Ch 17 Innate Nonspecific Host Defenses

Common PAMPs include

1. peptidoglycan, found in bacterial cell walls; 2. flagellin, a protein found in bacterial flagella; 3. lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria; 4. lipopeptides, molecules expressed by most bacteria; and 5. nucleic acids such as viral DNA or RNA.

antimicrobial peptides (AMPs)

AMPs may induce cell damage in microorganisms in a variety of ways, including by inflicting damage to membranes, destroying DNA and RNA, or interfering with cell-wall synthesis

hematopoiesis

All the formed elements of the blood arise by differentiation of hematopoietic stem cells in the bone marrow

membrane attack complex - MAC

Assembly of the complement proteins C6, C7, C8, and C9 assemble, which allows C9 to polymerize into pores in the membranes of gram-negative bacteria

oleic acid

Certain members of the microbiome can use lipase enzymes to degrade sebum, using it as a food source. Oleic Acid creates a mildly acidic environment on the surface of the skin that is inhospitable to many pathogenic microbes. Oleic acid is an example of an Exogenously produced mediator because it is produced by resident microbes and not directly by body cells.

transendothelial migration

Extravasation of white blood cells from the bloodstream into infected tissue occurs through the mechanism of "rolling adhesion" allows leukocytes to exit the bloodstream and enter the infected areas, where they can begin phagocytosing the invading pathogens.

leukocytes response to infection:

First: neutrophils, often within hours of a bacterial infection. By contract, monocytes may take several days to leave the bloodstream and differentiate into macrophages.

acute inflammation

Immediately following an injury, vasoconstriction of blood vessels will occur to minimize blood loss.

major basic protein MBP

MBP binds to the surface carbohydrates of parasites, and this binding is associated with disruption of the cell membrane and membrane permeability.

formed elements are:

RBCs, also called erythrocytes; platelets, also called thrombocytes; and WBCs, also called leukocytes.

pathogen-associated molecular patterns PAMPs

Recognition often takes place by the use of phagocyte receptors that bind molecules commonly found on pathogens known as

endothelia

The epithelial cells lining the urogenital tract, blood vessels, lymphatic vessels, and certain other tissues

lactate

The female reproductive system employs lactate, an exogenously produced chemical mediator, to inhibit microbial growth.

monocytes

The largest of the white blood cells, have a nucleus that lacks lobes, and they also lack granules in the cytoplasm When they leave the bloodstream and enter a specific body tissue, they differentiate into tissue-specific phagocytes called macrophages and dendritic cells

Chemotaxis

The process by which cells are drawn or attracted to an area by a microbe invader

pattern recognition receptors PRRs

The receptors that bind PAMPs , structures that allow phagocytic cells to detect PAMPs

Basophils

This cell type is important in allergic reactions and other responses that involve inflammation. One of the most abundant components of basophil granules is histamine

complement activation

This process is a cascade that can be triggered by one of three different mechanisms, known as the alternative, classical, and lectin pathways.

resident microbiota

Through their occupation of cellular binding sites and competition for available nutrients, the resident microbiota prevent the critical early steps of pathogen attachment and proliferation required for the establishment of an infection.

tubercle

a granuloma in the lung tissue of a patient with tuberculosis

perforin

a protein that creates pores in the target cell

peristalsis

a series of muscular contractions in the digestive tract, moves the sloughed mucus and other material through the intestines, rectum, and anus, excreting the material in feces

Cytokines 2

also bind mast cells and basophils, inducing them to release histamine

diapedesis

also called extravasation, is initiated by complement factor C5a, as well as cytokines released into the immediate vicinity by resident macrophages

neutrophils

also called polymorphonuclear neutrophils (PMNs), have a nucleus with three to five lobes and small, numerous, lilac-colored granules. Each lobe of the nucleus is connected by a thin strand of material to the other lobes

Cytokines 3

also stimulate the production of prostaglandins, chemical mediators that promote the inflammatory effects of kinins and histamines. Prostaglandins can also help to set the body temperature higher, leading to fever

acute-phase proteins

another class of antimicrobial mediators. primarily produced in the liver and secreted into the blood in response to inflammatory molecules from the immune system. Examples include C-reactive protein, serum amyloid A, ferritin, transferrin, fibrinogen, and mannose-binding lectin.

lysozyme

antibacterial enzyme found in mucus secreted by the esophagus

Eosinophils

are granulocytes that protect against protozoa and helminths; they also play a role in allergic reactions.

NK cells

are inhibited by the presence of the major histocompatibility cell MHC receptor on healthy cells. Cancer cells and virus-infected cells have reduced expression of MHC and increased expression of activating molecules. When a NK cell recognizes decreased MHC and increased activating molecules, it will kill the abnormal cell.

Superantigens

bacterial or viral proteins that can cause an excessive activation of T cells from the specific adaptive immune defense, as well as an excessive release of cytokines that overstimulates the inflammatory response - toxic shock syndrome and scarlet fever

pyrogens

chemicals that effectively alter the "thermostat setting" of the hypothalamus to elevate body temperature and cause fever.

chemokines

chemotactic factors that recruit leukocytes to sites of infection, tissue damage, and inflammation - very specific

neutrophils 2

contain a variety of defensins and hydrolytic enzymes that help them destroy bacteria through phagocytosis

Interferons

cytokines released by a cell infected with a virus. a diverse group of immune signaling molecules and are especially important in our defense against viruses

bradykinin

during the period of inflammation, causes capillaries to remain dilated, flooding tissues with fluids and leading to edema

five cardinal signs of inflammation

erythema, edema, heat, pain, and altered function. These largely result from innate responses that draw increased blood flow to the injured or infected tissue.

Antimicrobial peptides - AMPs

found on the skin and in other areas of the body are largely produced in response to the presence of pathogens. These include dermcidin, cathelicidin, defensins, histatins, and bacteriocins.

Mast cells

function similarly to basophils but can be found in tissues outside the bloodstream

mast cells

function similarly to basophils by inducing and promoting inflammatory responses but leave the circulating blood and are most frequently found residing in tissues.

the MAC is only effective against

gram-negative bacteria; it cannot penetrate the thick layer of peptidoglycan associated with cell walls of gram-positive bacteria.

complement system

group of plasma protein mediators that can act as an innate nonspecific defense while also serving to connect innate and adaptive immunity - composed of more than 30 proteins (including C1 through C9)

basophils

have a two-lobed nucleus and large granules that stain dark blue or purple

eosinophils

have fewer lobes in the nucleus, typically 2-3 and larger granules that stain reddish-orange

ciliated epithelial cells

have hair-like appendages known as cilia. Movement of the cilia propels debris-laden mucus out and away from the lungs

Lactoferrin

inhibits microbial growth by chemically binding and sequestering iron. This effectually starves many microbes that require iron for growth. In the eyes, tears contain the chemical mediators lysozyme and lactoferrin, both of which are capable of eliminating microbes that have found their way to the surface of the eyes

alternative pathway

initiated by the spontaneous activation of the complement protein C3. The hydrolysis of C3 produces two products, C3a and C3b

paracrine function

involves the release of cytokines from one cell to other nearby cells, stimulating some response from the recipient cells.

Granulocytes

leukocytes characterized by a lobed nucleus and granules in the cytoplasm. These include neutrophils (PMNs), eosinophils, and basophils.

Neutrophils are

leukocytes found in the largest numbers in the bloodstream and they primarily fight bacterial infections.

endothelial cells

line blood vessels have very tight cell-to-cell junctions, blocking microbes from gaining access to the bloodstream

lymphocytes

natural killer cells, which play an important role in nonspecific innate immune defenses. Lymphocytes also include the B cells and T cells, which are central players in the specific adaptive immune defenses.

endocrine function

occurs when cells release cytokines into the bloodstream to be carried to target cells much farther away.

Chronic inflammation

occurs when the inflammatory response is unsuccessful, and may result in the formation of granulomas e.g., with tuberculosis and scarring e.g., with hepatitis C viral infections and liver cirrhosis

Toll-like receptors (TLRs)

one type of PRR found on phagocytes.

Eosinophils target

parasitic infections. Eosinophils and basophils are involved in allergic reactions. Both release histamine and other proinflammatory compounds from their granules upon stimulation.

granulomas

pockets of infected tissue walled off and surrounded by WBCs

lipopolysaccharide LPS

produced by gram-negative bacteria, is an exogenous pyrogen that may induce the leukocytes to release endogenous pyrogens such as interleukin-1 (IL-1), IL-6, interferon-γ (IFN-γ), and tumor necrosis factor (TNF).

granzymes

proteases that enter through the pores into the target cell's cytoplasm

Nonspecific innate immunity

provides a first line of defense against infection by nonspecifically blocking entry of microbes and targeting them for destruction or removal from the body.

classical pathway

provides a more efficient mechanism of activating the complement cascade, but it depends upon the production of antibodies by the specific adaptive immune defenses

opsonization

refers to the coating of a pathogen by a chemical substance (called an opsonin) that allows phagocytic cells to recognize, engulf, and destroy it more easily.

sebum

released onto the skin surface through hair follicles. This sebum is an Endogenous mediator, providing an additional layer of defense by helping seal off the pore of the hair follicle, preventing bacteria on the skin's surface from invading sweat glands and surrounding tissue

Acute inflammation

short lived and localized to the site of injury or infection.

vasodilation

shortly after vasoconstriction, increased vascular permeability, as a direct result of the release of histamine from resident mast cells

Interferon-α and interferon-β

signal uninfected neighboring cells to inhibit mRNA synthesis, destroy RNA, and reduce protein synthesis, also promote apoptosis in cells infected with the virus

lectin activation pathway

similar to the classical pathway, but it is triggered by the binding of mannose-binding lectin, an acute-phase protein, to carbohydrates on the microbial surface

Cytokines

soluble proteins that act as communication signals between cells

Cytokines

stimulate the production of acute-phase proteins such as C-reactive protein and mannose-binding lectin in the liver. These acute-phase proteins act as opsonins, activating complement cascades through the lectin pathway.

autocrine function

the same cell that releases the cytokine is the recipient of the signal; in other words, autocrine function is a form of self-stimulation by a cell

During fever..

the skin may appear pale due to vasoconstriction of the blood vessels in the skin, which is mediated by the hypothalamus to divert blood flow away from extremities, minimizing the loss of heat and raising the core temperature.

natural killer cells - NK cells

these mononuclear lymphocytes use nonspecific mechanisms to recognize and destroy cells that are abnormal in some way. Cancer cells and cells infected with viruses

Skin

three layers, the epidermis, the dermis, and the hypodermis,

Crisis phase occurs...

when the fever breaks. The hypothalamus stimulates vasodilation, resulting in a return of blood flow to the skin and a subsequent release of heat from the body. The hypothalamus also stimulates sweating, which cools the skin as the sweat evaporates.