Table of Contents
The Cells of the Immune System
Already during the early stages of pregnancy, the precursors of T- and B-cells are detectable in the embryo. They migrate to the liver, the thymus and the spleen. The majority of T-cells and a portion of the lymphocytes remain in the blood and the lymphatic vessels and reach the lymphoid organs this way. Approximately 90 % of the lymphocytes detectable in blood are T cells.
The blood stem cells in the bone marrow are the basis for further cell types with different functions and tasks. The main task in the immune defense is attributed to the white blood cells (leukocytes), which are divided into granulocytes, lymphocytes and monocytes. The proportion of granulocytes accounts for about 50-70 %, lymphocytes for 20-40 % and monocytes for about 1-6 %.
The non-specific defense is fast and innate in fixed form. The specific defense is slow in the initial response, but responds adapted to the respective trigger (the pathogen). Thus, this immune response is acquired. The specific defense also leads to an immunological memory.
The Immune System Is Complex
The immune system, in focus, consists of two pillars. These include the acquired specific defense and the general innate defense. But this does not mean that the systems are independent of each other. They work together closely, even if they perform different tasks. The function of this is understandable with the knowledge that the systems are working at different levels. Defense cells are located in tissues, but also in the blood and other fluids. The cells that fight and elliminate the pathogen are assigned to the cell defenses.
Granulocytes, mast cells, killer cells
Cytokines (interferons), lysozyme
Cytolytic and regulatory T-cells
formed by plasma cells and B-lymphocytes
Defense Cells in Fluids
Defense cells are also found in blood and other fluids. They are soluble and consist mainly of proteins and antibodies, as well as short-chain amino acids. They serve the humoral defense.
In its role, the innate defense is directed towards inflammations. Myeloid cells are used for this purpose. Myeloid cells are neutrophils, eosinophils and basophils. Monocytes and macrophages are also added, as well as NK cells and cytokines. These are subgroups that are also referred to as phagocytes.
Humans produce more than 1,000 neutrophils in the bone marrow in a single day. They result from CMP, the ogliopotent myeloid stem cells. Young neutrophils differ from the old by a rod-shaped core. When they mature, three to five core segments are visible.
Therefore, they are referred to as neutrophils with segmented nuclei. Neutrophils are lured to sites of inflammation by attractants (chemokines). There, they destroy the cellular structure of the microbes that caused the inflammation.
High neutrophil values are an indication of different diseases or processes. These include:
- Chronic granulocytic leukemia
However, stress or pregnancy can also cause elevated levels. Low levels (neutropenia) are a possible indication of:
- Damage to the bone marrow (different possible triggers)
- Disturbed formation of neutrophils
- Increased consumption due to inflammation or disease
- DD Kostmann syndrome
Eosinophils are important in the defense against parasites. But they also play a role in allergies. Low levels are an indication of:
- Severe, acute infections
- Cushing’s syndrome
- DD Corticotherapy
High levels can also occur. They serve as a reference to:
- Worm infestation (e.g. echinococcus, ascaris and others)
- Allergies (e.g. asthma, neurodermatitis)
- A number of serious skin diseases (e.g. psoriasis)
- Autoimmune processes
- References to certain medications (such as penicillin, as well as aspirin)
- A number of cancer diseases (e.g. CML or Hodgkin’s disease)
Basophils are the smallest group of granulocytes. They transport many messenger substances and can even trigger allergic reactions, e.g. by releasing histamine under the skin. The result is severe itching. Basophils also play important roles in the immune response. If their share is decreased, this is an indication of:
- Contact with chemicals
- Some medications
- Radiation exposure
- Some cancers
- Vitamin B12 deficiency
- Folic acid deficiency
- Bacterial infection
- Viral infection
In addition, the basophil value drops after lupus erythematous. It is also possible that no granulocytes can be detected in the blood. This is when we talk about an agranulocytosis.
Monocytes initially move in the blood and migrate from there into the tissue. Here, the conversion to macrophages takes place. Their task is phagocytosis. Phagocytosis is the seizure of bacteria or tissue debris. Elevated levels after a long disease are an important indication that the body is recovering. A solely low value of monocytes without the general reduction of granulocytes does not exist.
Elevated values can be an indication of:
- Bacterial infections
- Viral infections
- Infectious diseases with participation of parasites (e.g. Malaria)
- Autoimmune diseases
- Some cancers
- Endocarditis lenta (endocarditis)
Cytokines are also important for the immune system. Cytokines are proteins. They are formed and released by immune cells. Cytokines are part of the acquired defense and act as messenger substances. They enable the immune cells to facilitate an exchange. Thus, they are able to stimulate or inhibit the immune response.
The Innate Immune System
The innate immune system is characterized by the ability of a fast reaction. One example is the immediate reaction to a wound with invading bacteria. The effectiveness is wide enough and not specific, therefore reaction is possible within only a few hours.
The innate immune system consists of several components: it concerns the skin and mucous membranes as the outer barriers, as well as orifices. Furthermore, it consists of various immune cells, which are attributed to the group of leukocytes (white blood cells) and of the various substances in body fluids, such as blood.
How Does the Innate Immunity Develop?
The innate immune system is much more than an initial defensive measure upon the penetration of pathogens, nor is it just a phenomenon limited to humankind. Even plants and invertebrates have this immunity for defense purposes.
The manifestation is genetically fixed and is not adjustable. This means that it will remain in the same shape that it was at birth for an entire lifetime. This constitutes a disadvantage. Thus, acquired immunity is an expansion and improvement – specialization – of innate immunity. Nevertheless, the innate immunity is able to repel and eliminate the majority of disease-causing substances. Just how effective the immune system is can be seen in patients with AIDS or even in people who need to take an immunosuppressive. Even a cold can turn into a life-threatening issue for them.
The Acquired Immune Defense
As opposed to innate immunity, the acquired immune defense is adaptive, i.e. trainable. It becomes active, if it appears that the innate immunity is not sufficient to eliminate a pathogen. One example are experienced children’s diseases that provide for a lifelong immunity in many cases. It is believed that this adaptive immune defense has developed in vertebrates only about 500 million years ago. The findings from the acquired immune defense were the prerequisites for the development of vaccines.
The acquired immune response is divided in dependence on the occurrence of pathogens that require a different response. Antibodies attack germs that occur in the blood or other body fluids. Pathogens that reside in the tissue are fought by a cell-mediated immune response.
It is to be distinguished between the active and passive vaccination.
The Active Immunization
In a vaccination with an active vaccine, attenuated pathogens or proteins are supplied. They hardly cause disease any more, but have an activating effect on the specific and non-specific immune defense. This works because they mimic an infection in the body. Thus, the body is able to produce specific antibodies. At the same time, memory cells are formed, which ensure that the vaccination protection remains for a long time. This makes the goal of vaccinations possible: Long-term protection.
If the organism comes into contact with the pathogen in the future, the immune system is able to respond accordingly. In most cases, a basic immunization is required, consisting of partial vaccinations. Repetitions after a few years (vaccination schedule) serve to ensure that the immune system “remembers”.
The Passive Immunization
If the organism has already come into contact with the pathogen, passive immunization is possible for some diseases. Thus, protection is quickly available. During a passive immunization, concentrates of antibodies are injected. These antibodies are derived from people who are immune to the relevant disease. The downside is that this protection does not last long and often is no longer present already after a few months. There are more than 80 types of autoimmune diseases.
In a healthy organism, the immune system can distinguish between the body’s own and other substances. If an error occurs, the immune system fights the body’s own cells. The consequences are inflammation and damage to the organs. We are talking about autoimmune processes. This is possible because the development of adaptive immunity is complex and prone to failure.
Typical autoimmune diseases occurring increasingly frequent are :
- Type 1Diabetes
- Multiple Sclerosis
- Myasthenia gravis
- Celiac disease
- Graves’ disease
- Inflammatory bowel diseases
The exact way how autoimmune diseases occur is still not fully investigated today.
Note: It is estimated that 7% of the people living in the USA, about 24 million, are affected by one of the autoimmune disease. Additionally, women are more affected by the diseases compared to men.
Explanation Approach for Autoimmune Diseases
One possible explanation sees the thymus as the trigger. The development and maturation of T-lymphocytes (T stands for the thymus origin) takes places in this organ. The processes are dependent on the transcription factor Foxn1. It is a protein that is active on the regulatory side. The protein coordinates genes that reside in the epithelial cells of the thymus. These genes attract progenitor cells to the thymus and control the subsequent differentiation into mature T-cells.
The defense via MHC proteins – basic knowledge
The adaptive immune response is dependent on T-cells and B-cells (produced in the bone marrow, the B stands for “bone”). Antibodies are able to recognize antigens. Antigens are proteins derived from pathogens that need to be combated in the organism. The antibodies attach to antigens.
Thus, pathogens are “marked”. Furthermore, it is also possible that they will be directly rendered harmless. T-cells, however, only respond after being notified by other body cells (B-cells, macrophages, dendritic cell) that fragments of peptides (pathogens proteins) are present.
They are aided by T-cell receptors. From a chemical point of view, this happens via MHC proteins (major histocompatibility complex). These MHC proteins are able to bind multiple protein fragments. The fragment results from the protein breakdown.
Presentation at the cell surface
On the cell surface, the peptide-MHC complex is visible. Once these complexes contain foreign peptide, the T-receptors of the T-cells can recognize them. The complex is destroyed as an infected cell. However, it is also possible that other immune cells are stimulated initially, which in turn destroy the infected cell.
Incurrence of T-receptors
T-receptors occurs virtually at random. In the thymus, T-cells receive different T-receptors. The T-cells are also trained, so they are able to distinguish foreign substances from their own. They also have to tolerate their own structures.
The learning process is carried out in several steps
Initially, only the T-cells that are able to recognize MHC molecules on the cell membranes survive. This already eliminates initial confounding factors. In the next step, the T-cells, which react too violently to cells that have marked the protein fragments must be eliminated. In this context, we talk about negative selection. The cell reacts to the foreign material but does so not in an adequate way. Negative selection is not completely understood yet.
The process takes place in the thymus. The T-cells are “shown” all the proteins present in the body. This is something which may be referred to as a test method. T-cells that react here later initiate the autoimmune processes in the body. The aim of the body is to eliminate all the responding cells and to produce only those who are able to distinguish and react exclusively to foreign peptides.
It is not clear how disorders arise. Using the example of type 1 diabetes, it is striking that the autoimmune disease often follows the acute disease. While the immune system is successful in cases of acute illness, the defense cells subsequently attack the insulin-producing beta cells of the pancreas.
Symptoms of autoimmune diseases include :
- Low grade fever
- Hair loss
- Skin rashes
- Numbness of the feet and hands
- Swelling and redness
- Achy muscles
- However it is worth noting that each patient might have his/her own unique symptoms. For instance, for a patient with type 1 diabetes, he may experience weight loss, fatigue and extreme thirst.
Popular Exam Questions about Immunology
The answers can be found below the references.
1. The innate immune defense…
- …only protects bodily orifices.
- …only protects the skin against invading pathogens.
- …only prevents the spreading of germs until the non-specific defense attacks.
- …has a long initial phase.
- …constitutes the outer barrier.
2. The non-specific defense…
- …is innate.
- …is acquired.
- …is developed through vaccinations.
- …only affects the body surface area.
- …is only important in newborns.
3. The mhc complex…
- …is located at the B-cells.
- …binds and destroys pathogens.
- …binds different proteins fragments.
- …is the abbreviation for hyper-histocompatibility complex.
- …only fights viruses.