1. 35 Immunity

2. Overview: Recognition and Response
Pathogens - agents that cause disease,
All animals and plants have innate immunity
Vertebrates also have adaptive immunity 2

3. Figure 35.1
Figure 35.1 What triggered this attack by an immune cell on a clump of rod-shaped bacteria? 3

4. Innate immunity involves nonspecific responses to pathogens
consists of external barriers plus cellular and chemical defenses 4

5. Adaptive (acquired) immunity develops after exposure
Adaptive Immunity
Adaptive (acquired) immunity develops after exposure
It involves a very specific response to pathogens 5

6. Pathogens (such as bacteria, fungi, and viruses)
Figure 35.2
Pathogens (such as bacteria, fungi, and viruses)
INNATE IMMUNITY
Barrier defenses:
(all animals)
Skin Mucous membranes Secretions
• Recognition of traits shared by broad ranges of pathogens, using a small set of receptors
Internal defenses:
Phagocytic cells Natural killer cells Antimicrobial proteins Inflammatory response
• Rapid response
Figure 35.2 Overview of animal immunity
ADAPTIVE IMMUNITY
Humoral response:
(vertebrates only)
Antibodies defend against infection in body fluids.
• Recognition of traits specific to particular pathogens, using a vast array of receptors
Cell-mediated response:
Cytotoxic cells defend against infection in body cells.
• Slower response 6

7. engulfed by endocytosis.
Figure 35.3
Pathogen 1
Pseudopodia
surround pathogens. 2
Pathogens
PHAGOCYTIC CELL
engulfed by endocytosis. 3
Vacuole forms.
Lysosome containing enzymes
Vacuole 4
Vacuole and
lysosome fuse.
Figure 35.3 Phagocytosis 5
Pathogens
destroyed. 6
Debris from
pathogens released. 7

8. Cellular Innate Defenses
2 mammalian phagocytic cells
Neutrophils in blood
Macrophages throughout the body

9. Vertebrate natural killer cells - detect abnormal cells & release chemicals leading to cell death.
Many cellular innate defenses involve the lymphatic system

10. Antimicrobial Peptides and Proteins
Interferons interfere with viruses and activate macrophages
The complement system … 30 proteins activated by microbe surface substances and lead to lysis of invaders

11. Inflammatory Response
inflammatory response, (pain swelling redness heat)
Mast cells release histamine, making blood vessels more permeable
macrophages and neutrophils release cytokines, promoting blood flow to the site of injury

12. 1 Pathogen Splinter Macro- phage Signaling molecules Mast cell
Figure
Pathogen
Splinter
Macro- phage
Signaling molecules
Mast cell
Capillary
Red blood cells
Figure Major events in a local inflammatory response (step 1)
Neutrophil 1
Histamines and cytokines released. Capillaries dilate. 12

13. 1 2 Pathogen Splinter Movement of fluid Macro- phage
Figure
Pathogen
Splinter
Movement of fluid
Macro- phage
Signaling molecules
Mast cell
Capillary
Red blood cells
Figure Major events in a local inflammatory response (step 2)
Neutrophil 1
Histamines and cytokines released. Capillaries dilate. 2
Antimicrobial peptides enter tissue. Neutrophils are recruited. 13

14. 1 2 3 Pathogen Splinter Movement of fluid Macro- phage
Figure
Pathogen
Splinter
Movement of fluid
Macro- phage
Signaling molecules
Mast cell
Capillary
Phagocytosis
Red blood cells
Figure Major events in a local inflammatory response (step 3)
Neutrophil 1
Histamines and cytokines released. Capillaries dilate. 2
Antimicrobial peptides enter tissue. Neutrophils are recruited. 3
Neutrophils digest pathogens and cell debris. Tissue heals. 14

15. adaptive immunity, pathogen-specific recognition
The adaptive response relies on B and T lymphocytes,
T cells mature in thymus
B cells mature in bone marrow
Antigens – substances that elicit a response when bound to an antigen receptor on or from a B or T cell
There are millions of different antigen receptors but on a single B cell or T cell all are identical

16. Antigen receptors Mature B cell Mature T cell
Figure 35.UN01
Antigen receptors
Figure 35.UN01 In-text figure, lymphocytes, p. 715
Mature B cell
Mature T cell 16

17. B cell antigen receptor Constant regions
Figure 35.6
Antigen- binding site
Antigen- binding site
Disulfide bridge V V V V
Variable regions C C
B cell antigen receptor
Constant regions
Light chain C C
Transmembrane regions
Figure 35.6 The structure of a B cell antigen receptor
Heavy chains
Plasma membrane
B cell
Cytoplasm of B cell 17

18. B cell activation can release a soluble form of the protein called an antibody or immunoglobulin (Ig)
antibodies, rather than B cells themselves, defend against pathogens

19. (a) B cell antigen receptors and antibodies
Figure 35.7
Antigen- receptor
Antibody
B cell
Antigen
Epitope
Pathogen
(a) B cell antigen receptors and antibodies
Antibody C
Figure 35.7 Antigen recognition by B cells and antibodies
Antibody A
Antibody B
Antigen
(b) Antigen receptor specificity 19

20. T cell antigen receptor Variable regions V V
Figure 35.8
Antigen- binding site
T cell antigen receptor
Variable
regions V V C C
Constant
regions
Disulfide bridge
Transmembrane region
Figure 35.8 The structure of a T cell antigen receptor
 chain
 chain
Plasma membrane
T cell
Cytoplasm of T cell 20

21. T cells bind to antigen fragments presented on host cell
MHC (major histocompatibility complex) -host proteins that display the antigen fragments on cell surface

22. In infected cells, antigens are cut up by enzymes
MHC molecules transport antigen fragments to the cell surface, (antigen presentation)
A T cell can then bind both the antigen fragment and the MHC molecule
This interaction is necessary for the T cell to participate in the adaptive immune response

23. Displayed antigen fragment T cell
Figure 35.9
Displayed antigen fragment
T cell
T cell antigen receptor
MHC molecule
Antigen fragment
Figure 35.9 Antigen recognition by T cells
Pathogen
Host cell 23

24. B and T Cell Diversity
immune system assembles a diverse variety of antigen receptors by rearrangement of the DNA

25. Variable region Constant region
Figure 35.10
DNA of undifferentiated B cell
V37
V38
V39
V40 J1 J2 J3 J4 J5
Intron C 1
Recombination deletes DNA between randomly selected V segment and J segment
DNA of differentiated B cell
V37
V38
V39 J5
Intron C
Functional gene 2
Transcription of permanently rearranged, functional gene
pre-mRNA
V39 J5
Intron C 3
RNA processing
Figure Immunoglobulin (antibody) gene rearrangement
mRNA
Cap
V39 J5 C
Poly-A tail V V 4
Translation V V C C
Light-chain polypeptide V C
Antigen receptor C C
Variable region
Constant region
B cell 25

26. DNA of undifferentiated B cell
Figure 35.10a
DNA of undifferentiated B cell
V37
V38
V39
V40 J1 J2 J3 J4 J5
Intron C
DNA of differentiated B cell 1
Recombination deletes DNA between randomly selected V segment and J segment
V37
V38
V39 J5
Intron C
Functional gene
Figure 35.10a Immunoglobulin (antibody) gene rearrangement (part 1) 2
Transcription of permanently rearranged, functional gene
pre-mRNA
V39 J5
Intron C 26

27. Light-chain polypeptide
Figure 35.10b
pre-mRNA
V39 J5
Intron C 3
RNA processing
mRNA
Cap
V39 J5 C
Poly-A tail V V 4
Translation V V C C
Light-chain polypeptide V C
Figure 35.10b Immunoglobulin (antibody) gene rearrangement (part 2)
Antigen receptor C C
Variable region
Constant region
B cell 27

28. Self-Tolerance
As lymphocytes mature they are tested, self-reactive ones are eliminated

29. Activated B or T cells divide producing clones (called clonal selection)
Two types produced
Short-lived effector cells - act immediately against the antigen
Long-lived memory cells – can produce effector cells if the same antigen is encountered again

30. B cells that differ in antigen specificity Antigen Antigen receptor
Figure 35.11
B cells that differ in antigen specificity
Antigen
Antigen receptor
Figure Clonal selection
Antibody
Memory cells
Plasma cells 30

31. Immunological Memory
1st exposure - primary immune response
B and T cells give rise to their effector forms
Later exposures - secondary immune response, memory cells facilitate a faster, stronger, and longer response
Immunological memory can span many decades

32. Antibody concentration (arbitrary units)
Figure 35.12
Primary immune response to antigen A
Secondary immune response to antigen A
Primary immune response to antigen B
104
103
Antibodies to A
Antibody concentration (arbitrary units)
102
Antibodies to B
101
Figure The specificity of immunological memory
100 7 14 21 28 35 42 49 56
Exposure to antigen A
Exposure to antigens A and B
Time (days) 32

33. Adaptive immunity
B and T lymphocytes produce a humoral and a cell-mediated immune response
humoral immune response, antibodies help neutralize or eliminate toxins and pathogens in the blood and lymph
cell-mediated immune response specialized T cells destroy infected host cells

34. Cytotoxic T Cells:
Cytotoxic T cells recognize foreign proteins produced by infected cells and trigger apoptosis

35. Cytotoxic T cell Accessory protein Antigen receptor
Figure
Cytotoxic T cell
Accessory protein
Antigen receptor
Class I MHC molecule
Infected cell
Figure The killing action of cytotoxic T cells on an infected host cell (step 1)
Antigen fragment 1 35

36. Cytotoxic T cell Granzymes Perforin Accessory protein Antigen receptor
Figure
Cytotoxic T cell
Granzymes
Perforin
Accessory protein
Antigen receptor
Class I MHC molecule
Pore
Infected cell
Figure The killing action of cytotoxic T cells on an infected host cell (step 2)
Antigen fragment 1 2 36

37. Released cytotoxic T cell Granzymes Perforin
Figure
Cytotoxic T cell
Released cytotoxic T cell
Granzymes
Perforin
Accessory protein
Antigen receptor
Dying infected cell
Class I MHC molecule
Pore
Infected cell
Figure The killing action of cytotoxic T cells on an infected host cell (step 3)
Antigen fragment 1 2 3 37

38. B Cells and Antibodies: A Response to Extracellular Pathogens
humoral response - characterized by secretion of antibodies by B cells

39. Antigen- presenting cell Pathogen
Figure
Antigen- presenting cell
Pathogen
Antigen fragments
MHC
CD4
Antigen receptor
Figure Activation of a B cell in the humoral immune response (step 1)
Helper T cell 1 39

40. Antigen- presenting cell Pathogen
Figure
Antigen- presenting cell
Pathogen
B cell
Antigen fragments
MHC
CD4
Cytokines
Antigen receptor
Figure Activation of a B cell in the humoral immune response (step 2)
Activated helper T cell
Helper T cell 1 2 40

41. Antigen- presenting cell Pathogen
Figure
Antigen- presenting cell
Pathogen
B cell
Memory B cells
Antigen fragments
MHC
CD4
Cytokines
Antigen receptor
Figure Activation of a B cell in the humoral immune response (step 3)
Activated helper T cell
Plasma cells
Secreted antibodies
Helper T cell 1 2 3 41

42. Antibodies... …mark pathogens for destruction
…prevent infection by binding to virus
…bind to toxins.

43. Humoral (antibody-mediated) immune response
Figure 35.16a
Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Antigen (1st exposure)
Stimulates
Engulfed by
Gives rise to
Antigen- presenting cell
Figure 35.16a An overview of the adaptive immune response (part 1)
Cytotoxic T cell
B cell
Helper T cell 43

44. Humoral (antibody-mediated) immune response
Figure 35.16b
Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Stimulates
Gives rise to
Cytotoxic T cell
B cell
Helper T cell
Memory helper T cell
Figure 35.16b An overview of the adaptive immune response (part 2)
Antigen (2nd exposure)
Plasma cells
Memory B cells
Memory cytotoxic T cells
Active cytotoxic T cells
Secreted antibodies
Defend against extracellular pathogens
Defend against intracellular pathogens and cancer 44

45. Immunization Active immunization -
Antigen-containing material is injected
long-lasting immunity
Passive –
antibody is injected
Protection is short lived

46. Vaccines
Fig a, p.694

47. Allergies
Immune reaction to a harmless substance

48. Fig a, p.694

49. Fig b, p.694