1. Introduction

2. Smallpox Eradication

3. THE IMMUNE SYSTEM The Invaders The Defender Spring 2004-05
BISC 005 / Defending Against Invasion / Part I

4. Overview of the Immune System

5. Overview of your immune system
First line of defense: Physical barriers that viruses, bacteria must cross
skin covers ~2 m2
Mucous membranes that line digestive, respiratory, reproductive tracts cover ~400 m2
Second line of defense: Innate immune system (germline-encoded receptors -- no adaptation to specific pathogens)
Macrophages (Greek for “big eater”), neutrophils, natural killer (NK) cells
Cytokines -- hormone-like proteins that mediate inflammation, Complement proteins
Third line of defense (vertebrates only): Adaptive immune system (adapts to defend against specific pathogens using variable receptors)
B cells make antibodies that vary -- can make an antibody specific for any new antigen
T cells mediate cellular responses using variable receptors (T cell receptors; TCRs)

6. COMPONENTS OF THE IMMUNE SYSTEM
Spring
COMPONENTS OF THE IMMUNE SYSTEM
Cellular components of the immune system
Lymphocytes
Phagocytes
Granulocytes
Others
B-cell
Mononuclear phagocyte
Basophil
Platelets
T-cell
Neurtrophil
Mast cell
Large granular lymphocyte
Eosinophil
Antibodies
Cytokines
Complement
Inflammatory mediators
Soluble mediators of the immune system
BISC 005 / Defending Against Invasion / Part I

7. Note these are adult stem cells, NOT embryonic stem cells.
Immune cells and other blood cells made in bone marrow -- all are descendents of self-renewing stem cells
Make variable antibodies
Membrane-bound variable T cell receptors
Kill cells that are missing self proteins
Phagocyte
Phagocyte
Note these are adult stem cells, NOT embryonic stem cells.
p. 4 “How the Immune System Works” by Lauren Sompayrac

9. Innate Immunity Initial response to microbes
Stimulates adaptive immune response
Components are directed by adaptive immune response to remove foreign material

14. The innate immune system responds more quickly than adaptive immune system. Why is a quick response important?
Starting with one bacterium that doubles every thirty minutes --> 100 x 1012 bacteria in one day
100 x 1012 bacteria equivalent to ~100 liters of a dense culture
Total volume of blood in human ~5 liters
VERY important to check a bacterial infection quickly!

15. Three components of the innate immune system
Phagocytes (cells) (e.g., macrophages)
Complement proteins
Natural killer (NK) cells
Innate immune receptors recognize features common to many pathogens. Receptors are employed by all cells of a given cell type. Response does not lead to immunological memory.
Adaptive immune receptors are antigen specific. Antigen receptors of adaptive immune system are clonally distributed on individual lymphocytes. Response can lead to immunological memory.

16. Macrophages can engulf and digest bacteria
Macrophage about to eat a bacterium
p. 4 “How the Immune System Works” by Lauren Sompayrac

17. Question
Which component of bacteria serves as a very potent stimulant of the innate immune system?
Ribosomes
Proteins
Carbohydrates
DNA
RNA
Plasmids

18. Question
Carbohydrates on viruses strongly activate the innate immune system.
True
False

19. Complement system
Ancient system (found in invertebrates such as sea urchins)
~20 different proteins that work together to destroy invaders and recruit immune cells
Activated three different ways
“Classical” pathway: by antibodies bound to pathogen (vertebrates only)
“Alternative” pathway: by bacterial surfaces
Lectin activation pathway: by binding of mannose-binding lectin (MBL) to yeast, bacteria, parasites or viruses (e.g., HIV)
Activation of complement system is tightly regulated because end results can be dangerous

20. Combination of adaptive and innate immune responses
The three pathways of complement activation converge
Figure 2-18
Combination of adaptive and innate immune responses
Innate immunity
Innate immunity

21. Binding of mannose-binding lectin, a plasma protein, initiates lectin pathway of complement activation. MBL discriminates self carbohydrates from non-self carbohydrates by recognition of a particular pattern of sugar residues
Figure 2-11

22. Figure 2-35 part 3 of 3
One of the end results of complement activation -- the membrane attack complex kills a cell
Electron micrographs of ~100 Å diameter membrane attack complex channels

23. Laboratory uses of complement: isolate one population of cells by killing off another population
Example:
Have mixture CD4 T-cells and CD8 T-cells
Want only CD8 T-cells
Add anti-CD4 antibody to mixture of T cells. It binds. Now add complement, and CD4 T-cells will be killed, leaving you with CD8 T-cells only.

24. Question
Which type of pathogen is easier for the innate immune system to deal with: bacteria or viruses?
1) Bacteria
2) Viruses

25. So far, we’ve talked only about active recognition of features of pathogens…
But pathogens have also developed ways to remove some of the cell’s critical proteins, often so that they can escape detection by the immune system.
For example, in the adaptive immune system, T lymphocytes (T cells) recognize viral fragments (peptides) bound to MHC proteins.
It’s hard for a virus to hide out in a cell if the cell surface MHC proteins contain viral fragments that can be recognized by T cells.
What’s a virus to do?
Get rid of the host MHC proteins!

26. They respond to “missing self”.
For every strategy a virus comes up with, the immune system (usually) has an answer…
Natural killer cells recognize cells that do not express adequate levels of MHC proteins on their surface.
They respond to “missing self”.

27. Natural killer (NK) cells
Can kill tumor cells, virus-infected cells, bacteria, parasites, fungi in tissues
Identify targets based on “missing self”
Two types of NK receptors: inhibitory and activating
If inhibitory receptor recognizes a self protein (a class I MHC molecule) on a target cell, the NK cell is turned OFF even if activating receptor binds a ligand on the same target cell
If activating receptor binds a ligand, but inhibitory receptor does not (target cell has down-regulated class I MHC proteins), NK cells kill
Many virally-infected cells and tumor cells down-regulate expression of class I MHC molecules (NK cells important for preventing cancers)

28. The immune cells we’re talking about are called white blood cells.
This means they are in the ____. How do they get to a site of infection?

29. Figure 1-7

30. Figure 1-5
Antibody
Secretion
Activation of
T and B cells,
Macrophages,
Inflammation
Target Cell
Lysis

31. Phases of Adaptive Immune Responses
Recognition
Activation
Effector
Homeostasis

32. Figure 1-10

33. Activation

40. Figure 2-13

41. Figure 2-14

42. Figure 2-16

43. Figure 2-18

45. Figure 2-19

46. Figure 2-20

47. Antigens

48. Figure 3-4

49. Figure 3-8