Question

1. List and explain a minimum of four different defense mechanisms at the cellular levels? 2. components of the human immune system and how what role did pathogens played in their evolution.

Answer 1

In a general sense, we can think of our defenses as consisting of three types.

• General, Non-specific (barriers and chemical defenses, such as skin and stomach acid)
• Non-specific recognition of certain molecular shapes on pathogens (the innate immune system)
• Highly specific (the acquired or adaptive immune system, which involves highly specific recognition of particular molecular shapes on pathogens and the ability to make highly specific antibodies to aid in the remove of specific pathogens)

General, Non-specific Defenses Against Infection

There are several simple physical and chemical barriers that constitute and important first line of defense.

Our skin provides a highly effective barrier to infectious agents despite the fact that skin is colonized by an impressive array of microbial agents. Injury to the skin (abrasions, cuts, incisions, burns, etc.) or penetration.(insect bites, splinters, needle sticks, stabs) can, of course, breach the barrier and provide a portal of entry for infectious agents.

Given the effectiveness of intact skin, our major vulnerabilities are:

• The respiratory tract: we take air from the external environment into our respiratory tract and lungs continually - every minute, every hour, every day, as long as we live.
• The gastrointestinal tract: we eat and drink every day, and this provides another potential portal for entry of pathogens.
• Even the eyes provide a portal of entry

These are our major vulnerabilities, but we have evolved non-specific defenses for these.

• The mucous membranes of the eyes are bathed in tears, which contain an enzyme called lysozyme that attacks bacteria and helps protect the eyes from infection.
• The hairs and mucus in our nose trap inhaled particles, and the walls of our respiratory tract are lined with cells that secrete mucus to trap particles and pathogens.
• The cells lining the respiratory tract have cilia, hair-like projections that beat in a coordinated way to sweep mucus and entrapped particles up to the pharynx, where it can be swallowed or expectorated.
• Coughing and sneezing can be thought of as mechanical means of expelling pathogens and noxious chemicals
• Our digestive tract also provides barriers. Acid in the stomach and enzymes in the intestine destroy pathogens. The gastrointestinal tract also has cells that secrete mucus, which acts as a barrier.
• The gastrointestinal tract is also surrounded my smooth muscle cells that propel the gastrointestinal contents in a wavelike fashion referred to as peristalsis. Noxious gastrointestinal contents can be expelled by diarrhea, which involves both increased flushing from secretion of fluid into the GI tract and increases peristalsis. Vomiting is a complicated reflex that provides another means of expelling noxious materials
• The urethra is periodically flushed by urine.

Innate (Natural) Immunity

Many bacteria, viruses, and protozoa have glycoproteins and glycolipids on their surface that have distinctive shapes (referred to as "pathogen-associated molecular patterns" or PAMPS) on their surface that enable them to be recognized in a non-specific way as "non-self" by the innate immune system. There are perhaps 100-200 of these PAMPs that have remained unchanged over the course of evolution, and they are molecular shapes that are not present in our tissues. The innate immune system has certain "sentinel cells (monocytes, macrophages, and specialized macrophages called a dendritic cells) that have so-called toll-like receptors that bind to PAMPs, triggering rapid cellular responses directed against the pathogens. The responses include:

• Phagocytosis and intracellular killing by dendritic cells, monocytes, and macrophages.
• Recruitment of other inflammatory cells by secreting cytokines that activate other defensive cells and attract them to the site of invasion.
• Communication with the adaptive immune system by presenting fragments of the pathogenic antigens to lymphocytes in order to activate them.
• Triggering an inflammatory response
• Triggering activation of the complement system

Adaptive (Acquired) Immunity

Cells of the lymphatic (or lymphoid) system provide adaptive immunity, which, unlike innate immunity, is highly specific in its ability to recognize and defend against specific foreign agents using both cellular weapons (e.g., cytotoxic T-lymphocytes) and humoral weapons (antibodies manufactured by plasma cells). The lymphatic system is distinct from the arterial and venous systems, but like them, it consists of a complex network of vessels (lymphatic ducts), and the distribution of the lymphatic network often runs in parallel with the arterial and venous systems. Along the lymphatic vessels, there are intermittent lymph nodes, which filter lymph and also house many defensive cells (leukocytes or "white blood cells") and provide a site where the various leukocytes can communicate with one another. When fighting an infection, nearby lymph nodes often become enlarged due to aggregation and increased production of leukocytes and and removal of foreign material. Filtered lymph eventually is emptied into the subclavian vein where it mixes with blood and contributes to the plasma fraction of blood. The thymus and the spleen are also important components of the lymphatic system. The lymphatic system, thymus, and spleen play important roles in immune function, but cellular elements of the immune system are the real "soldiers" in the battle against foreign agents.

Natural Killer Cells (NK Cells)

The PAMPs on the surface of bacteria and parasites are not present on the surface of viruses, but the innate immune system provides a means of defending against viral infection. .destroying our cells if they become infected with virus.

Vertebrates have "histocompatibility molecules," referred to as "major histocompatibility complex" molecules (MHC). Theses are large glycoprotein molecules that are found in the cell membranes of most vertebrate cells. In humans, the MHC molecules (also referred to as MHC antigens) are called Human Leukocyte Antigens (HLA). The MHC molecules play an important role in helping our immune cells to distinguish between our own cells (self) and foreign cells or substances (non-self). The degree of similarity in HLA antigens is a major factor in determining whether organ or stem cell transplantations will be successful. If a donor and recipient have similar HLA, the probability of success is much higher, and this is the basis on which the term "histocompatibility molecules" came into use. Prior to transplantation the laboratory will perform "tissue typing" in order to find a closely matching donor, i.e., one who has a similar set of HLA. on their cell membranes. In humans they are called the human leukocyte antigen system.