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Summary Immunology
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ImmunologyLecture 1 – introduction & Chapter 1
Immunology is the scientific discipline that studies the
Immune System, which serves to protect your body from infectious agents and cancer.
Infectious disease
- Microorganisms; like bacteria that can live outside and inside your cells.
- Viruses
- Fungi, that populate in your tissue.
- Parasites, that live in a warm environment, gut and lungs.
To deal with infectious diseases is the development of vaccination; since 1798 (Jenner).
Understanding that specific germs cause specific diseases.
Koch’s postulate; a critical step forward in identifying causal agents.
Robert Koch’s postulate; slide 14
1. The germ is found in diseased but not healthy organisms.
2. The germ can be isolated from the diseased organism.
3. The germ causes disease when transferred.
4. The germ can be isolated again.
Infectious diseases
- Polio: highly contagious virus; paralysis and deformation in 1/200 patients.
- Measles: highly contagious virus, very severe complications and often resulting in death.
- Diphteria: bacterial infection, most common cause of pediatric death before a vaccine
became available. After diagnosis: 10% of patients die with and 50% die without treatment.
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. (don’t know the number).
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 the Netherlands: 10-20 cases annually, but: 24 in 2018, >80 in 2019. Death due to measles
is still rare in the Netherlands.
- We can see that the incidence was raising due the effect of people were stopping with taking
vaccinations. So due the vaccines the disease becomes less otherwise it is raising!
- 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.
- Even when you vaccinated and you get in touch with the virus it boost your immune system.
The 2020 disease: COVID-19 (coronavirus induced disease 2019) caused by the infectious agent
SARS-CoV-2 (SARS coronavirus 2); today almost 1.5 million deaths!
1
,People who were affected are basically well defensed against the disease, unless you have under
heavy immune suppressors.
- Infection is something else then disease, infections means that the virus enters your cells and
you are positive to the virus, so you are not sick, you might get sick.
- If you are infected or if your immune system is being exposed to the pathogen, you build up
immunology memory and then have a protective immune response, it protects you usually
for 1~2 years.
- The thing is with the new virus, we just don’t know how the vaccine will work.’
- So disease is something else than the virus, HIV is the virus and H is the disease that is caused
by the virus HIV.
- Now we have the virus SARS-COVID-2 that causes the disease COVID-19.
- COVID-19 has a severe phenotype in elderly people, not so much in younger people.
- The severe phenotype of the disease is associated with acute respiratory distress syndrome
(SARS), people don’t get enough oxygen and can’t breathe anymore.
- The immune response to the virus destroyed the lung functions, especially in older high BMI.
- The older people have a bad ability to produce new immune responses vs the dependencies
on only regulatory responses. But long-term symptoms: reported in all age groups.
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 long 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 new zero-type means that it gives rise to a
different antibody response. So it is not recognized as the same cells of the other strains and
not included in the vaccine.
Here you see the new meningococcus strain. After 2015
it started to arise in numbers and in 2019 we started
vaccinating and the numbers dropped. But in 2020 we
don’t have data, because at RIVM you see only
COVID19.
So the vaccination actually worked quite well!
More vaccines are needed; RSV (respiratory syncytial virus)
- RSV, a cause of common cold with yearly seasonal epidemics around the globe. It is an RNA
virus that effects your lungs (similar to COVID).
- In preterm infants, RSV can cause very severe complications, in susceptible children, also
those carried to term, RSV infectionsin the first year contribute to asthma inception.
- It is a common cold virus, that everybody who survived their first two years, but in newborns
<1 years, if they get effected they get severe diseases.
- In non-Western countries, RSV epidemics completely congest the healthcare system! Most
important cause of death in children.
- No Vaccine available yet.. because there was an vaccine developed in the early 60th that
aggravate the disease. So drug companies lost their interest.
2
,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 well recognized by the immune system.so
most vaccines try to target the S protein, by using RNA
vaccine, DNA based vaccine or a recombinant protein vaccine.
- This vaccine can be delivered in various ways. Also: inactivated
virions might be used as vaccine. This has an higher risk of side
effects, because if in huge production something goes wrong
and the virus wat not really attenuated and you infect people.
- Most vaccines are in phase 3, almost ready, are based on RNA
or recombinant protein vaccines.
- The current vaccines seem effective in clinical studies.
The immune response to SARS-CoV-2
There are innate cells (dendritic, monocytes, macrophages) that will
respond to your virus. They will sense the corona virus PAMP
(pathogen associated molecular patterns) by their pattern recognition
receptors that are expressed by APCs. So these innate cells will
recognize the virus and then produce the immune response.
So you have the anti-viral response which gives rise to type 1 and 2
interferent’s and they will also induce the adaptive immune system
through pro-inflammatory cytokines.
Look back at this slide after all the lectures!
Slide 26, you also understand later on.
- SARS-CoV-2 vaccines A successfull 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 (cellmediated virus response).
Immunology
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, are the most important cells in the immune system. However, other cells also play an
important role, including epithelial and endothelial cells. Leucocytes 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. In the bone marrow the hematopoietic stem cell give rise to all blood cells!
The red blood cells are there for transport oxygen and the white blood cells are the immune cells, slide 29. Hematology is
the science how this stem cell develop in all the different linages, have a lot to do with cancers to the immune system.
3
, Your immune response has a time scale, so there is an immediate response
shortly after infection and a long-term response which takes days or weeks to
develop. The innate immune system developed the immediate response, here
are you born with. While the slow response is the adaptive immune system,
which is specific and really tailored to this one specific pathogen that infects you.
And to conclude the innate immune system act mostly on the same way to all
pathogens.
The innate immune system will recognize a sort of microbe you dealing with and attacks it, this is
short lived. And the adaptive immune system developed an unique immune response tailor to your
specific infection. So the adaptive immune cells against a virus are completely useless against a new
virus..
Slide 30; the immune response goes through different phases:
1. You have anatomic barriers that are used for keeping microbes out of your body (skin, oral
mucosa, respiratory epithelium and intestine).
2. Then you have soluble factors that are binding to microbes and killing them this is called the
complement/antimicrobial protein (C3, defensins and Reglllγ). So if your anatomic barrier
fails you still have these to attack the microbe.
3. If you have then still microbes in your body, you have the innate immune cells (macrophages,
granulocytes and the natural killer cells). These are innate immune cells that will actively try
to eat your bacteria that enter your tissue and kill them while there sitting in their own cell.
4. If that fails then the innate immune cells will lead to the adaptive immunity (B
cells/antibodies and T cells), this takes weeks!
So the innate immune system is encoded in
the germline DNA, you are born with it.
It is a non memory response by epigenetic
programming.
The adaptive immune system is slow and very
powerful! It attacks a single microorganisms!
It requires DNA rearrangements, that is why
it takes so long! If you vaccinate someone you
hope to make an adaptive immune response.
Slide 32, The different steps in the immune response start at different moments after infection, and
are then active for different time periods as well. Immunological memory of the adaptive immune
system can offer lifelong protection. A typical response of the innate immunity is an inflammatory
response, that is induced after a microbe passes your epithelial barrier and will be recognized by the
innate immune cells that are in your tissue. This gives inflammation that gives redness and swelling.
Adaptive immune response: B and T lymphocytes will educated to recognize the antigens of the
microbe and will either start to produce antibodies or will become effector T cells, that kill the virus
infected cells or activate the innate immunity cells to help clearing the microbe.
- Infections means microbe enters your tissue, either the epithelial cells.
- If it is recognized by the innate immunity you get an inflammatory response in the tissue.
- Inflammation is a tissue response, temperature goes up, swelling, red, all the cells come in
to your tissue and start killing the microbes.
- Immunity: you build an immune response to the pathogen.
The different parts of the immune system have evolved at different moments in evolution, slide 34
4
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