1. Chapter 43. Immune System phagocytic leukocyte lymphocytes attacking
cancer cell
lymph
system

2. Why an immune system? Attack from outside Attack from inside
animals must defend themselves against unwelcome invaders
viruses  protists
bacteria  fungi
we are a tasty vitamin-packed meal
cells are packages of macromolecules
no cell wall
traded mobility for susceptibility
Attack from inside
defend against abnormal body cells = cancers

3. Lines of defense 1st line: Barriers 2nd line: Non-specific patrol
broad, innate, external defense
“barbed wire”
skin & mucus membranes
2nd line: Non-specific patrol
broad, innate, internal defense
“untrained soldiers”
leukocytes (WBCs)
3rd line: Immune system
specific, acquired immunity
“elite trained units”
lymphocytes & antibodies

4. 1st: External defense non-specific defense external barrier
epithelial cells & mucus membranes
skin
respiratory system
digestive system
genito-urinary tract
Lining of trachea: ciliated cells & mucus secreting cells

5. 1st: Chemical barriers on epithelium
Skin & mucous membrane secretions
sweat
pH 3-5
tears
washing action
mucus
traps microbes
saliva
anti-baterial = “lick your wounds”
stomach acid
pH 2-3
anti-microbial proteins
lysozyme
digests bacterial cell walls

6. 2nd: Internal, broad range patrol
innate defense
rapid response
cells & proteins
attack invaders that penetrate body’s outer barriers
leukocytes
phagocytic white blood cells
anti-microbial proteins
inflammatory response
natural killer cells
leukocytes

7. Leukocytes: Phagocytic WBCs
Neutrophils
attracted by chemical signals released by damaged cells (interferon)
enter infected tissue, engulf & ingest microbes
amoeba-like
lysosomes
~3 day life span
Macrophages
“big eater”
bigger, long-lived phagocytes

8. Phagocytes
macrophage
yeast

9. Lymph system Production & transport of leukocytes
Traps foreign invaders
Lymph system
lymph vessels
(intertwined amongst blood vessels)
lymph node

10. Development of Red & White blood cells
Red blood cells
inflammatory response
fight parasites
develop into macrophages
short-lived phagocytes
60-70% WBC

11. Inflammatory response
Reaction to tissue damage
Pin or splinter
Blood clot
swelling
Bacteria
Chemical
alarm signals
Phagocytes
Blood vessel

12. Inflammatory response
Damage to tissue triggers local inflammatory response
histamines & prostaglandins released
capillaries dilate, more permeable
lead to clot formation
increased blood supply
swelling, redness & heat of inflammation & infection
delivers WBC, RBC, platelets, clotting factors

13. Fever When a local response is not enough
systemic response to infection
activated macrophages release interleukin-1
triggers hypothalamus in brain to readjust body thermostat to raise body temperature
higher temperature helps defense
inhibits bacterial growth
stimulates phagocytosis
speeds up repair of tissues
causes liver & spleen to store iron reducing blood iron levels
bacteria need large amounts of iron to grow
Certain bacterial infections can induce an overwhelming systemic inflammatory response leading to a condition known as septic shock.
Characterized by high fever and low blood pressure, septic shock is the most common cause of death in U.S. critical care units.
Clearly, while local inflammation is an essential step toward healing, widespread inflammation can be devastating.

14. 3rd: Acquired Immunity Specific defense Responds to… lymphocytes
B lymphocytes (B cells)
T lymphocytes (T cells)
antibodies
immunoglobulins
Responds to…
specific microorganisms
specific toxins
abnormal body cells
antigens

15. Antigens Proteins that serve as cellular name tags
foreign antigens cause response from WBCs
proteins belonging:
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
invaders in blood & lymph
T cells recognize antigen fragments
invaders which have infected cells
“self”
“foreign”

16. Lymphocytes B cells T 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
Tens of millions of different T cells are produced, each one specializing in the recognition of oen particar antigen.

17. B cells Humoral response = “in fluid” Specific response
defense against attackers circulating freely in blood & lymph
Specific response
recognizes specific antigen
produces antibodies against it
tagging protein = immunogloblin
millions of different B cells, each produces different antibodies, each recognizes a different antigen
types of B cells
plasma cells
immediate production of antibodies
short term release
memory cells
long term immunity

18. each B cell has ~100,000 antigen receptorsY Y Y Y Y
Antibodies Y Y Y
Proteins that bind to a specific antigen
multi-chain proteins produced by B cells
antibodies match molecular shape of antigens
immune system has antibodies to respond to millions of antigens (invaders)
tagging system
“this is foreign!” Y Y Y Y Y Y Y
variable binding region Y Y Y Y
each B cell has ~100,000 antigen receptors

19. How antibodies work

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

21. 1° vs 2° response to disease
Memory B cells allow a rapid, amplified response with future exposure to pathogen

22. How can we have so many antibody proteins & so few genes?
Variable region
Antibody
Constant region
Light chain
B cell
Heavy chain
Variable DNA combinations:
• 1M different B cells
• 10M different T cells
Translation of mRNA
Rearrangement
of DNA
Transcription
of gene V
mRNA
40 genes for Variable region
DNA of
differentiated
B cell D J C C
Chromosome
of undifferentiated B cell

23. Vaccinations Active immunity
immune system exposed to harmless version of pathogen
Stimulates immune system to produce antibodies to invader
rapid response if future exposure
Most successful against viral diseases

24. Jonas Salk 1914 – 1995 Developed first vaccine against polio
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.
April 12, 1955

25. Polio epidemics
1916 The first major polio epidemic strikes in the United States; 27,000 people suffer paralysis and 6,000 die. Increasing numbers of outbreaks occur each year.
1921 Franklin D. Roosevelt is diagnosed with polio.
1928 Iron lungs are introduced to help patients with acute polio breathe.
1932 Franklin D. Roosevelt is elected President of the United States
1949 Dr. John Enders, Dr. Frederick Robbins and Dr. Thomas Weller develop a way to grow poliovirus in tissue culture, a breakthrough that aided in the creation of the polio vaccine. Their work earned the three scientists the Nobel Prize in physiology and medicine in 1954.
1952 The United States reports 57,628 polio cases -- the worst U.S. epidemic on record.
1979 The last U.S. case of polio caused by wild poliovirus is reported.
1988 Worldwide, polio continues to affect some 350,000 people in 125 countries.
1994 The Americas are certified polio-free.
2000 The Western Pacific region is certified polio-free.
2002 Europe is certified polio-free.

26. Passive immunity Maternal immunity Injection
antibodies pass from mother to baby across placenta or in breast 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

27. T cells Immune response to infected cells Kinds of T cells
defense against invaders inside infected cells
viruses & bacteria within infected cells, fungi, protozoa & parasitic worms
defense against “non-self” cells
cancer & transplant cells
Kinds of T cells
helper T cells
stimulate immune system
killer T cells
attack infected body cells

28. How are cells tagged with antigens
Glycoproteins on surface of cells have unique “fingerprint”
major histocompatibility proteins (MHC)
human leukocyte antigens (HLA)
MHC proteins constantly export bits of cellular protein to cell surface
“snapshot” of what is going on inside cell
T cell
MHC proteins
displaying self-antigens

29. How do T cells know a cell is infected
Infected cells digest some pathogens & export pieces to MHC proteins on cell surface
antigen presenting cells (APC)
invading
pathogen
MHC proteins
displaying foreign antigens
T cell
T cell antigen receptors

30. activate killer T cells stimulate B cells & antibodies
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

31. 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
Perforin punctures cell membrane
Cell membrane
Cell membrane
Infected cell
destroyed
Target cell

32. pathogen invasion antigen exposure antigens on infected cells
Immune response
pathogen invasion antigen exposure
free antigens in blood
antigens on infected cells
macrophages
humoral response
cellular response
B cells
helper T cells
T cells
plasma B cells
memory B cells
memory T cells
cytotoxic T cells Y
antibodies

33. 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 or cancer

34. 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, from dust mites, in animal saliva

35. 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