2nd year Lecture-2022 cytokines and vaccination.pdf

1. Cytokines
A group of low molecular weight proteins that
are secreted by activated immunocytes and
some matrix cells, and that bear extremely
potent and multiple functions.
Cytokines have a multitude of effects, such as
inducing growth, differentiation, chemotaxis,
activation, enhanced cytoxicity and /or regulation
of immunity.

3. Characteristics
1. Most cytokines are low molecular weight proteins
or glycoproteins
2. Cytokines come from many kinds of cells-
activated immune cells, matrix cells and some
tumor cells.
3. Cytokines act on target cells by binding to
cytokine receptors.
4. Cytokines act on target cells by the way of
paracrine, autocrine or endocrine.
5. The biologic effects of cytokines are highly
efficient, multiple and overlapped, which act in a
network.

4. Characteristics
• Cytokines can have effect in spite of very low
concentration.
One picogram (10-12 g) was able to protect one million
cells from 10 million virus particles in a tissue culture
experiments
• One kind of cytokine may have multiple effects.
• Several kinds of cytokines may have the same or
similar effect.

5. One kind of cytokines can be produced by different
cells.
One kind of cells can secrete different cytokines.
IL-3,GM-CSF,TNF-
IL-2
IFN-γ,TNF-β
IL-4，6
IL-5
TH1 TH2

6. Distance
Autocrine
Endocrine
Blood circulation
Paracrine Nearby
self
Cytokines take effect in
three ways

7. pleiotropic, redundant, synergic, antagonistic,
1- Pleiotropism ……. one cytokine have multiple effects on
different cell types.
Effect of cytokines

8. Redundancy …….multiple cytokines have the
same functional effects.

9. Synergy ……..two or more cytokines have more powerful
effects.

10. Antagonism….. one cytokine inhibit the action
of another.

11. Classification
• 1. Interleukins (IL)
• 2. Interferons (IFN)
• 3. Tumor necrosis factors (TNF)
• 4. Growth-factors (GF)
• 5. Chemokines

12. Cytokine receptors

13. • Cytokine receptors are receptors that bind
cytokines.
• Cytokine receptors may be both membrane-
bound and soluble.
• Soluble cytokine receptors are extremely
common regulators of cytokine function.

15. Vaccination
- Artificially inducing immunity
• Goal of vaccination:
–Make memory to protect the vaccinated
person against future exposure to pathogen
Memory T helper cells.....Memory killer T cells
…….Memory B cells .
• Vaccine should have:
• Maximum effect
• Minimum danger

16. Immunization saves lives
• Immunization saves
the lives of
approximately 3
million people each
year, all over the
world.

17. What is needed to make memory cells?
• Memory B Cells & Memory Helper T Cells:
– B and T cell receptors must see virus orviral
debris
• Memory Killer T Cells:
–Antigen Presenting Cells must be
infected with virus

18. Figure 14-23 part 1 of 2

19. Figure 14-23 part 2 of 2

20. Types of Vaccines
• Non-infectious vaccines (Killed)
– DTaP
– Pneumococcus
• Live, attenuated bacterial or viral vaccines
– Chicken Pox
• Subunit Vaccines
• DNA Vaccines

21. Other vaccinations/components
• Booster Shots: same vaccine given at a later
date (e.g. DT given every 10 years
– to refresh the memory cell population
• Adjuvant: chemicals in the vaccine solution
that enhance the immune response
– Alum (e.g) – Ag in the vaccine clumps with the
alum such that the Ag is released
– Slowly, like a time-release capsule
– Gives more time for memory cells to form

22. Vaccines stimulate immune memory
•Killed virus vaccine requires
multiple doses (booster shots)
to adequately stimulate a
protective immune response
•Live virus vaccines replicate in
the host.
•No requirement for boosters.

23. Non-infectious vaccines
• Killed bacterial or inactivated viral vaccines
– Treat pathogen with chemicals (like formaldehyde)
– Impossible to guarantee that you have killed all the pathogen
– Salk (inactivated) Polio vaccine, rabies vaccine
• Subunit vaccines
– Use part of pathogen OR
– Use genetic engineering to manufacture pathogen protein
– No danger of infection
– Hepatitis A & B, Haemophilus influenza type b, pneumonoccocal
conjugate vaccines
• Toxoid vaccines
– Bacterial toxins that have been made harmless
– Diphtheria, tetanus and pertussis vaccines
• This approach will make memory B cells and memory
helper T cells, but NOT memory killer T cells
• Booster vaccines usually required

24. Subunit vaccines
• Single antigen or mixture of
antigens
• Safer (cannot reproduce)
• However, often less effective
than whole agent vaccines
• Can be costly
• Always require boosters
• Use adjuvants

25. Live, attenuated vaccines
• Grow pathogen in host cells
• Produces mutations which:
– Weaken pathogen so it cannot produce disease in healthy
people
– Pathogen still produces strong immune response that protects
against future infection
• Sabin Polio vaccine (oral Polio)
• Measles, mumps, rubella (MMR), varicella vaccines
• This approach makes memory B cells, memory helper T
cells, AND memory killer T cells
• Usually provide life-long immunity
• Can produce disease in immuno-compromised host

26. Whole agent vaccines -- Attenuated
• attenuated - a process that lessens the
virulence of a microbe
oral polio vaccine (Sabin),
MMR (measles, mumps, rubella)
Influenza -- Flumist
TM

27. Whole agent vaccines -- Killed using
heat or formaldehyde
Inactivated polio vaccine (Salk)
Influenza (Classic)
epitopes
epitopes
Live virus Killed virus

28. • Advantages for live vaccines
– multiply like natural organism
– require fewer doses and boosters
– long-lasting
• Disadvantages for live vaccines
– special storage
– back mutation
– side effects

29. DNA Vaccines
• DNA injections can produce memory B cells
and memory T killer cells
• Reasons are not fully understood
• DNA vaccine is made from a few viral genes
• No danger that it would cause infection

30. Effectiveness of Vaccines
• Vaccination Effectiveness
– About 1-2 of every 20 people immunized will not have
an adequate immune response to a vaccine
• Herd Immunity
– Vaccinated people have antibodies against a pathogen
– They are much less likely to transmit that germ to other
people
– Even people that have not been vaccinated are
protected
– About 95% of community must be vaccinated to achieve
herd immunity

31. Figure 14-22