Learning goals:
Describe the cellular and molecular structure of the immune system.
Explain the function of the primary, secondary, and tertiary immune organs,
Outline the structure and function of the HLA system.
Discuss the recognition of intracellular and extracellular antigens by the adaptive immune system.
Explain the use of gene fragment rearrangements in the generation of diversity of T and B cell
repertoire.
Outline the sequence of events during activation of adaptive immune cells.
Compare the basis for specificity, diversity, and memory function between the innate and adaptive
immune system.
Contrast the acquisition and maintenance of tolerance versus the induction of immunity.
Lecture 1, Introduction: Chapter 1
Immunology: the scientific discipline that studies the immune system, which serves to protect your body
from infectious agents and cancer.
Infectious diseases: specific diseases are caused by specific germs (extracellular/intracellular bacteria,
fungi, viruses, parasites).
Polio: highly contagious virus paralysis and deformation in 1/200 patients.
Measles: highly contagious virus severe complications and often death.
Diphtheria: bacterial infection pediatric death (10% with and 50% without treatment).
Koch’s postulates: critical step forward in identifying causal agents.
1. The germ is found in diseases but not in healthy organisms.
2. The germ can be isolated from the diseased organism.
3. The germ causes disease when transferred from diseased to healthy organism.
4. The germ can be isolated again from the experimentally diseased organism.
Vaccination: since 1798 (Jenner). Studying and understanding the interactions between infectious agents
and the immune system had 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 are reappearing: measles incidence in Europe is
strongly increasing (26.000 cases in 2017, 85.000 in 2018, >90.000 in June 2019). In the Netherlands 10-20
cases annually, but 24 in 2018, 84 in 2019, 2 in 2020, none in 2021 (lockdown!).
Samoa island (isolated): 1.5% of infected children died because of a recent measles outbreak.
COVID-19 (coronavirus induced disease 2019): caused by infectious agents SARS-CoV-2.
Last year: no vaccine & treatment 62,5 million cases & 1,5 million deaths.
This year: 8 billion vaccine doses given & better treatment 265 million cases & 5,2 million deaths.
Severe disease in COVID-19 is more common in elderly people, but long-term symptoms (long Covid) is
reported in all age groups.
Total numbers of hospitalized COVID-19 patients per day in 4 age groups: in younger age groups more
unvaccinated patients, in elderly more vaccinated patients are vaccines not working in elderly people?
Total numbers of COVID-19 patients in the ICU per day in 4 age groups: in younger age group more
unvaccinated patients, in elderly equal vaccination rate more people are vaccinated: look at proportion
Proportion of hospitalized COVID-19 patients per day in 4 age groups: in all age groups more unvaccinated
people hospitalized per 100.000.
Vaccines are effective: 20 out of 30 COVID-19 patients in the ICU are not vaccinated Vaccination
protects against severe COVID-19 after SARS-CoV-2 infection.
,Meningococcal disease: caused by 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.
Meningococcus type C: vaccination program in 2002 nearly eradicated this type.
Meningococcus type W: strong increase since 2017 and is very aggressive, leading to a new vaccine.
RSV (Respiratory Syncytial Virus): a cause of common cold with yearly seasonal epidemics around the
globe. In preterm infants, RSV can cause severe complications. In susceptible children (also full term) RSV
infections in the first year can contribute to asthma inception. Due to relief of the COVID-19 lockdown
restrictions, the Netherlands had an RSV epidemic with pediatric ICUs overflowing in summer 2021. There
is no vaccine available yet.
COVID-19 vaccine: mostly directed to the spike (S) protein, which is used by the virus to enter the cells in
the nose or the airways. This vaccine can be delivered in various ways. 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).
Omicron variant: has at least 30 amino acid substitutions in the spike (S) protein, 15 of which in the
receptor binding domain, which might lead to needing a new vaccine.
Innate immune system Adaptive immune system
Characteristics
Specificity For molecules shared by groups of related microbes For microbial and nonmicrobial antigens (a
and molecules produced by damaged host cells. single antigen per cell).
Speed Very fast, first defense. Slower, powerful induced response.
Diversity Limited; germline encoded. Very large; receptors are produced by somatic
recombination of gene segments.
Memory None (expect for epigenetic programming). Yes; basis of vaccination that can offer life-long
protection.
Nonreactivity to self Yes Yes
Components
Cellular and biochemical barriers Skin, mucosal epithelia; antimicrobial molecules. Lymphocytes in epithelia; antibodies secreted
at epithelial surfaces.
Blood proteins Complement, others Antibodies
Cells Phagocytes (macrophages, neutrophils), natural Lymphocytes (T cells and B cells).
killer cells, innate lymphoid cells.
The different parts of the immune system have evolved at different moments in evolution.
White blood cells (leukocytes): most important cells in the immune system that originate from the
hematopoietic stem cells. Mature leukocytes often circulate the body using the blood and lymph systems.
Tissues also harbor many specialized tissue-resident leukocytes.
The adaptive (acquired immune system)
Humoral system Cellular system
Directed to extracellular pathogens Directed to intracellular pathogens
Complement system Phagocytes (granulocytes, macrophages)
Anti-microbial peptides Antigen presentation (dendritic cells, macrophages)
Antibodies (immunoglobulins, Ig) Cytotoxicity (lymphocytes)
B cell: transferred by antibodies, blocks Helper T cell: transferred by T Cytotoxic T cell: transferred by T
infections and eliminates extracellular lymphocytes, activates macrophages to lymphocytes, kills infected cells and
microbes. kill phagocytosed microbes. eliminates reservoirs of infection.
Vaccination: can be transferred directly by Vaccination requires active immunization using dead or inactivated microbes.
antibody transfer (passive immunization)
Epithelia: barrier function and production of antimicrobial substances.
Macrophage: phagocytose microbes and dead cells, present antigens to T cells, produce cytokines to
induce inflammation and instruct adaptive immune responses, and are critical for tissue repair processes.
, Dendritic cell: process extracellular antigens through pinocytosis for presentation to T cells and detect
tissue damage and presence of pathogens such as viruses, bacteria, or fungi. These cells connect the innate
to the adaptive immune system by conveying information on the presence of microbes and/or tissue
damage to the adaptive immune system, and by transporting the associated antigens from the tissue to
the draining lymph node, where the adaptive immune cells are.
Neutrophil (neutrophilic granulocyte): most common leukocyte, essential for the first response to the
infection: phagocytosis + killing and activation of bactericidal mechanisms.
Eosinophil (eosinophilic granulocyte): present in the mucosa of the lung, the urogenital tract, and the
gastrointestinal tract. Can be recruited from the bloodstream during an inflammatory response and kill
antibody-coated parasites.
Basophil (basophilic granulocyte): relatively rare subset of blood leukocytes, which can enter the inflamed
tissue and through IgE bound on their cell surface promote allergic responses and augment anti-parasitic
immunity.
Mast cell: tissue resident cells of barrier tissues such as the skin and the mucosa of the lung, urogenital and
gastrointestinal tract. Can recognize parasites through IGE bound on their cell surface and contribute to
the release of granules containing histamine and active agents.
Natural killer cell (NK cell): type of innate lymphocytes that contribute to the killing of transformed (cancer
cells) or virus-infected cells by releasing lytic granules that kill some virus-infected cells.
Lymphatic system: system of vessels for transport of lymph from the tissues to the lymph nodes.
Lymph nodes: specialized secondary lymphoid structures where the lymph is filtered and inspected for
presence of pathogens. Here, initiation of the adaptive immune response takes place. Lymph and
lymphocytes are then transported back into the bloodstream via the vena cava.
B lymphocyte: neutralization of microbes, phagocytosis, complement activation.
Helper T lymphocyte: activation of macrophages, inflammation, activation of T and B lymphocytes.
Cytotoxic T lymphocyte (CTL): killing of infected cells.
Regulatory T lymphocyte: suppression of other T cells.
Type of pathogen Example Disease
Viruses (intracellular) Variola Smallpox
Influenza Flu
Intracellular bacteria, protozoa, parasites Mycobacterium leprae Leprosy
Plasmodium falciparum Malaria
Extracellular bacteria, parasites, fungi Streptococcus pneumoniae Pneumonia
Clostridium tetani Tetanus
Parasitic worms (extracellular) Ascaris Ascariasis
Schistosoma Schistosomiasis
The adaptive (acquired) immune system (1) is clonal, with each clone directed against a single antigen, (2)
can respond to an enormous number of antigens, (3) mounts a response matched to each class of
pathogen, (4) is dependent on a phase of clonal expansion followed by a phase of contraction (cell death)
and eventually homeostasis, and (5) has a memory response: a faster and stronger response upon re-
exposure to the same antigen.
Effector molecule Cell types, function, and mechanisms
Cytotoxicity NK cells, CD8 T cells
Elimination of virally infected and metabolically stressed cells.
Intracellular immunity (Type 1) ILC1, Th1 cells
Elimination of intracellular pathogens and activation of macrophages.
Mucosal and barrier immunity ILC2, Th2 cells
(Type 2) Elimination and expulsion of parasites, recruitment of eosinophils, basophils, and mast cells.
Extracellular immunity (Type 3) ILC3, Th17 cells
Elimination of extracellular bacteria and fungi, recruitment and activation of neutrophils.
ILC = innate lymphoid cell.
