PCAT Exam: Biological Processes - Microbiology

Physiologic Responses to Toxins
All plants and animals have some sort of innate immunity. Even bacteria have restriction enzymes that have evolved as a primitive defense against viruses. These are enzymes that recognize specific palindromic sequences of DNA along a molecule and cleave them at specific sites, dissecting them into smaller, non-harmful fragments.
Lysozymes, enzymes with natural antibiotic properties, protect against foreign invaders by damaging bacterial cell walls. They are found in many secretions, including tears, saliva, mucus, milk, and even egg whites. Insects have lysozymes in their digestive tracts that protect them from disease. Their exoskeletons, made of chitin, also serve as an effective barrier against foreign invaders. Should a pathogen evade these defenses, hemocytes travel in the hemolymph, the insect circulatory system, and ingest alien particles via phagocytosis. Some hemocytes trigger production of chemicals that kill parasites, bacteria, and fungi.
Mammals have an advanced immune system. Skin epithelial cells, as well as the epithelial lining of the inner mucous membranes, provide protective physical barriers. Mucus traps microbes and washes them away, along with saliva and tears. These physical defenses are enhanced by innate chemical defenses as well. Mucous, tears, and saliva contain lysozymes. The stomach, oil glands, and sweat glands produce acidic fluid that is hostile to many pathogens. Another non-specific chemical defense is stimulated by infected cells themselves. They release chemicals called interferons that provide a localized alarm to surrounding cells. These signals stimulate neighbors to produce substances that inhibit viral replication. Some interferons also recruit and activate white blood cells.

Inflammation
The inflammatory response is also nonspecific and part of the innate defense of mammals. It is characterized by heat, swelling, histamine release, redness, pain, and white blood cell recruitment.
At the site of an injury—a cut, for example—pathogens are released, and cells called mast cells release histamine, which causes the dilation of capillaries, allowing them to become more permeable and to increase blood flow to the area. This results in redness and swelling. Clotting elements then move from the blood to the injury, while a tiny army of white blood cells are recruited to the site due to increased circulation and are attracted to the injury via chemical signals called cytokines released by macrophages. The white blood cells, primarily neutrophils, phagocytose (“eat”) the pathogens, allowing the wound to heal. It is very common to feel pain during the inflammatory response, as the pressure caused by swelling stimulates nerves.
Other white blood cells play a role in this non-specific immune response. Dendritic cells are phagocytic cells that reside in tissues. Eosinophils are in mucous membranes and detect multicellular parasites, such as worms, and secrete toxic enzymes to destroy them. Finally, natural killer cells circulate and identify viral-infected and cancer cells and secrete toxins to destroy them.
This highly advanced homeostatic system has another component. If a pathogen is still not destroyed, there is a complicated specific immune response that ensues.
Pain, though deeply uncomfortable, is beneficial. It alerts the organism that there is an issue and helps to prevent further damage. For example, an animal that has a broken leg will not be able to run on it because this would damage an already vulnerable bone. A cat that licks its wounds does so in order to stimulate blood clotting. Without pain receptors, these adaptive responses wouldn’t happen.
Fever, an increase in body temperature as a result of the immune system’s defense against infection, helps to destroy bacteria and viruses that are sensitive to temperature change, as well as increase the number of lymphocytes capable of killing pathogens. The benefit of a fever may also be to increase enzymatic reactions to stave off infection. As temperature increases, the kinetic energy of substrates and enzymes increase, collisions happen faster, and reaction rates increase. If temperature exceeds a certain point, however, it can be very dangerous because enzymes begin to denature and completely lose functionality.

Immune Responses in Plants
The last section discussed animal innate immunity, but plants have defenses as well. Physical defenses, such as thorns and poison, are defenses against consumers.
Plants also have chemical defenses against microbes. It is not likely that plants will ever develop immune systems as complex as those in animals because it requires a costly energy investment. However, plants that have no immune system are unlikely to survive. Therefore, plants have co-evolved with avirulent strains of pathogens, which are much less harmful than virulent strains. Harmful viruses would decimate plants due to their weak immune systems, and in doing so, they would quickly destroy their host and then be homeless and starving. Less-damaging plant pathogens are, therefore, the norm, since they enable both the plant and the parasitic organism to survive.
Avirulent pathogens have protein effectors (Avr genes) that cause infection in plants that lack the specific resistance (R) protein—a gene responsible for resistance against pathogens. If the R protein is present and the pathogen effector protein binds to it, it initiates a signal transduction cascade that mounts a strong immune response. Part of that response is called the hypersensitive (HR) response, a localized general chemical defense that kills cells surrounding the site of infection. Additionally, modification to the surrounding cells’ walls prohibits spreading of the pathogen. There is also a distal immune response; the dying cells secrete methylsalicylic acid that is delivered to non-infected areas and converted to salicylic acid, which signals a systemic, or “whole-plant,” immune response.
This description of a plant’s general response is akin to innate immunity in animals. Mammals also have an adaptive, or specific, immune response. The cells involved in the adaptive immune response originate in bone marrow and are called B lymphocytes and T lymphocytes. The ones that mature in the bone marrow are B cells and the ones that travel to the thymus to mature are the T cells.
Antigens are anything that activates B and T cells by binding a small region called an epitope to one of their antigen-specific receptors. This may include pathogens, such as bacteria or viruses, toxins or foreign cells introduced by transplantation, or even an organism’s own cells in autoimmune responses.
B cells and T cells are different in structure and function, so antigen binding is different between them.
Upon an epitope binding to a B cell’s binding site, the B cell proliferates, and its daughter cells secrete its characteristic antigen receptor. This antigen receptor is referred to as an antibody or an immunoglobulin (Ig). T cells behave differently in that they only recognize host cells that present fragments of a pathogen’s antigen after ingestion.
There are millions of different B and T cell receptors, and this diversity is due to the many possible combinations of a transcribed immunoglobulin gene. The gene contains light and heavy chains of the B cell receptors, and each one can be arranged in several different structures due to recombinase, an important enzyme in antibody development.
These lymphocytes are involved with two different immune responses: cell-mediated and humoral.

The cell-mediated response involves T cell destruction of host cells, as outlined below.
1. An antigen-presenting dendritic cell, macrophage, or B-lymphocyte engulfs the pathogen and digests it. The pieces of digested antigens are displayed on MCH (major histocompatibility complex) class II on the surface of antigen-presenting cells. MCH class I complex contains the host cell’s peptides, allowing lymphocytes to recognize them. This ensures that the immune system does not attack its own cells when the antigen is not being presented, and is seen on all host cells. The white blood cells with both kinds of MHC molecules are the specific activators of the helper T cells.
2. Helper T cells bind to the antigen and stimulate the humoral and cell-mediated response via the cytokine release.
3. Cytotoxic T cells are activated by helper T cell signals.
4. Cytotoxic T cells recognize MHC class I molecules on host cells and secrete proteins that trigger cell death.

The humoral immune response includes B cell activation and involves antibody neutralization of pathogens in the circulatory and lymphatic vessels. It begins the same way as the cell-mediated immune response with antigen presentation and helper T cell signaling. In this response, B cells proliferate into memory B cells and effector cells, called plasma cells, that secrete antibodies.
Antibodies are tags that mark invaders for destruction. They neutralize surface proteins of a pathogen, preventing them from binding to and affecting its host cell. Antibodies can also cause apoptosis (programmed cell death) in infected body cells. Host cells that present epitopes recruit antibodies, which recruit natural killer cells.

Cell Death
Cells die via two different mechanisms: necrosis and apoptosis.

Necrosis is involuntary cell death, in which the cell is damaged via external forces, such as an injury, exposure to toxins, or lack of oxygen, and usually is the cause of the inflammatory response. Apoptosis, however, is when the cell essentially kills itself when it is no longer needed, by breaking itself down and then being engulfed by macrophages. Apoptosis is most common in embryonic and fetal development. For example, the webbing in-between the toes and fingers of the fetus in the womb gets broken down via apoptosis before the baby is born. These cells respond to signals in the body that instruct them to commit suicide.

B cell activation not only produces antibody-making cells, but it also produces memory B cells that keep circulating and are not transient. They remain behind and, should the pathogen be encountered again, they immediately recognize the invader and divide quickly to produce many more effector cells. This results in a much faster and stronger secondary immune response because there is no lag time while B cells are proliferating into plasma cells. Vaccines manipulate the immune systems of animals by delivering inactive pathogens that enable these memory cells to develop.