Human Anatomy

The Immune System

The immune system defends the body against invading pathogens, including bacteria, viruses, and other foreign substances. Both the circulatory and lymphatic systems play an integral role in the immune function.

Inflammatory and Immune Responses

Inflammation occurs when tissues are injured by trauma or microorganisms. Blood vessels leak fluid, which builds up in tissues and creates swelling. An immune response occurs in two different ways: direct attack by activated T cells, and antibodies released by activated B cells.

The immune system is a network of cells, tissues, and organs that defend the body from infection and disease. It offers three lines of defense: physical and chemical barriers (e.g., the skin, tears, mucus, lysozyme in sweat, and gastric juices.): innate immunity, also called nonspecific resistance; and acquired immunity, which is also called specific resistance.

Antigens are foreign substance that induce an immune response. They are how the immune system recognizes what is foreign, or “non self.” Cells of the body also present antigens such as the human leukocyte antigen (HLA), which allows the immune system to identify human cells as non-invasive, or “self.”

The inflammation response includes the dilation of blood vessels. Leaky blood vessels release white blood cells and water at the site of an injury, which collects in the surrounding tissue.

Cellular components of innate immunity include macrophages, granulocytes, and natural killer cells. Macrophages are a type of white blood cell that phagocytosis microorganisms and dead cells. They also stimulate cells by secreting cytokines, which promotes inflammation and attracts immune cells to the site of an infection.

Granulocytes are immune system cells that are characterized by the granules (i.e., small particles) in their cytoplasm, which secrete chemicals. Granulocytes are also called polymorphonuclear leukocytes, since they have oddly shaped nuclei. There are three classes of granulocytes: neutrophils, eosinophils, and basophils. The granulocytes’ secretion can be bactericidal and/or pro-inflammatory.

Natural killer cells are a type of white blood cell that can recognize cancer cells and virus-infected or defective cells by injecting granules that contain perforin (a protein) into them.

Basophils are a type of white blood cell. They are called granulocytes because they contain granules. These granules contain heparin, histamine, and other substances that induce inflammation.

Acquired immunity is so called because it develops as a person is exposed to the antigen in question. This system tends to respond more slowly than the innate immune system, but its response lats longer due to immunological memory. These are four types of acquired immunity, based on how the immunity is acquired: natural active immunity produces antibodies in response to a vaccine; natural passive immunity occurs when antibodies are received naturally through an external source, such as colostrum or breast milk; and artificial passive immunity occurs when antibodies are received via an external source, such as a monoclonal antibody injection or blood transfusion.

The cellular components of adaptive immunity include B cells and T cells. Cells mediate the production of antibodies. In response to antigens, B cells can also differentiate into plasma cells. each plasma cell secretes only one type of antibody, and each type of antibody can bind only one type of antigen.

Systemic Mastocytosis: Mast cells are similar to basophils but originate from different cells. They have granules that contain heparin, histamine, and other substances that induce inflammation. Mastocytosis is a condition characterized by an excess of mast cells. In systemic mastocytosis, mast cells accumulate in internal tissues and organs, such as the liver, spleen, bone marrow, and small intestines.

T Cell Activation: T cells, so called because they originate in the thymus, are a type of white blood cell (also called leukocyte) that is vital to the immune system. They are key to adaptive immunity, whereby the body’s immune system response targets a specific pathogen (i.e., an agent that causes disease). There are two types of T cells in the body: cytotoxic T cells (also called killer T cells) destroy infected cells, and helper T cells coordinate the attack. Cytotoxic T cells are specific to a particular antigen. The activation of T cells begins when the body recognizes the presence of an antigen: If a cell is infected with a virus, it has antigens on its surface, which alert the helper T cells to the presence of a cell that must be destroyed. Helper T cells send chemical messages via cytokines to other immune system cells. These instructions help the antigen-specific cytotoxic T cells replicate, so they can attack and kill the infected cells, which are then cleaned up by phagocytes, which are cells that can ingest dead cells and bacteria.

The Lymphatic System

The lymphatic system is a network of tissues and organs that helps rid the body of toxins and waste materials. As such, it forms an important part of the immune system. It also provides an alternate route for transporting hormones and nutrients and helps maintain blood volume and composition. The lymphatic system is a large near tat runs the length of the body, from the head to the lower limbs. It consists of lymph, lymph nest, and vessels. The primary function of this system is to transport lymph, which contains water, protein, salts, lipids, and white blood cells.

How Does the Lymphatic System Work?

The lymphatic system transports lymph throughout the body. Like blood, lymph is a fluid connective tissue. This clear fluid bathes tissues and diffuses through capillary walls into interstitial spaces (i.e., the spaces between capillaries and cells). Lymph contains water, proteins, salts, lipids, and white blood cells.

Like veins, lymphatic vessels carry fluid away from tissue. Lymphatic capillaries are saclike vessels that begin in interstitial spaces. The walls of lymph capillaries act as a simple one-way valve, allowing fluid to enter but not to exit.

Lymph capillaries join to form lymphatic vessels. Most lymphatic vessels have valves to keep the lymph flowing in a single direction. Lymphatic vessels join to form lymphatic trunks, which then merge to form the two lymphatic ducts. Skeletal muscle movements, respiratory movements, and contractions of smooth muscle in the vessel walls develop a pressure gradient that moves lymph through the vessels.

Before lymph passes to the central venous system, it travels through lymph nodes, which filter out cellular material and foreign particles. Lymph nodes contain immune cells, such as lymphocytes, macrophages, and dendritic cells, that are enmeshed in short, branching connective tissue fibers.

Lymphocytes are formed and mature in the primary lymphoid organs, which are the bone marrow and thymus. Bone marrow produces two lymphocytes, B cells and T cells. B cells produce antibodies, and T cells protect against intracellular pathogens, such as viruses, protozoans, and intercellular bacteria. B cells mature within the bone marrow, while T cells mature in the thymus.

The thymus is located below the sternum and aligns with the heart. Unlike other lumped organs, the thymus does not have lymphatic vessels draining into it. As they mature within the thymus, thymus lymphocytes adapt to perform specialized tasks.

The secondary lymphoid organs are arranged as a series of filters that process lymph and other extracellular fluids. These organs - the lymph nodes, tonsils, spleen, and mucosa-associated lymphoid tissue - also activate lymphocytes.

The tonsils are two small masses of lymphoid tissue on each side of the base of the tongue. They process fluids entering through the oronasal cavity. Four tonsils in the tongue and throat process ingested or inhaled microbes.

The spleen’s white pulp is involved in the production of lymphocytes, while its red pulp removes old and damaged red blood cells. It cleans the blood of bacteria and dead cells; where B cells become able to make antibodies.

The mucosa-associated lymphoid tissue (MALT) consists of isolated or aggregated lymphoid follicles that are associated with different submucosal regions of the body. MALTs are usually named for the anatomical location of the mucosa, so we have gut-associated lymphoid tissue (GALT), bronchus-associated lymphoid tissue (BALT), nasal-associated lymphoid tissue (NALT), conjunctival-associated lymphoid tissue (CALT), larynx-associated lymphoid tissue (LALT), skin-associated lymphoid tissue (SALT), vulvo-vaginal-associated lymphoid tissue (VALT), and testes-associated lymphoid tissue (TALT). GALT forms Peyer’s patches, which help the intestines develop immunity to antigens and bacteria.

Cervical nodes receive lymph from the tissue of the neck and head.

Right lymphatic duct receives lymph from the upper right side of the body.

Left jugular trunk receives lymph draining from the neck and head.

Left subclavian trunk receives lymph from the left arm and shoulders.

Thoracic duct is where most lymphatic trunks empty into.

Iliac nodes receive lymph from the lower limbs and pelvis.

Cisterna chili acts as a conduit for the lipid products of digestion.

Inguinal node is where lymph from the genitals and legs is first filtered.

Popliteal nodes services the lower legs and feet.

Lymph nodes are small, oval structures formed of a fibrous capsule that surrounds an internal cortex and medulla. The context consists of clusters of B and T cells. The B cell clusters are in the outer layer, while the deeper layer contains the T cell clusters. Lymph flows into and out of lymph nodes through lymphatic vessels. Afferent vessels direct lymph into the nodes, and efferent vessels (also called hula) direct lymph out.

White blood cells: Monocytes and neutrophils are both white blood cells that can phagocytose (i.e., “eat”) bacteria. Once monocytes leave the bloodstream, they can transform into tissue-resident phagocytes (e.g., monocytes, macrophages, granulocytes, or dendritic cells) in the lymph or lymph nodes. Ingestio by phagocytosis is an important mechanism that clears the body of bacteria and cell debris. Eosinophils are specialized cells that curb infection and boost inflammation.

Neutrophil: These phagocytose (i.e., ingest) bacteria and other pathogens.

Monocyte: Their primary role is phagocytosis.

Eosinophil: These control mechanisms associated with allergies.

Bacteria

Bacteria are unicellular microorganisms that have cell walls but do not have organelles or an enveloped nucleus. They can be cylindrical (bacilli), or spiral (spirochetes). Bacterial infections can affect many different parts of the body. Microbiota in the human gut are another form of bacteria, but these are essential for extracting nutrients from food.

Bacteria are composed of five essential anatomical components: a surface layer, a cell wall, a cell membrane, ribosomes, and an unenveloped nucleoid. Bacteria can be classified either by their shape or the composition of their cell walls.

The Gram stain’s is a test used to identify bacteria based on the composition of their cell walls. It involves staining bacteria that do not have outer membrane, which are called Gram-positive bacteria. Gram-negative bacteria do not pick up the stain.

These are about 10 times more bacterial cells than human cells in the body. The microbiome refers to the genetic material of all of the microbes found in the human body. Most microbiota are commensal and important for a healthy human body. (Ccommensualism is an association between two organisms where one benefits and the other does not benefit but is not harmed.)

When harmful strains of bacteria proliferate either inside the body or on its surface, it is called a bacterial infection. Bacterial infections are transmitted in one of five ways: contact, airborne, droplet, vectors, or vehicular. Transmission via contact requires direct contact with the bacterial source. Examples include direct skin-to-skin contact or contact involving the mucous membranes. Airborne transmission of bacteria describes when droplets are carried by air currents from one source to another. Droplet transmissions, however, involves the spread of bacteria via droplets that are 1/5 inch (.5 mm) in diameter or larger. This type of spread is not considered airborne since the droplet is unlikely to travel through the air further than 3 feet (1 m). Vector-borne transition typically involves arthropods like mosquitoes or tricks, which can feed on blood from an infected host and then transfer pathogens to an uninfected individual. Common vehicle transmission, meanwhile, usually involves contact with contaminated food, water, or surfaces.

Most bacteria rely on binary fusion for replication, where one cell splits into two “daughter” cells that are genetically identical. Some bacteria also have fertility factors, which are extraneous DNA that allow them to exchange DNA with other bacteria. This is one important mode of genetic variation in bacteria. In a clinical setting, this kind of DNA exchange usually results in the bacteria becoming resistant to antibiotics.

Although bacteria are the Earth’s most abundant organism, they are to small for the human eye to perceive. They were first observed in 1676 and first classified a century later.

Antibiotics are medications that specifically treat infections caused by bacteria; some also possess antiprotozoal properties (meaning they can destroy protozoans). Antibiotics can be bactericidal, meaning they kill bacteria, or bacteriostatic, meaning they slow the growth of bacteria. Narrow-spectrum antibiotics act on specific types of bacteria, while broad-spectrum antibiotics target a wide range. Overuse and improper use of antibiotic-resistant bacteria.

Flushing systems: Flushing is a mechanical means of removing microbes from the body. It can involve the physical flushing action of bodily fluids, such as tears, saliva, sweat, and urine. Blood flow from the body include mucus and cilia. Mucus traps microbes, and the lysozymes in mucus can degrade bacterial walls. The beating action of cilia can then move the mucus-trapped microbes either outside the body or into acidic stomach, where they are killed.

Fungal Infections and Parasitic Diseases

Fungi that invade human tissue can cause disorders that affect the skin, can spread into tissues, bones, and organs, and can even affect the whole body. Parasitic disorders are caused by invasive protozoans (which are single-celled organisms), worms, or ectoparasites that live outside the body.

Human beings have been susceptible to invasive organisms since their origin, but the first recorded parasites are likely the eggs of lung flukes that were found in fossilized feces from around 5900 BCE. As Homo sapiens migrated throughout the world, they brought their parasites with them. Fungal infections, likewise, are among the oldest recognized sources of human infection.

Fungal infections, also called mycoses, are diseases caused by fungi. They can be classified based on the site of the infection, the route through which the infection was acquired, or the nature of the disease.

Fungal classification based on the site of infection includes disorders that are divided into superficial, cutaneous, subcutaneous, and systemic infections. Superficial infections are usually limited to the outermost layer of the skin, called the stratum corneum, and typically do not involve inflammation. Cutaneous fungal infections may involve the stratum corner as well as the hair and nails. They often result in an inflammation. Subcutaneous fungal infections involve the deeper layers of the skin and usually occur following some form of trauma to the skin barrier, which led to inoculation with the fungi. These infections cause inflammation that can extend into the epidermis. Systemic infections can involve the lungs, viscera, bones, and central nervous system.

Fungal classification based on the route through which the infection was acquired include disorders that are exogenous (external) or endogenous (internal). Exogenous fungi are usually airborne, cutaneous (on the skin), or percutaneous (through the skin). Endogenous infections involve the body’s normal fungal flora.

Fungal classifications based on virulence includes primary pathogens, which establish infection in normal hosts (i.e., immunocompetent), and opportunistic pathogens, which require hosts with a compromised immune system (i.e., immunocompromised). In most cases, primmer fungi have well-defined geographic ranges, while opportunistic fungi tend to be ubiquitous. Primary fungal infections usually result from the localized pneumonia. These infections don’t usually become systemic in immunocompetent patients, but they can if the infection becomes chronic. Typically opportunistic fungal infections include candidiasis caused by Candida species of fungi and aspergillosis caused by Aspergillus species of fungi.

Parasitic infections are caused by parasites, which are organisms that live on or inside another organism and benefit at the host’s expense. Though this definition of a parasite can be applied to just about any microorganism, parasitic infections are, clinically, either of protozoan, helminthic (worm), or ectoparasitic in origin.

Protozoans, or protists, are single-celled microscopic animals. They feed on bacteria and other food sources. They reproduce by cell division and can multiply inside the human body. Protozoa species include a wide range of single-celled organisms, such as amoebas, flagellates, ciliates, and sporozoans. Common protozoans include Giardia species, which can cause diarrhea, and Plasmodium species, which cause malaria.

Worms, also called helminths, are multicellular animals that have internal organ systems. Unlike protozoans, worms usually produce eggs or larvae and develop outside the host before infecting them. Worms can also develop in an intermediate host (i.e., another animal). There are various types of worms, and they can be acquired in different ways. Roundworms, like hookworms, are transmitted primarily by walking barefoot on contaminated soil. Flatworms, like tapeworms, can be caught by eating undercooked beef or pork. Nematodes, like filariae, are transmitted by mosquito bites and can cause elephantiasis. However, most worms enter the body through the mouth or skin, and fecal-oral transmission is common. The latter happens when fecal matter from infected hosts contaminate a surface or food source. Skin transmission involves either the parasite directly boring into the skin, such as hookworms, or by the bite of an infected insect.

Ectoparasites that live on human skin include six-legged arthropods like bedbugs, which cause rashes; fleas, which can transmit typhus and bubonic plague; and lice, which can transmit typhus. Arachnids, which are eight-legged arthropods such as ticks, can carry ehrlichiosis, Rocky Mountain spotted fever, tularemia, and Lyme disease.

Allergic Responses

Allergic reactions, also called hypersensitivity reactions, are inappropriate or exaggerated responses by the immune system to a normally harmless substance. Autoimmune responses are also a kind of allergy. In these, the hypersensitive immune response is not to an external substance (exogenous) but rather to a naturally occurring substance in the body (endogenous).

Mast cells: These immune cells contain histamine granules that cause blood to flow into the site of an injury, which helps immune cells access the injury.

Allergic responses are the most common immune disorders. If the triggers for allergies are serious enough to affect quality of life and are not known, they can be identified allergens. In the scratch test, diluted potential allergens are pricked into the surface of the skin. In the intradermal allergy test, the diluted allergens are injected just below the skin’s surface. In both cases the patient is observed following the test and monitored, which helps determine which allergen (or allergens) is causing the reaction.

Allergic reactions to harmless substances can be classified into four categories: type I (immediate allergies), type II (cytotoxic allergies), type III (immune complex allergies), and type IV (cell-mediated allergies).

Type I reactions are also called immediate hypersensitivities. They are IgE mediated, which means that the immune system overreacts to the allergens by producing antibodies called immunoglobulin E (IgE). IgE forms a coating on certain granulocytes, such as meat cells and basophils, that is cross linked when it comes into contact with an antigen. This causes degranulation, which releases histamine and antigen. It also stimulates mediators such as prostaglandin, platelet-activating factor, and cytokine to synthesize, which triggers vasodilation, the secretion of mucus spasms. It also leads to eosinophils and other inflammatory cells to infiltrate tissues. Since this process is activated by the existing IgE coating, a type I reaction happens in less than an hour. Allergic rhinitis, also called hay fever, and allergic response to bee stings are examples of type I allergic reactions.

Type II reactions are also called antibody-dependent hypersensitivities and are immuonglobin G (IgG) or immuonglobin M (IgM) mediated. In this type of reaction, the antibody binds to antigens on the surface of a cell. This activates a complement system, which is a mechanism that can trigger lysis (i.e., the disintegration of a cell by rupturing its wall or membrane) and phagocytosis (i.e., ingestion) of cells. This antigen-antibody complex also activates cells involved in antibody-dependent cell-mediated cytotoxicity, including natural killer cells, eosinophils, and macrophages. (Antibody-dependent cell-mediated cytotoxicity simply means coating an antigen with antibodies and killing it.) This results in cell and tissue damage. Hyperacute graft rejection and Graves’ disease are examples of type II reactions.

Type III reactions are also called immune complex mediated hypersensitivities and are IgG mediated. In this reaction, antibodies bind to circulatory antigens, creating what are called immune complexes. The complexes are then deposited on vessels and tissues, and these deposits activate the complement system and attract neutrophils, which break down the cells and facilitate phagocytosis. This triggers the release of inflammatory mediators. Type III reactions generally develop within 10 days of exposure to an antigen and can become chronic with continued exposure to the antigen. Serum sickness and post-streptococcal glomerulonephritis are example of type III reactions.

Type IV reactions are also called delayed hypersensitivities and are T cell mediated. In this reaction, T cells are sensitized on contact with an antigen. A type of cytotoxic T called CD8+ T cells are pre-sensitized to recognize antigens on cells, leading to cell death. A type of helper T cell called CD4+ T cells are pre-sensitized to recognize antigens on other cells, which triggers the release of inflammatory cytokines. These, in turn, can activate eosinophils, monocytes, macrophages, neutrophils, or natural killer cells. Contact dermatitis and graft-versus-host disease are examples of type IV reactions.

Sources of Antibodies: IgA is found in the linings of the respiratory and digestive systems. IgG is a common antibody found in the blood and other bodily fluids. IgM is mainly found in blood and lymph. IgE is found in small amounts in blood. IgD is not well understood; small amounts are found in blood.

Viruses

Viruses are microscopic parasites that cannot live or replicate outside a host cell. However, not all viruses cause diseases. In fact, viruses help regulate the human microbiota as part of the virile (the collection of viruses in and on the body). Viruses’ primary function is to deliver their NDA or RNA genome into a host cell so they can produce new viruses.

The porcine circovirus, at about 17nm (about 7/10,000,000 inch) in diameter, is the smallest known virus, while the pandora viruses, which ranges up to 1,000 nm (4/1000,000 inch) in size, are the largest known virus to date.

Viruses are obligate parasites, meaning they completely depend on other cells in order to replicate. They have an outer protein coating, called a capsid, and sometimes also have outer lipid membranes. Their core genetic material can be RNA or DNA, both of which are nucleic acids that can carry genetic material.

Viruses use the cellular machinery and metabolism of a host cell to produce more visions, which is the complete, infective form of a virus outside a host cell. These have a core of RNA or DNA and a capsid. They can also contain enzymes needed for the first steps of viral replication.

Viruses are generally classified based on their genome and method of replication. Both DNA and RNA viruses may have single or double strands of genetic material. Single-strand RNA viruses can be classified into positive-sense RNA viruses and negative-sense RNA viruses. A positive-sense RNA virus can directly translate its RNA into viral proteins. A negative-sense RNA virus must synthesize a complementary RNA before it can translate its RNA into viral proteins. It must therefore carry an RNA polymerase inside its vision.

The human virile comprises all of the viruses inside and on a healthy human body. It includes about 400 trillion viruses, the majority of which are bacteriophages that infect the microbiota in the body, as well as viruses that infect human cells. Interactions between the virile and microbiota are critical to regulate the microbial homeostasis in the body (i.e., the self-regulation that happens between the virile and microbiota in order to maintain good health). The bacteriophages’ ability to kill bacteria has also been harnessed to treat life-threatening infections from multi drug-resistant bacteria. Viruses and bacteria have coevolved with us; they play a significant role in human health.