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Okay, so first we have the basic principles regarding immunology.
First of all, we need to understand the nature of our immune system. Our immune system is divided into two parts: we have innate immunity and adaptive immunity.
Innate immunity is naturally present at birth, which is why it is called "innate." This type of immunity does not have immunologic memory, which is why another name for innate immunity is non-specific immunity. It does not possess immunologic memory, meaning any foreign object or invader is attacked by our natural immune system.
The innate immune system covers the first two lines of our defenses. The first line of defense refers to our physical barriers, such as our skin, gastric secretions, sneezing and coughing reflexes, and the normal flora present in our intestines. These are all part of the first line of defense.
Whenever the first line of defense is breached, that’s when the second line of defense comes into play. The second line of defense is still part of innate immunity and refers to substances that are naturally present in our blood. It is divided into cellular and humoral components.
For the cellular component, we have phagocytes, which are the main cellular component of the second line of defense. Phagocytes are able to phagocytize foreign invaders.
We also have humoral components, which are soluble factors. The main humoral component of the second line of defense is the complement cascade. However, it is important to note that only the alternative cascade is part of innate immunity, as the classical cascade requires antigen-antibody interaction before it is activated. The classical cascade is part of adaptive immunity.
So, that is the innate immunity. The first line of defense consists of physical barriers, gastric secretions, sneezing and coughing reflexes, and normal flora in our intestines. The second line of defense is divided into humoral and cellular components, with the complement being the main component of the humoral aspect and phagocytes being the main component of the cellular aspect.
Another humoral component of the second line of defense is interferon, which works to prevent viral replication. This is why most viral infections are self-limiting; we have this natural component of our immunity that prevents them from replicating.
The highest form of defense is our third line of defense, which is adaptive immunity. This type of immunity is underdeveloped at birth, which is why it is called acquired immunity. Adaptive immunity has immunologic memory, making it specific.
The third line of defense is also found in our blood and is divided into cellular and humoral components. The cellular components refer to specialized lymphocytes, which are T cells and B cells. The humoral component consists of the products of these cells. For example, when B cells are activated, they become plasma cells. T cells, when activated, produce certain cytokines.
In terms of the mechanism of how these lymphocytes protect us from foreign invaders, T cells are primarily responsible for cellular immunity. Their main way of combating infection is through direct cell-to-cell interaction, which is why they mediate cellular immunity. B cells, on the other hand, elicit their function in our immune system through the production of antibodies. Antibodies are the major component of our humoral immunity when it comes to the acquired immune system.
We have several ways to acquire immunity. We can get it through natural means or artificial means.
Natural active immunity occurs when we produce antibodies after being exposed to antigens naturally. An example of this is through infection, where we produce antibodies against the antigens responsible for the infection.
Natural passive immunity occurs when we are given antibodies naturally, such as through transplacental transfer of IgG from mother to fetus during gestation.
Artificial active immunity occurs when we are given an antigen to produce an antibody, which is often the principle behind vaccinations.
Artificial passive immunity occurs when we are given antibodies directly, such as with hepatitis B immunoglobulin or Rhogam.
One advantage of passive immunity is that it is readily available, especially in situations like the early phases of COVID when vaccines were not yet available.
Another important component of our natural immunity is acute phase reactants. Acute phase reactants are humoral components of natural immunity produced mainly in the liver, driven by interleukin-6.
These substances increase in concentration during infection. Their function is to protect us against offending agents, but they can also cause collateral damage due to inflammation, which is a non-specific response of our immune system.
C-reactive protein is one of the most sensitive acute phase reactants, increasing rapidly with levels up to 1000 times higher, peaking 48 hours after the onset of inflammation. However, it is not specific; an increase in C-reactive protein cannot point to a single disease.
Another acute phase reactant activates monocytes and macrophages, producing inflammatory molecules.
Alpha-1 antitrypsin is another important component that protects us from proteases released by leukocytes during inflammation. A deficiency in alpha-1 antitrypsin can lead to pulmonary emphysema and juvenile cirrhosis due to the destruction of normal cells in the lungs and liver.
Haptoglobin is an antioxidant that binds irreversibly to free hemoglobin, protecting our kidneys from its toxic effects.
Fibrinogen is the most abundant coagulation factor and is also an acute phase reactant, helping to trap the spread of infection.
Ceruloplasmin is a copper-transporting protein in plasma that converts iron from its ferrous to ferric state, reducing its toxicity.
Most acute phase reactants are proteins that increase during inflammation, but not all proteins are acute phase reactants. Some proteins, like albumin, pre-albumin, and transferrin, decrease in level during inflammation and are considered negative acute phase reactants.
Now, let’s discuss phagocytosis, a major cellular component of innate immunity. The general steps for phagocytosis begin with initiation, which is made possible through pattern recognition receptors (PRRs) on the surface of phagocytes.
Next is diapedesis and chemotaxis. Diapedesis is the migration of phagocytes from blood vessels to the site of infection. Chemotaxis refers to the movement of phagocytes toward the site of infection, guided by chemoattractants.
Once at the site of infection, phagocytes engulf the offending agent and initiate a respiratory burst or oxidative burst to kill the invader.
If phagocytes cannot generate an oxidative burst, it can lead to diseases like chronic granulomatous disease, characterized by recurrent severe bacterial infections.
The nitro blue tetrazolium test is a classic test for chronic granulomatous disease. A positive result indicates the presence of a respiratory burst.
Flow cytometric assays can also be used to assess oxidative burst in neutrophils.
Now, let’s proceed to the different lymphocytes involved in adaptive immunity. We have T cells, which comprise approximately 60-80% of lymphocytes in our blood, B cells at 10-20%, and natural killer cells at 10-15%.
T cells are involved in cell-mediated immunity and elicit their function through direct cell-to-cell interaction. They produce cytotoxins, including perforins and granzymes, and are effective against viral and fungal infections, as well as in tumor and graft rejection.
B cells are involved in humoral immunity and produce antibodies, defending against bacterial infections.
Natural killer cells are part of innate immunity and produce cytotoxins to defend against virus-infected and tumor cells.
Now, let’s discuss the maturation stages of lymphocytes. For B cells, the first step is characterized by the rearrangement of genes coding for heavy and light chains.
In the pro-B cell stage, heavy and light chains are not yet produced; only the genes are rearranged. The distinctive markers of pro-B cells include CD19, CD45R, CD43, and CD24.
In the pre-B cell stage, the heavy chain appears, and the surface immunoglobulin is IgM, which is a monomer at this stage.
The mature B cell is characterized by the presence of both IgM and IgD, along with MHC class II for antigen recognition.
Activated B cells can become memory B cells or plasma cells, which produce antibodies. Plasma cells no longer have surface immunoglobulins; instead, they have cytoplasmic immunoglobulins.
For T cell development, the first stage is the double-negative thymocyte stage, where the cells are negative for both CD4 and CD8. The selection process starts in the double-positive thymocyte stage, where CD3 is present.
Mature T cells can be either CD4 positive or CD8 positive, depending on the antigen they recognize.
Now, let’s discuss laboratory identification of lymphocytes. The rosette test can be used to identify T cells, while flow cytometry is a rapid and convenient method for generating immunophenotypic data.
The human leukocyte antigen (HLA), or major histocompatibility complex (MHC), is located on the short arm of chromosome 6. HLA antigens are inherited as haplotypes from each parent.
Class I and Class II antigens are found on different cell types. Class I antigens are present on all nucleated cells, while Class II antigens are found on antigen-presenting cells.
HLA antigens play a role in autoimmune diseases and drug hypersensitivities.
Now, let’s talk about immunoglobulins or antibodies. Immunoglobulins are glycoproteins made up of proteins and carbohydrates, constituting about 20% of our plasma proteins.
They are composed of two identical heavy chains and two identical light chains. The heavy chain determines the class of the antibody, which can be IgM, IgG, IgA, IgE, or IgD.
Each chain has a variable region and one or more constant regions. The variable region is responsible for antigen binding, while the constant region determines the antibody's class.
The five immunoglobulin classes are IgG, IgA, IgD, IgE, and IgM. IgG is the only immunoglobulin that can cross the placenta, while IgM is the first immunoglobulin produced by a developing fetus.
Antibodies can be classified based on the type of heavy chain (isotype), variations present in some individuals (allotype), and the variable regions (idiotype).
The primary immune response occurs during the first encounter with an antigen, while the secondary immune response occurs upon re-exposure. The primary response has a longer lag phase and produces predominantly IgM, while the secondary response is faster and produces predominantly IgG.
Antibody fragmentation depends on the type of antibody. For IgM, the J chain must be broken, while for IgG, pepsin and papain can be used to produce different fragments.
Finally, the complement system is a series of proteins that enhance host defense mechanisms against foreign cells. It consists of three phases: recognition, activation, and membrane attack complex formation.
The classical cascade requires antigen-antibody complexes for activation, while the alternative cascade is triggered by bacterial products.
In summary, the immune system is a complex network of innate and adaptive components that work together to protect the body from foreign invaders.