Chapter 17
Immune Responses to
Infectious Disease
And Vaccines
Introduction
• Evolutionary race between microbe and man
• communicable diseases: mortality in millions & downfall of
nations
• Demise of dinosaurs
• Plague
• Smallpox
• Measles
• Only survivors to nurse the sick (430BC) & variolation
• World Health Organization (WHO) & Centers for Disease
Control and Prevention (CDC)
• Organize the accumulating data concerning infectious
disease.
• Monitor public health and disease, guide health care
policy
• Discussions, respond to sudden infectious disease
outbreaks, and report regularly on their findings.
Investment Economics
Prevalence of infectious diseases
Top 10 cause of death in children below 5
Entry through mucosal surfaces
• The Importance of Barriers in Infectious Disease
• Vectors Borne diseases: 1 in 6 of infectious
• Interventions
• Escape mechanisms of microbes
• Reduce their own antigenicity
• Growing within host cells
• shedding their membrane antigens
• Camouflage: similar cell membrane or covering with
CM
• Suppressing immune response
Link between Location and Immune Effector Mech.
Link between Location and Immune Effector
Mechanism
Some Facts
• Remember that only a small % of microbes are
pathogens
• Pathogens can be viruses, bacteria or eukaryotes
(protozoa & parasites)
• Pathogens can contribute to cancer, cardiovascular
disease and other chronic illnesses
• Primary Pathogens
Can cause disease in most healthy people
• Opportunistic pathogens
Usually cause disease only if the immune system
is weakened or if the microbe gains access to a
part of the body where it is normally not found
Emerging and Re-emerging Infectious
Diseases diseases
Factors leading to spread
• Population explosion • Re emergent: Ebola, Dengue &
• Globalization: Travel TB
• Lack of health care • Emergent
• Zika
• Increase contact with animals • Corona
• Alteration in microbes
• Environmental degradation
• Natural Disaster
CORONA VIRUS
Bioterrorism
Bioterrorism: Anthrax
• anthrax spores mailed to
congressmen
• and news offices
Introduction
• Immunization is the process of eliciting a state of protective immunity
against a disease-causing pathogen
• Vaccination, or intentional exposure to modified forms or parts of a
pathogen that do not cause disease
• vaccination is an event, whereas immunization (the development of a
protective memory response) is a potential outcome of that event.
• Recent Development: Convalescent plasma therapy and corona virus
Vaccines are still
needed against
many diseases
Vaccines that are
available need to be
administered
○ There are people that
are choosing not to
vaccinate……could
potentially create scary
scenario in future
Developing a vaccine
• Lots of research
• Time consuming, costly
• Idea is to isolate a component of the organism that proves to be
immunogenic….sometimes not possible
• Human trials are strictly regulated
• Might have vaccine developed but there might be adverse side effects
– can’t be used…
Active and passive Immunity
• Immunity can be achieved by active or
passive immunization
• Passive – transfer of preformed antibodies
• Maternal antibodies to fetus
• Antibody therapy for bites,
immunodeficiency
• Active – long term protection, immunologic
memory, actual exposure
• Coming into contact with any foreign
substance
• vaccines
Side Effects of Passive Immunity
• There is a chance of side effects in small no. of population
• That is the case with any treatment/drug
• However, if the benefits to the population out-weigh the risk of side effects, vaccines
must be used to protect the majority of the population
○ HERD IMMUNITY
• Produced in another species, such as a horse: Anti isotypic response
• Purified human antiserum or human gammaglobulin: anti-allotype
response
Designing Effective Vaccine
• Protective immunity must be achieved
• Must pay attention to how the antigen activates the humoral and cell-mediated
branches
• Must produce immunologic memory
• Vaccine that produces primary response but fails to produce secondary response is not
effective
Features of Ideal Vaccine
• Safe
• Effective in preventing infection
• Achievable given the population in question
• Geographical locale
• access to the target group (which may require several vaccinations),
• Act against Complicating coinfections
• Nutritional status
• Cost
• Steps: Dry Lab, Wet Lab,Animal Expts & Human Trials
Human Trials
• Phase I:human safety
• Phase II: Effectiveness against the pathogen
• Phase III:expanded volunteer populations, where natural evidence of
protection against “the real thing” is the desired outcome
• Phase IV: After marketing and distribution, and are used to monitor
safety, effectiveness, and any long-term impacts.
Live Attenuated Vaccines
• Historical example: cowpox inoculation of humans
confers immunity to smallpox
• Microorganisms can be attenuated so that they lose
ability to cause significant disease
• Retain capacity for growth in host
• Bacteria is grown for prolonged period in adverse conditions
• Those that survive will not be suited to grow in “better”
conditions in host
• BCG: M. Bovis grown in Bile ay high conc.
• A virus might be grown in cell type that is not normal host
• Accumulates mutations that might weaken it
• Measles, mumps, rubella vaccine is example
Live, Attenuated Vaccines
Advantages Disadvantages
○ Can grow in host therefore producing ○ Possibility that it will revert to virulent
immunologic memory with only single form
vaccination Polio – 1 in 2.4 million chance this will
○ Produces memory T cells happen
Good for distribution in Third World ○ Complications
countries Measles vaccine – encephalitis
Out of 75 million patients between
1970 and 1993, only 48 cases
○ Danger from remaining un-vaccinated
and getting disease is much greater
than complications to these proven
vaccines
Risks from vaccine are much much lower than risking having the
actual infection!!!!
Inactivated or “killed” vaccines
• Inactivation of pathogen by heat or chemical (formaldehyde)
• Not capable of replication in host
• Epitopes have to be maintained after killing process
• Often require boosters
• Risks
• Pathogen has to be grown in large #’s prior to inactivation – individuals
involved in manufacturing are at risk
• Some of the pathogen may not be killed
• Pertussis vaccine, typhoid vaccine, flu vaccine
• Salk polio vaccine: earlier manufacturing defect → paralytic
polio
• Advantage: Relative safety, stability, and ease of storage and
transport
Subunit Vaccines
Purified macromolecules derived from pathogens
Toxoids
○ Some bacteria are pathogenic because of exotoxins that they produce
○ Purify exotoxin, inactivate it with formaldehyde to form toxoid that can be used to
immunize
○ The immune system is then able to neutralize the toxin when an infection occurs
Bacterial polysaccharide capsules: activate B cells in a thymus-
independent type unless linked with protein
• Genes encoding surface antigens from pathogens → Protein → used
for vaccine dev.
• Recombinant HBsAg in yeast
Recombinant vaccine:
• DNA encoding protein antigen
Expressed in bacterial or
mammalian cells → Purification
→ Stimulates an CMI & HI
• Eg HBsAg
Recombinant vector vaccine - still in clinical testing
DNA Vaccine
DNA Vaccine
• Produce immunogenic protein in vivo → Endogenous MHC class I
presentation → CTL responses.
• Advantages
• Expressed in natural form
• HI & CMI
• No refrigeration of required,
• Tailored to insert DNA encoding a variety of proteins: Simultaneous vaccination to
multiple antigens (saving time and money)
• Delivery
• Gene gun
• Electroporation
• Mucosal administration via DNA-containing liposomes
• Bacterial delivery of DNA
• Transient gene expression: Poor immunogenicity
• approved for veterinary use: a West Nile virus vaccine in horses
Conjugate Vaccines
Polysaccharide
vaccines unable to
activate TH cells
○ Activate B cells in
thymus-independent
manner
○ IgM production but no
class switching, no
memory
Conjugate to protein
carrier that is
considerably more
immunogenic
Haemophilus influenza,
Strep pneumoniae
• Watch this video on DNA vaccines:
• https://www.youtube.com/watch?v=ybdMKEj_ZNQ
Adjuvants
