1. Topic 6: Human Physiology
Fighting the Enemy Within!
phagocytic leukocyte
Topic 6.3
Defense against the infectious disease
lymphocytes
attacking
cancer cell

2. What’s in your lunchbox?
Why an immune system?
Attack from outside
lots of organisms want you for lunch!
animals are a tasty nutrient- & vitamin-packed meal
cells are packages of macromolecules
no cell wall
traded mobility for susceptibility
animals must defend themselves against invaders
viruses
HIV, flu, cold, measles, chicken pox, SARS
bacteria
pneumonia, meningitis, tuberculosis
fungi
yeast (“Athlete’s foot”…)
protists
amoeba, Lyme disease, malaria
Attack from inside
defend against abnormal body cells = cancers
Mmmmm,
What’s in your lunchbox?

3. Avenues of attack Points of entry Routes of attack digestive system
respiratory system
urogenital tract
break in skin
Routes of attack
circulatory system
lymph system

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

5. Bacteria & insects inherit resistance. Vertebrates acquire immunity!
Lines of defense 1
1st line: Barriers
broad, external defense
“walls & moats”
skin & mucus membranes
2nd line: Non-specific patrol
broad, internal defense
“patrolling soldiers”
leukocytes = phagocytic WBC
macrophages
3rd line: Immune system
specific, acquired immunity
“elite trained units”
lymphocytes & antibodies
B cells & T cells
Bacteria & insects inherit resistance.
Vertebrates acquire immunity!

6. Lines of Defense 2
Nonspecific Defense Mechanisms……

7. 1st line: External defense
Physical & chemical defenses
non-specific defense
external barrier
epithelial cells & mucus membranes
skin
respiratory system
digestive system
uro-genital tract
Lining of trachea: ciliated cells & mucus secreting cells

8. 1st line: Chemical barriers on epithelium
Skin & mucous membrane secretions
sweat
pH 3-5
tears
washing action
mucus
traps microbes
saliva
anti-bacterial = “lick your wounds”
stomach acid
pH 2
anti-microbial proteins
lysozyme enzyme
digests bacterial cell walls

9. 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

10. Leukocytes: Phagocytic WBCs
Attracted by chemical signals released by damaged cells
enter infected tissue, engulf & ingest microbes
lysosomes
Neutrophils
most abundant WBC (~70%)
~ 3 day lifespan
Macrophages
“big eater”, long-lived
Natural Killer Cells
destroy virus-infected cells & cancer cells

11. Phagocytic and Natural Killer Cells
Neutrophils % WBCs; engulf and destroy microbes at infected tissue
Monocytes 5% WBCs; develop into….
Macrophages enzymatically destroy microbes
Eosinophils % WBCs; destroy large parasitic invaders (blood flukes)
Natural killer (NK) cells destroy virus-infected body cells & abnormal cells

12. Phagocytes
macrophage
yeast

13. 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

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

15. Inflammatory response 1
Damage to tissue triggers local non-specific inflammatory response
release histamines & prostaglandins
capillaries dilate, more permeable (leaky)
increase blood supply
delivers WBC, RBC, platelets, clotting factors
fight pathogens
clot formation
accounts for swelling, redness & heat of inflammation & infection

16. Inflammatory response 2
Reaction to tissue damage
Pin or splinter
Blood clot
swelling
Bacteria
Chemical
alarm signals
Phagocytes
Blood vessel

17. Fever When a local response is not enough
systemic response to infection
activated macrophages release interleukin-1 (IL-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.

18. The Inflammatory Response
1- Tissue injury; release of chemical signals~ • histamine (basophils/mast cells): causes Step • prostaglandins: increases blood flow & vessel permeability
2/3- Dilation and increased permeability of capillary~ • chemokines: secreted by blood vessel endothelial cells mediates phagocytotic migration of WBCs
4- Phagocytosis of pathogens~ • fever & pyrogens: leukocyte-released molecules increase body temperature

19. 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)

20. 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”

21. How are cells tagged with antigens
Major histocompatibility (MHC) proteins
antigen glycoproteins
MHC I – on all nucleated cells
MHC II – on macrophages, B-Ly, activated T-Ly
MHC proteins constantly carry bits of cellular material from the cytosol to the cell surface
“snapshot” of what is going on inside cell
give the surface of cells a unique label or “fingerprint”
Major Histocompatability Complex (MHC): body cell surface antigens coded by a family of genes
Class I MHC molecules: found on all nucleated cells
Class II MHC molecules: found on macrophages, B cells, and activated T cells
T cell
MHC proteins
displaying self-antigens

22. Specific Immunity
Lymphocyctes •pluripotent stem cells... • B Cells (bone marrow) • T Cells (thymus)
Antibodies: antigen-binding immunoglobulin, produced by B cells
Antigen = a foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms)
Antigen receptors = plasma membrane receptors on B and T cells

23. What else we’ll study? 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 T
Attack!
It’s too late…

24. To defend themselves against invaders!
Animals are a tasty nutrient- & vitamin-packed meal !
To defend
themselves
against invaders!
What’s the point?

25. HIV/AIDS - How to protect yourself…

26. 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

27. 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

28. It’s safe
to Ask Questions!

29. Ghost of Lectures past (storage)
Did I miss a joke? T

30. Abnormal immune function
Allergies (anaphylactic shock): hypersensitive responses to environmental antigens (allergens); causes dilation and blood vessel permeability (antihistamines); epinephrine
Autoimmune disease: multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus
Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S.

31. Induction of Immune Responses
Primary immune response: lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen
Plasma cells: antibody-producing effector B-cells
Secondary immune response: immune response if the individual is exposed to the same antigen at some later time~ Immunological memory