1. Chapter 24
The Immune System

2. About this Chapter
Anatomy & function of immune system, organs, & cells
How the body defends itself
Non-specific body defenses
Specific defenses that target one pathogen
Combined defenses against bacteria and viruses
Allergies and autoimmune problems

3. Immune System Functions: Overview of Defenses
Scavenge dead, dying or abnormal (cancerous) body cells
Protect from pathogens & foreign molecules
Parasites
Bacteria
Viruses

12. Immune System Functions: Overview of Defenses
Figure 24-1: Viruses

13. HIV or Human Immunodeficiency Virus

17. Life Cycle

18. Infectious Causes of Gastroenteritis.
Bok K, Green KY. N Engl J Med 2012;367:

19. Genomic Organization and Atomic Structure of the Norovirus Capsid.
Figure 1. Genomic Organization and Atomic Structure of the Norovirus Capsid. The RNA genome of the prototype norovirus strain, Norwalk virus (shown at the top), is organized into three open reading frames (ORF1, ORF2, and ORF3) that encode the designated nonstructural and structural proteins. Most diagnostic primers used in reverse-transcriptase–polymerase-chain-reaction assay target conserved areas in the RNA-dependent RNA polymerase region (NS7POL). VP1, the major capsid protein (shown below), is further organized into the N-terminal (N), shell (S), and protruding (P) domains defined by the indicated VP1 amino acid residues. The P2 region of the P domain (blue) is exposed on the surface of the capsid protein and is the site where histo–blood group antigens (HBGAs) (magenta) interact with the virion (dashed box). 5, 13
Bok K, Green KY. N Engl J Med 2012;367:

20. Body Defenses: Overview
Physical barriers: skin & epithelial linings & cilia
Chemical: acids, mucous & lysozymes
Immune defenses – internal
Innate, non-specific, immediate response (min/hrs)
Acquired – attack a specific pathogen (antigen)
Steps in Immune defense
Detect invader/foreign cells
Communicate alarm & recruit immune cells
Suppress or destroy invader

21. Lymphatic System: Overview of Immune Defense Organs & Cells
Bone marrow
Thymus
Lymph nodes
Spleen
Lymph vessels
Leukocytes:
(white blood cells – WBCs)

22. Lymphatic System: Overview of Immune Defense Organs & Cells
Figure 24-2 ab: Anatomy of the immune system

24. Key Cells & Overview of their Function in Immune Defense
Lymphocytes: helper, plasma, cytotoxic & natural killer (NK)
Basophils
Mast cells
Monocytes
Macrophages
Neutrophils
Eosinophils

25. Key Cells & Overview of their Function in Immune Defense
Figure 24-4: Cells of the immune system

26. Innate Immunity: Phagocytosis & Inflammation
Physical & chemical barriers
Phagocytosis: macrophages, neutrophils, NK cells
Engulf and digest recognized "foreign" cells – molecules
Inflammatory response

28. Innate Immunity: Phagocytosis & Inflammation
Figure 24-6: Phagocytosis

30. Cells of the Innate Immune System
The Innate Leukocytes include:
Natural killer cells
Mast cells
Eosinophils
Basophils
Phagocytic cells: including macrophages, neutrophils and dendritic cells, and
All these cells function within the immune system by identifying and eliminating pathogens that might cause infection

31. Chemical factors produced during inflammation
Histamine
Bradykinin
Serotonin
Leukotrienes
Prostaglandins
sensitize pain receptors, cause vasodilation of the blood vessels at the scene, and attract phagocytes, especially neutrophils

32. Inflammatory Response: Cytokines Signal Initiation
Histamines: from mast cells  swelling, edema, b. v . dilation
Interleukins: fever, b.v. gaps  WBC's & proteins  infection
Bradykinin: pain & swelling
Membrane attack complex proteins

33. Inflammatory Response: Cytokines Signal Initiation
Figure 24-8: Membrane attack complex

34. Acquired Immunity: Antigen-Specific Responses
Activate T lymphocytes: direct attack
Activate B lymphocytes to become:
Memory cells: 20 immune response to that antigen
Plasma cells: antibodies – attack that antigen

35. Antigen Presentation to Immature T Cells
Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells. Cytotoxic cells directly attack other cells carrying certain foreign or abnormal molecules on their surfaces. Helper T cells, or Th cells, coordinate immune responses by communicating with other cells. In most cases, T cells only recognize an antigen if it is carried on the surface of a cell by one of the body’s own MHC, or major histocompatibility complex, molecules.

36. T Cell Dependent B Cell Activation
A TH2 cell (left), B cell (right), and several interaction molecules

37. B Cell Activation

38. Stimulation of specific clone of B cells and its proliferation: Primary and Secondary Immune Response

45. Acquired Immunity: Antigen-Specific Responses
Figure 24-13: Functions of antibodies

49. The Human Leukocyte Antigen (HLA) System
Essential to immune function: HLA molecules present peptide antigens to the immune system (T-cells)
Important for self versus non-self distinction

50. HLA Class I Monitors Inside of the Cell
Tapasin CR CN
The MHC class I and class II molecules present antigens from different sources. Class I molecules present intracellular antigens that are processed in the cytoplasm and pumped into the endoplasmic reticulum, where new HLA molecules are being assembled. Processing of the antigens is performed by the proteosome, a multimeric enzyme composed of 28 subunits. Two subunits are encoded by the LMP genes found within the HLA region of the chromosome. The subunits may change in response to IFN-. LMP2, LMP7 and a third component, MECL-1, are induced by IFN- and displace the constitutive components and favor the processing of new peptides, thus insuring that newly synthesized viral proteins will be amply represented on the cell surface. The proteosome also favors the cleavage of proteins into 8-10 amino acids with hydrophobic or basic carboxy termini that fit nicely into the peptide binding groove of the HLA molecule.
Peptides that are processed in this manner are transported into the endoplasmic reticulum by TAP (transporter associated with antigen), which is comprised of two subunits, TAP-1 and TAP-2. TAP-2 as an ATP binding site, which regulates the active transport of peptides into the lumen of the ER. The TAP transporter has some specificity, preferring peptides of >8 amino acids with hydrophobic or basic amino acids at the carboxy terminus. This is the preferred peptide for binding in the MHC groove.
The newly synthesized HLA molecule is maintained in a partially folded conformation by calnexin (not shown). When 2-microglobulin binds to the HLA molecule, the complex dissociates from calnexin and binds a complex of calreticulin and tapasin, which then bind to TAP-1. The proper binding of a peptide to the HLA molecule dissociates the complex, and the HLA molecule is then transported through the Golgi complex to the cell surface.
Dr. Brian Freed

51. HLA Class II Monitors Outside of Cell
Peptides
Extra-cellular Proteins
DM monitors peptide specificity for DR
The presentation of peptides on MHC class II molecules is quite different. HLA-DR and related class II molecules are also assembled in the endoplasmic reticulum, but the associate with a third protein known as the invariant chain, which prevents peptide binding. The invariant chain is processed within endosomes to CLIP (class II-associated invariant chain peptide). In the presence of HLA-DM molecules, CLIP dissociates from HLA-DR or DQ molecules and allows binding of new peptides that have been endocytosed from the extracellular environment. Thus, MHC class II molecules differ from MHC class I molecules in that they preferentially present extracellular antigens rather intracellular ones. HLA-DM serves to ‘edit’ peptide binding, promoting association with high affinity peptides over lower affinity peptides. DM
Dr. Brian Freed

54. Antigen–presenting cells (APCs):
monocytes, macrophages, dendritic cells, B cells
Teaching slides:

55. Humoral
Versus
Cellular
Immune
Response

56. Class II (2.2 Mb) Class III (0.7 Mb) Class I (1.1 Mb) Complement
& cytokines
Class II (2.2 Mb)

57. HLA Genetic Nomenclature
Gene low high resolution typing
“subtype”=01
Allele:
HLA-DRB1*0401
Haplotype:
HLA-DRB1*0401
HLA-DQB1*0302
HLA-DRB1*0301
HLA-DQB1*0201
DRB1*02
Genotype:
HLA-DRB1*04
HLA-DQB1*0302
J. Noble

59. T Lymphocytes: Cell Mediated Immunity
T cell receptors: cell activated to antigen
Major histocompatability complex (MHC)
Helper T cells:
Cytotoxic T cells: perforins, granzymes, (apoptosis) & Fas

60. Defenses against Bacteria: Complement P Activates:
Make membrane attack complex  kill bacteria
Inflammation: + recruit phagocytes, B & T lymphocytes
(Acquired response  antibodies, cytotoxic Ts … if needed)

62. T Lymphocytes: Cell Mediated Immunity
Figure 24-16: T lymphocytes and NK cells

65. Antigen Presentation
Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells. Cytotoxic cells directly attack other cells carrying certain foreign or abnormal molecules on their surfaces. Helper T cells, or Th cells, coordinate immune responses by communicating with other cells. In most cases, T cells only recognize an antigen if it is carried on the surface of a cell by one of the body’s own MHC, or major histocompatibility complex, molecules.

66. Defenses against Bacteria: Complement P Activates
Figure 24-17: Immune responses to bacteria

67. Viral Defense: Summary of Innate & Acquired Responses
Circulating antibodies inactivate or target virus (opsins)
Macrophage  inflammation, interferon, cell activation
Helper, cytotoxic T, NK & B cells  plasma c. antibodies

68. Viral Defense: Summary of Innate & Acquired Responses
Figure 24-18: Immune responses to viruses

69. Allergic Response: Inflammation Reaction to Non-pathogen
First exposure: sensitization
Activation
Clone B cells
Form antibodies
Memory cells
Re-exposure
Many antibodies
Activated Ts
Intensified
Inflammation

70. Allergic Response: Inflammation Reaction to Non-pathogen
Figure 24-19: Allergic responses

78. Blood Types: Like Antibodies & antigens will agglutinate
Antigens on RBCs (A, B, AB or none = O)
Antibodies in plasma (anti A, anti B, anti AB)
Rh antigens & antibodies

79. Although there are over 600 known red blood cell antigens organized into 22 blood group systems, routine blood typing is usually concerned with only two systems: the ABO and Rh blood group systems. Antibody screening helps to identify antibodies against several other groups of red blood cell antigens.
Some of the other groups are the Duffy, Kell, Kidd, MNS, and P systems

80. Blood Types: Like Antibodies & antigens will agglutinate
Figure 24-20a: ABO blood groups

81. Autoimmune Diseases: Failure of “Self-Tolerance”
Type I diabetes mellitus – immune system attacks - cells
Graves disease – antibodies mimic TSH hyperthyroidism
Multiple Sclerosis – autoimmine attack on myelin nerve sheath
Rheumatoid arthritis – autoimmune attack on joint cartilage
Myasthenia gravis – ACh-receptors at endplate attacked by immune system

82. Interaction of Nervous, Endocrine & Immune Systems
Much yet to understand
Neuroimmunomodulation
All three share some:
Signal molecules
Receptors
Overlapping responses
Fight or flight
Chronic stress

83. Interaction of Nervous, Endocrine & Immune Systems
Figure 24-21: Model for interaction between nervous, endocrine, and immune systems

84. Summary
Body defends itself with barriers, chemicals & immune responses
WBCs and relatives conduct direct cellular attack: phagocytosis, activated NK & cytotoxic T cells and produce attack proteins (i.e. antibodies, complement, & membrane attack complex)

85. Summary
Cytokines, communicate cell activation, recruitment, swelling, pain, & fever in the inflammation response
Defense against bacteria is mostly innate while viral defense relies more on acquired immune responses
Autoimmune diseases are a failure of self-tolerance