1. Cell-Mediated Immunity

2. Cell Mediated Immunity
Involves specialized set of lymphocytes called T cells that recognize foreign antigens on the surface of cells, organisms, or tissues.
T cells regulate proliferation and activity of other cells of the immune system: B cells, macrophages, neutrophils, etc.
Defense against:
Bacteria and viruses that are inside host cells and are inaccessible to antibodies ( intracellular pathogens).
Fungi, protozoa, and helminths
Cancer cells
Involved in harmful effects of delayed hypersensitivity reactions included in transplant rejections, contact dermatitis, skin tests, and granuloma formation.

3. Cell Mediated Immunity is Carried Out by T Lymphocytes

4. T Cells and Cell Mediated Immunity
Antigens that stimulate this response are mainly intracellular.
Unlike humoral immunity, cell mediated immunity is not transferred to the fetus.
Cytokines: Chemical messengers of immune cells.
Over 100 have been identified.
Stimulate and/or regulate immune responses.
Interleukins: Communication between WBCs.
Interferons: Protect against viral infections.
Chemokines: Attract WBCs to infected areas.

5. T Cells and Cell Mediated Immunity
Antigen processing and presentation:
T cells have an antigen receptor that recognizes and reacts to a specific antigen (TCR).
T cell receptor only recognize antigens combined with major histocompatability (MHC) proteins on the surface of cells.
MHC Class I: Found on all cells.
MHC Class II: Found on phagocytes.
Clonal selection increases number of T cells recognizing a specific antigen.

6. T Cells Only Recognize Antigen Associated with MHC Molecules on Cell Surfaces

7. Ag processing and presentation by APCs
MHC Class II
MHC Class I
Antigen Presenting Cell (APC)

8. MHC Class II + peptide
MHC Class I + peptide
Antigen Presenting Cell (APC)

9. CD8 T cell
CD4 T cell
T cell receptor (TCR)
TCR
Class II
Class I
Antigen Presenting Cell (APC)

10. Association of peptide with an MHC II (exogenous Ag)

11. Association of peptide with an MHC I(endogenous Ag)

12. T Cells and Cell Mediated Immunity
Types of T cells
1. T Helper (TH) Cells: Central role in immune response.
They are CD4+
Recognize antigen associated with MHCII on the surface of antigen presenting cells (e.g.: macrophage, denteritic cells, and B cells).
Activate macrophages
Induce formation of cytotoxic T cells
Stimulate B cells to produce antibodies.

13. Central Role of Helper T Cells

14. Types of T cells (Continued)
2. Cytotoxic T (Tc) Cells: Destroy target cells.
They are CD8 positive & (CD4 -).
Recognize antigens associated with MHC I on the surface of all cells:
Kill host cells that are infected with viruses or bacteria.
Recognize and kill cancer cells.
Recognize and destroy transplanted tissue.
Release protein called perforin which forms a pore in target cell, causing lysis of infected cells.
Undergo apoptosis when stimulating antigen is gone.

15. Cytotoxic T Cells Lyse Infected Cells

16. Nonspecific Cellular Components
1. Activated Macrophages:
They are stimulated phagocytes.
Stimulated by ingestion of antigen or by cytokines.
Larger and more effective phagocytes.
Enhanced ability to eliminate intracellular bacteria, virus-infected and cancerous cells.

17. Nonspecific Cellular Components -cont.
2. Natural Killer (NK) Cells:
Lymphocytes that destroy virus infected and tumor cells.
Not specific. Don’t require antigen stimulation.
Not MHC restricted.
Not phagocytic, but must contact cell in order to lyse it.

18. Relationship Between Cell-Mediated and Humoral Immunity
1. Antibody Production
T- Dependent Antigens:
Antibody production requires assistance from T helper cells.
A macrophage cells ingest antigen and presents it to TH cell.
TH cell stimulates B cells specific for antigen to become plasma cells.
Antigens are mainly proteins on viruses, bacteria, foreign red blood cells, and hapten-carrier molecules.
T- Independent Antigens:
Antibody production does not require assistance from T cells.
Antigens are mainly polysaccharides or lipopolysaccharides with repeating subunits (bacterial capsules).
Weaker immune response than for T-dependent antigens.

19. Humoral Response to T Dependent Antigens

20. Relationship Between Cell-Mediated and Humoral Immunity
2. Antibody Dependent Cell Mediated Cytotoxicity
Target cell is covered with antibodies, leaving Fc portion sticking outwards.
Natural killer and other nonspecific cells that have receptors for Fc region are stimulated to kill targeted cells.
Target organism is lysed by substances secreted by attacking cells.
Used to destroy large organisms that cannot be phagocytosed.

21. Destruction of Large Parasites by ADCC

22. Phases of T cell responses
Ag processing and presentation by APCs
Activation of T lymphocytes requires
Recognition of Ag displayed on APCs
Costimulators: increase the strength of adhesion between APCs and T cells
Cytokines produced by APCs (IL-1,TNF-α , IL-12) and by T cells themselves (IL-2, INF-γ, LT)
Clonal expansion: proliferation and differention of T cells to effector T cells: in response to autocrine growth factor IL-2
Effector functions of T cells

23. T cell Recognition of Antigen on an APC
Endocytosis
CD4+
T cell
APC
T Cell Receptor
Peptide
MHC II

24. T cell Activation by an Activated APC
IL-1
IL-6
IL-12
IL-12 Receptor
CD4+
T cell
CD28
“Signal 3” B7
T Cell Receptor
LPS
“Signal 2”
TLR4
“Signal 1”
Signal 1: Specificity
Signal 2: Activation
Signal 3: Cytokines& differentiation
Peptide
MHC II
Antigen Presenting Cell (APC)

25. APC and T cell Interactions ( Costimulatory signals)
B7 (CD80/86)
CTLA-4
Activation
CD28
Activation
B7 (CD80/86)
CD4+ T Cell
TCR
Recognition
MHC II
APC
CD58 (LFA-3)
CD2
Adhesion
Activation
CD40L
CD40

26. Clonal Selection and expansion
Only those lymphocytes whose receptor recognizes the
antigen become activated, and then proliferate.

28. CD4 T cell cytokine effects
IL2,IFNγ
Th1
Macrophag Activation
IL12
Th0
IL4
IL2,IL4,IL12,
IL13, IFN-λ
IL4,IL13
Th2
B Cell Activation

29. Effector Functions of TH1 CD4+ T Cells (Cell-Mediated Immunity)

30. Effector Functions of TH2 CD4+ T Cells
(Humoral Immunity)

31. The Control of Activated CD4+ T Cells by Regulatory
CD4+CD25+ cells
Apoptosis
(- )
peptide/APC
IL-12/
IFN-g
TH1 CD4+ cells
(- )
IL-10
IFN-g
IL-4
(- )
Activated CD4 T cells
Resting CD4 T cells
(- )
TH2 CD4+ cells
Regulatory immunity
CD4/CD8 interactions
CD8 or CD4 suppressor effector
CD8 or CD4 suppressor
precursor
L. Chess 2002

32. Overview of the Immune Response

33. The body's second line of defense against infections is _____.
active immunity
inflammatory response
passive immunity
cell-mediated immunity
humoral immunity

34. Tissue macrophages begin their lives as neutrophils
have short life spans because they self-destruct after engulfing foreign invaders
originate from monocytes that leave the circulation and enter the tissues
do not attack microorganisms directly; instead, they destroy virus-infected body cells

35. Which of the following types of cells initiate a secondary immune response?
natural killer cells
immature white blood cells
memory cells
effector cells
plasma cells

36. The biggest difference between cell-mediated immunity and humoral immunity is _____.
how long their protection lasts
whether a subsequent secondary immune response can occur
whether clonal selection occurs
how they respond to and dispose of invaders
how fast they can respond to an invader

37. Helper T cells are part of
cell-mediated immune response
the first line of defense
the complement system
a group of phagocytic white blood cells

38. The role of cytotoxic T cells is to attack _____
body cells that have been infected
antibodies
proteins circulating in the body fluids
specific viruses and bacteria
complements

39. Viruses and bacteria in body fluids are attacked by _____.
antibodies from B cells
cytotoxic T cells
complement proteins
helper T cells
antigens

40. The role of cytotoxic T cells is the secretion of _____, which plays a role in the _____ immune response.
antibodies ... antibody-mediated
antibodies ... humoral
perforin ... cell-mediated
perforin ... humoral
interleukin humoral

41. A T cell recognizes Ag in association with MHC molecule, causes the APC to secrete:
IL-1
IL-2
1L-4
IL-6

42. All the following are true about CMI except:
Characterized by mononuclear cell infiltration
Can be transferred to non immune individual by serum
Delayed in time compared to humoral immunity
Initiated by intracellular Ags

43. B7 surface molecule on the APC can bind to ...... on Th:
CD28
CTLA4
LFA-1
a & b
b & c

44. A cytolytic T cell (Tc) may be able to kill a virally-infected antigen presenting cell (APC)
True
False

45. True
Explanation
All nucleated cells express class I MHC molecules. Cells infected with virus have some viral peptides associate with class I MHC molecules which are then expressed on the cell surface where they can be recognized by a cytolytic T cell and be killed. Therefore an antigen presenting cell (APC), which expresses both class I and class II MHC molecules and is infected by virus, is susceptible to killing by a cytolytic T cell.

46. Antigen presenting cells (APC) process superantigens
True
False

47. False
Explanation
 By definition, antigen processing involves the internal cellular fragmentation of proteins into peptides that can associate with class I or class II MHC molecules and then be presented on the cell surface to a T cell. Superantigens are not processed, but rather exert their effect externally by binding as an intact (non-fragmented) molecule to T cell receptor (TCR) molecule and to some portion of a class II MHC molecule on an antigen presenting cell

48. Th1 and Th2 cells are capable of interfering with each other's effector pathways
True
False

49. True
Explanation
Th1 cells produce interferon-gamma that interferes with the Th2 pathway, and Interleukin-10 (IL-10) produced in the Th2 pathway interferes with the Th1 pathway