Unit 3 Study Guide: Chapter 12
Discuss how T helper and T cytotoxic cells eliminate antigens and summarize memory T cell roles
Effector T cells eliminate antigens. When interferons recruit activated T cytotoxic cells to the area, MHC I production is simultaneously enhanced inside host cells and the immune system is put on high alert. When the receptor of a patrolling TC cell binds to an MHC-I antigen complex, it releases perforins, which form pores in the target cell, and granzymes, which enter through the pore, break down host cell proteins, and induce apoptosis. Cytokines released by TC cells also attract NK cells and macrophages, which clear the dead cells. TH cells do not directly attack invaders, cancer cells, or infected host cells; they support the action of cells that actually do the work, like T cells (TH1), B cells (TH2), and innate immunity leukocytes such as macrophages and natural killer cells. Memory T cells remain in lymphatic tissues as threat subsides, remaining ready to rapidly proliferate and differentiate upon a subsequent exposure.
Discuss the structural and functional features of each of the five antibody classes.
IgG: made later in infection, constitutes 85% of antibody in human blood; found in all bodily fluids; half-life of about 21 days in circulation; detecting IgG to a particular antigen indicates the patient has been exposed to that antigen; monomer; crosses placenta, activates complement, neturalizes antigens and promotes their phagocytosis, is a powerful opsonin; major antibody secreted during secondary response IgA: Secretory/found in secretions (e.g. tears, saliva, sweat, and milk); accounts for up to 15% of total antibodies, half life of about 6 days, prevalent in mucous and MALT (e.g., mucous membranes of gut, respiratory tract, and urogenital tract), exists as monomer (rarely) or dimer; has neutralizing and opsonization capabilities; second most abundant in body IgM: mainly in blood, accounts for up to 10% of total antibodies (third most abundant in body); half life of about 10 days; made early in infection upon primary antigen exposure; exists as either a monomer or pentamer; functions in agglutination, precipitation, and complement activation (not a strong opsonin) IgE: present in very low concentrations; found mostly in lungs, skin, and mucous membranes; half life of two days; monomer; functions to fight parasites and mediate allergic responses; causes mast cells and basophils to release allergy mediators (e.g., histamine, leukotriene) IgD: sparsely represented antibody; mainly found on surface of B cells; monomer; precise function remains unknown; serves as antigen receptor
Describe immunological memory and compare it to a primary response.
Immunological memory is provided by memory cells residing in lymphoid tissues. Memory cells allow for a rapid reactivation of cellular and humoral adaptive responses if the same antigen is encountered again later. Secondary immune response requires the coordinated activity of memory B and T cells. Primary exposure to an antigen generates IgM isotype antibodies first, then IgG; in secondary response to the same antigen, activated memory cells quickly generate a high titer of high affinity IgG antibodies and only a small amount of IgM antibodies. In secondary exposure, the surge in antibodies is faster and greater than in primary exposure.
Describe how the two types of MHCs present antigens, and summarize how MHCs impact transplant rejection.
MHC I is found on the surface of all body cells except red blood cells; acts like body's uniform; presents intracellular antigens to T cytotoxic cells; eliminated by killing host cell. MHC I presents antigens when viral proteins inside an infected cell are chopped up by a proteasome, the snippets are shipped to the cell's endoplasmic reticulum, where MHC I molecules bind to proteins to make MHC I-antigen complexes, and then the complex migrates to the cell surface, displaying the antigen. MHC I may bind to self-proteins and display them on the cell surface, where it is up to patrolling TC cells to decide if protein displaying is normal self-protein or not. Only T cytotoxic cells that have been trained by APCs to recognize the given antigen can effectively patrol the body an eliminate cells displaying suspicious antigens. MHC I interacts with CD8 on TC cells. MHC II is only made by antigen-presenting cells like macrophage, B-cells, and dendritic cells; presents extracellular antigens to T helper cells; can be directly attacked without need to kill host cells. APC's phagocytize dead self-cells and potential invaders, break down the ingested antigen, snippets associate with MHC II proteins to form MHC II-antigen complexes, and the migrate to the cell surface to display antigen. MHC II interacts with CD4 on T helper cells. MHCs—major histocompatibility complex proteins—are specialized "self-proteins" also known as human leukocyte antigens (HLAs). T cells must recognize "self" MHC so self-tissues are not attacked. If MHCs are not closely matched between a tissue donor and recipient, the recipient's immune system will recognize the transplanted tissue as foreign (allorecognition is the process that lymphocytes use to differentiate self from foreign MHCs).
Explain the two-signal mechanism of T cell activation and discuss the factors that affect subclass differentiation.
Primary activation signal: T cell receptor interacts with MHC-antigen complex Secondary activation signal: involves costimulatory proteins on the surface of the antigen-presenting cell binding to costimulatory proteins on the T cell's surface (B7 protein on APC's surface binds with CD28 on surface of T cells). When signal two is received, a signaling cascade is sparked. There are diverse co-stimulatory proteins and therefore diverse signaling cascades; the type of cascade triggered determines what class of interleukins and other factors the T cell will makes. This defines the specialized subclass of T cell.
Summarize how superantigens activate T helper cells.
Super antigens are especially potent T helper cell activators, they may be bacterial toxins (e.g., streptococcal exotoxin, staphylococcal toxic shock toxin). Superantigens are not processed and presented to TH cells, they directly crosslink MHC II and the TH cell receptor to cause a bulk, nonspecific activation. A large number of T cells are activated which releases dangerous levels of cytokines; can lead to shock and even death.
Define self-tolerance and describe how and why immature T and B cells are screened for this feature.
T and B cells recognize a wide variety of antigens due to gene shuffling mechanisms, or more correctly, alternate splicing of genes as mRNA is processed. Random processes may give rise to receptors that could bind to normal body tissues; if allowed to mature, these lymphocytes would attack self-tissues. To prevent that, the body has screening mechanisms that select for immune cells with self-tolerance. Lymphocytes that would damage health self-tissues undergo apoptosis. If T cells cannot recognize MHCs or are potentially self-reactive, they undergo apoptosis and do not mature; if B cells can make antibodies to self-antigens, the undergo apoptosis and do not mature.
Explain the role of T and B cell receptors in antigen recognition and state how receptor diversity comes about.
T cell receptors (TCRs) and B cell receptors (BCRs) are antigen recognition receptor. TCRs have one antigen binding site; BCR have two antigen binding sites. Each B and T cell has thousands of receptors on their surface that all recognize the same epitope; although a given T or B cell can only recognize one type of epitope, the immune system can still recognize a virtually limitless repertoire of antigens. Antigen recognition capacity is essentially unlimited because the body makes a vast number of T and B cells. Diversity is generated through a process called DNA arrangement/gene shuffling mechanisms, or more correctly, alternate splicing of genes as mRNA is processed. An immunoglobulin protein is encoded by different segments of DNA: variable (V), diversity (D), and joining (J) segments; which V, which D, and which J are chosen by any cell appears to be completely random, allowing human B cells to generate antibodies with over ten billion different antigen-binding sites. The genes coding for the variable regions of antibody molecules have multiple different sections along their lengths. As a result of alternative splicing, very different RNA transcripts are created from the same original gene. When those transcripts are translated, the resulting protein will have extremely variable amino acid sequences and, therefore, extremely variable shapes.
Compare and contrast T and B cells.
T-cells: -lymphocytes that are initially produced in bone marrow and mature in thymus -mature T cells are present at relatively low levels in circulation; reside in lymphatic tissues -each individual cell has thousands of receptors that can only recognize one epitope -part of cellular immune response, help coordinate humoral response -require antigen presenting cells (APCs) to show antigen -recognize antigens due to gene shuffling mechanisms that randomly give rise to receptors -undergo screening to select for immune cells with self-tolerance (inability to recognize MHCs and potential self-reaction leads to apoptosis) -chemical signals cause clonal expansion and differentiation into effector and memory cells; T cells can become T cytotoxic cells or T helper cells -have single-pronged T-cell receptors (TCRs) -have MHC I proteins present on cell surface -not considered antigen presenting cells B-cells: -lymphocytes that are produced and mature in bone marrow -mature B cells are present at relatively low levels in circulation; reside in lymphatic tissues -each individual cell has thousands of receptors that can only recognize on epitope; antibodies released can only recognize one epitope -part of humoral immune response only -B cells do not require APCs to show them antigens; instead they can directly interact with an antigen -recognize antigens due to gene shuffling mechanisms that randomly give rise to receptors -undergo screening to select for immune cells with self-tolerance (ability to make antibodies against self-antigens leads to apoptosis) -chemical signals cause clonal expansion and differentiation into effector and memory cells; effector B cells are called plasma cells and they make antibodies—secreted form of B cell receptor that binds to antigen that stimulated the activation event -have MHC I and II proteins present on cell surface -considered antigen-presenting cells
Explain how T-dependent and T-independent antigens activate B cells.
T-dependent antigens require T helper cells (especially TH2 cells) for full activation. An extracellular antigen binds to a B cell receptor, the antigen enters the cell by endocytosis and the epitopes are displayed on the cell surface by MHC-II. The MHC II-antigen complex on the B cell surface is bound by a T helper cell that can recognize the presented epitope, and cytokines are released upon proper TH cell binding. Costimulatory proteins interact as a secondary activation signal. T-independent antigens bind to B cells and instigate a direct activation cascade. Repetitive antigens may act as T-independent antigens, for example, bacterial capsule polysaccharides. In T-independent activation, multiple B cell receptors on the given B cell directly bind to the antigen, causing proliferation and differentiation to make plasma cells. T-independent activation has a limited capacity for memory and does not tend to confer the same long-term protection as T-dependent antigens. Once fully activated, B cells undergo proliferation and eventually differentiate into effector cells and memory cells. All of the resulting B cell clones recognize the exact same epitope of the antigen; clones become effector cells called plasma cells and a small number become memory B cells that will reside in lymphatic tissues.
Describe the cellular branch of adaptive immunity and name its key effector cells.
The cellular branch of adaptive immunity is mediated by T cells, including T helper cells and T cytotoxic cells. T cells are first produced in the bone marrow and mature in the thymus. T helper cells (TH cells) contain CD4 proteins, interact with MHC II, and does not directly seek and destroy invaders. T helper cells can be TH1 cells which activate T cytotoxic cells, macrophages, and natural killer cells to destroy pathogens, TH2 cells which stimulate B cells to make antibodies, or T regulatory cells which control functions of other white blood cells. T cytotoxic cells (TC cells) contain CD8 proteins, interact with MHC I, and directly destroy infected and cancerous cells.
Compare and contrast T helper versus T cytotoxic cells and discuss the various T helper cell subclasses.
We can tell T cell lineages apart by presence of cluster of differentiation (CD) proteins. T cytotoxic cells (Tc cells) directly destroy infected or cancerous cells and transplant tissues. TC cells are only in cell-mediated immunity. TC cells have CD8 proteins. TC cells interact with MHC I presenting intracellular antigens. Only TC cells that have been trained by APCs to recognize the given antigen can effectively patrol the body and eliminate cells displaying suspicious antigens. To train TC cells, APCs obtain viral antigen samples by being infected with the virus or by phagocytizing an infected host cell; if the APC is directly infected, it loads viral peptides with MHC I and displays them on the cell surface; if the infected host cell is phagocytized, viral antigens complex with MHC I for presentation to TC cells. T helper cells (TH cells) do not directly seek and destroy invaders; TH cells coordinate an adaptive immune response by stimulating other white blood cells (e.g., B cells, macrophages, and T cytotoxic cells). TH cells are the most abundant cells and they have CD4 proteins; they are the main organizers of both the cellular and humoral branches of adaptive immunity by releasing cytokines that can stimulate or suppress other white blood cells. TH1 cells promote T cytotoxic cells, macrophages, and natural killer cells to destroy intracellular pathogens; TH2 cells stimulate B cells to make antibodies; T regulatory cells decrease immune responses when threats pass by controlling functions of other white blood cells (e.g., dendritic cells, mast cells, and B and T cells). TH cells interact with MHC II presenting extracellular antigens.
Explain what isotype switching is and state why it's advantageous.
A given B cell can't change what epitope it recognizes, it can undergo isotype switching, a mechanism that changes B cell's production of antibody from one class to another (for example, from isotype IgM to isotype IgG. Naïve mature B cells produce both IgM and IgD. Different isotypes have different specializations and also predominate in different areas of the body. The specializations are described in the next question, "Discuss the structural and functional features of each of the five antibody classes."
Name the branches of adaptive immunity and compare adaptive to innate immunity.
Adaptive immunity includes cellular (T-cell-mediated immunity) and humoral (B-cell antibody-mediated with some T-cell-mediation) responses. The goal of both branches is the same: eliminate an antigen and remember it so that next time adaptive responses are faster. Cellular and humoral responses both progress through four main stages: antigen presentation, lymphocyte activation, lymphocyte proliferation and differentiation, and antigen elimination and memory. Adaptive immunity differs from innate responses because they take longer to mount (few days to more than a week between detection and response in primary exposure), are specific to a particular antigen, and exhibit memory (secondary exposure to same antigen is rapid and effective, frequently will not experience disease symptoms while bodies eliminate pathogen). Adaptive responses go into action when innate first- and second-line defenses fail to contain a threat.
Name and describe the four categories of adaptive immunity and state which confer long-term protection and why.
Adaptive immunity is natural or artificial and active or passive. Naturally acquired active immunity: contracting an infection that triggers the patient's immune system leads to memory cells and antibodies; it can be developed from either symptomatic or asymptomatic infections; confers long-term protection because of the production of memory cells. Artificially acquired active immunity: vaccines to trigger an immune response; confers long-term protection because of formation of memory cells and antibodies Naturally acquired passive immunity: patient receives antibodies to an antigen through nonmedical means (for example, maternal antibodies); temporary protection that does not confer long-term protection because memory cells or antibodies are not made. Artificially acquired passive immunity: patient receives protective antibodies from a medical treatment, source is often a horse, rabbit, or goat; antiserum is a preparation of antibodies developed to neutralize specific toxins or venoms; the post exposure rabies antiserum and snake antivenom are two examples of antiserums that yield passive immunity; they offer temporary protection and do not confer long-term protection because no memory cells are made; the patient may have an immune response (serum sickness).
Describe the basic structural and functional features of antibodies.
Antibodies, also known as immunoglobulins (Ig) are secreted by plasma cells. Antibodies bind to the antigen that triggered the B cell's activations; they can activate complement cascades, neutralize antigens, and promote phagocytosis of targeted antigens. Structural features: an antibody's single-unit, monomeric structure consists of 2 heavy chains, 2 light chains, held together by covalent disulfide bonds, forming a Y-shaped molecule. The Fab region (variable region; antigen-binding region) is the two "arms" and the Fc (constant region; constant fraction) region is the "stem" structure with five heavy-chain constant regions. At the end of the Fab region, away from the stem, are antigen-binding sites which recognize a specific epitope of an antigen; it can bind two identical epitopes to from antigen-antibody complexes. The Fc region is the site of complement binding. NOTE: There are five classes of immunoglobulins. IgD, IgG, and IgE are single antibody monomers as explained above. IgM isotypes can be monomers but are usually pentomers—five monomers bound at the stem. IgA isotypes is rarely a monomer and usually a dimer, two monomers bound at the stem. Key functions: -neutralize antigens (antibodies block toxins or antigens from binding to host cells) -activate complement (cascade leads to cytolysis, opsonization, and/or inflammation) -increase phagocytosis as antibodies precipitate, agglutinate, or opsonize.
Define antibody titer and state how it differs in a primary versus secondary antigen exposure.
Antibody titer is the number or amount of antibodies in a patient sample. In a primary exposure, IgM antibodies are generated first and then IgG. In secondary antigen exposure, the IgG titer will surge and be much higher than IgM, which may indicate immunity.
Define antigens, epitopes, and haptens and discuss the concept of immunogenicity.
Antigen—any substance that, if presented in the right context, may trigger an immune response. Mostly proteins or polysaccharides that come from a bacterium, virus, fungus, or protist; cancer cells also frequently make proteins and/or polysaccharide antigens. Epitopes—parts of an antigen that are recognized by B and T cells; a given antigen will usually have multiple epitopes Haptens— incomplete antigens; small molecules unable to stimulate an immune response unless they are linked to a more complex protein or polysaccharide Immunogenicity—ability of an antigen to successfully trigger an immune response; impacted by a combination of antigen size, molecular complexity, and chemical composition; most immunogenic to least: proteins> polysaccharides> lipids; another definition: the degree to which the antigen provokes an immune response and depends on the antigen's biochemical features.