Lymphatic System and Immunity

• The lymphatic system and innate immunity protect the body

Overview of the Lymphatic System

• Fluid balance occurs when excess interstitial fluid returns to the bloodstream
• Immune Surveillance involves lymphocytes (T & B cells) detecting and fighting pathogens
• Fat Absorption transports dietary lipids from the intestines

Components of the Lymphatic System

• Lymph is a clear fluid containing immune cells
• Lymphatic Capillaries are the smallest vessels and collect excess interstitial fluid
• Lymphatic Vessels transport lymph through lymph nodes
• Lymphatic Trunks & Ducts drain fluids
• The Right Lymphatic Duct drains the right upper body into the venous system
• The Thoracic Duct drains lymph from the rest of the body into the venous system

Lymphoid Organs & Immune Function

• Bone Marrow produces B cells & T cell precursors
• The Thymus is the site of T cell maturation & selection

Secondary Lymphoid Organs

• Lymph Nodes filter lymph, detect pathogens, and contain B & T cells, dendritic cells, and macrophages
• The Spleen contains white pulp that filters blood for pathogens and activates immune responses
• The Spleen also contains red pulp that destroys old RBCs and stores platelets
• Tonsils trap inhaled/ingested pathogens

Innate Immune System: First Line of Defense

• The innate immune system has key characteristics
• It is non-specific and targets broad pathogen categories
• It is fast-acting, with an immediate response within minutes to hours
• There is no memory, the response is the same every time

Physical & Chemical Barriers

• Skin & Mucous Membranes prevent pathogen entry
• Tears & Saliva contain lysozymes that break down bacterial walls
• Stomach Acid kills ingested microbes
• Cilia in Airways trap and remove inhaled pathogens

Cells of the Innate Immune System

• Macrophages are first responders found in tissues
• Macrophages recognize Pathogen-Associated Molecular Patterns (PAMPs)
• Phagocytosis occurs when pathogens are engulfed and digested
• Cytokine Secretion recruits immune cells
• Oxidative Burst uses reactive oxygen species (ROS) to kill microbes

Neutrophils

• Neutrophils are the most abundant WBC in blood
• Phagocytosis & oxidative burst are used to destroy pathogens
• They are short-lived and rapidly recruited to infection sites

Dendritic Cells

• Dendritic Cells bridge between innate and adaptive immunity
• They capture antigens, migrate to lymph nodes, and activate T cells

Natural Killer (NK) Cells

• Natural Killer Cells destroy virus-infected & cancerous cells
• They recognize the absence of MHC I molecules
• Perforin & granzymes are used to induce apoptosis
• They mediate Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

Complement System: Enhancing Immunity

• Opsonization involves marking pathogens for phagocytosis
• Inflammation recruits immune cells via C3a & C5a
• Direct Pathogen Lysis forms Membrane Attack Complex (MAC)

Pathways to Complement Activation

• The Classical Pathway is triggered by antibodies (IgG or IgM) bound to antigens
• C1 binds antibodies, activating C2 & C4 and forming C3 convertase
• The Lectin Pathway is triggered by mannose-binding lectin (MBL) binding mannose on bacterial walls
• The Lectin Pathway leads to C3 convertase formation
• The Alternative Pathway is triggered by direct C3b binding to microbial surfaces
• This pathway amplifies the immune response by forming C3 convertase

Formation of Membrane Attack Complex (MAC)

• C3 convertase cleaves C3 to produce C3b
• C5 convertase forms and cleaves C5 into C5a & C5b
• C5b binds C6, C7, C8, and multiple C9 molecules to form MAC
• MAC creates a pore in bacterial membranes, causing lysis and death

Immune System Coordination

• The Innate Immune system has an immediate response (minutes to hours), while the Adaptive Immunity system has a delayed response (days to weeks)
• The Innate Immune system is non-specific, while the Adaptive Immune system is highly specific (recognizes unique antigens)
• The Innate Immune system has no memory, while the Adaptive Immune system has memory cells that allow faster future responses
• The Innate Immune system involves Macrophages, Neutrophils, NK cells, and the Complement system
• The Adaptive Immune system involves B cells (Antibody Production) and T cells (CD4/CD8 activation)