BMS 545 Immunology Lecture Slides PDF

WELCOME! BMS 545 IMMUNOLOGY NOVEMBER 6, 2024  THE REST OF THE SEMESTER (ALL MODULE 4)  11/6- Vaccines (Exam 4)  11/8- Exam 3 2:30 pm  11/11- PBS Vaccine documentary (Asynchronous)  11/13- Primary Immunodeficiency  11/15- Secondary Immunodeficiency (Asynchronous). Research Days 1-4 pm ...

WELCOME! BMS 545 IMMUNOLOGY NOVEMBER 6, 2024  THE REST OF THE SEMESTER (ALL MODULE 4)  11/6- Vaccines (Exam 4)  11/8- Exam 3 2:30 pm  11/11- PBS Vaccine documentary (Asynchronous)  11/13- Primary Immunodeficiency  11/15- Secondary Immunodeficiency (Asynchronous). Research Days 1-4 pm  11/18- Transplantation & Immune Pharmacotherapy  11/20- Transplantation & Immune Pharmacotherapy & Cancer  11/22- Cancer & Tumor Immunity  11/25- Hypersensitivity (Asynchronous- Enjoy Thanksgiving break)  11/27-11/29- Thanksgiving break  12/2- Autoimmune Disorders  12/4- “What’s Wrong with Me?” Case Study  12/6- Final Immunology debrief: The Well Patient WHY YOU SHOULD CARE  CLASS OBJECTIVES  Relate concepts of B & T cell immunity and memory to vaccination  Identify, compare, & contrast the different type of memory cells (e.g. B, plasma, TCM,TEM, TRM )  Describe why are memory cells better at being activated? (e.g. FcγRIIB1, CD45RA/RO)  Describe the asymmetric division of naïve T cells & differentiate naïve & effector or memory cells  Understand & describe why vaccines are important  Differentiate the origination of inoculation & vaccination (slide 18- it’s the video that’s fair game)  Define the different types of vaccines & their characteristics & pros/cons  Define adjuvants and be able to identify an example  Be able to have a discussion with an anti-vax or on-the-fence patient/patient's parent about vaccination, why it's important, and debunk some common vaccine myths  Learn where to find out more information on vaccines if you don’t remember, or want to learn more Immunological memory and the secondary immune response FACT: Immunological memory is essential for the survival of human populations For example: Specific anti-vaccinia antibodies continue to be made ~75 years after last exposure to vaccinia virus (smallpox vaccine surrogate) & CD4 & CD8 memory T cells are retained – #s of antibody represent international units (IU) of antibody- standardized way of measuring an antibody response  Immunological memory and the secondary immune response 11-2 Antibodies made in primary response persist in circulation to prevent reinfection  Immunological memory and the secondary immune response 11-5 Long-lived plasma cells are the major mediators of B-cell memory A large wave of short-lived plasma cells is followed by a smaller, selected group of long-lived plasma cells Figure 11.4 Complexes of IgG and polymeric antigen prevent the activation of naive B cells by crosslinking the B- cell receptor to the inhibitory FcγRIIB1 receptor  The inhibitory FcγRIIB1 receptor keeps more naïve B cells from becoming activated  BCR & FcγRIIB1 on a naive B cell can be cross-linked by pathogen coated with IgG, delivering a negative signal that prevents naive B cell from being activated  Memory B cells activated do NOT express FcγRIIB1 & are capable of being activated  Most Memory B cells make high affinity IgG1 on re-stimulation Immunological memory and the secondary immune response 11-7 Antigen-mediated activation of naive T cells gives rise to effector and memory T cells Figure 11.9 Antigen activation of a naive CD8 T cell  On activation, naive T cell becomes metabolically reprogrammed & undergo asymmetric division to give one effector T cell (TE) & one memory T cell (TM) Figure 11.11 Naive, effector, and memory T cells differ in cell-surface phenotype Both CD4 & CD8 T cells can have CD45 RO or RA Figure 11.12 Different isoforms of CD45 make memory T cells easier to activate than naive T cells  CD45- a transmembrane tyrosine phosphatase involved in CD4 & CD8 T-cell activation (pic example is CD4)  Naive T cells = express CD45RA isoform,  Memory T cells = express CD45RO isoform  CD45RA is bigger than CD45RO & less able to interact with T-cell receptor complex & activate T cells, making memory T cells easier to activate than naïve T cells  There are 3 subtypes of memory T cells based on where they are found: TCM, TEM, TRM  Immunological memory and the secondary immune response 11-8 Two subpopulations of circulating memory cells patrol different tissues of the body 1. Central memory T cells (TCM):  Preference for T-cell zones of secondary lymphoid tissues & take longer than TEM cells to mature into functioning effector T cells after encounter with their specific antigen  Express L-selectin & CCR7 which allow them to enter secondary lymphoid organs to survey antigens 2. Effector memory T cells (TEM):  Preference for inflamed tissues & are activated more quickly than central memory cells to mature into functioning effector T cells after encounter with their specific antigen  Lack L-selectin & CCR7, but have other chemokine receptors allowing them to enter non-lymphoid tissues, like inflamed tissues  Immunological memory and the secondary immune response 11-9 Primary infections of a non-lymphoid tissue produce resident memory T cells that live within the tissue  Resident memory T cells (TRM)- long-lived memory T cells produced during an adaptive immune response that enter infected non-lymphoid tissue & reside there forever Figure 11.13 Three types of memory CD4+ T cells have different patterns of migration through tissues Resident memory T cells are the most numerous type of memory T cell For each type of cell, the tissues it circulates through are in color; the other tissues are gray  Like naive T cells, TCM cells circulate between blood, lymph, & secondary lymphoid tissues  TEM cells circulate from blood to non-lymphoid tissues & return in lymph to the blood  TRM cells are based in non-lymphoid tissue, where they can rapidly respond to local infections Figure 11.15 Differences between the primary and secondary immune responses Vaccines use premises from both Primary & Secondary responses to pathogens to keep us safe! HOW ARE VACCINES GENERALLY MADE?  Vaccination to prevent infectious disease 11-11 Protection against smallpox is achieved by immunization with the less dangerous cowpox virus  Vaccination with cowpox virus elicits neutralizing antibodies against epitopes shared with smallpox virus Fun fact!: Smallpox is the only infectious disease of humans that has been eradicated worldwide by vaccination Figure 11.17 Childhood vaccination schedules in the United States  Each red box denotes a time at which a vaccine dose should be given  Boxes spanning multiple months indicate a range of times during which the vaccine may be given  DTaP- diphtheria, tetanus, and acellular pertussis vaccine *Based on CDC Prevention immunization schedules **No, don’t memorize Figure 11.14 The amount and affinity of antibody increase after successive immunizations with the same antigen  Experiment (using mice) that mimics development of specific antibodies during a course of 3 immunizations with same vaccine  Upper panel shows how amounts of IgM (green) & IgG (blue) present in blood serum change over time  Lower panel shows changes in average antibody affinity that occur  You’re literally viewing affinity maturation! ☺ *Vertical axis of each graph has a logarithmic scale because the observed changes in antibody concentration & affinity are so large BEST IMMUNE RESPONSE: LIVE-ATTENUATED VACCINES → INACTIVATED VACCINES → EVERYTHING ELSE REPLICATING ORGANISMS = GOOD IMMUNE RESPONSES *SAFETY OF A VACCINE MAY BE INVERSELY PROPORTIONAL TO ITS EFFECTIVENESS*  VACCINES CAN BE PREPARED FROM VARIOUS MATERIALS DERIVED FROM PATHOGENIC ORGANISMS  Live-Attenuated vaccines- use whole, living organisms but have virulence & ability to replicate reduced by treatment with heat, chemicals, etc.  Typically cause only subclinical or mild forms of disease can occur but carry possibility that mutation might enable organisms to revert to wild type  Booster shots not usually needed  Ex. MMR, smallpox, chickenpox, yellow fever, Sabin polio vaccine  Inactivated (killed) vaccines- organisms that are dead because of treatment with physical or chemical agents  Incapable of infection, replication, or function but still provokes immunity  Difficult to guarantee that every organism in a preparation is dead  Booster shots sometimes needed  Most viral vaccines are made from killed or inactivated viruses  Ex. Hep A, Influenza, Salk polio vaccine  *Toxoid vaccines like diphtheria & tetanus can be considered inactivated since they use inactivated toxins  VACCINES CAN BE PREPARED FROM VARIOUS MATERIALS DERIVED FROM PATHOGENIC ORGANISMS  Subunit, recombinant, polysaccharide, & conjugate vaccines- use specific pieces of the pathogen—like its protein, sugar, or capsid  Some can infect host cells but cannot induce disease  Boosters sometimes needed; Adjuvants often used  Ex. Hib, Hep B, HPV, Shingles, J&J Covid uses a recombinant vax model- weakened live adenovirus with Covid spike protein  RNA vaccines- RNA vaccines work by introducing an mRNA sequence (molecule which tells cells what to build) which is coded for a disease specific antigen  Faster & cheaper to produce than “traditional” vaccines  Boosters sometimes needed  Ex. Pfizer & Moderna Covid Vax  DNA vaccines- naked DNA extracted from pathogen & engineered to remove some of genes critical to development of disease. Host cells to take up DNA & express the pathogen gene products  Typically lasts longer than other methods where vaccine is rapidly eliminated from host  Ex. India’s Covid vax, no DNA vaccines approved for humans in US (yet) Figure 11.18 Attenuated viruses are obtained by growing pathogenic human viruses in non-human cells  To produce an attenuated form of a virus, virus is first grown in quantity in human tissue culture cells  Virus is then isolated & grown in cells of non-human species (e.g. monkey species), until it adapts fully to non-human cells & consequently grows poorly in human cells  The adaptation is result of selection for a mutant virus that outgrows original virus & Attenuated mutant usually differs from original virus by an accumulation of several point mutations  While slow growing in human host, attenuated virus of a vaccine is present in amounts that stimulate an immune response but are insufficient to cause disease  Vaccination to prevent infectious disease 11-14 Both inactivated and live-attenuated vaccines protect against poliovirus Poliomyelitis has been virtually eliminated from the US  Campaign to eradicate polio began in1950s with introduction of Salk inactivated vaccine  1960s- Introduction of Sabin live-attenuated oral vaccine  1970-2000 polio had become a rare disease in which public concern turned away from epidemic polio & toward the cases of polio caused by the attenuated viral strains of the oral vaccine  2000- oral vaccine was withdrawn  Because poliovirus has not been eradicated worldwide & volume of international travel is so high, immunization must be maintained in majority of US population to prevent recurrence of epidemic disease  Vaccination to prevent infectious disease 11-15 Vaccination can inadvertently cause disease Figure 11.20 Childhood mortality from rotavirus infection in the 10 most affected countries, 2008 and 2016  11-17 Invention & application of rotavirus vaccines took decades of research and development  RotaTeq & Rotarix vaccines were licensed in 2006 & 2008  By 2017, ~28% of 1-year-old children worldwide were vaccinated against rotavirus  Shown here are estimated annual numbers of deaths from rotavirus infection in children