Lymphoid and Immune System Comprehensive Notes

Immune and Lymphoid System

  • Immune system: A cell population inhabiting all organs, defending the body from disease agents; not an organ system.
  • Lymphoid (lymphatic) system: Lymphatic vessels penetrating nearly every tissue, plus lymphoid tissues and organs where immune cells are produced and activated.

Lymphoid System Functions

  • Fluid Recovery:
    • Fluid continually filters from blood capillaries into tissue spaces.
    • Blood capillaries reabsorb 85%; the remaining 15% enters lymphatic vessels.
  • Immune Surveillance:
    • Excess filtered fluid picks up foreign cells and chemicals.
    • Fluid passes through lymph nodes where immune cells guard against foreign matter.
    • This activates a protective immune response.
  • Lipid Absorption:
    • Lacteals in the small intestine absorb dietary lipids not absorbed by blood capillaries.

Lymphoid System Components

  • Lymph: The recovered fluid.
  • Lymphatic vessels: Transport the lymph.
  • Lymphoid tissue: Aggregates of lymphocytes and macrophages in many organs.
  • Lymphoid organs: Organs with concentrated lymphoid cells, surrounded by a connective tissue capsule.

Lymphatic Vessels

  • Lymph flows through lymphatic vessels:
    • Lymphatic capillaries: Microscopic, penetrating nearly every tissue.
    • Collecting vessels: Formed by merging lymphatic capillaries, converge to form larger lymphatic trunks.
  • Lymphatic trunks converge to form two collecting ducts.

Lymphatic Ducts

  • Right lymphatic duct: Receives lymph from the right arm, and the right side of the head and thorax; empties into the right subclavian vein.
  • Thoracic duct: Larger and longer, begins as the cisterna chyli in the abdomen; receives lymph from below the diaphragm, the left arm, and the left side of the head, neck, and thorax; empties into the left subclavian vein.

Lymphoid Tissues and Organs

  • Lymphoid tissue: Concentration of lymphocytes within various organs, particularly mucous membranes (e.g., respiratory, digestive, urinary, and reproductive tracts).
  • Lymphatic organs: Anatomicall well-defined.
    • Divided into primary and secondary lymphoid organs.

Lymphoid Organs

  • Primary lymphoid organs: Red bone marrow and thymus.
    • Sites where T and B cells become immunocompetent, able to recognize and respond to antigens.
  • Secondary lymphoid organs: Lymph nodes, tonsils, and spleen.
    • Locations where immunocompetent cells meet and activate.

Lymph Nodes

  • Lymph nodes: Bean-shaped structures that filter lymph and are sites of lymphocyte activation.
  • Concentrated in:
    • Cervical lymph nodes (neck).
    • Axillary lymph nodes (armpit).
    • Inguinal lymph nodes (groin).
    • Popliteal lymph nodes (back of knee).

Spleen

  • Spleen: The body’s largest lymphoid organ.
  • Functions:
    • Site of lymphocyte proliferation and immune surveillance and response.
    • Cleanses blood of aged blood cells and platelets; macrophages remove debris.

Immunity

  • Immune system: Widely distributed population of cells, diverse chemicals, physical barriers, and physiological responses.
  • Two broad forms of defense:
    • Innate immunity: Defenses we are born with; protect from a broad spectrum of disease agents.
    • Adaptive immunity: Defenses against specific pathogens, developed upon exposure (adaptive), and maintains immune memory.

Innate vs. Adaptive Immunity

  • Innate immunity:
    • Local effect: Defends at the point of invasion (exceptions: fever).
    • Non-specific: Defenses against a broad spectrum of disease agents.
    • No memory: Does not “remember” exposure to a specific pathogen.
    • Uses inflammation, fever, mucous membrane, various WBC.
  • Adaptive immunity:
    • Systemic effect: System-wide activation of immune cells.
    • Specific: Defenses against one particular pathogen.
    • Has memory: “Remembers” exposure to a specific pathogen; second exposure results in stronger response.
    • Relies on T and B lymphocytes and antibodies.

Lines of Defense

  • Pathogens: Agents capable of producing disease, including viruses, bacteria, fungi, and other microbes.
  • Three lines of defenses against pathogens:
    • First line of defense: Skin and mucous membranes, physical barrier.
    • Second line of defense: Protections against pathogens that penetrate the skin & mucous membrane barriers, including leukocytes and macrophages, antimicrobial proteins, natural killer cells, fever, and inflammation.
    • Third line of defense: Adaptive immunity, mechanisms that defeat a specific pathogen and leave the body with a memory of it.

Innate Immunity: First Line - Skin

  • First line of defense: skin and mucous membranes.
  • Protective features of the skin:
    • Toughness of keratin, difficult to penetrate.
    • Too dry and nutrient-poor to support microbial growth.
    • Microbes adhered to skin are continually shed with dead keratinocytes.
    • Presence of an acid mantle: Thin film of lactic and fatty acids from sweat and sebum that inhibits bacterial growth.

Innate Immunity: First Line - Mucous Membranes

  • First line of defense: skin and mucous membranes.
  • Digestive, respiratory, urinary, and reproductive tracts are open to the exterior and protected by mucous membranes.
  • Protective features of mucous membranes:
    • Sticky mucus physically traps microbes.
    • Presence of lysozyme: Enzyme destroys bacterial cell walls.

Innate Immunity: Second Line - Cells

  • When skin and mucous membranes are penetrated, internal defenses await:
    • Phagocytes: Cells that ingest foreign matter.
    • Five types of leukocytes (some of which are phagocytes):
      • Neutrophils: Kill bacteria.
      • Eosinophils: Guard against parasites (tapeworms, roundworms); inflammation & allergies.
      • Basophils: Secrete chemicals that attract other leukocytes; inflammation.
      • Monocytes: Transform into macrophages.
      • Lymphocytes: T and B cells part of adaptive immunity; natural killer (NK) cells kill infected cells.

Innate Immunity: Second Line - NK Cells

  • Natural killer (NK) cells continually patrol the body looking for pathogens and diseased host cells.
  • NK cells attack and destroy microbes, transplanted cells, cells infected with viruses, and cancer cells.
  • Recognize infected cell and bind to it.
  • Release proteins called perforins, which create a pore in the plasma membrane of the target cell.
  • Secrete a group of protein-degrading enzymes called granzymes that enter through the pore and induce apoptosis (programmed cell death).

Innate Immunity: Second Line - Antimicrobial Proteins

  • Blood-borne antimicrobial proteins:
    • Interferons: Proteins secreted by virus-infected cells; serve as an “alarm” to nearby cells.
    • Bind to receptors on nearby cells, stimulating their synthesis of defensive antiviral proteins.

Innate Immunity: Second Line - Complement System

  • Blood-borne antimicrobial proteins:
    • Complement system: Group of 30 or more proteins that contribute to both innate and adaptive immunity.
    • Synthesized mainly by liver.
    • Circulate in the blood in inactive form.
    • Detection and binding to microbes leads to their activation.
    • Activated complement contributes to inflammation, cytolysis, and phagocytosis.

Innate Immunity: Second Line - Fever

  • Fever (pyrexia): An abnormal elevation of body temperature.
  • Results from trauma, infections, drug reactions, brain tumors, and other causes.
  • Defense mechanism that, in moderation, does more good than harm.
  • Promotes interferon activity.
  • Elevates metabolic rate and accelerates tissue repair.
  • Inhibits reproduction of bacteria and viruses.
  • Recovery is sometimes faster when allowing fever to take its course, rather than taking antipyretics (fever-reducing medications).

Innate Immunity: Second Line - Inflammation

  • Inflammation: Local defensive response to tissue injury, including trauma and infection.
  • Purposes of inflammation:
    • Limit spread of pathogens, then destroys them.
    • Remove debris from damaged tissue and initiate tissue repair.
  • Four cardinal signs of inflammation: Redness, swelling, heat, pain.
  • Involves numerous cytokines: Small proteins that function in chemical communication between cells.

Innate Immunity: Second Line - Inflammation Mechanism

  • Damaged tissue or pathogens trigger the release of inflammatory chemicals.
  • Blood vessels dilate to increase blood flow and transport of WBC, causing redness, swelling, heat, and pain.
  • Neutrophils are first to arrive; adhere to the blood vessel wall (margination) and squeeze through it (diapedesis).
  • Neutrophils and macrophages (arrive later) engulf pathogens and debris (phagocytosis).

Adaptive Immunity

  • Adaptive immunity serves as the third line of defense.
  • Two types of adaptive immunity:
    • Humoral (antibody-mediated) immunity
      • Mediated by B lymphocytes that produce antibodies.
      • Do not directly destroy a pathogen but mark it for destruction.
      • Effective against viruses, bacteria, toxins, venoms, and allergens (extracellular targets).
    • Cellular (cell-mediated) immunity
      • Mediated by T lymphocytes that directly attack and destroy diseased cells or foreign host cells (cellular targets).
      • Also acts against parasitic worms, cancer cells, and transplanted cells.
      • Rids the body of pathogens that reside inside human cells.

Adaptive Immunity: Antigens & Antibodies

  • Antigen: Any molecule that can bind an antibody, found on cell membrane of cells
  • Antibodies (immunoglobulins or Igs): Proteins that play defensive roles.
    • Made by B lymphocytes (B cells).
    • Found in blood, lymphoid tissue, mucus, saliva, breast milk, intestinal secretions.

Adaptive Immunity: Lymphocytes (T Cells)

  • T lymphocytes (T cells):
    • Three developmental stages: “Born” in bone marrow, “Educated” in thymus, “Deployed” to locations to carry out immune function
    • Developing T cells are tested within the thymus.
      • Positive selection: Ensures T cells can recognize and bind antigens (immunocompetent).
      • Negative selection: Ensures T cells do not react to self-antigens (self-tolerance).
    • T cells that fail either test are eliminated.
    • Successful T cells become naïve T cells and travel to lymphoid tissue to patrol for antigens.

Adaptive Immunity: Lymphocytes (B Cells)

  • B lymphocytes (B cells):
    • B cells develop entirely in bone marrow.
    • B cells that react to self-antigens are eliminated, same as T cell selection.
    • Self-tolerant B cells synthesize antigen surface receptors, divide rapidly, produce immunocompetent clones.
    • Leave bone marrow and colonize same lymphoid tissues and organs as T cells.

Adaptive Immunity: Antigen-Presenting Cells (APCs)

  • T cells can only recognize antigens presented by antigen-presenting cells (APCs).
  • APCs include dendritic cells, macrophages, and B cells.
  • Antigen processing:
    • APC encounters antigen, internalizes it by endocytosis, and digests it into fragments.
    • Displays fragments in the grooves of the MHC protein.
    • Antigen presented to T cells.
    • If APC displays a self-antigen, the T cells disregard it.
    • If APC displays a non-self antigen, the appropriate T cell will initiate an immune response against the source of that antigen.

Adaptive Immunity: Cellular Immunity and T-Cells

  • Cellular (cell-mediated) immunity: A form of specific defense in which the T lymphocytes directly attack and destroy diseased or foreign cells.
  • Uses four classes of T-cells:
    • Cytotoxic T cells (TC): Carry out attack; kill other cells.
    • Helper T cells (TH): Activate other immune cells (B cells, T cells, macrophages).
    • Memory T cells (TM): Responsible for memory of cellular immunity.

Adaptive Immunity: Cellular Immunity Stages

  • General stages of response: Recognition, attack, and memory.
  • Recognition:
    • Antigen presentation: APC encounters and processes an antigen, migrates to nearest lymph node, and presents it to T cells.
    • Double recognition:
      • T cell binds to antigen on MHC complex.
      • T cell binds to co-stimulatory molecules on APC that ensure APC is functioning normally (fail-safe mechanism).
      • Only when both bindings occur (co-stimulation/double recognition) will naïve T cell activate.
  • Clone formation:
    • Activated T cells will undergo repeated mitosis to give rise to identical clones programmed against same antigen.
    • Some clones differentiate into effector cells, and some into memory cells.

Adaptive Immunity: Cellular Immunity - Attack

  • Role of helper T cells:
    • Activate cytotoxic T cells (cellular immunity).
    • Induce B cell activation and production of antibodies (humoral immunity).
    • Secrete cytokines (chemical signals that recruit other immune cells (innate immunity).
    • Without helper T cells there is no immune response.
  • Role of cytotoxic T cells:
    • Only T cells that directly attack other cells.
    • Activated TC cells circulate in blood and lymph and lymphoid organs in search of cells displaying antigen they recognize.
    • Cytotoxic T cells deliver lethal hit using two mechanisms:
      • TC cell releases perforins and granzymes by exocytosis.
        • Perforins create pores through which granzymes enter target cell.
        • Granzymes stimulate apoptosis.
      • TC cell binds specific membrane receptor on target cell and stimulates apoptosis.

Adaptive Immunity: Cellular Immunity - Memory

  • Memory cells:
    • Clones of activated T cells that remain in the body.
    • Long-lived.
    • Fewer steps to be activated, so they respond more rapidly if the body encounters the same antigen a second time.

Adaptive Immunity: Humoral Immunity - Recognition

  • Recognition, attack, memory
  • Recognition:
    • Antigen recognition: Antigen binds to B cell receptor; engulfed, processed, and displayed on MHC protein.
    • Antigen presentation: Antigen presented to helper T cell; helper T cell activates B cell.
    • Clonal selection: B cell activation triggers mitosis giving rise to clones of identical B cells to the one that recognized the antigen.
    • Differentiation: Clones become plasma cells or memory cells.

Adaptive Immunity: Humoral Immunity - Attack

  • Plasma cells secrete antibodies at a rate of 2,000 molecules per second.
  • Antibodies bind perfectly to the antigen.
  • Circulate blood and lymph looking for antigen.
  • Eliminate antigen in various ways:
    • Neutralization: Block binding regions on pathogens to prevent them from entering cells.
    • Agglutination: Clumping of enemy cells, immobilizing them.

Adaptive Immunity: Humoral Immunity - Memory

  • Memory B cells
    • Clones of activated B cell saved in the body
    • Mount an accelerated attack to future exposure to same antigen

Adaptive Immunity: Humoral Immunity - Primary vs. Secondary Reponse

  • Primary response: Immune reaction brought about by the first exposure to an antigen.
    • Appearance of antibodies delayed for 3-6 days (time it takes for B cells to activate, multiply, differentiate).
    • Antibody levels peak around day 10 then decline.
  • Secondary response: Immune response when re-exposed to the same antigen.
    • Plasma cells form within hours, not days.
    • Antibody levels rise sharply and peak within days.
    • Antibody levels remain high for weeks to months.
    • Bases for vaccinations.