Chapter Pgs Objective: I can describe how adaptive immunity (immunological memory) works. Challenging but cool, like a Rube Goldberg device (complex mechanism)

 Lymphocytes involved (type of leukocyte) 2 types: B cells and T cells  2 sub-types of T cells…(more later)  Cytokines: proteins that activate lymphocytes; secreted by phagocytes  Antigen: any foreign molecule recognized by lymphocytes (protein, polysaccharide, etc.) Some extend from cell surface Others dissolved in extracellular fluid  All have epitopes: portions of antigen that lymphocyte specifically binds to

 All blood cells start in bone marrow (pluripotent stem cells) B cells develop in Bone marrow T cells develop in Thymus  Each individual lymphocyte (B or T cell) has ~100,000 antigen receptors on its cell surface  bind to antigen But, ALL receptors identical!!! (for a given cell)  Thus, have millions of different B/T cells

 B Cell Receptor (BCR) is Y-shaped (2 antigens) Made of 2 heavy chains & 2 light chains  Chains have C (constant) & V (variable)  C region = same amino acids (from cell to cell)  V regions = variable amino acids (from cell to cell) Results in different shapes for different antigens  B cells bind to intact, native antigens  Secrete antibodies (a.k.a immunoglobulins)

 T Cell Receptor (TCR) has 1 binding site Made of 2 chains: α-chain and β-chain  Each chain has C region and V region  Tips of V region create different shapes for cells to bind to different antigens  T cells bind to broken fragments of antigens 1) From Infected Cell 2) From Phagocyte  2 types of T Cells (but first how get V region?)

 V region is due to combination of different genes  leads to diversity of Lymphocytes  Looks like alternative splicing  Splice in 1 V gene (out of 40) 1 J gene (out of 5)  Makes up V region  Done for each chain

 Possible that a combination is picked that selects for molecules found WITHIN the body (“not foreign but native antigens”)  During development, lymphocytes with receptors for the body’s own molecules are removed or rendered nonfunctional This is called self-tolerance  Many autoimmune disorders result form a failure in this system

 B cells Develop in Bone Marrow Binds to intact, native antigens Y-shaped receptors (2 heavy & 2 light chains) = can bind to 2 antigens Secrete Antibodies  T cells Develop in Thymus Binds to fragments of antigens 1 α & 1 β chain = bind to 1 antigen Kills or signals others to kill (2 types)  Similarities between B cell and T cells  Lymphocytes activated by cytokines  Have V regions for many antigens, but each cell binds to one type of antigen

 Major Histocompatibility Complex (MHC) molecule: binds to antigen fragments within a cell (infect/digest)  then, antigen presentation  If cell infected, Class I MHC molecules brings “antigen” to surface for Cytotoxic “killer” T Cells TO KILL whole cell  If phagocyte digests, Class II MHC molecules brings “antigen” to surface for Helper T Cells to signal

 So many different B and T cells (own receptor for different antigen), but how many cells for 1 infection? (need lots!)  When lymphocyte binds to antigen, triggers clonal selection Activated lymphocyte stimulates division  Cloned and differentiates into 2 types 1) Effector cells: short-lived cells that start fighting (how fights depends on…)  If B cell = secrete antibody  If T cell = kill or send signal to kill 2) Memory cells: long-lived cells w/ receptor

 Primary Immune Response: 1 st time exposed Creates Effectors and Memory Cells  Secondary Immune Response Due to memory cells, more effective at responding to antigen the 2 nd time  This is how you “develop an immunity” to a disease (i.e. adaptive or acquired imm.)

 B cells secrete antibodies (proteins called…) Immunoglobulins float around in the fluid Type of Humoral Immunity  Note: effector cells for B cells are specialized to produce MANY proteins  Called Plasma Cells (extensive ER)  T cells directly attack or signal to attack Type of Cell-Mediated Immunity  Note: effector cells for T cells specialized, but 2 types: helper and cytotoxic What do these guys do again? (effector-wise?)

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 Respond to nearly all antigens, especially fragments from phagocytes; thus, use… Class II MHC molecules  Release cytokines to activate B cell (and Cytotoxic T cells / can activate itself, too!) Cell-Mediated So, what do helper T cells actually do? (Effector cells)

 Respond to select antigens that are presented from within an infected cell (cancer, too!); thus, use… Class I MHC molecules  Release proteins (granzymes) to destroy cell Creates pores that causes cells to lyse + signal apoptosis Cell-Mediated So, what do killer T cells actually do? (Effector cells)

 Bind to intact antigens (float or on surface of pathogen)  T-independent antigens  Sometimes, activated by Helper T Cells T-dependent antigens (fragments)  What do B cells ( effector called? ) actually do? Humoral Effector Plasmid Cells: secrete antibodies So, what do antibodies do?

 Viral Neutralization: bind to block virus from infecting cells  Opsonization: enhance ability for macrophages to phagocytize bacteria  Activation of complement system (used in) Forms a Membrane Attack Complex (MAC)  makes a pore  cell lyses Humoral watch?v=hQmaPwP0KRI watch?v=lrYlZJiuf18

 Active Immunization Person’s own lymphocytes (B & T) create a response (antibodies)  Vaccinations (made of dead, dying pathogens or pieces of them - antigens)  Passive Immunization Antibodies given to person for a disease  triggers destruction of pathogens  But will not (by itself) trigger long-lasting immunity  no memory cells made  Active can happen with passive (depends)…