Download Cellular Immunity - ADAM Interactive Anatomy

Cellular Immunity
Graphics are used with permission of
Pearson Education Inc., publishing as Benjamin Cummings (http://www.aw-bc.com).
Page 1: Introduction
 Host defense mechanisms directed by T cells are referred to as cell-mediated immunity.
 Cytotoxic T cells engage in direct cell-to-cell attacks that destroy the body’s own cells when
they have become infected or cancerous.
 Helper T cells orchestrate the immune system’s various responses.
Page 2: Goals
 To define cytokines and list some of their functions.
 To list the types and subtypes of T lymphocytes.
 To distinguish between Class I MHC proteins and Class II MHC proteins in terms of cellular
expression and the source of antigen they display.
 To describe T cell activation.
 To describe how cytotoxic T cells kill their target cells.
 To explain the central role of helper T cells in adaptive immunity.
 To describe the role of regulatory T cells.
Page 3: Cytokines
 Cytokines are peptide mediators secreted by and affecting a variety of cells involved in host
defense.
 Cytokines carry out many different functions, which include promoting activating cells,
promoting inflammation, stimulating cell proliferation and differentiation, blocking virus
replication, inducing apoptosis, and inducing fever.
 Interleukin-1 released from macrophages promotes activation of lymphocytes, stimulates
Interleukin-2 secretion from helper T cells, and induces fever.
 Interleukin-2 promotes T cell proliferation.
Page 4: CD4 and CD8 Cells
 There are two major groups of T cells: CD4 cells and CD8 cells.
 CD8 cells are cytotoxic and kill infected cells, tumor cells, and transplanted cells.
 Subsets of CD4 cells function either as helper T cells or regulatory T cells (TREG) through the
secretion of cytokines.
Page 5: MHC Proteins: Introduction
 The major histocompatibility complex (MHC) proteins are required for antigen presentation
to T cells.
 T cells recognize protein antigens only after they have been digested into short peptides and
displayed on MHC proteins in the plasma membrane of another cell.
Page 6: MHC Proteins: Class I
 Class I MHC proteins are expressed by all cells except mature red blood cells. They present
antigens to CD8 lymphocytes.
1



CD8 lymphocytes monitor the health of cells by examining the antigens displayed on their
class I MHC proteins.
Normal cell proteins are broken down into peptides. The peptides bind and are transported to
the plasma membrane by class I MHC proteins.
Pathogen proteins within an infected cell are also degraded and displayed on class I MHC.
Page 7: MHC Proteins: Class II
 Class II MHC proteins are expressed by antigen-presenting cells (dendritic cells,
macrophages, and B cells). They present antigens to CD4 lymphocytes.
 Antigen-presenting cells phagocytize exogenous antigens, break them down, bind them to
class II MHC proteins, and display portions of them on their cell surface.
 Antigen presentation on dendritic cells and macrophages activates CD4 cells, causing them
to become helper T cells.
 Previously-activated helper T cells further activate B cells and macrophages by binding to
their antigen-loaded class II MHC proteins.
Page 8: MHC Proteins: Summary
 Class I and class II MHC proteins, although structurally distinct are homologous in function.
Page 9: Activation of Naive T Cells
 Activation of T cells almost always begins with a dendritic cell.
 Dendritic cells have the special ability to also present exogenous antigens on MHC I
molecules to CD8 cells.
 Naive CD4 and CD8 cells are activated in secondary lymphoid tissue (lymph nodes, spleen,
MALT).
 Activation of T cells requires antigen presentation, as well as signals generated from the costimulatory molecule.
 Clonal expansion with the formation of effector and memory cells requires the presence of
cytokines.
Page 10: Anergy
 T cells that bind to antigen in the absence of co-stimulation are permanently inactivated.
Page 11: Cytotoxic T Cell Effector Mechanisms
 CD8 cells are also known as cytotoxic T lymphocytes.
 Cytotoxic T cells kill by binding to target cells and secreting perforins and granzymes.
 Perforins insert into plasma membranes forming a pore.
 Granzymes and other chemical mediators pass through the pore and cause apoptosis (cell
suicide) of the target cell.
 Natural Killer (NK) cells use the same killing mechanism.
Page 12: Helper T Cells: Central Role
 Helper T cells are essential for both humoral and cell-mediated immunity because they are
required to activate and induce proliferation of both B and T cells.
2
Page 13: Helper T Cells: Two Types
 Whether a helper T cell functions as a TH1 or TH2 cell depends on which cytokines the cell
was exposed to during activation.
 TH1 cells secrete cytokines that promote macrophages and CD8 cells.
 TH2 cells secrete cytokines that stimulate B cells and antibody secretion.
Page 14: Regulatory T Cells
 TREG cells suppress self-reactive T cells either by secreting cytokines or by direct cell-to-cell
interactions.
Page 16: Summary
 Cytokines are small peptides that mediate interactions between immune system cells.
 CD8 cells become cytotoxic T cells; CD4 cells become helper T cells (TH1 or TH2) or
regulatory T cells.
 Class I MHC proteins, found on all cells, present endogenous antigens to CD8 cells; Class II
MHC proteins, found on antigen-presenting cells, present exogenous antigens to CD4 cells.
 T cell activation requires antigen presentation by an antigen-presenting cell along with the
appropriate co-stimulatory molecules.
 Cytotoxic T cells induce apoptosis of target cells by releasing perforins and granzymes.
 Helper T cells are required for activation of most B cells and CD8 cells, and release
cytokines to direct the immune response.
 Regulatory T cells act to suppress self-reactive T cells, preventing autoimmune diseases.
Study Questions
1. (Goal 1, Page 3) What are cytokines and what are their functions?
2. (Goal 1, Page 3) List the cell type that releases interleukin-1 and explain its function.
3. (Goal 1, Page 3) List the cell type that releases interleukin-2 and explain its function.
4. (Goal 2, Page 4) Name the two types of T cells and the cell surface receptor associated with
each type.
5. (Goal 2, Page 4) Explain the roles of T cells with CD8 receptors and T cells with CD4
receptors.
6. (Goal 2, Page 4) What determines whether a CD4 cell functions as a regulatory cell or a helper
cell?
7. (Goal 3, Page 5) What is the role of the major histocompatibility complex (MHC) proteins?
8. (Goal 3, Page 5) Under what circumstances do T cells recognize antigens?
9. (Goal 3, Page 6) Which types of cells express Class I MHC proteins? Which type of T cell do
they present antigen to?
10. (Goal 3, Page 6) Describe the function of CD8 lymphocytes and how they accomplish it.
11. (Goal 3, Page 6) In terms of MHC proteins, explain how normal cells differ from infected
cells.
12. (Goal 3, Page 7) Which cell types express MHC II proteins? Which type of T cell do APCs
present antigen to?
13. (Goal 3, Page 7) What happens to an antigen that is phagocytized by an antigen-presenting
cell?
3
14. (Goal 3, Page 7) Explain what happens when a dendritic cell or macrophage presents antigen
to a CD4 lymphocyte.
15. (Goal 3, Page 9) Which cell type is primarily responsible for activating naive CD4 and CD8
cells?
16. (Goal 4, Page 9) Name the locations where naive T cells are activated.
17. (Goal 4, Page 9) What is required to activate a T cell?
18. (Goal 4, Page 9) What is required to clone a T cell in order to produce effector and memory
cells?
19. (Goal 4, Page 10) What will happen if a T cell binds to antigen and co-stimulation does not
occur?
20. (Goal 5, Page 11) Describe how cytotoxic T lymphocytes kill.
21. (Goal 5, Page 11) Which other cell type uses the same killing mechanism?
22. (Goal 6, Page 12) Explain why helper T cells are needed for both humoral and cell-mediated
immunity.
23. (Goal 6, Page 13) What determines whether a helper T cell becomes a TH1 or a TH2 cell?
24. (Goal 6, Page 13) Which population of helper T cells promotes macrophage and CD8
lymphocyte activity, and which stimulates B cells and antibody production?
25. (Goal 7, Page 14) Explain the role of regulatory T cells and how they perform their task.
Summary
Fill-in-the-blanks. Fill in each blank with the correct term.
__________________ are small peptides that mediate interactions between immune system
cells. _________ cells become cytoxic T cells, and _______become helper T cells (TH 1 or TH2)
or regulatory cells.
Class I MHC proteins, found on ______ cells, present endogenous antigens to CD8 cells, and
Class II MHC proteins, found on _______________________________cells, present exogenous
antigen to CD4 cells.
T cell ___________________ requires antigen presentation by an antigen-presenting cell along
with co-stimulatory molecules. Cytotoxic T cells induce _________________ of target cells by
releasing perforins and granzymes. Helper T cells are required for activation of most B cells and
___________cells, and release cytokines to direct the immune response. Regulatory T cells act
to suppress self-reactive T cells, preventing _________________________________________.
4