T cell-mediated immune responses

Contrast active and passive cell-mediated immunity

- Active immunity: host defenses (innate and adaptive/acquired and specific) contribute to the containment/elimination of the antigen; the optimal defenses will depend on the antigen - Passive immunity: derives from the transfer of specific antibodies or activated T cells from an immune individual, or animal, to a non-immune individual - Passive antibody immunization: the injection of specific antibodies to provide protection against a pathogen or toxin; the protective antibodies may derive from human blood donors or immunized animals • Example: activation of a patients lymphocytes to their own tumor in vitro and transfer of these activated cells back to the patient

Explain the terms "antigen presentation" and "antigen processing"

- Antigen processing: is a biological process that prepares antigens for presentation to special cells of the immune system called T lymphocytes. This process involves two distinct pathways for processing of antigens from an organism's own (self) proteins/ intracellular pathogens (e.g. viruses), or from phagocytosed pathogens (e.g. bacteria); subsequent presentation of these antigens on class I or class II MHC molecules is dependent on which pathway is used. - Antigen presentation: process by which an APC epitope fragments of foreign antigen with host cell class I or class II MHC protein, which are transported to the host cells surface; MHC class I or II are required to bind antigen before they are stably expressed on a cell surface.

List the major types of T cell-mediated immunity and their primary functions

- CD4+ T helper cell mediated activation of non-specific macrophage: here the activated macrophage (or NK cells) are the ultimate effector cells bringing about antigen elimination - Activated CD8+ cytotoxic T cells directly recognize infected host cells: the activation of CD8+ T cells may also require CD4+ T cells help to complete their differentiation to effector cells

Describe the difference between Class I and Class II MHC molecules - what cells express them and the role they play in defense

- Class I molecule consists of three alpha and one beta chains; bind CD8+ cytotoxic T cells when fighting viruses/cancer cells (found on all cells in the body) - Class II molecules consist of two beta and two alpha chains; bind CD4+ helper T cells when fighting bacteria (found only on APCs) T cell receptors will recognize a complex of antigen-derived peptide epitope and portions of the presenting, self MHC molecule

Define clonal deletion and clonal inactivation, and describe the significance of each in the development of immune tolerance

- During fetal and early postnatal life, T cells are exposed to a wide mix of self-proteins in the thymus. Those T cells with receptors capable of binding self-proteins are destroyed by apoptosis = clonal deletion (do not want T cells recognizing "self" cells at "antigens" and then killing them) - Clonal inactivation occurs in the periphery and causes potentially self-reacting T cells to become non-responsive Remember: in order for cytotoxic T cells you need a costimlus (in addition to T cell binding) and if this costimulus is absence the T cell not only fails to become activated by antigen but dies or become inactive forever - REMEMBER: this is different from the recognition of MHC "self" proteins; those T cells that are NOT reactive to MHC will be deleted B cells will also be deleted for in the absence of self-reactivity

Describe the general functions of helper T-cells, cytotoxic T cells, regulatory T cells and NK cells

- Helper T cells: the class of T cells that, via secreted cytokines, play a stimulatory role in the activation of B cells and cytotoxic T cell; also can activate NK cells and macrophages; and bind antigen associated with class II MHC proteins - Cytotoxic T cell: the class of T lymphocytes, upon activation by specific antigen, directly attack the cells bearing that type of antigen; are major killers of virus-infected cells and cancer cells; and bind antigen associated with class I MHC proteins - Regulatory T cell: a type of immune cell that is believed to suppress immune function and may minimize the likelihood of autoimmunity Control the level of activation in T cell responses to antigen Poor regulation by these cells may lead to hypersensitivity Regulate potential autoreactive cells Have receptors for IL-2 therefore are stimulated along with immune cell stimulation - NK cells: class of lymphocytes that bind to cells bearing foreign antigen without specific recognition and kill them directly; major targets are virus-infected cells and cancer cells; participate in anti-body dependent cellular toxicity (ADCC)

Define "major histocompatibility complex (MHC)" and its role in the immune response

- MHC complex: the self-proteins that must be complexed with the antigen in order for T-cell recognition to occur Once a T cell binds to this MHC-antigen complex the cells of the immune system will be activated

List the types of antigen presenting cells and describe their key features

- Macrophage: engulfs antigen and forms a phagosome which fuses with a lysosome allowing fragmentation of the antigenic DNA/material; binds helper T cell using class II MHC complex - Dendritic cells: phagocytosis also and presentation of antigen (same as macrophage) - B cells: have some function as APCs (antigen presenting cells) also but once binding and activation of T cell will have subsequent "activation" of the B cell stimulating it to release antibodies specific for the antigen

Describe how CD4+ helper T cell-mediated immunity functions in antibody-mediated immunity

- Presentation to CD4+ helper T cells (these require class II MHC to function which is only expressed by antigen presenting cells) APCs: macrophages, B cells, and dendritic cells After an antigen has been phagocytosed by a macrophage or dendritic cell (in a non-specific response) it is broken down into smaller peptide fragments the fragments are then bound to class II MHC proteins synthesized by the cell. This entire complex is then transported to the cell surface, where it is displayed in the plasma membrane The helper T cell recognize this complex and in response secrete interleukin-2, which stimulates the helper T cell themselves to proliferate and secrete more IL-2/cytokines (sensitization phase) The helper T cell itself (along with cytokines/IL-2) then go activate antigen-bound B cells stimulating them to proliferate and differentiate into antibody-secreting plasma cells (some B cells differentiate into memory cells rather than plasma cells) • OR the sensitized CD4+ T cell will bind to a resting macrophage and "activate" it therefore increase the macrophages MHC receptors making it more efficient at killing bacteria (this is the adaptive function of macrophages, B cells, and dendritic cells) • Activities enhances in activated macrophage o Enhances fusion of phagosomes with lysosomes o Increased synthesis of reactive O2/N intermediates o Increased production of proteases o Increased in cell surface molecule involved in antigen presentation and co-stimulation o Production of inflammatory cytokines - Presentation to the CD8+ cytotoxic T cell (these require class I MHC to function which is expressed on all cells of the body except RBC) Virus or cancer infected cell produces foreign proteins INSIDE the cell which are processed and presented on the plasma membrane of the cell complexed with class I MHC proteins Cytotoxic T cells specific for that particular antigen can bind to the complex; but the binding alone does not cause activation of the cytotoxic T cell, cytokines from the adjacent activated helper T cells are also required Once the T cell is activated it will secrete perforin via exocytosis which "drills" a hole in the antigenic cell membrane causing water to move in therefore the cell will die and the virus cannot replicate - Differences between MHC class II and MHC class I presentation Class II MHC proteins are not loaded until they are fused with the phagosome and MHC "self" protein binding is blocked in the Golgi to make this binding process more efficient Class I MHC proteins are loaded inside the Golgi because you are technically loading "endogenous" viral/cancer protein fragments

Describe T cell antigen receptors and how they differ in structure and function from B cell antigen receptors

- T-independent antigens bind to B cells and stimulate them to proliferate and secrete antibodies directly Rapid response, usually IgM is produced, but no immunologic memory if established - Most antigens are T-dependent antigens where the responding antigen-specific B cells require CD4+ T cells help to proliferate and differentiate into antibody secreting cells - CD4+ cells must be activated 1st; antibodies produced are those other than IgM, and immunologic memory is established

Describe the optimal acquired, specific defense against an extracellular pathogen, a pathogen maintained in an intracellular vesicular compartment and a pathogen in the cytoplasm of a host cell

Extracellular - Interstitial space, blood, or lymph: - Organisms: viruses, bacteria, protozoa, fungi, and worms - Protective immunity: antibodies, complement, phagocytosis, and neutralization Extracellular - Epithelial surfaces: - Organisms: e.coli, gonorrhea, pneumonia - Protective immunity: antibodies (esp IgA), antimicrobials, and peptides Intracellular - Cytoplasmic: - viruses, chlamydia, listeria, protozoa - Protective immunity: cytotoxic T cells and NK cells Intracellular - Vesicular: - Organisms: mycobacterium, listeria, salmonella, legionella, andc histoplasma - T cells and NK cells depending on macrophage activation