Chapter 16: Innate Immunity: Nonspecific Defenses of the Host

16.1 The Concept of Immunity

Immunity: also called resistance, is the ability to ward off disease caused by microbes or their products and to protect against environmental agents such as pollen, chemicals, and animal dander.
- Innate immunity refers to defenses that are present at birth.
- Adaptive immunity is based on a specific response to a specific microbe once a microbe has breached the innate immunity defenses.
Susceptibility: lack of immunity
Responses of the innate system are activated by protein receptors in the plasma membranes of defensive cells. Among these activators are Toll-like receptors* (TLRs).
These TLRs attach to various components commonly found on pathogens that are called pathogen-associated molecular patterns (PAMPs)
Cytokines are proteins that regulate the intensity and duration of immune responses. \n

First Line of Defense: Skin and Mucous Membranes

Dermis: the skin’s inner, thicker portion, is composed of connective tissue.
Epidermis: the outer, thinner portion, is in direct contact with the external environment.
The top layer of epidermal cells is dead and contains a protective protein called keratin.
Mucous membranes also consist of an epithelial layer and an underlying connective tissue layer. They are an important component of the first line of defense.

16.2 Physical Factors

The intact skin is the human body’s largest organ in terms of surface area and tracts
Mucus: a slightly viscous (thick) glycoprotein produced by goblet cells of a mucous membrane
- The mucous membrane of the nose also has mucus-coated hairs that filter inhaled air and trap particles greater than 10 mm.
- The cells of the mucous membrane of the lower respiratory tract are covered with cilia.
Lacrimal apparatus: a group of structures that manufactures and drains tears
Microorganisms are also prevented from entering the lower respiratory tract by a small lid of cartilage called the epiglottis, which covers the larynx (voicebox) during swallowing
The external ear canal contains hairs and earwax (cerumen), which help prevent microbes, dust, insects, and water from entering the ear
The cleansing of the urethra by the flow of urine is another physical factor that prevents microbial colonization in the genitourinary tract.
Vaginal secretions likewise move microorganisms out of the female body.
Peristalsis, defecation, vomiting, and diarrhea also expel microbes.

16.3 Chemical Factors

Sebaceous (oil) glands of the skin produce an oily substance called sebum that prevents hair from drying and becoming brittle.
- ==Sebum also forms a protective film over the surface of the skin.==
The sweat glands of the skin produce perspiration, which helps maintain body temperature, eliminates certain wastes, and flushes microorganisms from the surface of the skin.
- Perspiration also contains lysozyme, an enzyme capable of breaking down cell walls of gram-positive bacteria and, to a lesser extent, gram-negative bacteria
Earwax, besides serving as a physical barrier, also functions as a chemical protectant.
Saliva contains not only the enzyme salivary amylase that digests starch, but also a number of substances that inhibit microbial growth.
Gastric juice is produced by the glands of the stomach. It is a mixture of hydrochloric acid, enzymes, and mucus.
Vaginal secretions play a role in antibacterial activity in two ways.
Urine, in addition to containing lysozyme, has an acidic pH (average 6) that inhibits microbes.

16.4 Normal Microbiota and Innate Immunity

In commensalism, one organism uses the body of a larger organism as its physical environment and may make use of the body to obtain nutrients.
Probiotics are live microbial cultures applied to or ingested that are intended to exert a beneficial effect.

16.5 Formed Elements in Blood

==Blood consists of fluid, called plasma, and formed elements==—that is, cells and cell fragments suspended in plasma. The formed elements include erythrocytes, or red blood cells (RBCs); leukocytes, or white blood cells (WBCs); and platelets.
Formed elements are created in red bone marrow by stem cells in a process called hematopoiesis
Granulocytes owe their name to the presence of large granules in their cytoplasm that can be seen with a light microscope after staining.
- Neutrophils stain pale lilac with a mixture of acidic and basic dyes.
- Basophils stain blue-purple with the basic dye methylene blue. Basophils release substances, such as histamine, that are important in inflammation and allergic responses.
- Eosinophils stain red or orange with the acidic dye eosin.
Agranulocytes also have granules in their cytoplasm, but the granules are not visible under the light microscope after staining.
Monocytes are not actively phagocytic until they leave circulating blood, enter body tissues, and mature into macrophages.
Dendritic cells are also believed to be derived from the same precursor cells as monocytes.
Lymphocytes include natural killer cells, T cells, and B cells
Natural killer (NK) cells are found in blood and in the spleen, lymph nodes, and red bone marrow.
Some granules contain a protein called perforin, which inserts into the plasma membrane of the target cell and creates channels (perforations) in the membrane.
T cells and B cells are not usually phagocytic but play a key role in adaptive immunity
Leukocyte increase or decrease can be detected by a differential white blood cell count, which is a calculation of the percentage of each kind of white cell in a sample of 100 white blood cells.

16.6 The Lymphatic System

The lymphatic system consists of a fluid called lymph, vessels called lymphatic vessels, a number of structures and organs containing lymphoid tissue, and red bone marrow, where stem cells develop into blood cells, including lymphocytes

16.7 Phagocytes

Phagocytosis (from Greek words meaning eat and cell) is the ingestion of a microorganism or other substance by a cell.
Other macrophages are motile and are called free (wandering) macrophages, which roam the tissues and gather at sites of infection or inflammation.
The Mechanism of Phagocytosis

Chemotaxis is the chemical attraction of phagocytes to microorganisms
Following adherence, ingestion occurs. The plasma membrane of the phagocyte extends projections called pseudopods that engulf the microorganism.
Once the microorganism is surrounded, the pseudopods meet and fuse, surrounding the microorganism with a sac called a phagosome, or phagocytic vesicle.
On contact, the phagosome and lysosome membranes fuse to form a single, larger structure called a phagolysosome.
The contents of the phagolysosome brought in by ingestion are digested in the phagolysosome.
After enzymes have digested the contents of the phagolysosome brought into the cell by ingestion, the phagolysosome contains indigestible material and is called a residual body
This residual body then moves toward the cell boundary and discharges its wastes outside the cell.

16.8 Inflammation

Damage to the body’s tissues triggers a local defensive response called inflammation, another component of the second line of defense.
- In acute inflammation, the signs and symptoms develop rapidly and usually last for a few days or even a few weeks.
- In chronic inflammation, the signs and symptoms develop more slowly and can last for up to several months or years.
Dilation of blood vessels, called vasodilation, is responsible for the redness (erythema) and heat associated with inflammation.
Increased permeability permits defensive substances normally retained in the blood to pass through the walls of the blood vessels and enter the injured area.
Kinins are another group of substances that cause vasodilation and increased permeability of blood vessels.
Prostaglandins, substances released by damaged cells, intensify the effects of histamine and kinins and help phagocytes move through capillary walls.
==A tissue is repaired when its stroma or parenchyma produces new cells.==

16.9 Fever

One of the most important is fever, an abnormally high body temperature, a third component of the second line of defense.

16.10 Antimicrobial Substances

The complement system consists of over 30 proteins produced by the liver that circulate in blood serum and within tissues throughout the body.
The cascade of complement proteins that occurs during an infection is called complement activation.
Classical Pathway

Antibodies attach to antigens (for example, proteins or large polysaccharides on the surface of a bacterium or other cell), forming antigen–antibody complexes.
Next, activated C1 activates C2 and C4 by splitting each of them. Then C2 splits into fragments C2a and C2b, and C4 is split into C4a and C4b
C2a and C4b combine and together activate C3 by splitting it into C3a and C3b fragments. C3a participates in inflammation, and C3b functions in cytolysis and opsonization

Alternate Pathway

C3, constantly present in the blood, combines with complement proteins called factor B, factor D, and factor P (properdin) on the microbe’s surface.
Once the complement proteins combine and interact, C3 splits into fragments C3a and C3b. As in the classical pathway, C3a participates in inflammation, and C3b functions in cytolysis and opsonization

The Lectin Pathway

Mannose-binding lectin (MBL) binds to the carbohydrate mannose. MBL binds to many pathogens because MBL molecules recognize a distinctive pattern of carbohydrates that includes mannose, which is found in bacterial cell walls and on some viruses.
As a result of binding, MBL functions as an opsonin to enhance phagocytosis and activates C2 and C4.
C2a and C4b activate C3. As with the other two b 5 6 7 8 9 10 mechanisms, C3 splits into fragments C3a, which participates in inflammation; and C3b, which functions in cytolysis and opsonization.