1. Immunology
Overview
Kristine Krafts, M.D.

2. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells
Effector cells
Responses
The innate immune response
Capturing and displaying antigens
Cell-mediated immunity
Humoral immunity
Immunologic memory

3. Immunology Overview
Definitions

4. Definitions Immunity = protection against infections
Immune system = collection of cells and molecules that defend us against microbes
Immune deficiencies → infections
Immune excesses → autoimmune diseases

5. Innate (Natural) Immunity
Always present (innate); doesn’t change over time
First line of defense when bugs come
Major components:
Epithelial barriers (skin, GI, respiratory)
Phagocytes
NK cells
Complement

6. Adaptive (Acquired) Immunity
Second line of defense
More specific (adaptive) and powerful than innate
Major components:
Lymphocytes
Lymphocyte products
Two types of adaptive immunity:
Humoral immunity (mediated by antibodies)
Cellular immunity (mediated by T cells)

8. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells
Effector cells

9. Lymphocytes Present in lymphoid organs and in blood Groups
T-lymphocytes (grow up in thymus)
B-lymphocytes (grow up in bone marrow)
Each one has receptors for a specific antigen
Recognize millions of different antigens!
Diversity generated by:
rearrangement of antigen receptor genes
different joining of the gene segments
Gene rearrangement studies

10. Lymphocyte (could be B cell or T cell!)

11. T Lymphocytes Two basic functions: Kill stuff (cytotoxic T cells)
Help other cells do their jobs (helper T cells)
T-cell receptor (TCR) complex recognizes antigens
Binds antigen
Sends signals to the T cell
Antigens must be:
Displayed by other cells…
…AND bound to an MHC receptor

12. The T-Cell Receptor Bound to Antigen
Antigen-presenting cell
T cell

13. Cytotoxic T cells surrounding tumor cell

14. Major Histocompatibility Complex (MHC)
class II MHC genes
class III MHC genes
class I MHC genes
Class II MHC molecule
Class I MHC molecule

15. Class I and II MHC Molecules
Class I molecules
Display antigens from within the cell (e.g., viral antigens) to CD8+ T cells.
Present on all nucleated cells! (Good idea.)
Class II molecules
Display extracellular antigens (e.g., bacterial antigens the cell has eaten) to CD4+ T cells
Present mainly on antigen presenting cells, like macrophages! (Makes sense.)

16. B Lymphocytes Basic function: make antibodies
B-cell receptor complex recognizes antigens
Binds antigen
Sends signals to B cells
Antigens can be free and circulating (don’t have to be bound to MHCs or displayed by other cells to be recognized!)

17. Natural Killer (NK) Cells
Belong to innate immunity arm
Receptors not highly variable (like T and B cell receptors)
Main job: recognize and kill damaged or infected cells

18. Natural killer cell

19. Natural killer cell (top) killing infected cell (bottom)

20. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells

21. Antigen-Presenting Cells
Main job: catch antigens and display them to lymphocytes
Dendritic cells
Have fine cytoplasmic projections
Present all over body: skin, lymph nodes, organs
Capture bug antigens, display to B and T cells
Macrophages
Macrophages also eat bugs and present antigens to and T cells
Their role in activating the adaptive system is not as pivotal though!

23. Dendritic cell surrounded by lymphocytes

24. Dendritic cell (right) talking to lymphocyte (left)

25. Monocyte
Macrophage

26. Macrophage reaching for bacterium

27. Macrophage gorging on bacteria

28. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells
Effector cells

29. Effector Cells
These guys carry out the ultimate immune system task: eliminate infection
Types of effector cells
NK cells
Plasma cells
T cells (both CD4+ and CD8+)
Macrophages
Other leukocytes (e.g., neutrophils)

30. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells
Effector cells
Responses
The innate immune response
Capturing and displaying antigens
Cell-mediated immunity
Humoral immunity
Immunologic memory

31. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells
Effector cells
Responses
The innate immune response

32. The Innate Immune Response
Main bug barriers: skin, mucosa
If bugs make it through epithelium, they encounter innate immune system
What happens in the innate immune system?
Phagocytes eat bugs, kill them
Cytokines are released
Complement is activated
The adaptive immune system is activated

34. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells
Effector cells
Responses
The innate immune response
Capturing and displaying antigens

35. Capturing and Displaying Antigens
Dendritic cells in epithelium capture bug antigens, transport them to lymph nodes
Dendritic cells display antigens (using their MHC receptors) to T cells
B cells in lymph nodes also recognize antigens
Antigens and molecules produced during innate immune response trigger proliferation and differentiation of B and T cells

36. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells
Effector cells
Responses
The innate immune response
Capturing and displaying antigens
Cell-mediated immunity

37. Cell-Mediated Immunity
Humoral Immunity
Cell-Mediated Immunity

38. Cell-Mediated Immunity
Humoral Immunity
Cell-Mediated Immunity

39. Naïve T Cells Turn Into Effector T Cells
Naïve T cells are activated by antigen and costimulators in lymph nodes…
…then they proliferate and differentiate into effector cells that go find the antigen.
CD4+ T cells help macrophages eat bugs
CD8+ T cells kill infected cells directly
All these steps are dependent upon cytokines

40. What are cytokines? Polypeptides that do lots of different things:
Help leukocytes grow and differentiate
Activate T cells, B cells and macrophages
Help leukocytes communicate
Recruit neutrophils
Made by lymphocytes and macrophages
Examples: tumor necrosis factor (TNF), interleukins, interferons

41. Types of Effector T Cells
CD4+ T cells differentiate helper T cells
These guys go to the site of infection and help other cells do their thing.
CD8+ T cells differentiate into cytotoxic T cells
These guys kill cells that have microbes in their cytoplasm.
They are like little assassins.

42. Matt Damon and the “asset”

43. Cell-Mediated Immunity

44. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells
Effector cells
Responses
The innate immune response
Capturing and displaying antigens
Cell-mediated immunity
Humoral immunity

45. Cell-Mediated Immunity
Humoral Immunity
Cell-Mediated Immunity

46. Humoral Immunity
B cells are activated by exposure to antigens (sometimes with the help of CD4+ T cells)
B cells differentiate into plasma cells (which make antibodies)
The antibodies do nasty things to bugs

47. What is an antibody? Y-shaped glycoprotein 2 light chains (κ or λ)
2 heavy chains (α, γ, δ, ε, or μ)
Constant regions of heavy chain form Fc fragment
Binds to APCs
Defines isotype (Ig class: IgA, IgE, etc.)
Variable regions of both chains form Fab fragments
Binds to antigen
Defines idiotype

50. What do antibodies do?
Bind to – and “neutralize” – bugs, so they can’t infect cells.
Coat (“opsonize”) bugs, making them yummy to macrophages and neutrophils (which have receptors for the Fc portion of IgG! How handy!).
Activate complement.

51. What is complement? Just give me the bottom line.
It’s a bunch of proteins that poke holes in cells.

52. Okay, give me a little more information.
Consists of about 20 plasma proteins (C1, C2, etc.)
Can be activated in a few different ways
Activation proceeds in a cascade fashion
End results:
Cell lysis
Chemotaxis
Opsonization

53. Complement, ridiculously oversimplified

54. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells
Effector cells
Responses
The innate immune response
Capturing and displaying antigens
Cell-mediated immunity
Humoral immunity
Immunologic memory

55. Immunologic Memory
Most effector lymphocytes die after killing the bug.
A few memory cells live on for years.
Expanded pool of antigen-specific lymphocytes
Respond faster, better than naïve cells
Vaccines depend on these guys

56. Summary of the Adaptive Immune Response

57. Immunology Overview Definitions Cells Lymphocytes
Antigen-presenting cells
Effector cells
Responses
The innate immune response
Capturing and displaying antigens
Cell-mediated immunity
Humoral immunity
Immunologic memory