The Immune System

The Immune System

1. Adaptive/specific immunity

   • Defenses that can target specific pathogens. Slower to react, but can retain memory for faster attack in subsequent identical infections
   • Lyphocytes
     • White blood cells. All lymphocytes are created in the bone marrow. Agranulocytes (have one-lobed nucleus & lack granules in the cytoplasm).
     • Humoral immunity
       • B-cells
         • Mature in the bone marrow
         • Activated in spleen and lymph nodes
         • Each B-cell makes only one type of antibody
         • Primary response
           • Upon activation by antigen, naive B cells produce 2 daughter cells. Initial activation takes ~7-10 days
           • Plasma cells
             • Produce large amounts of antibodies
             • Antibodies/immunoglobulins (Ig)
               • Y-shaped, made up of 2 heavy chains+2 light chains held together by disulfide bonds and noncovalent interactions
               • Constant domain
                 • Cells of the innate immune system (macrophages, eosinophils, NK, etc) bind to this region to initiate complement cascade.
               • 5 isotypes
                 • Isotype switching
                   • Stimulation by cytokines can change which isotype cells produce.
                 • IgG, IgE, IgA, IgD, IgM
               • Hypermutation
                 • What the B-cell undergoes to create best antigen binding region for a specific antigen
                 • Antigen Binding site (V)
                   • Variable domain at tip of Y that can bind to one specific antigen polypeptide sequence
               • Clonal selection
                 • Only antibodies that can bind to an antigen with high affinity survive
         • Secondary response
           • Memory B-cells
             • Formed after primary response. Last a lifetime and recognize subsequent identical infections
           • More rapid and robust because its activated in response to recognizing specific pathogens
       • Production of antibodies
     • Cell-mediated (cytotoxic) immunity
       • T cells
         • Mature in the thymus but naive until antigen exposure. Undergo same clonal selection as B-cells
         • Positive selection
           • Matures cells that can respond to MHC antigen presentation
         • Negative selection
           • Causes apoptosis in self-reactive cells
         • Helper (Th) T-cells / CD4+ T-cells
           • Lymphokines
             • Chemicals secreted that can recruit other immune cells (plasma cells, cytotoxic T-cells, macrophages)
           • Fight against extracellular infections.
           • HIV
             • Loss of CD4+ cells occurs in HIV, preventing immune system from mounting an adequate response
           • MHC II
             • CD4+ cells respond to antigens presented by MHC II cells(see innate immune description)
         • Supressor T-cells / T-reg Cells
           • Downregulate immune response once infection has been contained. Also express CD4 but different than T-helper cells because they also express Foxp3
           • Foxp3
             • Regulator of development/function of T-reg cells
           • Self-reactive lymphocytes
             • Turned OFF by T-reg cells to prevent autoimmune disease
         • Cytotoxic (killer) T-cells / CD8+
           • Respond to MHC I-presented antigens. Kill by injecting toxic chemicals that promote apoptosis. Most effective against viral (intracellular bacterial or fungal) infections.
         • Memory T-cells
           • Same generation as memory B-cells. Generate a more robust response when activated
       • Thymosin
         • Peptide hormone facilitates maturation of T-cells
   • Activation of the Adaptive immune system
     • Bacterial (extracellular pathogen) infection
       • Macrophages
         • Engulf/digest bacteria
         • Macrophages +MHC II + cytokines
           • Present antigens on surface
           • Attract inflammatory cells (neutrophils + additional macrophages)
             • Mast Cells
               • Activated by inflammation & degranulate resulting in histamine release & increased capillary leakiness
               • Immune cells leave bloodstream/travel to affected tissue
                 • Dendritic cells
                   • Leave infected tissue
                   • Present antigen to T-cells
                     • CD4+ T cells
                       • Th1
                         • Release interferon gamma (IFN-y)
                           • Activate macrophages
                       • Th2
                         • Help activate B-cells
                   • Present antigen to B-cells
                     • B-cells produce correct antibody
                     • Antibodies travel to infected tissue
                       • Tag bacteria for destruction
     • Viral (intracellular pathogen) infection
       • Interferons produced within virally infected cell
         • Reduce permeability/transcription rate of nearby cells
           • Decreases ability of virus to infect nearby cells/proliferate
           • Causes systemic symptoms
           • Infected cells & MHC-I display (virally infected) intracellular proteins
             • CD8+ T-cells inject toxin into cell to promote apoptosis
               • Infection shut down before it can spread
               • NK cells activated in absence of MHC-I molecules
                 • Cause apoptosis of cell

2. Lymphatic system

   • Type of circulatory system
   • Lymphatic vessels
     • One-way vessels that become larger as they move towards center of the body
     • Lymph nodes
       • Contain lymphatic channel + artery and vein. Where cells can be exposed to possible pathogens
   • Thoracic duct
     • Joined lymph vessels. Located in posterior chest. Connected to cardiovascular system here
     • Left Subclavian vein
       • Near heart. Fluid delivered here by thoracic duct
   • Function
     • Equalization of fluid distribution
       • Drain tissue of excess fluid distributed by capillaries and return it to the bloodstream. Edema occurs if draining doesn't happen fast enough
     • Immunity
       • Germinal centers
         • Locations within the lymph node where B-cells mature in clusters
     • Transport of biomolecules
       • Fats from digestive system to blood stream.
       • Chyle
         • Milky-white substance of lymphatic fluid carrying packaged fats through small intestine

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