IMMUNOLOGY // LECTURE 1 // INTRODUCTOIN //
CHAPTER 1
➢ Learning goals
At the end of the course, the student is able to:
1. Describe the cellular and molecular structure of the immune system.
2. Explain the function of primary, secondary and tertiary immune organs.
3. Outline the structure and function of the HLA system.
4. Discuss the recognition of intracellular and extracellular antigens by the adaptive
immune system.
5. Explain the use of gene fragment rearrangements in the generation of diversity of T and
B cell repertoire.
6. Outline the sequence of events during activation of adaptive immune cells.
7. Compare the basis for specificity, diversity and memory function between the innate
and adaptive immune system.
8. Contrast the acquisition and maintenance of tolerance versus the induction of
immunity.
➢ Immunology
Immunology = The scientific discipline that studies the Immune System, which serves to
protect your body from infectious agents and cancer.
→ Immune system = An organ that is all over your body, because its cells are spread out to
the other tissues
→ Key concepts in Immunology
- Innate versus adaptive immune system
- Specific versus aspecific immune responses
- Self versus non-self
- Immunological memory
- Immunity versus Tolerance
- Cellular versus Humoral Immunity
- Differentiation and specialization of leucocytes
- Antibodies: Specificity, selectivity, affinity
➢ Infectious disease
→ Vaccination: since 1798 (Jenner)
→ Understanding that specific germs cause specific diseases.
→ Koch’s postulate: A critical step forward in identifying causal agents.
→ We distinguish microorganisms that can be infectious, but also parasites.
→ Microorganisms are things like bacteria, which can either live outside or inside your cells
(extracellular and intracellular bacteria) or viruses, fungi and parasites stay in this warm
environment (lungs, guts)
,➢ Koch’s postulate
→ Koch’s postulate = Robert koch’s experimental proof that a specific germ would be
causing a specific disease
→ He said that if there is a specific germ causing a disease it should be possible to isolate
that germ from a diseased individual → So you can take this germ out of a diseased
individual and grow it in a lab → For a virus this is more tricky, because you need a specific
cell for a virus → But for the extracellular bacteria this is quite easily done
→ If you then purify in culture this germ and then incubate this germ in to a new host
(animals) then that animal has to get sick again from the same disease as the original animal
where you isolated this germ from → You have to be able to re-isolate this germ from the
animal again and if you meet those four criteria you basically have met Koch’s postulate
and can claim that this specific germ is the cause for this specific infectious disease
→ If you have a diseased animal and you can treat the germ (kill/antibodies to neutralize it)
then the animal should also recover from the disease → So you should be able to take away
the cause of the disease and be able to recover the animal
→ In general the Koch’s postulate is quite often used and helps us understand
→ If we look at the SARS2 coronavirus, we use specific cell lines (Vero cells) to grow these
viruses in → So each virus has a specific sort of cell type they want to infect, and if you have
an idea which cell type this is, then we use a viral isolate (so you take a nasal swap from a
patient) and you put that swap on to cells that can then be infected with the virus
➢ Infectious diseases
→ Diphtheria: Bacterial infection, most common cause of pediatric (in kids) death before a
vaccine became available. After diagnosis: 10% of patients die with and 50% die without
treatment
→ Polio: Highly contagious (besmettelijk) virus → Induces paralysis and deformation in
1/200 patients (still common in Asia, while there is a good vaccine)
→ Measles: Highly contagious virus, with very severe complications and often resulting in
death (luckily there is a good vaccine now)
➢ Vaccinations
→ Studying and understanding the interactions between infectious agents and the
immune system has led to eradication of the viral disease smallpox and strong reductions
in the incidence of a large series of other infectious diseases.
→ With loss of confidence in vaccines, infectious diseases reappear.
➢ Do we really need vaccines?
,→ Measles incidence is strongly increasing in Europe: 26.000 cases in 2017, 85000 in 2018,
>90000 in the first 6 months of 2019!
→ In 2020 probably less, because people are being isolated due to Covid → So all the other
infectious diseases are also going down as a consequence
→ In the Netherlands: 10-20 cases annually, but: 24 in 2018, >80 in 2019. Death due to
measles is still rare in the Netherlands.
→ This time last year (2019 course), children in Samoa were dying due to a recent
outbreak of measles. Death rate is 1,5% of all infected
→ If nobody gets infected, then the whole population doesn’t get exposed (for example on
an island) → So if you’re vaccinated and you will be exposed to the virus it will be a boost to
your immune system and that will reinforce your immune system → If you aren’t exposed to
the virus for 30 years the vaccination might not work as well anymore either
→ If you’re not exposed to the pathogen for a long time, then the memory cells that are
important for the vaccine effect for your immune memory might be lost or inactive, but
also the pathogen can develop / mutate → The influenza virus mutates every year and then
you might not have immunity
→ The 2020 disease: COVID-19 (coronavirus induced disease 2019) caused by the
infectious agent SARS-CoV-2 (SARS coronavirus 2)
→ To date – almost 1.5 Million deaths (within 1 year!). Vaccinate?
→ Infection is something else than disease → Infection means that the virus is entering the
cells, but it doesn’t mean that you’re sick yet
→ The thing is that with this novel virus we don’t know how long the vaccine will work → If
you have a solid antibody response and solid cellular response, it should last for up to a year
at least, but we don’t know
→ Severe disease in COVID-19 is more common in elderly people
→ This has something to do with the induction of new T-cell responses that depend on only
memory responses in elderly people & It has something to do with the fact that your
immune system reacts slower in elderly people & It has something to do with the fact that
elder people have co-morbidities, which are also other morbidities
→ But long-term symptoms (long Covid): reported in all age groups!
→ The very severe phenotype of the disease is associated with ARDS (acute respiratory
distress syndrome) → So people can’t breathe anymore, because their lung structure is
destroyed, not so much by the virus, but by the immune response to the virus → So your
alveoli where gas exchanges occur are destroyed and fluid starts leaking in to the lungs
and you drown in your own fluid
→ A vaccination is more effective in elderly people than in younger people
→ People of all ages that get infected with covid-2 and get even mild disease (younger
people) around 10% develop long-term symptoms which are seen in all age groups and
they’re quite disabling → So people have been sick for after 6 months after the initial
infection (fever, pains, fatigue) and we don’t know how this works → This is another reason
to vaccinate everyone, because this long-term disease after covid is something you want to
prevent
,➢ Do vaccines actually help?
→ Meningococcal disease: Caused by a bacteria that can inhabit the mouth and throat. In
rare occasions, the bacteria can enter the circulation leading to sepsis and meningitis, with
a death rate of around 10% and severe complications with the survivors including
neurological symptoms, deformations and amputations.
→ In 2002, a vaccination program against type C has nearly eradicated this meningococcus
type
→ Meningococcus type W has seen a strong increase since 2017, and is very aggressive,
leading to a new vaccination program for this disease.
→ So if there is a disease that is spreading amongst the population and we start to
vaccinate, the disease is suppressed quite effectively, so yes it works
→ Vaccination campaign:
- Started in Fall 2018, in 13/14 year olds; 2019: all 14-18 year olds
- Incidence dropped in 2019 except for the 80+ group; death toll (23/103 in 2018) is
also down (8/51 in 2019 up to November)
➢ More vaccines are needed
→ RSV: respiratory syncytial virus
→ RSV = A cause of common cold with yearly seasonal epidemics around the globe.
→ In preterm infants, RSV can cause very severe complications, in susceptible children,
also those carried to term, RSV infections in the first year contribute to asthma inception.
→ In non-Western countries, RSV epidemics completely congest the healthcare system!
→ Most important cause of death in children.
→ No Vaccine available yet → There was no interest anymore when the vaccine turned out
to be not working, but now with the Covid situation we think that the interest might rise
again
→ It’s a RNA virus that infects your lungs
→ COVID-19 vaccine
→ Mostly directed to the Spike (S) protein = The protein that the virus uses to enter the
cells in the nose or the airways.
→ The S-protein is also the protein most well recognized by the immune system → So
most vaccines are trying to target this S-protein by either using a RNA or DNA based
vaccine or commonly protein vaccine
,→ Those live attenuated (verzwakt) virus vaccines have a higher risk of side-effects, because
if in huge production facilities something goes wrong and the virus wasn’t really attenuated
then you start to infect people → So most of the vaccines which are almost ready for the
market are based on RNA or recombinant proteins vaccines which will be quite safe
→ This vaccine can be delivered in various ways.
→ Also: inactivated virions might be used as vaccine
→ The current vaccines seem effective in clinical studies.
→ There are cells that will be respond to your virus and these are innate cells (dendritic cells
and monocytes macrophages) and they will sense the corona virus PAMPS (pathogen
associated molecular patterns) by their pattern recognition receptors (PRRs) that are
expressed by these APC’s
→ So these innate cells will recognize the virus somehow and then induce immune response
→ So you have the antiviral response which gives rise to type I and type II interferons and
they will also induce the adaptive immune system to pro-preceptory cytokines
→ SARS-CoV-2 vaccines
→ A successful SARS-CoV-2 vaccine might work through a variety of immunological
mechanisms, involving the innate immune system and activation of the adaptive immune
response and establishment of memory B cells (antibody production) and memory T cells
(cell- mediated virus response)
→ In 3 weeks you will understand what it means!
→ So we want to have a B-cell response and all kinds of T-cell responses → So the B-cell
makes antibodies which give you protection for the virus because it neutralizes the virus
→ The T-cells either help making antibody responses (CD4 T-cells) or they will start killing
virus infected cells (CD8 T-cells) → This needs to be induced in a proper way by a vaccine
→ So we try to induce B- and T-cell responses that are specific for the virus, because they
will have memory function and they will allow you to respond very aggressive to the virus
the next time it comes by and suppress it
→ The immune cells sit on the inside of your body, whereas the virus infects the barrier
epithelium → So the virus gets in to your nose/airways and then infects the epithelial cells
with its spike protein and those infected epithelial cells will be killed by the immune system
→ The process of that initial infection you can’t stop and that’s why even if there is a vaccine
you still have some virally infected cells → They’re being cleared by the immune system and
the virus doesn’t spread and you don’t spread the virus to your neighbors, but you will still
have that initial infection
➢ Immunology
→ Features of the immune system
, → Clearly, a potent immune response is of critical importance to combat infectious
disease
→ Features of the immune response:
- Innate versus adaptive immune system
- Specific versus aspecific immune responses
- Self versus non-self
- Immunological memory
- Immunity versus Tolerance
- Cellular versus Humoral Immunity
- Differentiation and specialization of leucocytes
- Antibodies: Specificity, selectivity, affinity
➢ Cells of the immune system
→ White blood cells, or leucocytes = The most important cells in the immune system.
However, other cells also play an important role, including epithelial and endothelial cells.
→ Leucocytes (and red blood cells) originate from the hematopoietic stem cell.
→ Mature leucocytes often circulate the body using the blood and lymph systems.
However, tissue also harbor a large number of specialized tissue-resident leucocytes.
→ The immune system is an organ that sits throughout your body, because it’s largely made
out of blood cells which can travel and enter tissues and leave tissues
→ The hematopoietic stem cell differentiates in to the different lineages of the immune
system
➢ The immune response
→ Your immune response has a time scale → There is an immediate response shortly after
infection and a short term response which takes days to develop
→ The early immediate response is often delivered by the innate immune system with
which you’re born with → Is the same for every pathogen → They will recognize the
microbe and start attaching it right away → It’s always there
→ The slow response which takes days / weeks to develop is the adaptive immune system
which makes a specific immune response which is highly tailed to that one pathogen that
infected you and is different for every pathogen → This develops an unique immune
response tailing to the specific infection that you’re dealing with at that moment → You
need to develop a novel adaptive immune system for every new virus
→ That is also what a vaccine does, it’s teaching your adaptive immune response
