MICR J 210 1st Edition Lecture 9Outline of Last Lecture 1. Overview of Adaptive Immunity2. Elements of Adaptive Immunity3. Lymph Nodes4. Antigen Provoke a Specific Immune Response5. B Lymphocytes6. Classes of Antibodies7. T Lymphocytes8. Types of T Lymphocytes9. Clonal Section Theory10. Diversity of BCR and TCR11. Cytokines12. Preparation for an Adaptive Immune ResponseOutline of Current Lecture 1. MCH Proteins2. Antigen Presenting Cells3. Dendritic Cells4. Cell Mediated Response5. Cytotoxic LymphocytesThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.6. Memory T Cells7. Humoral Immune Response8. T-Dependent9. Plasma Cells10. Production of Humoral Immune ResponsesCurrent LectureMCH ProteinsTwo classes of MHC proteins- MHC class I o Present on the surface of all nucleated cells o Class I are found on every nucleated cell. Every cell with a nucleus is capable ofmaking them…they cells that don’t have them are erythrocytes (bc they lack a nucleus)o Transmembrane proteins- MHC class II o Present on the surface of all professional antigen presenting cellso Class II are only presented by specific types of cells, APC (antigen professional cells) which means that APC carry class I and class IIo Transmembrane proteinsAntigen Presenting Cells- Dendritic cells: Phagocytosis and sentinel/stay where an infection may be near (close to the skin) macro pinocytosis: engulf tissue fluid to check and sample for antigens- Macrophages: phagocytosis and activate active immune system- B cells: not a phagocyte but does present MCH II- APC interact with T cellso Neutrophils are NOT APCsDendritic Cells- Antigen that enters the skin is loaded on dendritic cells, which migrate to draining lymph nodes.- In the lymph nodes, naive T cells are activated by antigen-loaded dendritic cells and start to proliferate and differentiate. - These antigen-responsive cells acquire expression of specific adhesion molecules and chemokine receptors that enable them to migrate into the effector site.o Dendritic cell picks up the antigens and presents in on MCH I and MCH II and travels to the nearest lymph node to show the T cell what has entered the bodywhich then activates a responsePreparation for the Adaptive Immune Response- Antigen Processingo Antigens processed for MHC proteins to display epitopeso Different processes for endogenous and exogenous antigens Exogenous antigens: derived from a non-self organisms (like bacteria)- Every APA has to be folded in a certain way-if misfolded, the are tagged for destruction by ubiquitin - Protease: grinds up the proteins that were not folded correctly and small peptides result- TAP is a transporter associated with antigen processing and allows small peptides to ER- Class I are proteins that present peptides- It is normal for nucleated cells to present MCH I but not if it has been infected with a virus Endogenous antigens: associated with a virus—the self-cell is infected and forced to produce antigens for the virus - Viral protein will be misfolded and processed the same way—and then the MCH I present the viral DNA on the surface- MHC II is also made in the endoplasmic reticulum. They fuse with the phagosome with the lysosome which contain the MHC II- Lysosomal protease chops up the antigen to create smaller antigens- MCH II is a foreign peptide on the surface from an outside sourceCell-Mediated Response• Respond to intracellular pathogens and abnormal body cells• The most common intracellular pathogens are viruses• The response is also effective against cancer cells, intracellular protozoa, and intracellular bacteria• Effector cells are the cytotoxic T cells (CTL) expressing CD8.• CD8 cells respond to intracellular pathogens-bind to Class I ONLY• Normal CD8 cells are naïve when they first come out of the thymus bc they haven’t seen any antigens yet (they haven’t been activated yet)Activation of CD8 Cells- Antigen presenting cells present antigen to naïve cytotoxic lymphocytes by linking the antigen to MHC-I molecule which is recognized by CD8 molecule on the surface of cytotoxic T cells.- The Processo CD8 T cells need a stimulation of sort some to be activated- Dendritic cells present the antigen on MCH class I and class II- T helper cell picks up MCH class II and interleukin 12 is secreted- This cell then differentiates into a Th1 cello Th1 secreted interleukin 2 which binds to a low affinity receptor on the CD8 cell(then becomes a high affinity receptor bc it is now activated)- The CD8 cell also secretes interleukin 2 to stimulate themselves and causes clonal expansion- Clonal expansion occurs with binding to MCH class 1 and the production of interleukin 2 - Only the few cells that originally recognized the MCH class 1 will become activated andproliferate- Interleukin 2 only stimulated the cells that have recognized the MCH I antigen from thedendritic cello Once they are activated, they remain activated as cytotoxic T cellsCytotoxic LymphocytesCytotoxic cells have granules that kill pathogensCTLs kill using 2 primary mechanisms• Perforin-Granzyme Cytotoxic pathway• Perforin (create pores) • CD95 cytotoxic pathway• Granzyme (apoptosis pathway)Alpha and beta interferons slow down viral proliferations• NK cells kills as much as it can• Cytotoxic T cells then come along and finish the job• CD8 cells are important for viral infectionsMemory Cells• Some activated T cells become memory T cells• Persist for months or years in lymphoid tissues• Immediately functional upon subsequent contacts with epitope specific to its TCR• IN viral infections 2 types of T cells are being used• Memory t cells and mature Tc cells (cytotoxic)• CD4 are helper T cells• CD8 are cytotoxic T cellsHumoral Immune ResponseAdaptive responses mounted against exogenous pathogensProvides the soluble component of adaptive immunity (humors)• Is by activation of B cells which release immunoglobulins (Ab.)• T-independent activation of B cells• Does not require T cell help• T-dependent activation of B cells• Requires signals provided by TH2 cells• Activation of B cells to make antibodies (mostly against exogenous proteins)• B cells don’t require MCH in order to become activated • TCR have to be bound to MCH with a peptide that has been processed but BCR can recognize any shape—doesn’t have to be a peptide—could be a