Adaptive Immune Response (Lec. 20 and 21) Flashcards
Define antigen
Any substance that, if presented in the right context, may trigger an immune response
Define epitope
Part of an antigen that interacts with the antibody or T cell receptor
Rank immunogenicity of different molecules
Protein > polysaccharides > lipids > small molecules (haptens)
Define MHC and HLA
Major Histocompatability Complex (MHC) molecules are “self” proteins unique to each person (close relatives have similar MHC molecules); also called HLA (human leukocyte antigen) molecules, where HLA is human-specific but MHC molecules can be found in many species
Describe immune specificity
Specificity: lymphocytes have surface receptor proteins (T cells have T cell receptors or TCRs and B cells have B cell receptors or BCRs) that interact with specific foreign epitopes. Each lymphocyte has a unique surface receptor. The immune system can produce almost limitless diversity in BCR and TCR due to somatic recombination, random reassortment of chains, imprecise V-D-J or V-J joining, and hypermutation (BCR only). Drawback: potential to create TCR and BCR that bind to self antigens (solution: tolerance!).
Describe immune memory
The ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously
Describe immune tolerance
Discrimination between self antigens and foreign antigens; lack of self tolerance is called autoimmunity. Precursor T cells travel to the thymus, where the ones that bind to self-antigens undergo apoptosis. Self-reactive B cells undergo apoptosis in the bone marrow.
Compare and contrast MHCI and MHCII relative to expression patterns
MHCI are expressed on ALL nucleated human cells (not erythrocytes!); bind to and display antigens that originate in the cytoplasm. MHCII is only expressed by macrophages, dendritic cells, and B cells (known as antigen-presenting cells or APCs); bind to and originate antigens that originate outside the cell and are a critical link between innate and adaptive immune responses.
Describe the sequence of events for processing and presenting intracellular antigens
The proteasome in the cell degrades the antigen into peptides, which are then transported into the ER by the transporter associated with antigen processing (TAP complex). In the ER, newly synthesized MHCI molecules are assembled with the transported peptides, and they are then transported through the Golgi to the cell membrane, where the MHCI molecule presents the processed antigen peptide to cytotoxic T cells, which can recognize the complex and initiate an immune response.
Describe the sequence of events for processing and presenting extracellular antigens
The extracellular antigen is taken up by the cell through mechanisms like phagocytosis, pinocytosis, or receptor-mediated endocytosis, and degraded into peptides by proteolytic enzymes in an endosome. Meanwhile, MHCII molecules are assembled in the ER and then transported to the endosome. The processed antigenic peptides bind to the MHCII, and then it’s transported to the cell membrane via the Golgi. It’s expressed on the surface of the cell, where it is recognized by CD4+ T cells (aka helper T cells), which stimulate other immune cells.
Describe immunological memory in the context of primary and secondary immune response
When the body first encounters an antigen, there is a slower primary immune response, which involves activation of naive immune cells, clonal expansion, and production of antibodies against the pathogen. During this primary response, a subset of the activated immune cells differentiate into long-lived “memory cells” that retain the ability to recognize the specific antigen. If the body is exposed to the same antigen again, the memory cells are rapidly activated, leading to a much faster and stronger immune response.
Describe T cytotoxic cells relative to activation, differentiation, and elimination of antigens
A naive cytotoxic T cell (aka killer T cell or CD8+ cell) recognizes a specific antigen presented on an MHCI molecule on the surface of an antigen-presenting cell (APC). This triggers a signaling cascade within the T cell, leading to activation and clonal expansion. The proliferating cells differentiate into effector cytotoxic T cells, which are fully capable of killing target cells. Upon contact with the target cell, they release granules that contain perforin (creates pores in the target cell membrane) and granzyme (enters the cell and induces apoptosis).
Differentiate between effector lymphocytes and memory lymphocytes
Effector lymphocytes directly attack pathogens during an active infection. Effector B cells (plasma cells) produce antibodies against specific antigens during an infection. Effector T cells (cytotoxic T cells) directly kill infected cells).
Memory lymphocytes remain dormant until they encounter the same pathogen again. Memory B cells store information about past infections and can quickly produce antibodies if the same pathogen is encountered again. Memory T cells remain in the body after an infection and can rapidly proliferate and differentiate into effector T cells upon re-exposure to the same antigen.
Describe the role of antigen-presenting cells in humoral immunity and list the three APCs.
APCs capture, process, and present antigens to B cells (often helped by helper T cells), which then differentiate into plasma cells to produce specific antibodies against the presented antigen.
Dendritic cells: capture and present protein antigens to naive T-lymphocytes.
Macrophages: engulf and process antigens and present fragments on their surface for T cells to recognize.
B cells: use the B cell receptor for antigen uptake.
Compare and contrast TCR and BCR relative to # of peptide chains, # of epitope binding sites, and interaction with MHC molecules.
TCR: two polypeptide chains (alpha and beta); a single binding site. Bind to antigens and cause T cells to attack the target cells.
BCR: four polypeptide chains, two binding sites. Bind to antigens and activate B cells (triggers the secretion of antibodies).
Describe three ways antibodies help eliminate specific pathogens
Neutralization: antibodies bind to pathogens, preventing them from entering or damaging cells.
Opsonization: antibodies coat the surface of foreign particles, which stimulates removal of them by macrophages and other cells.
Antibodies activate the complement system, which can directly destroy pathogens or enhance phagocytosis.
Differentiate T helper cells from T cytotoxic cells: include details on co-receptors, activation, function, and elimination of antigens.
T helper cells secrete cytokines, which (once activated) enhance the activity of cytotoxic T cells, and are often the activation signal for B cells. They have a T cell receptor which has specificity for a specific MHCII-epitope complex and are also called CD4.
T cytotoxic cells recognize foreign peptides on the surface of cells, and then release perforin (which creates holes in the target cell membrane) and granzyme (which induces apoptosis). They are able to kill infected cells while leaving healthy cells unharmed. The co-receptor for cytotoxic T cells is CD8, which binds to MHC I molecules.
Describe how the T helper cells and B cells are activated and how that leads to destruction of extracellular pathogens.
T helper cells are activated by MHCII molecules on the surface of APCs, and the T helper cells will proliferate and differentiate into effector T helper cells, which then interact with B cells that have already bound the same antigen via their BCRs. This leads to B cell activation, proliferation, and differentiation into plasma cells, which secrete antibodies specific to the pathogen, ultimately marking the extracellular pathogen for destruction by immune cells.
Compare and contrast cell-mediated and humoral immunity.
Humoral immunity produces antigen-specific antibodies and is primarily driven by B cells. Cell-mediated immunity does not depend on antibodies and is primarily driven by mature T cells, macrophages, and cytokines.
Describe the specific characteristics of IgA, IgM, IgD, and IgE.
IgM: found in serum, first Ig produced in infection.
IgA: found at mucosal surfaces; in saliva, tears, breast milk, colostrum, and mucosal secretions.
IgE: found in serum, binds to eosinophils, mediates allergies and responds to parasites
IgD: present in serum and has no known function
Define isotype switching
Isotype switching (aka immunoglobulin class switching) occurs when a B cell is activated by an antigen and changes the type of immunoglobulin that B cell produces (involves a DNA rearrangement). This improves the cell’s ability to eliminate the pathogen.
