1. Immunology

2. Immunity
Is the body’s ability to recognize infectious disease causing organisms like bacteria and viruses, and protect the body from these organisms

3. Immunology
Study of the system that fights infectious diseases

4. Smallpox Used to be one of the worldwide scourges
But because of immunization, smallpox no longer exists in the world

5. Before 1979
Smallpox killed 80% of the children who contracted the virus, and about half the adults

6. Smallpox
Since 1900, it is estimated that smallpox was responsible for 500 million deaths
In 1967, the World Health Organization estimated that 15 million people contracted the disease and that two million people died in that year
After successful vaccination campaign,eradication of smallpox was declared in December, 1979.

7. AIDS/HIV The hunt is on for a vaccine for HIV and AIDS
Many millions will die from AIDS before then

8. How do immunizations work?
Lock and key model

9. Antibodies are made by lymphocytes

10. Fab binds to antigen
Fc binds to immune component

11. Antibodies bind to specific antigen
Antigen – it can be any part of something, part of a bacteria, part of a virus that stimulates the immune system

12. Please do not confuse:
Antigen (Ag) – any protein or structure that can stimulate an immune reaction
Antibody (Ab) – Y shaped proteins that bind to antigens to mark them for phagocytosis. B lymphocytes make Antibodies

13. Antibody binds to antigen picture

14. Antibodies can be free in the blood.
Antigen/Antibody complexes can signal digestion by macrophage
Antigen Antibody complex picture

15. Antibodies can be attached to lymphocytes Ag/Ab complexes can signal the lymphocyte to reproduce making more of the same antibody
Antigen Antibody complex picture

16. Immunization
Now the body has a huge increase in the number of “receptors” that can activate the immune system in case of exposure to specific bacteria or viruses
Antibody picture

17. Immunization
So the next time the body is exposed to the specific bacteria or virus…
There are already lots of antibodies to attack it

18. Immunity
Immunity prevents infection by the increased ability for Ab to signal the destruction of the infectious organism

19. Serum
SERUM is the liquid base of Blood
It is mostly salt water

20. SERUM Contains small proteins called ANTIBODIES and COMPLEMENT
Again antibodies are made by lymphocytes
Complements are designed to attach to viruses and bacteria for phagocytosis

21. SERUM
ANTIBODIES and COMPLEMENT attach to foreign substances such as bacteria to help the IMMUNE SYSTEM fight these substances.

22. SERUM
Antibodies (Ab) are made by LYMPHOCYTES, a type of WHITE BLOOD CELL (WBC)
Complement are proteins made by the LIVER
Antibodies are very specific for antigens
Complements are not specific for antigens

23. Plasma = Serum + Clotting Factors
Clotting factors are proteins made by the LIVER
Clotting factors make your blood clot
- if you have no clotting factors, you would not stop bleeding from a tiny cut.

24. Blood Cells Red Blood Cells (RBC) - erythrocytes
White Blood Cells (WBC)
- leukocytes
Platelets (Plt)

25. Blood Cells RBCs, WBCs, and Platelets are ALL made by the bone marrow
During fetal development, the LIVER also makes these cells

26. Peripheral Blood Smear picture

29. WBCs – Neutrophils Neutrophils have many names
Poly Morpho Nuclear Leukocytes
Segmented Neutrophils (Segs)
Granulocytes

30. WBCs – Neutrophils
Neutrophils have many names:
Poly Morpho

31. Neutrophils Picture

32. Granulocytes Picture

33. WBCs – Granulocytes
There are other WBC Granulocytes besides Neutrophils
- Eosinophils
- Basophils

34. Eosinophils and Basophils Picture

35. Granulocytes The granulocytes contain granules
These granules carry various kinds of poisons designed to kill infectious organisms
That’s why people with neutropenia (too few neutrophils) are easily infected
*penia – means too few

36. WBCs Non granulocytes WBCs that are not granulocytes are: Lymphocytes
Monocytes

37. Lymphocyte and Monocyte Picture

38. Blood is made of: Substances that provide: Nutrient supply
Waste removal
Oxygen supply
Carbon dioxide removal
Stop bleeding
IMMUNITY

39. Hematopoiesis
How blood cells are made

40. Bone Marrow
The cells we are about to see are only seen on bone marrow biopsy

41. The Stem Cell gives rise to 2 lines
Myeloid Line
- Erythrocytes (RBC) - Granulocytes
- Neutrophils
- Eosinophils
- Basophils
- Monocytes
- Platelets

42. Lymphoid Line
- Lymphocytes

43. Differentiation
As the cells differentiate, they become different from the stem cells, and become the final product
The more differentiated the cells are, the more they are like the final product

44. Stem Cell All of the cells of the blood begin as stem cells
The stem cells divide rapidly, making not only more stem cells but cells that differentiate into their final form

45. Stem Cell Myeloid and Lymphoid Progenitor Picture

46. Lymphoid Line Picture

48. Plasma cell is a B lymphocyte that has been activated to make lots of antibodies

49. Myeloid Line picture

50. Granulocyte Stimulating Factor
Filgrastim
- Neupogen
- G – CSF
- this drug stimulates the body to make more granulocytes

51. Do not confuse G – CSF - Granulocyte Colony Stimulating Factor With:
GM – CSF
- Granulocyte Macrophage Colony Stimulating Factor

52. Body’s Defense Mechanism
Everyday the body is exposed to numerous:
- Bacteria
- Viruses
- Fungi
- Parasites
Our bodies are constantly fighting these organisms

53. Myeloid Line Neutrophils

54. Elevated White Count and Left Shift
Seeing immature cells in the microscope we call it a left shift because in the old days laboratorians use the left hand to count using a cell counter

59. Reticulocytes – no nucleus
- reticulated means a net-like pattern
- still has parts of a nucleus
Reticulocyte Count – to see if the bone marrow is making a normal amount of reticulocytes

60. Erythropoietin
Erythropoietin is synthesized by the kidneys to stimulate the production of red blood cells

61. Epoetin Epoetin stimulates the production of red blood cells epoetin
- Epogen
- Procrit
- EPO

62. Body’s Defense Mechanism
Our bodies are really good at fighting off organisms which they encounter for the first time

63. Body’s Defense Mechanism
Our bodies remember many of these organisms, so we can fight them even better in subsequent exposure

64. Immunity
Immunity is the body’s ability to remember foreign substances, and attack them even better the next time

65. Immunity
Immunity is NOT the developed tolerance to a drug, or a bacterial resistance to a drug

66. Picture of virus entering a healthy cell

67. Know that viral antigens are expressed on the surface of an infected cell
The virus DNA/RNA go to the cell’s nucleus to replicate

68. Major Histocompatibility Complex
Major – most important
Histo – tissue
Compatibility – how we get along
Complex – not simple
This is how immune cells identify self from foreign tissues

69. Cellular Immunity
The macrophage expresses viral antigens on its surface with a MHC and secretes interleukin 1 or IL1

70. Interleukin is short for interleukocytokines
Inter – between
Leuko – white
Cyto – cell
Kine – communication

71. Interleukocytokines are how white cells communicate with each other

75. Interleukin 1 is how the macrophage calls for help
IL1 attracts other macrophages
IL1 also attracts other T helper cells
T helper cells (CD4 cells) are a type of lymphocytes

76. Cellular Immunity
So when our Macrophage has expressed Viral Antigen on MHC it calls for help
Using IL1

77. T helper to the rescue
IL1
T helper = TH = CD4

78. IL2 in T helper cell

79. Review Macrophage ingests the microbial product Presents the antigen
Major Histocompatibility Complex
Secretes IL1
T cell activation
T helper lymphocyte
TH = CD4
T helper cells identify antigen presentation
Secretes IL2

80. Interleukins There are many interleukins
It is important that you know that interleukins are how various white cells communicate
Interleukins are also used as drugs

81. Interleukins and Interferons
Interferons “interfere” with a virus ability to replicate it’s DNA/RNA

82. Interleukins and interferons
Naturally occuring substances

83. Humoral Immunity
Antibodies recognizing things in the bloodstream

86. Epitope – the part of an antigen molecule to which an antibody attaches itself

89. Humoral Immunity
B cell exposure to antigen causes B cells to make antibodies

90. These antibodies stick to the specific antigen to mark or opsonize the antigen to make it easier to be attacked by granulocytes and monocytes

92. Gammaglobulins – class of plasma proteins composed almost entirely of immunoglobulins (Igs), the proteins that functions as antibodies

93. What is immunology?
The production of immunoglobulins (antibodies) as a reaction of the human body when infected with an agent.

94. Immunoglobulins
Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies

95. Each immunoglobulin actually binds to a specific antigenic determinant
Antigen binding by antibodies is the primary function of antibodies and can result in protection of the host

98. Different immunoglobulins
IgG is the major Ig in extra vascular spaces
Placental transfer – IgG is the only class of Ig that crosses the placenta
75% of total Ig’s

99. IgM
IgM is the first Ig to be made by the fetus and the first Ig to be made by virgin B cells when stimulated by antigen
Pentameric structure therefore IgM is a good complement fixing antibody
Third most common Ig

101. IgA Second most common Ig
It is a major class in Ig secretions such as tears, saliva, mucus
Therefore, it is important in local (humoral) immunity

103. Other immunoglobulins
IgE
monomer with extra domain in the constant region
least common Ig
involved in allergic reactions
IgE also plays a role in parasitic helminth diseases
does not fix complement
For Internal Use Only

104. IgD
monomer
low levels in serum
uncertain role
does not fix complement

105. Immunoreaction primary humoral immune response to an antigen:
following exposure, IgM is the first antibody to appear
followed by a much higher titre of IgG

106. Criteria for diagnosing primary Infection
Seroconversion: changing from a previously antibody (Ab) negative status (seronegative) to a positive status (seropositive). Negative IgM & IgG do not exclude exposure to antigen (incubation time).

107. Presence of IgM: - offers rapid diagnosis
- might be negative at convalescent phase

108. Presence of IgG: - significant rise between acute and convalescent (recovery) phase

109. - sharp rise of IgG - low or absent IgM

110. Screening population: - IgG present at acute & recovery phase and will remain detectable for mainy years, even for life time

111. Affinity: - Ab affinity is the strength of the reaction between a single antigenic determinant and a single combining site on the antibody …. in other words: the degree of match between Ag & Ab

112. Avidity:
the eagerness of the Ab to match with an Ag - avidity is more than the sum of the individual affinities - the older the infection, the higher the avidity - the higher the avidity, the stronger the Ag-Ab binding

113. IgG Avidity
Avidity increases with the maturation of the immune response
For Internal Use Only

114. Polyclonal and monoclonal Ab’s
Polyclonal Ab’s: - each B-cell clone produces Ab specific for one particular Ag epitope - but serum Ab’s are produced as a response to complex Ag, therefore contains a mixture of Ab’s raised against different Ag epitopes - each cell clone produce Ab’s specific for one of the various epitopes of the Ag  this polyclonal response is advantageous for the immune system because it helps localization, phagocytosis, and complement mediated lysis of the Ag
Monoclonal Ab’s: - derived from a single plasma cell and specific for one epitope - useful for in vitro & in vivo diagnostic products
For Internal Use Only

115. Antigens Viruses – Bacteria - Parasites
Bacteria:prokayotic organisms
single-celled organisms able to reproduce by duplicating themselves
responsive to antibiotics
typical bacterium: rigid cell wall, thin rubbery cell membrane surrounding the cytoplasma, various shapes (coccus, rod, vibrion etc)
contains all genetic information to copy itself – DNA in the chromosome
plasmids: extra circular bits of DNA
ribosomes: necessary for copying DNA
some have flagella
For Internal Use Only

116. Antigens Viruses – Bacteria - Parasites
The biggest viruses are only as large as the tiniest bacteria.
Virus:
lives within a cell (intracellular) to survive and needs host cell for multiplication
not responsive to antibiotics
protection through vaccination (not for all viruses)
envelope: outermost spiky layer
protein coat
core of genetic material: DNA or RNA
For Internal Use Only

117. Antigens Viruses – Bacteria - Parasites
Parasite: eukaryotic organisms
lives in or on the living tissue of a host organism
lives at the expense of the host
parasitism = biological interaction between host and parasite
Some parasites:
Toxoplasma gondii
Cryptosporidium parvum oocytes
Giardia intestinalis
For Internal Use Only

118. Infectious diseases
Kits currently available for the detection of Ab’s against:
TORCH panel: Toxoplasma gondii Rubella virus Cytomegalovirus (CMV)
Epstein-Barr virus (EBV)
Measles
Mumps
Herpes Simplex virus type 1 & 2
Varicella zoster virus (VZV)
Helicobacter pylori
Treponema pallidum (Syphilis)
For Internal Use Only

119. Viruses: different families (1)
HERPESVIRIDEA (DNA viruses)
8 human herpes types
Alpha group
HV-1
Herpes simplex 1
Fever blisters, encephalitis
HV-2
Herpes simplex 2
Genital, meningitis/enecephalitis (newborns)
HV-3
Varicella zoster
Chicken pox, shingles
Beta group
HV-4
Cytomegalovirus
Infectious mononucleosis, neonatal fatality
Gamma group
HV-5
Epstein-Barr virus
Infectious mononucleosis, cancer (Lymphoma)
Other
HV-6
HBLV (human B-lymphotropic virus)
B cells
HV-7
T cells (CD4+)
HV-8
Sarcoma, lymphoma
For Internal Use Only

120. Vaccinations
Aim is to prevent epidemics which caused many deaths in the past.
Vaccines help the body produce antibodies  protection.
Most common vaccines:
MMR: measles, mumps & rubella
IPV: inactivated poliovirus
DTaP: diphetheria, tetanus & pertussis
Varicella vaccine
HBV & HAV: hepatitis A & B
Influenza
PCV: pneumococcal conjugate vaccine
……….
Pipeline: hepatitis C, RSV, HIV, CMV, EBV, …..
Far future: HSV 1&2, adenovirus, toxoplasmose
For Internal Use Only

121. Herpes Simplex 1 & 2 (1) both belonging to the Herpesviridea
slight antigenic difference between HSV-1 and HSV-2
HSV-1
oral-facial lesions
most common HSV
usually acquired in childhood
fever blisters inside mouth
transmitted by infected saliva
90% of adults have Ab’s
HSV-2
genital lesions (ulcers or sores)
possible complications: meningoencephalitis or infection of the eye (acquired at birth, passing through infected mother’s birth canal)
can also be asymptomatic
sexually transmitted
25% of years old of US population
Cross-infection of type 1& 2 viruses may occur from oral-genital contact.
For Internal Use Only

122. Herpes Simplex 1 & 2 (2) Why testing ? Human response to infection:
primary infection often subclinal and rarely diagnosed
primary infection ?  first IgM followed by IgG
virus stays in your system once you’ve been infected
reactivation after latency period, may or may not rise lesions
Why testing ?
Infection contracted during birth is of particular interest  important cause of morbidity and mortality
!! Important to determine the immunitary state of women during pregnancy in order to detect serum conversion !!
For Internal Use Only

123. Herpes Simplex 1 & 2 (3)
Recommended testing:
For Internal Use Only

124. Helicobacter pylori (1)
a bacteria responsible for most ulcers and many cases of chronic gastritis
weakens protective coating of stomach & duodendum  digestive juices will iritate sensitive lining of these organs
H. pylori infection is linked to stomach cancer
having H. pylori in gastrointestinal tract is not always leading to ulcer or gastritis  other factors increase risk
For Internal Use Only

125. Helicobacter pylori (2)
Human response to infection:
most patients exhibit a strong immune response
locally mostly IgA antibodies
circulating antibodies are primarily IgG
IgGs remain constantly high until infection is eliminated (antibiotics)
Treatment of H. pylori:
concentration of Ab’s does not correlate with disease severity but succesful treatment can be monitored by decrease of Ab’s
Efficacy of treatment  decrease in IgG level over time
No treatment:
Spontaneous clearing of H. pylori by IgA & IgG is rare
 elevated IgA & IgG levels, indicates current infection
For Internal Use Only