells.
• MHC II molecules are found on immune cells and are used to activate helper T cells.
• Helper T cells bind to the MHC II-antigen complex and secrete IL-2.
• Cytotoxic T cells bind to MHC I-antigen and kill infected or tumor cells.

Immune Responses in Health & Disease

• Active immunity develops from vaccines or infection, creating memory cells.
• Passive immunity is acquired through antibodies from another source (e.g., mother to baby), without creating memory cells.
• Blood types: A, B, AB (universal recipient), O (universal donor).
• Organ rejection occurs due to a mismatch in HLA (MHC) antigens.
• Bone marrow transplants carry the risk of graft-versus-host disease.
• Allergies involve a hypersensitive IgE response, leading to histamine release.
• Anaphylactic shock is a systemic reaction that decreases total peripheral resistance (TPR) and mean arterial pressure (MAP), and is treated with epinephrine.
• Autoimmune diseases result from a self-recognition failure, examples include lupus, rheumatoid arthritis (RA), and multiple sclerosis (MS).
• Immunodeficiency disorders:
  • Severe combined immunodeficiency (SCID) involves no B/T cell function.
  • Acquired immunodeficiency syndrome (AIDS) targets helper T cells.
  • Hodgkin’s lymphoma is a cancer of the lymph system.
• Stress & Immunity:
  • Cortisol, a stress hormone, suppresses immune function.
  • Stress reduces leukocytes and alters cytokine signaling.