Exam 3: Topic 17 Flashcards
Know the purpose of two key molecules in the adaptive immune response: antibodies and MHC.
• Antibodies:
○ recognizing and binding to foreign invaders (antigens) like viruses and bacteria, marking them for destruction by other immune cells, providing targeted protection against specific pathogens and enabling the body to remember past infections for future defense.
• MHC:
○ MHC I: all nucleated cells have ability to make MHC I
○ MHC II: “trophy case” for antigens
§ Macrophages: presents multiple different antigens that are remnants of phagocytotic conquests.
Distinguish between antibodies and antigens. Be able to draw a “stick figure” of an antibody and label the region that has a variable shape.
• Antibody/Immunoglobulin (IgA, IgG, IgM, IgD, IgE, etc)
○ Antibodies are made by you and bind to antigens.
• Antigen: “foreign” molecule; molecule that elicits an immune response.
○ Large molecule (~10k mW)
§ Typically a protein or carbohydrate or some combo.
§ extracellular fluid
Which type of lymphocyte makes antibodies?
B cells:
○ When activated by an antigen, they differentiate into plasma cells which then secrete antibodies specifically designed to target that antigen
Can each B cell make many different forms of antibodies, or only one form of an antibody? Moreover, are there B cells in our bodies that make antibodies that match ‘unseen’ antigens?
• Each individual B cell can only produce one specific type of antibody, meaning it cannot make many different forms of antibodies; each B cell is programmed to generate a unique antibody with a specific antigen-binding site, ensuring targeted immune response against a single antigen.
• When a B cell encounters its specific antigen, it becomes activated and differentiates into a plasma cell, which then mass-produces the same type of antibody
• The immune system generates a vast array of B cells, each with a different antibody specificity, allowing the body to recognize a wide range of antigens.
What is a naive B cell?
• Naive B cell is a B cell that has not yet encountered an antigen. B cells are bone marrow-derived cells that express a B cell antigen receptor (BCR) that allows them to bind to specific antigens
What is MHC stand for? Which cell types can make MHC I and which can make MHC II?
• MHC = Major Histocompatability Complex
• MHC I: all nucleated cells have ability to make MHC I
• MHC II: “trophy case” for antigens.
○ Macrophages: presents multiple different antigens that are remnants of phagocytotic conquests.
What is MHC stand for? Which cell types can make MHC I and which can make MHC II?
• MHC = Major Histocompatability Complex
• MHC I: all nucleated cells have ability to make MHC I
• MHC II: “trophy case” for antigens.
○ Macrophages: presents multiple different antigens that are remnants of phagocytotic conquests.
What two WBC classes can present antigens in MHC II? How do these two classes differ in the number of different antigen types they can present?
• Dendritic cell: presents multiple different antigens that are remnants of phagocytotic conquests.
• B cell: Interaction between the BCRs on a naïve matureB cell and a free protein antigen stimulate internalization of the antigen, whereas interaction with antigensassociated with an intact pathogen initiates the extraction of the antigen from the pathogen before internalization.Once internalized inside the B cell, the protein antigen is processed and presented with MHC II.
Understand which leukocytes carry antibodies (will bind FREE antigen) and which carry receptors (NOT antibodies) for antigens presented in MHC.
• B cells carry antibodies
• T cells carry receptors for antigens presented in MHC
BIG OBJECTIVE: Give a detailed account of the humoral immune response. Be sure to address the roles of the macrophage, helper T cells, and B cells.
• Helper T cells can only be activated by APCs presenting processed foreign epitopes in association with MHC II. The first step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC IIantigen-binding cleft. The second step involves the interaction of CD4 on the helper T cell with a region of the MHCII molecule separate from the antigen-binding cleft. This second interaction anchors the MHC II-TCR complex andensures that the helper T cell is recognizing both the foreign (“nonself”) epitope and “self” antigen of the APC; bothrecognitions are required for activation of the cell. In the third step, the APC and T cell secrete cytokines thatactivate the helper T cell. The activated helper T cell then proliferates, dividing by mitosis to produce clonal naïvehelper T cells that differentiate into subtypes with different functions
Understand the elegance of clonal selection, and why activated B cells differentiate into mostly plasma cells but also retain some as memory cells.
• Clonal selection: selecting the right B cell for the job:
○ the process where a specific B cell, with a unique antigen receptor that matches a particular antigen, is activated and rapidly multiplies to produce a large number of identical “clones” of itself, all capable of producing antibodies against that specific antigen, effectively tailoring the immune response to the invading pathogen;
○ B cells differentiate primarily into plasma cells because their main function upon encountering a specific antigen is to rapidly produce large quantities of antibodies with the exact specificity to that antigen
○ A subset of activated B cells differentiate into memory B cells, which persist after the infection has cleared and allow for a faster and stronger response upon re-exposure to the same antigen.
Explain two mechanisms by which antibodies coating infectious bacteria can help decrease infectious agents.
• Neutralization: Antibodies can also neutralize bacteria by binding to specific sites on the bacterial surface, preventing them from attaching to host cells and causing infection.
• Complement activation: Antibody binding can trigger the complement cascade, a system of proteins that further damages the bacterial cell membrane and enhances phagocytosis.
• Fc receptor activation: Phagocytes have receptors that specifically bind to the “Fc” region of antibodies, allowing them to readily identify and engulf antibody-coated bacteria.
In 3 to 4 sentences, explain why humoral immunity alone is not enough to combat viral infections. At which stage (if any) in the viral life cycle is humoral immunity effective?
• Humoral immunity plays a critical role in clearing viruses from the body. When a virus enters the body, B lymphocytes respond by producing antibodies that bind to and neutralize the virus.
• This is not enough for cells that are already infected by viruses, because this type of infection is invasive and enters the cells of the body.
• Cell mediated immunity would then be required to neutralize the virus. The virus enters the cell and protein antigens specific to the pathogen are processed in the proteasomes and bind with MHC I molecules for presentation on the cell surface. This presentationof pathogen-specific antigens with MHC I signals that the infected cell must be targeted for destruction along with the pathogen.
Upon antigen binding, identify which three lymphocytes proliferate to make many copies (clones).
• B cells
○ Once a B cell is activated, it undergoes clonal proliferation and daughter cells differentiate into plasma cells. Plasmacells are antibody factories that secrete large quantities of antibodies.
• Helper T cells
○ Thefirst step in the activation process is TCR recognition of the specific foreign epitope presented within the MHC IIantigen-binding cleft. The second step involves the interaction of CD4 on the helper T cell with a region of the MHCII molecule separate from the antigen-binding cleft. This second interaction anchors the MHC II-TCR complex andensures that the helper T cell is recognizing both the foreign (“nonself”) epitope and “self” antigen of the APC; bothrecognitions are required for activation of the cell. In the third step, the APC and T cell secrete cytokines thatactivate the helper T cell. The activated helper T cell then proliferates, dividing by mitosis to produce clonal naïvehelper T cells that differentiate into subtypes with different functions
• Cytotixic T cells
○ The key difference is that the activation of cytotoxic T cells involves recognition of anantigen presented with MHC I (as opposed to MHC II) and interaction of CD8 (as opposed to CD4) with the receptorcomplex.
○ After the successful co-recognition of foreign epitope and self-antigen, the production of cytokines by theAPC and the cytotoxic T cell activate clonal proliferation and differentiation.
Describe the mechanism by which cytotoxic T cells kill viral-infected cells. What is the role of MHC I and perforin?
• The key difference is that the activation of cytotoxic T cells involves recognition of anantigen presented with MHC I (as opposed to MHC II) and interaction of CD8 (as opposed to CD4) with the receptorcomplex. After the successful co-recognition of foreign epitope and self-antigen, the production of cytokines by theAPC and the cytotoxic T cell activate clonal proliferation and differentiation. Activated cytotoxic T cells candifferentiate into effector cytotoxic T cells that target pathogens for destruction or memory cells that are ready torespond to subsequent exposures.
• cytotoxic T cells recognize infected cells through antigenpresentation of pathogen-specific epitopes associated with MHC I
• Once an infected cell is recognized, the TCR ofthe cytotoxic T cell binds to the epitope and releases perforin and granzymes that destroy the infected cell.
• Perforin is a protein that creates pores in the target cell, and granzymes are proteases that enter the poresand induce apoptosis. This mechanism of programmed cell death is a controlled and efficient means of destroyingand removing infected cells without releasing the pathogens inside to infect neighboring cells, as might occur if theinfected cells were simply lysed.
• Perforin creates pores to allow granzynes to enter the infected cell.
