Class 2: Acquired immunity and vaccination (part 1)

Transcription

1 Class 2: Acquired immunity and vaccination (part 1) Ed Ishiguro Department of Biochemistry and Microbiology And The UVic Speakers Bureau

2 A quick summary Main properties of innate and acquired (adaptive) immunity Innate Nonspecific Rapid response No memory of previous encounter Acquired Pathogen-specific Slow initial response Retains memory of first encounter

3 Overview of Acquired Immunity

4 Acquired immunity Immune response to foreign chemical substance called an antigen (Ag) usually associated with infectious agent Response involves production of proteins called antibodies (Abs) that bind specifically to Ag Binding of Ab to Ag inactivates pathogen

5 General structure of an antibody

6 Humans capable of producing billions of different Abs, each capable of binding a different Ag Each pathogen has unique set of Ags Human immune system set to protect against almost any threat

7 Anatomy of Influenza Virus Brock, Fig H proteins N proteins Genome Portrait of Flu Viruses (magnified 265,000 times)

8 The parasitic lifestyle of viruses H protein binds flu virus to respiratory tract tissue receptors

9 Flu virus infection is inhibited by Abs that bind flu surface Ags

10 Acquired immune system mediated by T and B cells with help from phagocytes

11 Figure 24.2, Brock Biology of Microorganisms, 14 th ed., Pearson Education, Inc., 2015 B cells mature in bone marrow; T cells develop in thymus (during first year of life)

12 Pathway for development and activation of B cells Clones of immature B cells Clones of dormant non-selfreactive mature B cells enter lymphatic circulation (note B cell receptors are Abs) Exposure to foreign Ag induces Ab production 4 Introduction of Ag (4) results in by specific clones specific activation of B cell clone 4 Production of specific Abs against Ag 4 (requires help from T cells)

13 Development of T cells T cell precursors leave bone marrow and migrate ( home ) to thymus Differentiate into billions of different clones of dormant T cells that enter lymphatic circulation Each clone capable of recognizing one specific Ag through T cell receptor Thus, for each specific B cell clone, there is corresponding ( cognate )T cell clone

14 Comparison between B cell receptor and T cell receptor Bacterium Very strong binding affinity Very weak binding affinity B cell T cell

15 Ability of the thymus to produce T cells decreases with age (unlike bone marrow function) Sections of thymus from 3-day-old infant (a) and 70-year-old person (b). Stained regions active in T cell production. 15

16 Anatomical distribution of lymph nodes in lymphatic system: major site of immune surveillance along with spleen, tonsils, appendix, and mucosal-associated lymphoid tissue

17 B cells capture pathogens by binding their surface Ags and carry them to closest lymph node ( draining lymph node )

18 (Activation and proliferation of B cells) Architecture of the lymph node

19 Events leading to Ab production 1. B cell receptors (BCR) bind Ags of pathogen 2. B cell engulfs pathogen and dismantles it 3. B cell displays only the Ag on its surface 4. Cognate T helper cell (T H ) binds Ag through its T cell receptor 5. Activated T cell produces chemical signals that drive B cell proliferation and differentiation to Ab-producing cells (6) 4. T cell receptor 3. Ag display BCR 5. Chemical signals

20 Comparison between B cell receptor and T cell receptor Bacterium Very strong binding affinity Very weak binding affinity B cell T cell

21 Five classes of Abs (immunoglobulins or Igs) default Ab Underlined classes perform protective function

22 Kinetics of humoral immune response ( Booster ) T helper cells provide B cells with chemical signals that cause switch from IgM to IgG during late stages of primary response

23 Questions about primary response Why is IgM the default? Ten Ag-binding sites to provide jump-start to immune protection Why switch to IgG? Disadvantage of IgM is that it is large and cannot efficiently enter tissues where infections may localize Why is response terminated? Terminated when infection controlled Ab-producing B cells do not proliferate and are shortlived

24 Kinetics of humoral immune response ( Booster ) Secondary response is faster and more robust due to presence of memory cells from primary response

25 During primary response, T helper cell chemical signals not only control proliferation and differentiation of B cells to short-lived Ab producers (left) but also to long-lived memory cells (right) Short-lived Long-lived

26 A quick summary Main properties of innate and acquired (adaptive) immunity Innate Nonspecific Rapid response No memory of previous encounter Acquired Pathogen-specific Slow initial response Retains memory of first encounter

27 Ab levels from fetus to adult: we are born immunocompromised were it not for maternal Abs Fig 13.9, Janeway s Immunobiology, 8 th ed Garland Science 27

28 Vaccines and immunization Types of vaccines 28

29 Common examples of vaccines Killed vaccine: example, influenza vaccine contains mixture of 3 different killed influenza viruses Live attenuated vaccines: contain viable organisms which have been disarmed by introduction of mutations Sabin polio vaccine Measles, mumps, and rubella vaccine Chickenpox and shingles vaccines Subunit vaccines composed of purified antigens from pathogens Inactivated tetanus toxin from Clostridium tetani Surface proteins of human papilloma virus

30 Vaccines and immunization Vaccine-preventable diseases and vaccination theory 30

31 Global polio eradication program 2015: total of 71 cases in two countries (Pakistan and Afghanistan

32 Largest measles outbreak in 30 years ends in Fraser Valley Health officials announce end of historic outbreak after 400 cases CBC News Apr 28, 2014 Over a four-week period earlier this spring, the Fraser Health region had over 400 cases of measles with some patients requiring hospitalization. "The size of, and speed at, which this outbreak spread resulted in more cases of measles than the province has seen in the past 15 years, and was the largest outbreak in almost 30 years," says Dr. Van Buynder.

33 Recent outbreaks caused by vaccine hesitancy

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35 The theory of vaccination Not only for protection of individuals receiving vaccination Designed to protect vulnerable population (includes immunocompromised individuals who cannot receive vaccination) against infectious pathogens ( herd immunity )

36 Relationship between R0 and threshold level needed for herd immunity Photo credit: Tangled Bank Studios; data from Epidemiologic Reviews R0 = how many people in an unprotected population one infected person could pass the disease along to (measles and pertussis are most contagious)

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