Unit 12-Lesson 7: T-cell Immunity
Terms in this set (33)
-Humoral Antibodies- effective against pathogens circulating freely where antibodies can contact them
-intracellular antigens (ex viruses)- not exposed to circulating antibodies!
Cell-mediated immunity; is the type of adaptive immunity mediated by T lymphocytes.
Cell-mediated immunity is the main defense mechanism against microbes that survive within phagocytes (i.e. the bacteria that causes Tuberculosis) or that infect the cytosol of non-phagocytic cells (i.e. many viruses).
*List the components of the cell-mediated arm of the immune system
Components of the innate immunity
1. Epithelial barriers
3. Dendritic cells
4. Plasma proteins (complement)
5. NK cells
Components of adaptive immunity
1. B cell immunity
a. B lymphocytes that differentiate into plasma cells that secrete antibodies. After a response, B memory cells persist, which "remember" the particular antigen
2. T cell immunity
a. T lymphocytes
i. CD4+ "helper" T cells secrete soluble molecules which help B cells to produce antibodies and activate macrophages to eliminate endocytosed microbes
ii. CD8+ "cytotoxic" T cells can also secrete soluble mediators but play a more important role in directly killing virus-infected or tumor cells. After a response, T memory cells persist, which "remember" particular antigens
b. Effector T cells
*Distinguish between B cells and T cells
- Both originate from stem cells in bone marrow or fetal liver
- Stem cell diverges into two cell lines:
○ B cell line
§ Goes into red bone marrow in adults
§ Differentiate to B cell in adult red bone marrow
§ Coating of immuglobulins
§ Immature B cells are eliminated by clonal deletion
○ T cell line
§ Goes into the thymus
§ Differentiate to T cell in thymus
§ TCRs - TH cell receptors
§ Immature T cells are eliminated by thymic selection
- Both migrate to lymphoid tissues e.g. spleen, tonsils, mucosal tissues, but especially lymph nodes
B cells recognize circulating antigens of many chemical structures, while T cells can only recognize peptide fragments displayed by MHC molecules on the surfaces of antigen presenting cells (APCs). This ensures that T cells are able to recognize antigens that might be floating in the cytosol or contained within ingested vesicles of various cells.
*Compare helper T cells and cytotoxic T cells
T(h)-A specialized T cell that often interacts with an antigen before B cells interact with the antigen
-cooperate w/ B cells in production of antibodies (through cytokine signaling)- imp part of humoral immunity! Even more essential element of cellular immunity
-CD4+ binds to MHC II on B cells and APCs
-Helper T cells can recognize an antigen presented on the surface of a macrophage and activate the macrophage, making it more effective in both phagocytosis and in antigen presentation.\-to activate a CD4+ T helper cell, 2 signals are required, the first signal is the binding of the TCR to the processd antigen, and the second signal requires a costimulating cytokine, such as IL-2 and others. Once activated, the T(h) cell secretes cytokines that affect the effector functions of multiple cll types of the immune system
T(c) (cytotoxic T cell)-A precursor to a cytotoxic T lymphocyte (CTL)
-have the capability of attacking any target cell as they emerge from the thymus
-requires sequential and complex activation of the precursor Tc by an antigen processed by a dendritic cell and interaction with a helper T cell and costimulatory signals.
-resulting CTL is an effector cell that has the ability to recognize and kill target cells that are considered nonself
-these target cells are self-cells that have been altered by infection with a pathogen, esp viruses.
-Other important target cells: tumor cells and ransplanted foreign tissue
- Rather than reacting with antigenic fragments presented by an APC in complex with MHC class II molecules, , CD8+T cell recognizes endogenous antigens on the target cell's surface that are in combination with an MHC I molecule.
-CTL can attack almost any cell of the host that's been altered
-CD8+ binds to MHC I molecules
-A normal cell will not trigger a response by a CTL, but a virus-infected cell or a cancer cell produces abnormal endogenous antigens.
-The abnormal antigen is presented on MHC I molecules. CD8+ T cells with receptors for the antigen are transformed into CTLs
-The CTL induces destruction of virus-infected cell by apoptosis
-CTL- attaches to target cell and releases a pore-forming protein, perforin-- causes pore formation and subsequent death of the cell
-Granzymes- proteases that induce apoptosis are then able to enter through the pore
Clusters of differentiation
Clusters of differentiation (CD) - classification of T cells are based on certain membrane molecules or glycoproteins
TH cells are classified as CD4+ which bind to MHC class II molecules on B cells and APCs
TC cells are classified as CD8+ which bind to MHC class I molecules
Activation and proliferation of T Helper Cells (CD4+ T Cells)
To activate a CD4+ T helper cell, at least two signals are required: the first signal is the binding of the TCR to the processed antigen, and the second signal requires a costimulating cytokine, such as IL-2 and others. Once activated, the TH cell secretes cytokines that affect the effector functions of multiple cell types of the immune system.
Activation and proliferating TH cells differentiate into 2 subset populations:
1. TH1 - cell-mediated immunity, control of intracellular pathogens, delayed hypersenstivity reactions, stimulates macrophages
2. TH2 - important in allergic responses, especially by production of IgE, stimulates activity of eosinophils to control extracellular parasites such as helminths
TH17 - recruits neutrophils, provides protection against extra-cellular bacteria and fungi
T Cytotoxic Cells (CD8+ T cells)
- Are precursors to cytotoxic T lymphocyte (CTL) cells
- TC cells first need to undergo activation by an antigen that have been 1) processed by a dendritic cell and 2) interaction with a TH cell and costimulatory signals
- CTLs are effector cells that have the ability to recognize and kill target cells
○ Target cells
§ Nonself target cells
□ Cells that have been altered by infection with a pathogen, especially viruses
□ On their surface, they carry fragments of endogenous antigens that are generally synthesized within the cell and are mostly of viral or parasitic origin
§ Tumor cells
§ Transplanted foreign tissue
- Recognize endogenous antigens on the target cell's surface that are in combination with MHC class I molecules
- In its attack, a CTL attaches to a target cell and releases a pore-forming protein, perforin. Pore formation contributes to the subsequent death of cell.
*Define antigen-presenting cell (APC)
A macrophage, dendritic cell, or B cell that engulfs an antigen and presents fragments to T cells.
Are important in adaptive cellular immunity because they activate CD4+ TH cells in developing their effector functions.
Type of antigen-presenting cell characterized by long finger like extensions; found in lymphatic tissue and skin
- Engulf invading microbes, degrade them, and transfer them to lymph nodes for display to T cells located there.
- Dendritic cells are the principal APCs to induce immune responses by T cells.
Is a phagocytic cell
- Important for innate immunity and for ridding the body of worn out blood cells and other debris e.g. cellular remnants from apoptosis
- Are stimulated to become activated macrophages activated by ingestion of antigenic material or by cytokines produced by an activated T helper cell
*Define major histocompatibility complex
The genes that code for histocompatibility antigens; also known as human leukocyte antigen (HLA) complex.
*Describe the function of natural killer cells
A lymphoid cell that destroys tumor cells and virus-infected cells.
-can attack parasites (larger than bacteria)
-in contrast to CTLs, NK cells are not immunoglobulin specific- they dont need to be stimulated b an antigen
-first contact target cell, and determine whether it expresses MHC I self-antigens
-if it does not (which is often the case in early stages of viral infection and w/ some infecting viruses that have developed a system of interfering w/ the usual presentation of antigens on an APC) they kill the target cell by mechanisms similar to that of a CTL
-NK cells- distinguish normal cells from transformed cells, or cells infected w/ intracellular pathogens
-Tumor cells- have a reduced # of MHC I molecules on their surfaces
-NK cells- cause pores to form in target cell lysis or apoptosis
-cell-mediated immune system can stimulate NK cells and cells of the innate defense system (macrophages) to kill target cells w/ the help of antibodies produced by the humoral immune response.
*Describe the role of cytokines in immune response
-immune response requires complex interactions between diff cells
-the communication required for this is mediated by chemical messengers called cytokines
-Cytokines- soluble proteins or glycoproteins that are produced by practically all cells of the immune system in response to a stimulus.
-a cytokine acts only on a cell that has a receptor for it
Families of cytokines
1. Interleukines; cytokines that communicate between leukocytes (white blood cells) e.g. IL-1
2. Chemokines; cytokines that induce migration of leukocytes into areas of infection or tissue damage. Are important especially in inflammation.
3. Interferons; cytokines that protect cells from viral infection e.g. IFN-a
4. Tumor necrosis factor; aka TNF, cytokines for tumor cells and inflammatory reactions of autoimmune diseases
5. Hematopoietic cytokines; function in controlling the pathways by which stem cells develop into different red or white blood cells e.g. colony stimulating factors (CSF) or G-CSF (granulocyte-colony stimulating factor)
-cytokines may stimulate cells to produce more cytokines
-feedback loop- ocassionally gets out of control- resulting in harmful overproduction of cytokines- a CYTOKINE STORM
-can do significant damage to tissues (appears to be a factor in the pathogly of certain diseases and conditions such as influenza, graft-versus host disease, and sepsis.
Mechanisms to prevent adaptive immune system from attacking so-called self
-deletion of immune system cells that fail to recognize the host's own tissues
-major histocompatibility complex system- which must combine w/ foreign antigens before they stimulate humoral or cellular immune reactions.
Principal cells that function in cell-mediated immunity
the Dual nature of the adaptive immune system
Contrast the terms in the following pairs:
a. innate and adaptive immunity
b. humoral and cellular immunity
c. active and passive immunity
d. TH1 and TH2 cells
e. natural and artificial immunity
f. T-dependent and T-independent antigens
g. CD8+ T cell and CTL
h.immunoglobulin and TCR
a. Adaptive immunity is the resistance to infection obtained during the life of the individual; it results from the production of antibodies and T cells. Innate immunity refers to the resistance of species or individuals to certain diseases that is not dependent on antigen-specific immunity.
b. Humoral immunity is due to antibodies (and B cells). Cellular immunity is due to T cells.
c. Active immunity refers to antibodies produced by the individual who carries them. Passive immunity refers to antibodies produced by another source and then transferred to the individual who needs the antibodies.
d. TH1 cells produce cytokines that activate T cells. Cytokines produced by TH2 cells activate B cells.
e. Natural immunity is acquired naturally, i.e., from mother to newborn, or following an infection. Artificial immunity is acquired from medical treatment, i.e., by injection of antibodies or by vaccination.
f. T-dependent antigens: Certain antigens must combine with self-antigens to be recognized by TH cells and then by B cells. T-independent antigens can elicit an antibody response without T cells.
g. T cells can be classified by their surface antigens: TH cells possess the CD4 antigen; TC cells have the CD8 antigen.
h. Immunoglobins = antibodies; TCRs = antigen-receptors on T cells.
What does MHC stand for? What is the function of MHC?
What types of T cells interact with MHC class I? With MHC class II?
Major histocompatability complex (MHC) are self-antigens.
TH cells react with MHC II; TC cells react with MHC I.
Explain a function for the following types of cells: TC, TH, and Treg. What is a cytokine?
Activated TC cells (CTLs) destroy target cells on contact. TH cells interact with an antigen to "present" it to a B cell for antibody formation. TR cells suppress the immune response. Cytokines are chemicals released by cells that initiate a response by other cells.
A positive tuberculin skin test shows cellular immunity to Mycobacterium tuberculosis. How could a person acquire this immunity?
By being previously exposed to it (naturally acquired active immunity), activated B cells do not become antibody-producing plasma cells but rather persist as long-lived, non-proliferating memory cells.
Years, or even decades later, if these cells are stimulated by the same antigen, they very rapidly differentiate into antibody-producing plasma cells.
T cells and cellular immunity
• 1. Red bone marrow stem cells give rise to T cells, which mature in the thymus gland. Thymic selection removes T cells that don't recognize MHC-self molecules.
• 2. T-cell receptors on T cells recognize antigens.
• 3. T cells recognize antigens processed by antigen-presenting cells.
• 4. T cells recognize antigens in association with MHC on an APC.
What does MHC stand for? What is the function of MHC?
-What types of T cells interact with MHC I and which types interact w/ MHC II
The major histocompatability complex (MHC) are self-antigens. T(h)cells react with MHC II; T(c) cells react with MHC I.
Explain function for T(c), T(h), and T(re)
Activated TC cells (CTLs) destroy target cells on contact. TH cells interact with an antigen to "present" it to a B cell for antibody formation. TR cells suppress the immune response.
What is a cytokine?
Cytokines are chemicals released by cells that initiate a response by other cells.
Classes of T cells
• 5. T cells are classified according to their functions and cell-surface glycoproteins called CDs.
T Helper Cells (CD4+ T cells)
• 6. TH1 cells activate cells involved in cellular immunity.
• 7. TH2 cells are associated with allergic reactions and parasitic infections.
• 8. TH 17 cells activate innate immunity and responses to extracellular bacteria.
• 9. T helper cells, or CD4+ T cells, are activated by MHC class II on APCs. After binding an APC, CD4+ T cells secrete cytokines that activate other T cells and B cells.
T Regulatory Cells
• 10. T regulatory cells (Treg) suppress T cells against self.
T Cytotoxic Cells (CD8+ T Cells)
• 11. T cytotoxic cells (TC), or CD8+ T cells, are activated by endogenous antigens and MHC class I on a target cell and are transformed into a CTL.
• 12. CTLs lyse or induce apoptosis in the target cell.
Antigen-Presenting Cells (APCs)
• 1. APCs include B cells, dendritic cells, and macrophages.
• 2. Dendritic cells are the primary APCs.
• 3. Activated macrophages are effective phagocytes and APCs.
• 4. APCs carry antigens to lymphoid tissues where T cells that recognize the antigen are located.
Extracellular Killing by the Immune System
• 1. Natural killer (NK) cells lyse virus-infected cells, tumor cells, and parasites. They kill cells that do not express MHC class I antigens.
Antibody-Dependent Cell-Mediated Cytotoxicity
• 1. In ADCC, NK cells and macrophages lyse antibody-coated cells.
Cytokines: Chemical Messengers of Immune Cells
• 1. Cells of the immune system communicate with each other by means of chemicals called cytokines.
• 2. Interleukins (IL) are cytokines that serve as communicators between leukocytes.
• 3. Chemokines cause leukocytes to migrate to an infection.
• 4. Alpha interferon and IFN-β protect cells against viruses. Gamma interferon increases phagocytosis.
• 5. Tumor necrosis factor promotes the inflammatory reaction.
• 6. Hematopoietic cytokines promote development of white blood cells.
• 7. Overproduction of cytokines leads to a cytokine storm, which results in tissue damage.
The thymus gland is very important in early life, when the immune cells of the body begin to develop a specific identity. Once stem cells emerge from bone marrow and other sites, some pass through the thymus gland, where a number of hormones and potent cytokines are secreted. These substances provide the signals necessary for T cells to mature and differentiate into distinct subpopulations. These subpopulations are described in Table 17.2 (p. 496).
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