history

1. IMMUNOLOGY
PROF. FATIMA MayTESORO,RPH,MSPHARMDefenses of the
Host

2. Nonspecific Defenses of the Host
• Susceptibility Lack of resistance to a
disease
• Resistance Ability to ward off disease
• Nonspecific resistance Defenses against any
pathogen
• Specific resistance Immunity, resistance to a
specific pathogen
• Virulence Degree of pathogenecity
• Attenuation Reduction of virulence
• ANTIGEN Component of foreign material w./c
interacts with immune system
• Epitope antigenic determinant

3. 2 IMMUNE SYSTEM RESPONSE
• INNATE – non- specific; no time lag,not
intrinsically affected by contact to infectious
agent.
• ADAPTIVE – time lags; requires highly specific
recognition of antigen and immunological
memory ( DIPTHERIA)
– Humoral
– Cell mediated

4. • HUMORAL – effector cells are B lymphocytes
& antigen recognition occur through
interaction with antibody
• CELL MEDIATED – effector cells is T
lymphocytes and antigen recognition occur
through interaction with a peptide antigen w/
T receptors

5. CELL OF THE IMMUNE SYSTEM

6. Host Defenses
Figure 16.1

7. • Skin
• Epidermis consists of tightly packed cells with
• Keratin, a protective protein
Mechanical Factors

8. • Mucous membranes
• Ciliary escalator: Microbes trapped in mucus are
transported away from the lungs
• Lacrimal apparatus: Washes eye
• Saliva: Washes microbes off
• Urine: Flows out
• Vaginal secretions: Flow out
Mechanical Factors

9. • Fungistatic fatty acid in sebum
• Low pH (3-5) of skin
• Lysozyme in perspiration, tears, saliva, and tissue
fluids
• Low pH (1.2-3.0) of gastric juice
• Transferrins in blood find iron
• NO inhibits ATP production
Chemical Factors

10. • Microbial antagonism/competitive exclusion: Normal
microbiota compete with pathogens.
Normal Microbiota

11. Formed Elements In Blood
Table 16.1

12. • Percentage of each type of white cell in a sample of 100
white blood cells
Differential White Cell Count
Neutrophils 60-70%
Basophils 0.5-1%
Eosinophils 2-4%
Monocytes 3-8%
Lymphocytes 20-25%

13. • Neutrophils: Phagocytic
• Basophils: Produce histamine
• Eosinophils: Toxic to parasites, some phagocytosis
• Monocytes: Phagocytic as mature macrophages
• Fixed macrophages in lungs, liver, bronchi
• Wandering macrophages roam tissues
• Lymphocytes: Involved in specific immunity
White Blood Cells

14. • Phago: eat
• Cyte: cell
• Ingestion of microbes or particles by a cell,
performed by phagocytes
Phagocytosis

15. Phagocytosis
Figure 16.8a

16. Microbial Evasion of Phagocytosis
• Inhibit adherence: M protein,
capsules
Streptococcus pyogenes, S. pneumoniae
• Kill phagocytes: Leukocidins Staphylococcus aureus
• Lyse phagocytes: Membrane
attack complex
Listeriamonocytogenes
• Escape phagosome Shigella
• Prevent phagosome-lysosome
fusion
HIV
• Survive in phagolysosome Coxiella burnetti

17. • Redness
• Pain
• Heat
• Swelling (edema)
• Acute-phase proteins activated (complement,
cytokine, kinins)
• Vasodilation (histamine, kinins, prostaglandins,
leukotrienes)
• Margination and emigration of WBCs
• Tissue repair
Inflammation

18. Chemicals Released by Damaged Cells
• Histamine Vasodilation, increased permeability of blood
vessels
• Kinins Vasodilation, increased permeability of blood
vessels
• Prostaglandins Intensity histamine and kinin effect
• Leukotrienes Increased permeability of blood vessels,
phagocytic attachment

19. Inflammation
Figure 16.9a, b

20. Inflammation
Figure 16.9c, d

21. • Hypothalamus normally set at 37°C
• Gram-negative endotoxin cause phagocytes to
release interleukin 1
• Hypothalamus releases prostaglandins that reset
the hypothalamus to a high temperature
• Body increases rate of metabolism and shivering to
raise temperature
• When IL-1 is eliminated, body temperature falls.
(Crisis)
Fever: Abnormally High Body
Temperature

22. • Serum proteins
activated in a
cascade.
The Complement System
Figure 16.10

23. Effects of Complement Activation
• Opsonization or
immune adherence:
enhanced
phagocytosis
• Membrane attack
complex: cytolysis
• Attract phagocytes
Figure 16.11

24. Effects of Complement Activation
Figure 16.12

25. Classical Pathway
Figure 16.13

26. Alternative Pathway
Figure 16.14

27. Lectin Pathway
Figure 16.15

28. Some bacteria evade complement
• Capsules prevent C activation
• Surface lipid-carbohydrates prevent MAC formation
• Enzymatic digestion of C5a

29. • Alpha IFN & Beta IFN: Cause cells to produce
antiviral proteins that inhibit viral replication
• Gamma IFN: Causes neutrophils and macrophages
to phagocytize bacteria
Interferons (IFNs)

30. Interferons (IFNs)
Figure 16.16
1
2
3
4
5
Viral RNA from an
infecting virus
enters the cell.
The infecting
virus replicates
into new
viruses.
The infecting virus also
induces the host cell to
produce interferon on
RNA (IFN-mRNA), which
is translated into alpha
and beta interferons.
Interferons released by the virus-infected host cell bind to plasma
membrane or nuclear membrane receptors on uninfected neighboring
host cells, inducing them to synthesize antiviral proteins (AVPs). These
include oligoadenylate synthetase, and protein kinase.
New viruses released
by the virus-infected
host cell infect
neighboring host
cells. 6 AVPs degrade viral
m-RNA and inhibit
protein synthesis and
thus interfere with viral
replication.

31. • Innate (nonspecific) Defenses against any pathogen
• Immunity Specific antibody and lymphocyte
response to an antigen
• Antigen (Ag) A substances that causes the
body to produce specific
antibodies or sensitized T cells
• Antibody (Ab) Proteins made in response to an
antigen

32. Terminology
• Serology Study of reactions between
antibodies and antigens
• Antiserum Generic term for serum
because it contains Ab
• Globulins Serum proteins
• Gamma (γ) globulin Serum fraction containing Ab

33. Serum Proteins
Figure 17.2

34. The Immune Response
• Acquired immunity Developed during an
individual's lifetime
• Humoral immunity Involves Ab produced
by B cells
• Cell-mediated immunity Involves T cells

35. Acquired Immunity
• Naturally acquired active immunity
– Resulting from infection
• Naturally acquired passive immunity
– Transplacental or via colostrum
• Artificially acquired active immunity
– Injection of Ag (vaccination)
• Artificially acquired passive immunity
– Injection of Ab

36. Antigenic Determinants• Antibodies recognize and react with antigenic
determinants or epitopes.
Figure 17.3

37. Haptens
Figure 17.4

38. Antibody Structure
Figure 17.5a-c

39. • Monomer
• 80% of serum antibodies
• Fix complement
• In blood, lymph, intestine
• Cross placenta
• Enhance phagocytosis;
neutralize toxins & viruses;
protects fetus & newborn
• Half-life = 23 days
IgG antibodies

40. • Pentamer
• 5-10% of serum
antibodies
• Fix complement
• In blood, lymph, on B
cells
• Agglutinates
microbes; first Ab
produced in response
to infection
IgM antibodies

41. • Dimer
• 10-15% of serum
antibodies
• In secretions
• Mucosal protection
• Half-life = 6 days
IgA antibodies

42. • Monomer
• 0.2% of serum
antibodies
• In blood, lymph, on B
cells
• On B cells, initiate
immune response
• Half-life = 3 days
IgD antibodies

43. • Monomer
• 0.002% of serum
antibodies
• On mast cells and
basophils, in blood
• Allergic reactions; lysis
of parasitic worms
• Half-life = 2 days
IgE antibodies

44. • Bone marrow gives rise to B cells.
• Mature B cells migrate to lymphoid organs.
• A mature B cells recognizes epitopes.
Clonal Selection

45. Clonal Selection
Figure 17.8

46. Self-tolerance
• Body doesn't make Ab against self
• Clonal deletion
– The process of destroying B and T cells that react to self
antigens

47. The Results of Ag-Ab Binding
Figure 17.9

48. Antibody titer:• Is the amount of Ab in serum
Figure 17.10

49. Monoclonal Antibodies
• Hybridomas are produced by fusing a cancer cell
with an Ab-secreting plasma cells
• The hybridoma cell culture is immortal and
produces monoclonal Abs (Mabs)
• Immunotoxins: Mabs conjugated with a toxin to
target cancer cells
• Chimeric Mabs: Genetically modified mice that
produce Ab with a human constant region
• Humanized Mabs: Mabs that are mostly human,
except for mouse antigen-binding

50. Monoclonal Antibodies
Figure 17.11

51. • Interleukin-1 Stimulates TH cells
• Interleukin-2 Activates TH, B, TC, and NK cells
• Interleukin-12 Differentiation of CD4 cells
• γ-Interferon Increase activity of macrophages
• Chemokines Cause leukocytes to move to an
infection
Immune system cells communicate via
cytokines

52. • Specialized lymphocytes, mostly T cells, respond to
intracellular Ags
• After differentiating in the thymus, T cells migrate
to lymphoid tissue
• T cells differentiate into effector T cells when
stimulated by an Ag
• Some effector T cells become memory cells
Cell-Mediated Immunity

53. • M (microfold) cells in
• Peyer's patches which contains
• Dendritic cells which are antigen-presenting cells
and
• T cells
Pathogens entering the gastrointestinal or
respiratory tracts pass through:

54. Dendritic cells present antigens
Figure 17.12

55. • Helper T Cells (CD4, TH)
– TH1 Activate cells related to cell-mediated
immunity
– TH2 Activate B cells to produce eosinophils, IgM,
and IgE
• Cytotoxic T Cells (CD8, TC)
– Destroy target cells with perforin
T Cells

56. • Delayed Hypersensitivity T Cells (TD)
– Associated with allergic reaction, transplant
rejection, and tuberculin skin test
• Suppressor T cells (TS)
– Turn off immune response when Ag no longer
present
T Cells

57. Helper T Cells
Figure 17.13

58. Cell-mediated Cytotoxicity
Figure 17.14

59. Nonspecific Cells
• Activated
macrophages:
Macrophages
stimulated by
ingesting Ag or by
cytokines
• Natural killer cells:
Lymphocytes that
destroy virus-
infected cells,
tumor
Figure 17.15

60. T-independent Antigens
Figure 17.17
B cell

61. T-independent Antigens
Figure 17.16

62. Antibody-Dependent Cell-Mediated
Cytotoxicity
Figure 17.18

63. Vaccine History
• Variolation: Inoculation of smallpox into
skin (18th
century)
• Vaccination: Inoculation of cowpox into skin
• Herd immunity results when most of a
population is immune to a disease.

64. • DtaP
– Diphtheria: Purified diphtheria toxoid
– Pertussis: Acellular fragments of B. pertussis
– Tetanus: Purified tetanus toxoid
• Meningococcal meningitis: Purified polysaccharide
from N. meningitidis
• Haemophilus influenzae type b meningitis:
Polysaccharides conjugated with protein
• Pneumococcal conjugate vaccine: S. pneumoniae
antigens conjugated with protein
Principal Vaccines

65. • Smallpox: Live vaccinia virus
• Poliomyelitis: Inactivated virus
• Rabies: Inactivated virus
• Hepatitis A: Inactivated virus
• Influenza: Inactivated or attenuated virus
• Measles: Attenuated virus
• Mumps: Attenuated virus
• Rubella: Attenuated virus
• Chickenpox: Attenuated virus
• Hepatitis B: Antigenic fragments (recombinant
vaccine)
Principal Vaccines Used in the United
States to Prevent Viral Diseases in Humans

66. Precipitation Reactions
• Involve soluble
antigens with
antibodies
Figure 18.3

67. Agglutination Reactions
• Involve particulate
antigens and
antibodies
• Antigens may be:
• On a cell (direct
agglutination)
• Attached to latex
spheres (indirect or
passive
agglutination)
Figure 18.4

68. Antibody Titer
• Is the concentration
of antibodies against
a particular antigen
Figure 18.5

69. Hemagglutination
• Hemagglutination involves agglutination of
RBCs.
• Viral hemagglutination inhibition tests for
antibodies by the antibodies' ability to prevent
viruses from agglutinating RBCs.
Figure 18.7

70. Neutralization Reactions
• Eliminate the harmful effect of a virus or
exotoxin
Figure 18.8b

71. Complement Fixation
Figure 18.9.1

72. Complement Fixation
Figure 18.9.2

73. Fluorescent Antibody Techniques
(Direct)
Figure 18.10a

74. Fluorescent Antibody Techniques
(Indirect)
Figure 18.10b

75. Enzyme-Linked Immunosorbent Assay
(Direct ELISA)
Figure 18.12a

76. Enzyme-Linked Immunosorbent Assay
(Indirect ELISA)
Figure 18.12b

77. Serological Tests
Figure 18.13

78. Serological Tests
• Direct tests detect antigens (from patient
sample)
• Indirect tests detect antibodies (in patient's
serum)

79. Serological Tests
• Agglutination: Particulate antigens
• Hemagglutination: Agglutination of RBCs
• Precipitation: Soluble antigens
• Fluorescent-antibody technique: Antibodies
linked to fluorescent dye
• Complement fixation: RBCs are indicator
• Neutralization: Inactivates toxin or virus
• ELISA: Peroxidase enzyme is the indicator