Adaptive Immunity Introduction PDF

Adaptive Immune Response (Acquired Immunity) PAMPs vs Antigens Innate vs Adaptive  The other Immunity Adaptive or specific immunity – Removes specific pathogens – Remembers pathogens in case… Division of labor – Humeral immunity – extracellular – Cellular immunity – intr...

Adaptive Immune Response (Acquired Immunity) PAMPs vs Antigens Innate vs Adaptive  The other Immunity Adaptive or specific immunity – Removes specific pathogens – Remembers pathogens in case… Division of labor – Humeral immunity – extracellular – Cellular immunity – intracellular Innate immunity: Defenses against any pathogen- PAMP recognition Adaptive immunity: Induced resistance to specific small shapes that make up a pathogen http://textbookofbacteriology.net/cellsindefenses75.jpg  Phagocytic cells Non-specific – recognize PAMPs – multiple (Toll and Nod) – Some are Antigen Presenting cells Dendritic Cells and Macrophages Each cell – many receptors – any pathogen Specific – only one shape – T-cells – T cell receptor Only recognizes single antigen – B-Cells – Immunoglobulin receptor Only recognizes single antigen  Dual Nature of Adaptive Immunity T and B cells develop from stem cells in red bone marrow Humoral immunity – B cells mature in the bone marrow (Chickens: Bursa of Fabricius ) – Effect Due to antibodies Cellular immunity – T cells mature in the thymus – Effect Due to T cells Where have we been, Where are we going?  Adaptive Response Stimulated by Antigens T-independent – Strong signal – Triggers B or T cells to proliferate and differentiate – Attack Pathogen T-Dependent – Weaker signal – Needs confirmation from Helper T-Cell – Helper T cell stimulates Proliferation and differentiation  Antigens Antigen = antibody generators Shape = conformations Antigens are mostly proteins, (few carbohydrates) – Small pieces, 5-9 amino acids – Secondary structures (especially for carbohydrates) Self Antigens – normal produced by body Non-self Antigens = foreign or exogenous  Antigen Presentation General Characteristics – During antigen presentation, antigen cradled in grove of major histocompatability complex molecule (MHC molecule) Two types MHC – MHC class I » Bind endogenous antigen – MHC class II  Quality Control Factory – random samples – Run tests – Advertise Cell – random samples – Process –proteasome – Advertise – Major Histocompatibility Complex Immune system is big brother – Makes sure your cells are behaving From: "Making sense of mass destruction: quantitating MHC class I antigen presentation", Jonathan W. Yewdell, Eric Reits & Jacques Neefjes, Nature Reviews Immunology 3, 952-961 (December 2003) doi:10.1038/nri1250 Courtesy Eric Rei  In General Antigen = “antibody generator” All cellular proteins and some carbohydrates can potentially act as antigens Shape or conformation of protein that can bind to cell surface receptor of immune cells – Usually only few amino acids in length – Shape is it! – Each protein can have multiple shapes  More on Antigens Self Antigens – Own proteins made by normal cellular metabolism – Sampled during processing by Golgi Apparatus – Presented on Cell Surface to Identify self from “non-self” (MHC I) External Antigen – (Foreign) Proteins and other “antigenic” molecules – Processed by phagocytic cells and presented on specialized receptors to activate Adaptive immunity (MHC II)  Stop and Catch up What is an antigen? How is this different than a PAMP? What is a self antigen? What is an exogenous antigen? Compare roles of MHCI to MHCII – What types of cells – What types of antigens  More in General Antigen Presenting Cells digest pathogens – Hydrolyze Their proteins into small pieces – The shapes (based on 2o structure) act as distinct patterns (Like keys) – “key holder” is MHCII Patterns Match receptors (like locks) – CD4 (Helper T-Cells) – CD8 (Cytotoxic T-Cells) Immune cells “preadapted” recognize antigens (Bergstrom and Antia 2006).  Non-specific Phagocytosis Antigen Processing and presentation Activation of Activation cytotoxic T of Helper T cell cell Cellular Immunity Humoral Immunity Activation Intercellul Intracellular of ar Pathogens B-cells Pathogens  Overview of Immune respon ses Pathogen associated Molecular patterns Pattern Recognition molecules B cells bind soluble antigen With B cell receptor then Display antigen on MHCII For Th cell  Catch up Outline or explain the T-dependent Humoral response Which B cells are selected? What gives them the go ahead to clone and differentiate? What do they differentiate into? Humoral Response = B cells Chapter 21, Immune System 21 Figure 21.9  T Lymphocytes Cellular Immune Response General characteristics – Two major function T cell populations Cytotoxic T cells – Proliferate and differentiate to destroy infected or cancerous “self” cells – Have CD8 receptor – Recognize MHC class I Helper T cells – Multiply and develop into cells that activate B cells and macrophages – Stimulate other T cells; orchestrate immune response – Have CD4 marker – Recognize antigen display by MHC class II  T Lymphocytes Antigen Recognition and Response Functions of TH (CD4) cells – Orchestrate immune response Recognize antigen presented by MHC class II molecules – MHC class II molecules found only on APC If TH cell recognizes antigen, cytokines are delivered – Cytokines activate APC to destroy antigen  T Lymphocytes Antigen Recognition and Response  T Lymphocytes Antigen Recognition and Response Role of TH cells in B cell activation – If TH cell encounters B cell bearing peptide: MHC calls II complex TH cell responds by producing cytokines – B cell is activated in response to cytokine stimulation B cell proliferates and undergoes class switching Also drives formation of B memory cells Lymphocyte Development  T Lymphocytes Antigen Recognition and Response Functions of Tc (CD8) cells – Induce apoptosis in “self” cells Cells infected with virus or intracellular microbe Destroys cancerous “self” cells – Nucleated cells degrade portion of proteins Load peptides into groove of MHC class I molecule MHC class I molecule recognized by circulating Tc cell – Cell destroyed by lethal effector function of Tc cell Tc cells releases pre-formed cytokines to  Natural Killer Cells Natural killer cells descend from lymphoid stem cells – They lack antigen specificity No antigen receptors Recognize antigens by means of Fc portion of IgG antibodies – Allow NK cells to attach to antibody coated cells Actions augment adaptive immune response – Important in process of antibody dependent cellular toxicity Enable killing of host cells with foreign protein in membrane Natural killer cells recognize destroyed host cells with no MHC class I surface  Fill in the Summary Table Cell Type MHC Receptor MHC Receptor Outcome of activation Presented? Recognized? Dendritic Cells Helper T-Cells (CD4) Cytotoxic T-Cells (CD8) Natural Killer Cells  What do you Remember? What is the difference between: – Humeral Immunity Humeral response video – Cellular Immunity – http://www.dnatube.com/video/194/Specif ic-Adaptive-immunity-humoral-and-cell-m ediated – More Videos Humoral Response Cellular Response  Next Time – Microbes and Disease