1. Immunity

2. Human Immune Defenses
Protection against foreign invaders (bacteria, viruses, fungi, etc.)
Three levels of defense:
First line of defense = barrier to prevent entry (skin, mucous membranes)
Second line of defense = general reaction to minimize infection via intruder (inflammation, etc.)
Third line of defense = specific reaction to minimize infection via intruder (MHC, antibodies, T cells, etc.)
Supplementary developments:
Antibiotics, vaccines, and passive immunity

3. First Line of Defense
Skin – physical barrier, covered with oily & acidic (pH 3-5) secretions from sweat glands
Antimicrobial proteins (e.g. lysozyme) – in saliva, tears, and other mucosal secretions
Cilia – line the lungs to sweep intruders up and out
Gastric juice – in stomach (pH ~2), kills most microbes
Symbiotic bacteria – in digestive tract and vagina, outcompete pathogenic organisms

4. Second Line of Defense Nonspecific mechanisms
Phagocytes – white blood cells (leukocytes) that phagocytose pathogens, circulate constantly
Complement – proteins (~20 different kinds) that attract phagocytes to foreign cells & promote lysis of pathogens, precursors circulate constantly
Interferons – secreted by cells infected with viruses, stimulate neighboring cells to produce proteins to defend against viral infection
Inflammation – swelling in response to tissue damage

5. Phagocytes: Neutrophils
Engulf pathogens via phagocytosis

6. Neutrophils Travel to infection site via chemotaxis
Remember this little guy from the
Inner Life of a Cell?

7. Phagocytes: Monocytes
Mature into large macrophages
Engulf pathogens via phagocytosis

8. Phagocytes: Natural Killer Cells
Attack pathogen-infected body cells
Attack abnormal body cells (tumors)
Nonspecific attack on compromised cells
Action based on activation and inhibitory receptors
Granules
containing
digestive
enzymes

9. Phagocytes: Natural Killer Cells
Loss of “self” ID tag, no longer inhibits NK cell

10. Complement Pathogen Detection
Antibodies bind pathogens and trigger compliment-activating enzymes
Pathogen surface receptors trigger complement-activating enzymes
Complement Activation
Inactive precursors in blood cleaved (by proteases) to become active compliment proteins
Amplification of Immune Response
Recruitment of Phagocytes
Enhancement of Phagocytosis of Pathogens
Perforation of Pathogen Cell Membrane (Lysis)

11. Complement: Perforation of Pathogens

12. Interferons

13. Inflammatory Response
Occurs when skin is damaged (damage allows pathogens to enter body)
Histamine secretion by basophils & mast cells (WBC), stimulates vasodialation
Vasodialation – increases blood supply to damaged area, allows WBC and fluids (including complement) to move easier through blood vessel walls (increased permeability of blood vessels)
Phagocytes attracted to site of injury by complement, engulf pathogens
Complement helps phagocytes, stimulates basophil secretion of histamine, helps lyse pathogens

14. Histamine Release
Basophils (WBC) normally circulate in blood (recruited into tissues when needed)
Mast cells (WBC) exist in tissues, particularly near interface with external environmental (skin, lungs, digestive, nose, mouth, eye)
Release histamines in response to pathogens or allergens
Pathogen or

15. Vasodialation Dialation (widening) of blood vessels
Causes redness, increase in temperature, and swelling
Increases delivery of WBC & complement to site of damage
Increase in temperature may stimulate WBC and make environment inhospitable to pathogens

16. Third Line of Defense Targets specific antigens (on pathogens)
Major histocompatibility complex (MHC) self vs. nonself proteins at surface of all cells
Lymphocytes (WBC)
B cells (make antibodies)
respond to antigens on pathogens
produce plasma & memory cells
T cells
respond to nonself cells
produce cytotoxic/killer T cells & helper T cells

17. Antigens
Antigen = any molecule (usually protein or polysaccharide) identified as foreign
Part of protein coat of virus
Unique molecule in plasma membrane of bacteria, protozoa, pollen, or other foreign cells
Toxin injected by insect sting

18. Antigen Presenting Cells: Macrophages & Dendritic Cells
Phagocytosis of pathogen
Presentation of antigens to other immune cells

19. Major histocompatibility complex (MHC)
Collection of glycoproteins (proteins with carbohydrate groups) on the membranes of all body cells (ID tag)
Each individual has unique MHC proteins
Self vs. Non-self recognition
Carbohydrate groups
Polypeptide
chains

20. MHC Class I & MHC Class II
>Found in all nucleated cells
>Function as “ID tag”
>Present antigens when cell is
infected or malignant
MHC Class II
>Found in antigen presenting cells
>Activate other immune cells
>Present antigens after phagocytosis
of pathogen

21. Antibodies On surface of B cells (antigen receptors)
Specific to particular antigens
Y-shaped proteins with constant and variable regions (variable provides antigen specificity)
5 classes (immunoglobulins): IgA, IgD, IgE, IgG, IgM (different particular activities)

22. Antibodies Inactivate antigens by binding to them
(phagocyte)
Agglutination and inactivation of pathogen

23. Antibodies
Binding “flags” cells for death (macrophage phagocytosis, compliment protein lysis)
Response to parasites
Macrophage
Flagged “foreign” cells

24. Antibodies Binding leads to B cell proliferation (by division):
Plasma cells – release antibodies to circulate through the body
Memory cells – long-lived, circulate & release antibodies with subsequent infection of same pathogen (immunity)

25. T cell Lymphocytes Work with MHC to identify/destroy non-self cells
Infected cell displays a combo of self and non-self markers (T cell interprets as non-self)
Cancer cells & transplant cells also interpreted as non-self
T cell
Cancer
cell

26. T cell Lyphocytes T cells encounter non-self cells, divide & produce:
Cytotoxic/killer T cells – recognize & destroy non-self cells by puncturing them (lysis) and activating apoptosis, induced by antigen-presenting cells
Helper T cells – stimulate production of B cells and cytotoxic T cells by secreting interleukins

27. Cytotoxic/Killer T cells
Lysis
Cytotoxic
T cell
Apoptosis

28. Don’t confuse your KILLERS!
Natural Killer Cells
Killer (Cytotoxic) T Cells
Second line of defense
Non-specific response
No APC activation
Circulate constantly (INNATE immunity)
Third line of defense
Specific response
Require APC activation
Proliferate in response to an infection (ADAPTIVE immunity)
Innate immunity is a non-specific and immediate response, responding in a general way that does not confer long-lasting immunity
Adaptive immunity is a specific and acquired response, producing antibodies and conferring long-lasting immunity through memory cells

29. Helper T cells

30. Immune Reactions Cell-mediated Response Humoral Response
Response to any non-self cells (including infected body cells and tumor cells)
Non-self cell binds to T cell
T cells produce cytotoxic T cells (destroy nonself cells) and helper T cells
Helper T cells bind to macrophages (that engulfed pathogens and are now presenting antigens)
Helper T cells produce interleukins (stimulate production of T cells and B cells)
Response to antigens or pathogens circulating in lymph/blood
B cells produce plasma cells and memory cells
Plasma cells release antibodies (bind to antigens)
Memory cells provide future immunity
Macrophage & helper T cells stimulate B cell production (helper T cells bind to macrophages that have engulfed pathogens, then secrete interleukins)

32. Supplementation of Immunity
Antibiotics – derived from bacteria & fungi, harmful to pathogenic microorganisms
Vaccines – inactivated pathogens (or fragments of pathogens), stimulate production of memory cells (prevent disease if pathogen introduced)
Passive immunity – transferred antibodies from immune person to non-immune and infected person (ex: newborns get mom’s antibodies through placenta and via breastmilk)

33. Antibiotics

34. Vaccines Produces memory cells for subsequent antigen exposures
Herd immunity reduces spread of infectious diseases

35. Passive Immunity Artificial – serum infusion
(placenta)
pathogen, etc.
Artificial – serum infusion
(used for infection, poisoning, immunodeficiency therapy)
Natural – placenta (IgG only),
breast milk (IgA only)