3. lymph

CHECKPOINT QUESTIONS

  1. Similarities and Differences Between Interstitial Fluid and Lymph

    • Both are considered extracellular fluids that are involved in transporting nutrients and waste.

    • However, interstitial fluid is found in the spaces between cells, while lymph is interstitial fluid that enters lymphatic vessels.

  2. Structural Differences Between Lymphatic Vessels and Veins

    • Lymphatic vessels have thinner walls compared to veins.

    • They possess more valves to prevent backflow and ensure one-way flow of lymph.

    • Lymphatic vessels have a more irregular shape and are usually not associated with arteries.

  3. Route of Lymph Circulation

    • Lymph begins in lymphatic capillaries, travels through lymphatic vessels, and moves into lymph nodes where it is filtered.

    • It continues into larger lymphatic trunks, ultimately draining into the thoracic or right lymphatic duct, and returns to the bloodstream via the subclavian veins.

  4. Role of the Thymus in Immunity

    • The thymus is responsible for the maturation of T cells, a type of lymphocyte that plays a crucial role in adaptive immunity by recognizing specific antigens and mediating immune responses.

  5. Functions of Lymph Nodes, Spleen, and Tonsils

    • Lymph Nodes: Filter lymph, trap pathogens, and are sites for lymphocyte activation.

    • Spleen: Filters blood, removes old red blood cells, and stores lymphocytes and macrophages.

    • Tonsils: Protect against pathogens entering through the oral and nasal cavities, containing lymphoid tissues that produce immune responses.

DEVELOPMENT OF LYMPHATIC TISSUES

Overview

  • Lymphatic tissues begin developing by the end of the fifth week of embryonic life.

  • Lymphatic vessels originate from lymph sacs derived from developing veins, which arise from mesoderm.

Formation of Lymphatic Sac Structures

  1. Paired Jugular Lymph Sacs

    • Formed at the junction of the internal jugular and subclavian veins.

    • Lymphatic capillary plexuses expand into thorax, upper limbs, neck, and head, eventually forming lymphatic vessels.

    • One connection remains with its jugular vein, leading into the superior portion of the thoracic duct (left lymphatic duct).

  2. Retroperitoneal Lymph Sac

    • Unpaired, develops at the root of the mesentery of the intestine from primitive vena cava and mesonephric veins.

    • Forms capillary plexuses and lymphatic vessels to the abdominal viscera and diaphragm.

    • Establishes connection with cisterna chyli.

  3. Cisterna Chyli

    • Develops into the inferior portion of the thoracic duct.

    • Like retroperitoneal lymph sac, it loses connections with surrounding veins.

  4. Posterior Lymph Sacs

    • Paired and form from iliac veins, producing vessels for the abdominal wall, pelvic region, and lower limbs.

    • Join with cisterna chyli and lose connections with adjacent veins.

  • All lymph sacs, except anteriorly for cisterna chyli, become invaded by mesenchymal cells and turn into lymph nodes.

  • The spleen evolves from mesenchymal cells between the layers of the dorsal mesentery of the stomach.

  • The thymus arises as an outgrowth of the third pharyngeal pouch.

INNATE IMMUNITY

Components of Innate Immunity

  • Composed of external barriers (skin, mucous membranes) and internal defenses (antimicrobial substances, natural killer cells, phagocytes, inflammation, fever).

First Line of Defense: Skin and Mucous Membranes

  1. Physical Barrier provided by Skin

    • The epidermis consists of tightly packed keratinized cells, preventing pathogens from entering.

    • Regular shedding of epidermal cells removes microbes from the skin surface.

    • Intact skin rarely allows pathogen penetration; breaches (cuts, burns) can allow invasion.

  2. Chemical Barrier of Mucous Membranes

    • Secretes mucus to trap microbes, lubricate surfaces.

    • Nose contains mucus-coated hairs that filter inhaled substances.

    • Upper respiratory tract utilizes cilia to move trapped pathogens toward the throat for expulsion.

    • Urinary flow and vaginal secretions help expel microbes; digestive actions (defecation, vomiting) remove pathogens.

  3. Fluids for Defense

    • Tears (Lacrimal apparatus): Wash out microorganisms; contain lysozyme.

    • Saliva: Washes microbes in the oral cavity.

    • Urine: Cleanses urethra to reduce bacterial colonization.

    • Sebum: Oily secretion from skin that inhibits pathogen growth.

    • Gastric Juice: Strong acidity (pH 1.2-3.0) destroys many bacteria and their toxins.

Second Line of Defense: Internal Defenses

  • When pathogens breach existing barriers, they encounter internal defenses that involve antimicrobial substances, phagocytes, NK cells, and inflammatory responses.

Antimicrobial Substances

  1. Interferons

    • Proteins produced by virus-infected cells that halt viral replication in neighboring cells.

    • Three types: alpha-, beta-, gamma-IFN.

  2. Complement System

    • Group of proteins that enhance immune reactions, promote microbial lysis, and assist in inflammation.

  3. Iron-Binding Proteins

    • Limit free iron to inhibit bacterial growth (e.g., transferrin, lactoferrin).

  4. Antimicrobial Proteins (AMPs)

    • Short peptides with a broad action against microbes and stimulation of immune responses.

    • Examples: dermicidin, defensins, cathelicidins, thrombocidin.

Natural Killer Cells and Phagocytes

  1. Natural Killer (NK) Cells

    • Subset of lymphocytes that kill infected or abnormal cells without needing prior sensitization.

    • Release cytotoxic granules: perforin creates pores causing cytolysis, while granzymes induce apoptosis.

  2. Phagocytes

    • Special cells that ingest and destroy microbes via phagocytosis; key types include neutrophils and macrophages.

    • Phagocytosis phases include chemotaxis, adherence, ingestion, digestion, and killing.

Clinical Connection: Microbial Evasion of Phagocytosis

  • Some microbes evade phagocytosis through mechanisms like capsules that prevent adherence and toxins that kill phagocytes.

Phagocytosis Phases

  1. Chemotaxis

    • Movement of phagocytes towards damaged sites influenced by chemicals from pathogens or tissue damage.

  2. Adherence

    • Binding of phagocytes to microbes enhanced by complement proteins.

  3. Ingestion

    • Engulfing of the microbe by extending pseudopods to form a phagosome.

  4. Digestion

    • Phagosome fuses with lysosome to form a phagolysosome, enabling microbial digestion through enzymes and oxidants.

  5. Killing

    • The toxic environment within the phagolysosome kills the microbes, and indigestible materials become residual bodies.

Inflammation

  • Defensive and nonspecific response characterized by redness, heat, swelling, pain, and loss of function to damaged tissue.

  • The stages include:

    1. Vasodilation and Increased Permability

    • Blood vessel dilation allowing more blood to flow to the injured area and increased permeability allowing essential proteins and antibodies access.

    • Histamine, kinins, prostaglandins, and leukotrienes are key agents promoting these changes.

    1. Phagocyte Emigration

    • Phagocytes migrate from the bloodstream to the damaged tissue area, driven by chemotaxis.

    • Neutrophils dominate early in inflammation, followed by monocytes which become macrophages.

    1. Tissue Repair

    • Following the elimination of pathogens, the tissue begins the repair process.

  • Accumulation of dead cells and fluid in inflammation leads to pus formation.

Clinical Connection: Abscesses and Ulcers

  • Abscess: local accumulation of pus in a confined space;

  • Ulcer: open sore formed by the sloughing of inflamed tissue.

Fever

  • Fever results from re-setting the hypothalamic thermostat during infection.

  • Caused by bacterial toxins or release of cytokines like interleukin-1.

  • Raised temperatures optimize immune response and inhibit microbial growth.

ADAPTIVE IMMUNITY

Overview

  • Adaptive immunity provides the ability for the body to mount a specific defense against identified pathogens.

  • Antigens (Ags) are substances that provoke these immune responses.

  • Key characteristics include:

    1. Specificity for individual antigens.

    2. Memory to mount faster, stronger responses upon re-exposure.

Maturation of T Cells and B Cells

  • Adaptive immunity relies on B and T lymphocytes that originate from pluripotent stem cells.

  • B cells mature in the red bone marrow; T cells mature in the thymus.

  • Upon maturation, they achieve immunocompetence, enabling them to respond to specific antigens.

Conclusion

  • The immune system requires both innate and adaptive responses to provide effective defense against infections.

  • Continued study in immunology aids in understanding and advancing medical treatments.

CHECKPOINT QUESTIONS

  1. Protection through skin/mucous membrane factors.

  2. Internal defenses against microbes that bypass initial barriers.

  3. Similarities and differences between NK cells and phagocytes.

  4. Main signs, symptoms, and stages of inflammation.