1. IMMUNITY
Chapter 35

2. IMMUNE SYSTEM Immune System
Enables an animal to avoid or limit many infections
2 types of immunity
Innate
Non specific responses to pathogens
Consists of external barriers plus internal cellular and chemical defenses
Adaptive
Develops after exposure to agents
Requires a very specific response to pathogens

3. 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
Figure 35.2 Overview of animal immunity
• Rapid response
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 3

4. Innate Barrier Defenses
Barriers at body surfaces
Intact skin
Mucus membranes
Traps and allows removal of microbes
Prevents colonization
Lysozyme
Break down bacterial cell walls
Tear / Saliva
Low pH

5. Barriers at Body Surface

6. Innate Cellular Defenses
Nonspecific Responses
Lymph nodes
Types of phagocytic cells
Neutrophills
Circulate in the blood
Attracted by signals from infected tissues
Macrophages
Found throughout the body

7. Innate Cellular Defenses
Dendritic cells
Stimulate development of adaptive immunity in cells that contact the environment
Eosinophils
Discharge destructive enzymes beneath mucus surfaces
Natural Killer cells (NK)
Circulate through body and detect abnormal cells
Release chemicals leading to cell death
Inhibit the spread of virally infected or cancerous cells

8. Innate Cellular Defenses
Antimicrobial Peptides and Proteins
pathogen recognition triggers release of peptides and proteins that attack pathogens or impede their reproduction
Interferons
provide innate defense, interfering with viruses and helping activate macrophages
Complement system
consists of about 30 proteins that are activated by substances on microbe surfaces
Activation can lead to lysis of invading cells

9. Cells Involved in Immune Responses
neutrophil
basophil
mast cell
eosinophil
NK cell
B lymphocyte
T lymphocyte

10. Cells Involved in Immune Responses
dendritic cell
macrophage

11. Chemical Weapons in Immunity

12. Innate Cellular Defenses
Inflammatory Response
Purpose
Destroys invaders
removes debris
promotes healing
Mast cells release histamine
Enhanced blood flow to the site helps deliver antimicrobial peptides
This results in an accumulation of pus, a fluid rich in white blood cells, dead pathogens, and cell debris from damaged tissues

13. 1 Pathogen Splinter Macro- phage Signaling molecules Mast cell
Figure Major events in a local inflammatory response (step 1)
Capillary
Red blood cells
Neutrophil 1
Histamines and cytokines released. Capillaries dilate. 13

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

15. 1 2 3 Pathogen Splinter Movement of fluid Macro- phage
Signaling molecules
Mast cell
Figure Major events in a local inflammatory response (step 3)
Capillary
Phagocytosis
Red blood cells
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. 15

16. Adaptive Immunity The adaptive response relies Lymphocytes
mature in the thymus
T cells
mature in the bone marrow
B cells
white blood cells

17. Antigen receptors Mature B cell Mature T cell
Figure 35.UN01 In-text figure, lymphocytes, p. 715
Mature B cell
Mature T cell 17

18. Antigens
substances that can elicit a response from a B or T cell
Recognition occurs when a B or T cell binds to an antigen, via an antigen receptor
Epitope
accessible part of an antigen that binds to an antigen receptor

19. Antigen Recognition by B Cells and Antibodies
Each B cell antigen receptor is a Y-shaped molecule
The constant (C) regions of the chains vary little among B cells, whereas the variable (V) regions differ greatly

20. B cell antigen receptor Constant regions
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
Figure 35.6 The structure of a B cell antigen receptor
Transmembrane regions
Heavy chains
Plasma membrane
B cell
Cytoplasm of B cell 20

21. Binding of a B cell antigen receptor to an antigen is an early step in B cell activation
This gives rise to cells that secrete a soluble form of the protein called an antibody or immunoglobulin (Ig)
Secreted antibodies are similar to B cell receptors but are not membrane bound
The antibodies, rather than B cells themselves, defend against pathogens

22. Animation: Antibodies
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23. 5 Classes of Immunoglobulins
IgG
found in blood plasma
all body fluids
smallest but most common
primary and secondary response
IgA
found in your nose, digestive tract, ears, eyes
protects mucous membranes
saliva, mucus tears, breast milk

24. 5 Classes of Immunoglobulins
IgM
found in the blood and lymph
used to fight a new infection
causes clumping of antigens, transfusion reactions
IgE
found in your lungs, skin
responsible for allergic reactions
IgD
found in your stomach, chest
very small amount

25. 5 Classes of Immunoglobulins
IgG, IgD, and IgE
IgA
IgM

26. (a) B cell antigen receptors and antibodies
Antibody
B cell
Antigen
Epitope
Pathogen
Figure 35.7 Antigen recognition by B cells and antibodies
(a) B cell antigen receptors and antibodies
Antibody C
Antibody A
Antibody B
Antigen
(b) Antigen receptor specificity 26

27. Antigen Recognition by T Cells
Each T cell receptor consists of two different polypeptide chains (called  and )
The tips of the chain form a variable (V) region; the rest is a constant (C) region
The V regions of the a and b chains together form an antigen-binding site

28. T cell antigen receptor Variable regions V V
Antigen- binding site
T cell antigen receptor
Variable
regions V V C C
Constant
regions
Figure 35.8 The structure of a T cell antigen receptor
Disulfide bridge
Transmembrane region
 chain
 chain
Plasma membrane
T cell
Cytoplasm of T cell 28

29. Antigen Recognition by T Cells
In infected cells, antigens are cleaved into smaller peptides by enzymes
T cells bind only to antigen fragments displayed or presented on a host cell
MHC (major histocompatibility complex)
MHC molecules bind and transport the antigen fragments to the cell surface, a process called antigen presentation
This interaction is necessary for the T cell to participate in the adaptive immune response

30. Displayed antigen fragment T cell
T cell antigen receptor
MHC molecule
Figure 35.9 Antigen recognition by T cells
Antigen fragment
Pathogen
Host cell 30

31. B Cell and T Cell Development
The adaptive immune system has four major characteristics
Diversity of lymphocytes and receptors
Self-tolerance; lack of reactivity against an animal’s own molecules
Proliferation of B and T cells after activation
Immunological memory

32. Generation of B and T Cell Diversity
By combining variable elements, the immune system assembles a diverse variety of antigen receptors
The capacity to generate diversity is built into the structure of Ig genes
Many different chains can be produced from the same gene by rearrangement of the DNA
Rearranged DNA is transcribed and translated and the antigen receptor formed

33. 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
Figure 35.10a Immunoglobulin (antibody) gene rearrangement (part 1)
V37
V38
V39 J5
Intron C
Functional gene 2
Transcription of permanently rearranged, functional gene
pre-mRNA
V39 J5
Intron C 33

34. Light-chain polypeptide
pre-mRNA
V39 J5
Intron C 3
RNA processing
mRNA
Cap
V39 J5 C
Poly-A tail V
Figure 35.10b Immunoglobulin (antibody) gene rearrangement (part 2) V 4
Translation V V C C
Light-chain polypeptide V C
Antigen receptor C C
Variable region
Constant region
B cell 34

35. Proliferation of B Cells and T Cells
In the body only a tiny fraction of antigen receptors are specific for a given epitope
In the lymph nodes, an antigen is exposed to a steady stream of lymphocytes until a match is made
This binding of a mature lymphocyte to an antigen initiates events that activate the lymphocyte

36. Proliferation of B Cells and T Cells
Once activated, a B or T cell undergoes multiple cell divisions to produce a clone of identical cells (called clonal selection)
Two types of clones are produced
effector cells
short lived
act immediately against the antigen
memory cells
long lived
can give rise to effector cells if the same antigen is encountered again

37. Animation: Role of B Cells
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38. Immunological Memory
Immunological memory is responsible for long-term protections against diseases, due to a prior infection
primary immune response
first exposure to a specific antigen represents the selected B and T cells give rise to their effector forms and memory forms
secondary immune response
memory cells facilitate a faster, stronger, and longer response
Immunological memory can span many decades

39. Primary and Secondary Immune Response

40. Humoral vs Cell-Mediated
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

41. Helper T Cells: A Response to Nearly All Antigens
A type of T cell called a helper T cell triggers both the humoral and cell-mediated immune responses
Antigen-presenting cells are recognized by the helper T cells
Signals are then exchanged between the two cells
The helper T cell is activated, proliferates, and forms a clone of helper T cells, which then activate the appropriate B cells

42. Animation: Helper T Cells
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43. Cell-mediated immunity
Antigen- presenting cell
Antigen fragment
Pathogen
Class II MHC molecule 1
Accessory protein (CD4)
Antigen receptor
Helper T cell
Figure The central role of helper T cells in humoral and cell-mediated immune responses
Cytokines 2 3 3
B cell
Cytotoxic T cell
Humoral immunity
Cell-mediated immunity 43

44. Cytotoxic T Cells: A Response to Infected Cells
effector cells in the cell-mediated immune response
recognize fragments of foreign proteins produced by infected cells
secretes proteins that disrupt the membranes of target cells and trigger apoptosis

45. Animation: Cytotoxic T Cells
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46. Cytotoxic T cell Accessory protein Antigen receptor
Class I MHC molecule
Figure The killing action of cytotoxic T cells on an infected host cell (step 1)
Infected cell
Antigen fragment 1 46

47. Cytotoxic T cell Granzymes Perforin Accessory protein Antigen receptor
Class I MHC molecule
Figure The killing action of cytotoxic T cells on an infected host cell (step 2)
Pore
Infected cell
Antigen fragment 1 2 47

48. Released cytotoxic T cell Granzymes Perforin
Accessory protein
Antigen receptor
Dying infected cell
Class I MHC molecule
Figure The killing action of cytotoxic T cells on an infected host cell (step 3)
Pore
Infected cell
Antigen fragment 1 2 3 48

49. B Cells and Antibodies: A Response to Extracellular Pathogens
The humoral response is characterized by secretion of antibodies by clonally selected B cells
Activation of B cells involves helper T cells and proteins on the surface of pathogens
In response to cytokines from helper T cells and an antigen, a B cell proliferates and differentiates into memory B cells and antibody-secreting effector cells called plasma cells

50. Antigen- presenting cell Pathogen
Antigen fragments
MHC
Figure Activation of a B cell in the humoral immune response (step 1)
CD4
Antigen receptor
Helper T cell 1 50

51. Antigen- presenting cell Pathogen
B cell
Antigen fragments
MHC
Figure Activation of a B cell in the humoral immune response (step 2)
CD4
Cytokines
Antigen receptor
Activated helper T cell
Helper T cell 1 2 51

52. Antigen- presenting cell Pathogen
B cell
Memory B cells
Antigen fragments
MHC
Figure Activation of a B cell in the humoral immune response (step 3)
CD4
Cytokines
Antigen receptor
Activated helper T cell
Plasma cells
Secreted antibodies
Helper T cell 1 2 3 52

53. Antibodies do not kill pathogens; instead, they mark pathogens for destruction
In neutralization, antibodies bind to viral surface proteins, preventing infection of a host cell
Antibodies may also bind to toxins in body fluids and prevent them from entering body cells
Antigen-antibody complexes may bind to a complement protein
A cascade of subsequent events leads to formation of a pore in the membrane of the foreign cell, leading to its lysis

54. Animation: Immunology

55. Figure 35.16 An overview of the adaptive immune response
Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Antigen (1st exposure)
Stimulates
Engulfed by
Gives rise to
Antigen- presenting cell
Cytotoxic T cell
B cell
Helper T cell
Figure An overview of the adaptive immune response
Memory helper T cell
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 55

56. Autoimmune Disorders
Immune system makes antibodies against self antigens
Grave’s disease
hyperthyroidism
Myasthenia gravis
body produces antibodies that prevent muscles from receiving message from nerve cell
Type I Diabetes
Celiacs
Villi becomes damaged due to gluten

57. Active and Passive Immunization
Active immunity
occurs naturally when a pathogen infects the body
induced when antigens are introduced into the body in vaccines
Passive immunity
provides immediate, short-term protection
naturally when antibodies cross the placenta from mother to fetus or pass from mother to infant in breast milk
conferred artificially by injecting antibodies into a nonimmune person