1. UNIT X HUMAN IMMUNE SYSTEM & DISEASE
Baby Campbell – Ch 9, 17, 24, 35
Big Campbell – Ch 12, 19, 27, 43

2. I. IMMUNE SYSTEM OVERVIEW2

3. II. INNATE IMMUITY Barrier Defenses
Skin
Secretions
Mucus
Ciliated Epithelial Cells
Lysozyme pH
Normal Flora 3

4. II. INNATE IMMUNITY, cont Internal Defenses - Cellular
Phagocytic Cells
Detect pathogens using several types of receptors that are indicative of a type of pathogen
Known as Toll-like receptors (TLRs)
Recognize PAMPs – “Pathogen-Associated Molecular Patterns” 4

5. II. INNATE IMMUNITY, cont Internal Defenses - Cellular
Phagocytic Cells
Neutrophils
60-70% of WBCs
Circulate in blood
Respond to signals from infected tissue
Macrophages
5% WBCs
Begin as monocytes
Migrate through body or reside in specific organs, tissues
Dendritic Cells
Found in tissues that are in contact with environment; skin
Migrate to lymph nodes; stimulate adaptive immunity

6. II. INNATE IMMUNITY, cont Internal Defenses - Cellular
Natural Killer (NK) Cells
Lymphocytes
Circulate throughout body
Recognize lack of Class I MHC molecules –
Class I MHC molecules are found in all normal cells; missing in virus-infected, cancer cells
Trigger apoptosis by releasing perforins, other proteins

7. II. INNATE IMMUNITY, cont Internal Defenses - Cellular

8. II. INNATE IMMUNITY, cont Internal Defenses - Chemical
Fever
Interferon
Proteins released by virus-infected cells
Diffuse to healthy cells; stimulates production of proteins that inhibit viral replication

9. II. INNATE IMMUNITY, cont Internal Defenses - Chemical
Complement System
~30 proteins that circulate in inactive form
Activated by presence of pathogens
Activation results in a cascade of biochemical reactions
May result in lysis of pathogen, activation of inflammatory response

10. II. INNATE IMMUNITY, cont Internal Defenses - Chemical
Inflammatory Response
Histamine released by mast cells in response to injury, infection
Causes blood vessels in area to dilate, increase permeability
Macrophages, neutrophils in area respond, release cytokines
Causes increased blood flow to region, resulting in redness & swelling 10

11. III. ADAPTIVE IMMUNITY Unique to vertebrates
Based on function of white blood cells known as
Four important properties of adaptive immunity
Specificity
Diversity
Self from non-self
Immunologic Memory
Effector Cells
Memory Cells

12. III. ADAPTIVE IMMUNITY, cont
Lymphocytes further categorized based on mechanism for identification, response to pathogen/abnormal cell
T Lymphocytes
Mature in thymus
Only capable of recognizing “displayed” antigens
Respond by releasing toxic proteins to destroy infected cells
B Lymphocytes
Mature in bone marrow
Bind to intact antigens in blood and lymph
Antigens may be present on pathogen

13. III. ADAPTIVE IMMUNITY
B and T Cell function based on interactions between…
Receptor proteins
Plasma membrane receptors on B and T cells
Every receptor (~100,000) on a single cell is identical
Binds to a specific foreign molecule
Antigen
Foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms, foreign cells) 13

14. III. ADAPTIVE IMMUNITY, cont Overview

15. III. ADAPTIVE IMMUNITY, cont Humoral Immunity & B Cells
Activation of B cells
Binding of B cell antigen receptor to epitope
Triggers secretion of antibodies
Antigen-binding immunoglobulin
Soluble form of antigen receptor
Composed of 2 heavy chains and 2 light chains joined by disulfide bridges
Five classes of antibodies
IgG is most abundant
Effective against bacteria, toxins, and viruses free in the lymph and blood plasma 15

16. III. ADAPTIVE IMMUNITY, cont B Cells, cont

17. III. ADAPTIVE IMMUNITY, cont B Cells, cont
Antibody Function

18. III. ADAPTIVE IMMUNITY Humoral Immunity, cont18

19. III. ADAPTIVE IMMUNITY Humoral Immunity, cont

20. III. ADAPTIVE IMMUNITY Cell Mediated Immunity & T Cells
T cells respond to displayed antigen on Antigen Presenting Cells (APCs)
Antigen is bound to surface proteins found on virtually all cells known as Class I Major Histocompatibility Complex or Class I MHC
Activated T cells are cytotoxic
Secrete proteins that trigger cell death by causing lysis, destruction of cell membrane integrity
T cells defend against cells infected with bacteria, viruses, fungi, protozoa, and parasites; nonself interaction

21. III. ADAPTIVE IMMUNITY Cell-Mediated Immunity, cont

22. III. ADAPTIVE IMMUNITY The Role of Helper T Cells
Trigger both humoral and cell-mediated response
Antigen is displayed on Class II MHC complex on “professional” Antigen Presenting Cells
Include dendritic cells, macrophages, and B cells

23. III. ADAPTIVE IMMUNITY Clonal Selection
Binding of antigen to receptor molecule activates particular lymphocyte
Response is amplified by rapid division of B, T cells; known as clonal selection
Effector cells are short-lived plasma cells that combat the antigen
Primary Immune Response
Memory cells are long-lived cells that bear receptors for the antigen
Secondary Immune Response 23

24. IV. IMMUNIZATION Acquired Immunity Passive Immunity
Conferred immunity by recovering from disease
Immunization produces an immune response
Passive Immunity
Transfer of immunity from one individual to another
Natural – Mother to fetus; lactation
Artificial – Rabies antibodies

25. V. IMMUNE REJECTION
ABO blood groups
Rh factor
Organ Transplants

26. VI. MISREGULATION OF IMMUNE SYSTEM
Allergies
Autoimmune Diseases

27. VI. MISREGULATION OF IMMUNE SYSTEM, cont
Immunodeficiency Diseases
SCIDS

28. VII. STRESS & IMMUNE SYSTEM

29. INFECTIOUS DISEASE

30. I. VIRUSES

31. I. VIRUSES, cont

32. II. HUMAN VIRAL REPLICATION
Lytic Infection

33. II. HUMAN VIRAL REPLICATION, cont
Latent Infection

34. II. HUMAN VIRAL REPLICATION, cont HIV Infection

35. III. PREVENTION & TREATMENT OF VIRAL DISEASES
Containment

36. III. VIRAL DISEASES, cont
Prevention
Vaccination

37. III. VIRAL DISEASES, etc
Treatment

38. IV. BACTERIA 38

39. IV. BACTERIA, cont Adaptations for Virulence
Capsule
Endospore
Quorum Sensing 39

40. IV. BACTERIA Pathogenesis
Direct Attack
Toxin Production
Exotoxins
Bacterial proteins that can produce disease w/o the prokaryote present
Examples include botulism, cholera
Endotoxins
Components of gram negative membranes
Examples include typhoid fever, Salmonella food poisoning
Hypersensitivity 40

41. V. PREVENTION & TREATMENT OF BACTERIAL DISEASE
Normal flora

42. V. PREVENTION & TREATMENT OF BACTERIAL DISEASE

44. I. CANCER – AN OVERVIEW

45. I. CANCER OVERVIEW, cont Tumor versus Cancer Benign tumor
Malignant tumor
Metastasis

46. II. CELL CYCLE REGULATION
Drivers
Checkpoints
G2 Checkpoint
Is my DNA correctly replicated?
Are chromosomes ready for separation?
Mitosis Checkpoint
Is environment ok?
Is my DNA intact?
G1 Checkpoint/ Restriction Point

47. II. CELL CYCLE REGULATION, cont
G1 Driver
Cyclin D
S Driver 1
Cyclin E
S Driver 2
Cyclin A
G2/M Driver
Cyclin B

48. III. A CLOSER LOOK AT CANCER
Cancer-causing mutations can generally be placed in one of two categories:
Oncogenes/Proto-oncogenes
Tumor Suppressor Genes 48

49. III. A CLOSER LOOK AT CANCER, cont Oncogenes
Examples
HER-2/neu (erbB-2): a growth factor receptor.
ras: a signal transduction molecule
myc: a transcription factor
src: a protein tyrosine kinase.
hTERT: an enzyme that functions in DNA replication.
Bcl-2: a membrane associated protein that functions to prevent apoptosis.

50. III. A CLOSER LOOK AT CANCER, cont Oncogenes, cont

51. III. A CLOSER LOOK AT CANCER, cont Tumor Suppressor Genes
Encode for proteins that inhibit cell division therefore any mutation that inhibits activity of tumor-suppressor gene may lead to abnormal cell growth and formation of tumors.
Act by producing proteins that repair damaged DNA, control density-dependent inhibition & anchorage dependence, or act as CDKs
Examples
INK proteins
p53 Rb
BRCA1
BRCA2
APC

52. III. A CLOSER LOOK AT CANCER, cont Tumor Suppressor Genes, cont
Gene that is most often defective in human cancers codes for transcription factor known as p53
Known as the “guardian angel of the genome”
Serves as the master brake on the cell cycle when DNA damage has occurred
p53 activates several genes with multiple effects
Genes activated to halt cell cycle
DNA repair genes turned on
If DNA damage cannot be repaired, “suicide genes” are activated; results in apoptosis

53. III. A CLOSER LOOK AT CANCER, cont Tumor Suppressor Genes, cont
Apoptosis
Nucleus
Nucleus
Nucleus
blebs
blebs
The cell blebs
Nucleus condenses
Nucleus fragments
The blebs are phagocytosed

54. III. A CLOSER LOOK AT CANCER, cont Tumor Suppressor Genes, cont
BRCA 1 and BRCA 2 54

55. IV. CANCER & IMMUNOTHERAPY

56. IV. CANCER & IMMUNOTHERAPY, cont