Lymphatic ch22

Functions of the Lymphatic System

1. Drain IS Fluid

2. Transport Dietary Fats

3. Carry Out Immune Responses

Introduction to the Lymphatic System

• Immunology: Study of the body’s defense against infection.

  • Paired with inflammation (body’s response to tissue injury).

  • Tissue injury makes the body more susceptible to pathogen invasion.

Immune Responses

1. Nonspecific (Innate) Immunity:

   • General defense against many pathogens.

   • Born with it.

2. Adaptive (Specific) Immunity:

   • Develops after exposure to specific antigens.

   • Features specificity and memory.

Components of the Lymphatic System

1. Lymph

2. Lymphatic Vessels

3. Lymphatic Organs & Tissues

4. Red Bone Marrow

Lymphatic Vessels and Capillaries

• Capillaries merge into larger vessels.

Routes of Drainage

• Exit Lymph Nodes → Regional Lymph Trunks:

  • Principal Lymph Trunks: Lumbar, Intestinal, Bronchomediastinal, Subclavian, Jugular.

• Thoracic Duct: Main collecting duct (drains most of the body).

• Right Lymphatic Duct: Drains the upper right side of the body.

Flow of Lymph

1. IS Fluid

2. Lymph Capillaries

3. Lymph Vessels

4. Lymph Trunks

5. Lymph Ducts

6. Subclavian Veins

• Associations: Systemic and Pulmonary Circulations.

Lymphatic Organ Classification

1. Primary Lymphatic Organs:

   • Red Bone Marrow: B & T cell generation.

   • Thymus: T cell maturation.

2. Secondary Lymphatic Organs:

   • Lymph Nodes: Main immune response site.

   • Spleen: Largest lymphatic tissue mass (smooth and visceral surfaces).

   • Lymphatic Nodules: No capsule, produce lymphocytes.

Immune Defense Levels

1. Innate Immunity (Nonspecific)

2. Adaptive Immunity (Specific)

First Line of Defense: External Barriers

• Mechanical Protection:

  • Skin, mucous membranes, saliva, etc.

• Chemical Protection:

  • Sebum, sweat, gastric juices, low pH in various parts (skin, stomach, urinary system).

Second Line of Defense: Innate Immunity

• Antimicrobial Substances:

  • Interferons (IFNs): Viral protection.

  • Complement: Enhances immune responses.

  • Iron-binding Proteins: Prevent microbes from using iron.

  • Antimicrobial Proteins (AMPs): Broad-spectrum defense.

• Inflammation:

  • Phagocytes (neutrophils & macrophages), NK cells involved.

Complement System

• ~30 proteins involved in:

  • Chemotaxis

  • Promoting Phagocytosis

  • Cytolysis

  • Promoting Inflammation

Innate Immunity: NK Cells

• Cytotoxic activity against viral and tumor cells.

• Perforins: Create holes in target cells.

• Granzymes: Induce apoptosis in target cells.

Phagocytosis Process

1. Chemotaxis: WBCs move towards microbes.

2. Adherence: Phagocyte attaches to microbe.

3. Ingestion: Microbe taken into phagocyte.

4. Digestion: Phagosome merges with lysosome.

5. Killing: Residual bodies formed after digestion.

Innate Immunity: Inflammation

• Triggers: Mechanical, chemical, microbial, ischemic.

• Mediators: Histamine, kinins, prostaglandins, cytokines, etc.

• Signs/Symptoms: Redness, swelling, heat, pain, loss of function.

• Stages:

  1. Vasodilation

  2. Microvascular Permeability Increase

  3. Phagocyte Emigration

Fever

• Triggered by pyrogens: Microbial products or immune system mediators.

• Benefits: Kills microbes and increases WBC activity.

Third Line of Defense: Adaptive Immunity

• Specificity and Memory.

• Activation occurs in lymphoid tissues.

• Antigens are recognized by TCR or BCR.

Adaptive Immunity: Lymphocytes

1. B Cells:

   • Origin in red bone marrow.

   • Activation: Clone formation, plasma cells, memory B cells.

2. T Cells:

   • Develop from pre-T cells in thymus.

   • Activation: Formation of cytotoxic T cell clone, active cytotoxic T cells, memory T cells.

Activation & Clonal Selection

1. Effector Cells: Carry out immune response.

   • Helper T Cells, Cytotoxic T Cells, B Cells, Plasma Cells.

2. Memory Cells:

   • Long-lived in secondary lymphoid tissues.

   • Provide faster responses in subsequent exposures.

Antigens & Antigen Receptors

• Antigens: Substances that bind to antibodies or TCRs.

• Epitope: Part of antigen that triggers immune response.

Major Histocompatibility Complex (MHC)

• MHC Class 1: Found on all cells (except RBCs), interacts with CD8+ T cells.

• MHC Class 2: Found on antigen-presenting cells (APCs), interacts with CD4+ T cells.

Pathways of Antigen Processing

1. Exogenous Antigen Processing:

   • Processed by APCs, presented with MHC II to CD4+ T cells.

2. Endogenous Antigen Processing:

   • Processed inside cells, presented with MHC I to CD8+ T cells.

Cell-Mediated Immunity

• T Cell Activation: Requires co-stimulation (cytokines, membrane molecules).

• Cytotoxic T Cells: Kill infected cells using perforins, granzymes, and granulysin.

Clonal Selection & Memory

• Helper T Cells: Help other immune cells.

• Cytotoxic T Cells: Kill infected body cells.

• Costimulation: Cytokines like IL-2 stimulate T cells and B cells.

Types of Defenses:

1. Innate Immunity:

   • Surface Barriers: Physical barriers (e.g., skin, mucous membranes, tears, hairs)

   • Internal Defenses: Non-specific responses (e.g., inflammation, fever, phagocytosis)

2. Adaptive Immunity:

   • Train Immunity Cells: Specific response, memory-based, learned immunity against pathogens

Second Line of Defense (Innate Immunity):

• Antimicrobial Substances:

  • Complement Proteins: Enhance immune responses, promote inflammation

  • Interferons (IFNs): Interfere with viral replication

• Phagocytes: Cells that engulf pathogens (e.g., neutrophils, macrophages)

• Natural Killer (NK) Cells: Target virus-infected and tumor cells

• Fever: Elevated body temperature to inhibit microbe growth and enhance immune function

• Inflammation: Localized defense response to tissue damage (e.g., redness, swelling)

Third Line of Defense (Adaptive Immunity):

• T Cells:

  • Memory Cells: Store information for future encounters

  • Effector Cells: Actively fight infections (e.g., cytotoxic T cells)

• B Cells:

  • Memory Cells: Store information about pathogens

  • Effector Cells (Plasma Cells): Produce antibodies against specific antigens

• Clonal Selection: Activation of both T and B cells to generate clones that fight specific pathogens

Immunological Surveillance:

• Tumor Surveillance:

  • Carried out by T cells and NK cells

  • Recognize Tumor Antigens: Identify and destroy tumor cells

• Transplantation:

  • Graft Rejection: Immune response against transplanted organs

  • T Cells & Antibodies: Primarily responsible for rejection

  • Innate Immunity: Plays a role in chronic rejection

Antibody-Mediated Immunity (Humoral Immunity):

• T Cells: Primarily for cell-mediated immunity

• B Cells: Produce antibodies, capable of responding to specific antigens

  • B Cell Activation: Co-stimulation by helper T cells → B cell proliferation → differentiation into plasma cells and memory B cells

Functions of Antibodies:

• Neutralization: Inactivates toxins and viruses

• Immobilization: Prevents bacterial spread

• Agglutination/Precipitation: Enhances phagocytosis by clumping antigens

• Activation of Complement: Boosts immune responses

• Opsonization: Marks pathogens for phagocytosis

Immunological Memory:

• Memory Cells: Long-lived cells that store information for rapid response to future infections

  • Primary Response: First encounter with antigen (via natural exposure or vaccination)

  • Secondary Response: Faster and stronger immune response upon re-exposure to the same antigen

Thymic Selection (T Cells):

• Positive Selection: T cells that recognize self-MHC survive

  • Ensures T cells can recognize self-MHC

• Negative Selection: T cells that strongly bind self-antigens are eliminated (prevents autoimmunity)

T Cells: Self-Recognition and Self-Tolerance:

• Positive Selection: T cells that recognize self-MHC are selected

• Negative Selection: T cells that react strongly to self-antigens are destroyed

B Cells: Development of Self-Recognition and Self-Tolerance:

• Negative Selection: B cells that bind self-antigens are deleted in the bone marrow

• Anergy: Inactivation of B cells once released

Stress and Immunity (PNI):

• Psychoneuroimmunology (PNI): Studies how the nervous, endocrine, and immune systems interact

  • Can influence health and disease progression

Age and the Immune System:

• Aging Effects:

  • Thinning skin → Decreased barrier protection

  • Less acidic gastric juices → Increased microbial survival

  • Decreased immune function: Reduced T cell/B cell response, less effective immune system

  • Increased susceptibility: More prone to infections, malignancies, and weakened vaccine responses