1. IMMUNE SYSTEM
FOR STUDENT COPY

2. Key attributes of immune system
4 attributes that characterize the immune system as a whole
specificity
antigen-antibody specificity
diversity
react to millions of antigens
memory
rapid 2° response
ability to distinguish self vs. non-self
maturation & training process to reduce auto-immune disease

3. Immune System must be able to identify nonself from self
detection determined by molecular recognition of receptor & cell-identity markers molecules

5. Innate Immunity
nonspecific defense that is active immediately upon infection
found in all animals & plants
includes:
outer covering
skin
chemical secretions
@ openings to interior of body
Mucous membranes
Sweat glands

6. Innate Immunity defenses that body naturally has: Skin Secretions
Phagocytes
Natural killer cells

7. Barrier Defenses epithelial tissues block entry of many pathogens skin
mucous membranes
line organs that have opening to outside of body
mucus: viscous fluid that blocks microbes & other particles
saliva, tears have “washing” action keeping microbes from colonizing

8. Barrier Defenses cellular secretions
lysozyme kills by breaking down cell walls
saliva, tears dilute & prevent colonization
sweat pH 3 – 4
stomach pH 2

9. Adaptive Immunity found only in vertebrates very specific
aka acquired immune response
activated after innate responses & develops more slowly

10. 2nd line: Internal, broad range patrol
Innate, general defense
rapid response
Patrolling cells & proteins
attack invaders that penetrate body’s outer barriers
leukocytes
phagocytic white blood cells
complement system
anti-microbial proteins
inflammatory response
leukocytes

11. Internal Innate Defenses
1. phagocytes
cells that can detect fungi & bacteria
then engulf them

13. Types of Phagocytic Cells(#4)
Neutrophils
circulate in blood
attracted by signals sent from infected cells
Macrophages
larger cells migrate thru tissues or reside permanently in organs/tissues likely to have invaders

14. Types of Phagocytic Cells
3. Dendritic cells
mainly found in tissues with contact to outside (skin)
stimulate adaptive immunity after engulfing pathogen
4. Eosinophils
found beneath mucous membranes
low phagocytic activity
speciality: able to defend against parasitic worms  secrete enzymes

15. Neutrophils 60 to70 % of all WBCs Active phagocytes
Number increases rapidly during short term or acute infections

16. Eosinophils 2 to 4 % of all WBCs Increase during allergy attacks
React to parasitic worms
Inactivate some inflammatory chemicals

18. Lymphocytes 20 to 25 % of all WBCs
Provides Immunity (eg. Killer T-Cell)
Produces antibodies
Nucleus fills most of the cell

19. Inflammatory Response
innate immune defense triggered by physical injury or infection of tissue involving the release of substances that promote swelling, enhance the infiltration of WBCs, & aid in tissue repair & destruction of invading pathogens

20. Inflammatory Response

21. Histamine 1 of inflammatory signaling molecules
stored in granules of mast cells (in CT)

22. Fever: Abnormally High Body Temperature
Hypothalamus normally set at 37°C.
Gram-negative endotoxin cause phagocytes to release interleukin–1 (IL–1).
Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature.
Body increases rate of metabolism and shivering which raise temperature.
When IL–1 is eliminated, body temperature falls (crisis).

23. Fever Advantages Disadvantages Increase transferrins Tachycardia
Increase IL–1 activity
Disadvantages
Tachycardia
Acidosis
Dehydration

24. Some Pathogens Evade Innate Immunity
Bacteria:
some have outer capsule that interferes with recognition & phagocytosis
Streptococcus pneumoniae

25. Natural Killer Cells
circulate thru body detecting abnl surface proteins of cells infected with virus or cancer cells
on detection  secrete chemicals that kill affected cell

26. Destroying cells gone bad!
Natural Killer Cells perforate cells
release perforin protein
insert into membrane of target cell
forms pore allowing fluid to flow into cell
cell ruptures (lysis)
apoptosis
vesicle
natural killer cell
perforin
cell membrane
perforin punctures cell membrane
cell membrane
virus-infected cell

27. Anti-microbial proteins
Complement system
~20 proteins circulating in blood plasma
attack bacterial & fungal cells
form a membrane attack complex
perforate target cell
apoptosis
cell lysis
extracellular fluid
complement proteins form cellular lesion
plasma membrane of invading microbe
complement proteins
bacterial cell

28. 3rd line: Acquired (active) Immunity
Specific defense
lymphocytes
B lymphocytes (B cells)
T lymphocytes (T cells)
antibodies
immunoglobulins
Responds to…
antigens
specific pathogens
specific toxins
abnormal body cells (cancer)

29. 4 Major Characteristics of Acquired Immunity
immense diversity of lymphocytes & receptors
enables immune system to detect pathogens never before encountered
adaptive immunity normally has “self” tolerance
arises as B cell matures

30. 4 Major Characteristics of Adaptive Immunity
cell proliferation triggered by activation greatly increases the # of B and T cells
there is a stronger & more rapid response to agn previously encountered
immunological memory occurs after mature lymphocyte encounters & binds to a specific agn

31. How are invaders recognized: antigens
proteins that serve as cellular name tags
foreign antigens cause response from WBCs
viruses, bacteria, protozoa, parasitic worms, fungi, toxins
non-pathogens: pollen & transplanted tissue
B cells & T cells respond to different antigens
B cells recognize intact antigens
pathogens in blood & lymph
T cells recognize antigen fragments
pathogens which have already infected cells
“self”
“foreign”

32. Thymus organ in thoracic cavity
some new lymphocytes travel from bone marrow  thymus & are “taught” how to respond in immune attack  mature into T cells

33. Lymphocytes B cells T cells
bone marrow
B cells
mature in bone marrow
humoral response system
“humors” = body fluids
produce antibodies
T cells
mature in thymus
cellular response system
Learn to distinguish “self” from “non-self” antigens during maturation
if they react to “self” antigens, they are destroyed during maturation
Tens of millions of different T cells are produced, each one specializing in the recognition of oen particar antigen.

34. B cells Humoral response = “in fluid” Specific response
defense against attackers circulating freely in blood & lymph
Specific response
produce specific antibodies against specific antigen
Types of B cells
plasma cells
immediate production of antibodies
rapid response, short term release
memory cells
long term immunity

35. Antibodies Proteins that bind to a specific antigenY Y Y Y Y Y Y Y Y Y
Proteins that bind to a specific antigen
multi-chain proteins produced by B cells
binding region matches molecular shape of antigens
each antibody is unique & specific
millions of antibodies respond to millions of foreign antigens
tagging “handcuffs”
“this is foreign…gotcha!” Y Y Y
antigen- binding site on antibody
antigen Y Y Y Y
variable binding region Y Y
each B cell has ~100,000 antigen receptors

36. Structure of antibodiesY Y
antigen-binding site Y Y Y s Y
variable region Y Y Y Y Y
light
chain
light
chain
light chains
antigen-binding
site
heavy chains
heavy
chains
B cell
membrane

37. How antibodies work Y invading pathogens tagged with antibodies
macrophage eating tagged invaders
invading pathogens tagged with antibodies Y

38. B Cell Activation starts when agn binds to a B cell agn receptor
ends with B cell secreting soluble form of its agn receptor = antibody (aby) or immunoglobulin (Ig)
abys have same “Y” shaped organization as the B cell agn receptor

39. B cell immune response 10 to 17 days for full response
B cells + antibodies Y
invader (foreign antigen)
tested by B cells
(in blood & lymph)
memory cells
“reserves” Y Y
recognition Y
captured invaders Y
clone
1000s of clone cells
plasma cells
release antibodies Y Y

40. Humoral Immunity B-Cells
Long Term Memory
B-Cells make antibodies which trigger a T-Cell reaction to kill the invader
Vaccines, Chicken Pox, Viral Infections
Humoral
Immunity
(Go animation)

41. Types of Antibodies IgG IgA IgM
major immunoglobulin in extra vascular spaces
crosses placenta
IgA
in secretions
IgM
1st immunoglobulin to be made by fetus
very good at clumping microorganisms

42. Types of Antibodies IgD IgE mostly found on B cell surfaces
involved in allergic reactions
levels rise in helminthic parasitic infections (worms)

43. Antibody Function do not kill pathogens
bind to agns  inactivation or destruction

45. Immunological Memory
gives individual long term protection from an infection or vaccination
Primary Immune Response
produces effector cells from a clone of lymphocytes
peaks days after initial exposure

46. 1° vs 2° response to disease
Memory B cells allow a rapid, amplified response with future exposure to pathogen

48. Humoral Immune Response
occurs in blood & lymph
abys neutralize or eliminate toxins & pathogen in blood or lymph
includes a primary & secondary immune response

49. Cell-Mediated Immune Response
specialized T cells destroy infected host cells
includes primary & secondary immune responses

50. Vaccinations Immune system exposed to harmless version of pathogen
triggers active immunity
stimulates immune system to produce antibodies to invader
rapid response if future exposure
Most successful against viral diseases

51. Jonas Salk 1914 – 1995 Developed first vaccine against polio
April 12, 1955
Developed first vaccine
against polio
attacks motor neurons
Albert Sabin
1962
oral vaccine
Poliomyelitis (polio) is caused by a virus that enters the body through the mouth. The virus multiplies in the intestine and invades the nervous system. It can cause total paralysis in a matter of hours.
One in 200 infections leads to irreversible paralysis. Among those paralyzed, 5-10 percent die when their breathing muscles are immobilized.
Polio mainly affects children under age 5.
Salk vaccine = inactivated poliovirus vaccine (IPV), based on poliovirus grown in a type of monkey kidney tissue culture, which is chemically inactivated with formalin
Sabin vaccine = oral polio vaccine (OPV) using live but weakened (attenuated) virus, produced by the repeated passage of the virus through non-human cells at sub-physiological temperatures

52. Passive Immunity Obtaining antibodies from another individual
Maternal immunity
antibodies pass from mother to baby across placenta or in mother’s milk
critical role of breastfeeding in infant health
mother is creating antibodies against pathogens baby is being exposed to
Injection
injection of antibodies
short-term immunity

53. Artificial Active Immunity
Immunizations: introduce agns to body  abys develop giving immunity to person receiving vaccination
Jenner: took cowpox virus to induce adaptive immunity against small pox (closely related viruses)

54. Small Pox Vaccination

55. Tissue & Organ Transplants
MHC molecules stimulate the immune response that  rejection
MHC molecules have many alleles and any 1 individual has many that vary in shape & charge
for most transplant recipients there will be some MHC molecules seen as foreign

56. Moon Face

57. Graft Versus Host Rejection
seen in bone marrow transplants
recipient’s bone marrow radiated b/4 to get rid of abnl cells  also wipes out their immune system
lymphocytes in donor’s marrow react to “foreign” recipients tissues and cells

59. Allergic Response agn attaches to IgE abys on mast cells
when cross linked  release of histamine  typical allergic symptoms of itchy eyes, sneezing, runny nose, teary eyes, smooth muscle contraction  constriction of airways

60. You need trained assassins to kill off these infected cells!
What if the attacker gets past the B cells in the blood & actually infects some of your cells?
You need trained assassins to kill off these infected cells! T
Attack of the Killer T cells!

61. T cells Cell-mediated response Types of T cells
immune response to infected cells
viruses, bacteria & parasites (pathogens) within cells
defense against “non-self” cells
cancer & transplant cells
Types of T cells
helper T cells
alerts immune system
killer (cytotoxic) T cells
attack infected body cells

62. How do T cells know a cell is infected?
Infected cells digest pathogens & MHC proteins bind & carry pieces to cell surface
antigen presenting cells (APC)
alerts Helper T cells
infected cell
MHC proteins displaying foreign antigens
T cell
WANTED
T cell antigen receptors

63. Cytotoxic T Cells in cell-mediated immune response
role: effector cells
synthesize toxic gene products that kill infected cells
activated by signaling molecules from helper T cells + interaction with APC

64. T Cell response killer T cell activate killer T cells
infected cell
helper T cell
interleukin 2
helper T cell
interleukin 1 or
stimulate B cells & antibodies Y
activated
macrophage
interleukin 2
helper T cell Y

65. Attack of the Killer T cells
Destroys infected body cells
binds to target cell
secretes perforin protein
punctures cell membrane of infected cell
vesicle
Killer T cell
Killer T cell binds to infected cell
cell membrane
perforin punctures cell membrane
cell membrane
infected cell
destroyed
target cell

66. HIV & AIDS Human Immunodeficiency Virus
virus infects helper T cells
helper T cells don’t activate rest of immune system: T cells & B cells
also destroy T cells
Acquired ImmunoDeficiency Syndrome
infections by opportunistic diseases
death usually from other infections
pneumonia, cancer

67. How to protect yourself…

68. Immune system malfunctions
Auto-immune diseases
immune system attacks own molecules & cells
lupus
antibodies against many molecules released by normal breakdown of cells
rheumatoid arthritis
antibodies causing damage to cartilage & bone
diabetes
beta-islet cells of pancreas attacked & destroyed
multiple sclerosis
T cells attack myelin sheath of brain & spinal cord nerves
Allergies
over-reaction to environmental antigens
allergens = proteins on pollen, dust mites, in animal saliva
stimulates release of histamine

69. Allergies
exaggerated hypersensitivity reactions to allergens: agn that triggers exaggerated immune response
most involve aby of IgE class
example:
hayfever
agn on surface of pollen grains

70. Autoimmune Diseases
Immune system reacts to some molecules of self

71. Stress & the Immune System
psychological stress disrupts immune system by altering interplay of the nervous system endocrine system & immune system
rest important for immunity
adults with < 7 hrs sleep/nite : 3x more likely to get sick when exposed to cold virus as those who average 8 hrs sleep/nite

72. Lymphatic System
network of vessels that connect lymphatic tissues thru out body
ECF  lymph vessels  lymph nodes  lymph vessels  venous drainage
some macrophages in lymph nodes

73. Lymphatic System