Section 21.2: Second Line of Defense of the Innante Immune System

Neutrophils and macrophages Generally kill ingested prey by ______ the phagolysosome and digesting its contents with ______ enzymes. (2) However some pathogens (such as the tuberculosis bacillus & certain parasites) are resistant to these enzymes (they can even multiply within the phagolysosome). In this case, what Immune cells are activated/recruited to help eradicate the pathogens & how are the resistant pathogens eliminated?

(1) Acidifying; Lysosomal enzymes (2) Helper T cells are activated & stimulate macrophages (& the book does not say but i believe they stimulate neutrophils as well) to activate additional enzymes within them that result in the production of a Respiratory Burst

Kinins promote the release of lysosomal enzymes by ___ (2) this promote of the release of lysosomal enzymes enhances the generation of what plasma protein? A. Macrophages B. Basophils C. Neutrophils D. Eosinophils

(1) B. Neutrophils (2) Kinins

The first stage of phagocyte mobilization is called? (2) What is it? (3) How does it begin?

(1) Leukocytosis (2) Leukocytosis is an increase in the number of Leukocytes (WBCs) (3) Leukocytosis begins when damaged cells release chemicals called leukocytosis-inducing factors. This results in Neutrophils entering the blood from the red bone marrow & traveling to the site of damaged tissue.

_______ _______ ____ is released by injured cells & is what causes the release of Neutrophils from red bone marrow & an increase in Leukocytes blood count. (2) Inflammed endothelial cells during Margination sprout _____ that signal Neutrophils this is the place. (3) During Chemotaxis, inflammatory chemicals called _____ _____ released by cells at the site of damage act as "homing beacons" & attract the Neutrophils to the damaged site (4) After the inflammed endothelial cells have released additonal chemicals that prompt the neutrophils to flatten & squeeze through the endothelial cells of the capillary walls during _____

(1) Leukocytosis inducing Factors (2) CAMs (Cell Adhesion Molecules) (3) Chemotactic Agents (4) Margination

What is the name of the receptors that Immune cells use to differentiate between Normal healthy human cells & infectious organisms (Bacteria, etc..). (2) Explain how they are able to identify the infectious organisms.

(1) Pattern Recognition receptors (2) They do this via recognition. They bind to molecules with specific shapes that are part of the infectious organism.

What is/are the physiological effect of Histamine?

(1) promotes vasodilation of local arterioles, increases blood flow to injured areas. Increases permeability of local capillaries, promotes formation of exudate. Vasodilation, Blood flow, Capillary permeability

transmembrane protein of immune cells that recognizes pathogens and activates an immune response directed against those pathogens

Toll-Like Receptors (TLRs)

A variety of cells have TLRs, including macrophages and cells of certain boundary tissues such as the epithelial cells lining the gastrointestinal and respiratory tracts. T or F?

True

A Class of Pattern Recogniton Receptors that plays a central role in triggering immune responses. (2) These pattern recognition receptors allow the cells to recognize invaders and sound a chemical "alarm" that initiates what?

What is Toll Like Receptors (TLRs)? (2) Inflammation

Pathogen

a bacterium, virus, or other microorganism that can cause disease.

pedesis

a leaping or stepping

natural killer cells

a lymphocyte able to bind to certain tumor cells and virus-infected cells without the stimulation of antigens, and kill them by the insertion of granules containing perforin; (2)A lymphocyte that can kill cancer cells & virus-infected body cells before the adaptive immune system is activated.

Phagocytes

a type of cell within the body capable of engulfing and absorbing bacteria and other small cells and particles.

Sprout

begin to grow; give off shoots or buds; N: new growth on a plant; shoot

Emia

blood (condition of)

Vaso

blood vessel

Inflammatory chemicals increase the permeability of local capilaries & venules. What is a consequence of this increased permeability?

fluid containing clotting factors and antibodies called exudate seeps from the blood into the tissue spaces.

exudate

fluid that accumulates in a wound; may contain serum, cellular debris, bacteria, and white blood cells or clotting factors & antibodies

Mast cells

found in the connective tissue of the dermis; respond to injury, infection, or allergy by producing and releasing substances, including heparin and histamine

Which Inflammatory chemicals promote vasodilation?

histamine, prostacyclin, and kinins (Bradykinin) are potent vasodilators

itis

inflammation (of)

For a phagocyte to ingest a pathogen it must first do what? (2) How is it capable of doing this?

it must first adhere to the pathogen (2) it can recognize (bind to) the pathogens carbohydrate "signature"

arthro

joint, articulation

interstitial fluid

liquid found between the cells of the body that provides much of the liquid environment of the body

cyte

mature cell

Microbe

microscopic life form; microorganism; germ

large granular lymphocytes

natural killer (NK cells), lymphocytes of innate immunity

Free radicals

naturally occurring, highly reactive chemicals that form in the presence of oxygen

Most abundant type of white blood cell (2) These cells become _____ on encountering infectious material in tissues

neutrophil (2) Phagocytic

types of phagocytes

neutrophils, monocytes, macrophages

cytic

pertaining to cells

The body uses an enormous number of nonspecific cellular and chemical means to protect itself, Such as

phagocytes, natural killer cells, antimicrobial proteins, and fever

athero

plaque, fatty substance

Kininogen

plasma protein from which kinins are generated from.

leukocytosis-inducing factors

promote the rapid release of neutrophils from the red bone marrow.

prosta

prostate

cell adhesion molecules (CAMs)

proteins found on the surface of most cells that aid in the binding of the cell to the extracellular matrix or other cells; integral membrane proteins; three major families: cadherins, integrins, selectins

pattern recognition receptors.

proteins on or in cells that recognize specific compounds unique to microbes or tissue damage, allowing the cells to sense the presence of invading microbes or damage

Hyperemia

redness of the skin due to increased blood flow

Toll-like receptors (TLRs)

-A type of PRR -Recognize PAMPs -Set in motion a cascade of events inside the cell that amplifies and orchestrates a defense response to the pathogen

What are the benefits of Inflammation?

-Prevents spread of damaging agents -Disposes of cell debris and pathogens -Alerts adaptive immune system -Sets the stage for repair

How are free radicals formed?

-oxidation-reduction reactions (normal cell processes) -pollution -ultraviolet light and radiation (tanning) -toxic substances they are formed from molecules via the breakage of a chemical bond such that each fragment keeps one electron, by cleavage of a radical to give another radical and, also via redox reactions

what are the four steps of phagocyte mobilization?

1. Leukocytosis 2. Margination 3. Diapedesis 4. Chemotaxis

What is the protective mechanism of Inflammation?

1. Prevents injurious agents from spreading to adjacent tissues, disposes of pathogens & dead tissue cells & promotes tissue repair 2. Released inflammatory chemicals attract phagocytes (& other immune cells) to the area

The inflammatory process begins with what?

A chemical "alarm" - inflammatory chemicals are released into the extracellular fluid

opsonization

An immune response in which a pathogen is coated with Opsonins, which are either Complement proteins or Antibodies. As a result, phagocytosis is accelerated & enhanced.

NK cells are part of a small group of A. Small Granular lymphocytes B. Large Granular lymphocytes C. Small Agranular lymphocytes D. Large Agranular lymphocytes

B.

Kinins

Blood proteins that help inflammation, blood pressure control, coagulation, and pain

There are _____ types of human TLRs, each recognizing a particular class of attacking microbe. A. 10 B. 12 C. 11 D. 15

C. 11

Aside from causing vasodilation of arterioles, inflammatory chemicals can also increase the permeability of local ____ & ____. (2) This causes _______ a fluid containing Clotting factors & antibodies

Capillaries & venules

Many bacteria have external capsules that conceal their ______ signature. (2) What does this allow them? (3) How does our immune system deal with this adaption made by pathogens?

Carbohydrate Signature. (2) It allows the bacteria to elude capture because phagocytes cannot bind to them. (if they cannot bind to them, they cannot recognize them. Phagocytes must be able to bind to a pathogen to recognize it.) (3) Our immune system coats the pathogen in Opsonins, which are complement proteins (or Antibodies)

During Margination Inflamed endothelial cells sprout what?

Cell Adhesion Molecules (CAMs)

What is the 4th stage of phagocyte mobilization? (2) Leukocytosis-

Chemotaxis

Exudate is a fluid that contains ____ & _____ & it seeps into tissue spaces due to the release of inflammatory chemicals that increase the permeability of ____ & ____. (2) This fluid is responsible for what?

Clotting Factors & Antibodies Local capillaries & Venules (2) It sweeps foreign material into lymphatic vessels & carried to lymph nodes where it is processed.

If pathogens invoke the inflammatory process, a group of plasma proteins known as _____ is activated to form potent inflammatory chemicals.

Complement Proteins

Aside from sweeping foregin material into lymphatic vessels, Exudate also delivers important proteins such as _____ proteins & _____ factors to the interstital fluid. (2) what important role do these factors play?

Complement proteins & Clotting factors. (2) The clotting factors form a gel-like fibrin mesh that act as a scaffolding for repair. Also isolates the injured area & prevents bacteria & other harmful agents from spreading.

What are Cell Adhesion Molecules? (2) What role do they play in phagocyte mobilization?

During Margination (2nd phase) inflammed endothelial cells sprout CAMs. They provide a signal (act as a beacon) to neutrophils. The neutrophils bind to the CAMs briefly This slows down the neutrophils & allows them to roll along the inner surface of the blood vessel. This slows down the Neutrophils long enough for circulating Inflammatry chemicals to activate the neutrophils. Once activated, the Neutrophils bound to the CAMS of the Endothelial cells begin to sprout their own CAMs, allowing them to remain bound to the CAMS of the Endothelial cells.

Prostaglandins are generated by what?

Enzymes of Neutrophils, Basophils, Mast cells, & others.

Soon after inflammation begins damaged tissue gets flooded with _____________ , which leads to an increased WBC count

Exudate

How is Exudate formed? (2) What role does it play in the inflammatory process?

Exudate is a protein rich fluid that contains antibodies & clotting factors. When inflammatory chemicals are released they increase the permeability of local capillaries & venules. Fluid (Exudate) leaks into the tissue space. Once the exudate is in the injured tissue space, the proteins contained within it serve to "sweep" foregin debris/material into lymphatic vessels where it is then carried to lymph nodes & is processed. The clotting factors of the Exudate also serve to form a gel-like fibrin mesh that acts as a sort of scaffolding to allow for repair to occur. The mesh also serves to contain any foreign pathogens (bacteria, etc..) from spreading. Exudate: Sweeps foreign debris/material into lymphatic vessels, where it is then carried to lymph nodes for processing. Clotting Factors Act as a scaffolding for repair & a net to prevent bacteria,pathogens,etc from spreading (I.E. Contain them).

NK cells are phagocytic cells. T or F?

False; they are not. they kill by directly contacting the target cell & cause it to undergo apoptosis.

A molecule with one or more unpaired electron in its outer shell is called a _____ _____

Free Radical

Macrophages are either ____ or ____ (2) What is the difference between the 2

Free or fixed (2) Free macrophages wander throughout the tissue space in search of cellular debris or "foreign invaders". Fixed macrophages such as stellate macrophages in the liver, are permanent residents of particular organs.

Histamine is stored in what cells? (2) it is released in response to what?

Granules of mast cells & basophils (2) It is released in response to mechanical injury, the presence of certain microorganisms, & chemicals released by neutrophils.

some pathogens such as the tuberculosis bacillus and certain parasites are resistant to lysosomal enzymes and can even multiply within the phagolysosome of macrophages/neutrophils. In this case, other immune cells called ____ __ cells release chemicals that stimulate ______ (2) These stimulated cells activate what?

Helper T cells release chemicals that stimulate Macrophages. (2) The chemicals stimulate the macrophages to activate additional enzymes that produce a respiratory burst.

Vasodilation of arterioles causes ____ which brings more cells & chemicals of the immune system to the injured tissue. (2) It accounts for what 2 cardinal signs of inflammation?

Hyperemia Redness & Heat

Vasodilation of local arterioles causes local _____ (2) This results in what?

Hyperemia (increased Blood Flow) (2) it results in more cells & chemicals of the immune system to enter the injured tissues/area.

Macrophage

Immune cell type common in Connective Tissue, Lymphoid Tissue, & many body organs; Phagocytes tissue cells, bacteria, & other foreign debris; Presents antigens to T cells in Immune Response

nonspecific response to any tissue injury. Causes include physical trauma, intense heat, irritating chemicals, or infection

Inflammation

Inflammatory chemicals are released by

Injured or stressed tissue cells and immune cells or formed from proteins circulating in the blood

phagosome

Intracellular vesicle containing material taken up by phagocytosis.

phagolysosome

Intracellular vesicle formed by fusion of a phagosome with a lysosome, in which the phagocytosed material is broken down by degradative lysosomal enzymes.

This is a plasma protein that is formed from the plasma protein Kininogen when it is split by the enzyme Kalikrein, which is found in plasma, urine, saliva & in the lysosomes of neutrophils (& other types of cells)

Kinins

increase in the number of Leukocytes (white blood cells); Usually the result of a pathogen attack on the body

Leukocytosis

the phenomenon of phagocytes clinging to the inner walls (margins) of the capillaries and postcapillary venules; (2) What step in phagocyte mobilization is this?

Margination

Respiratory Burst

Metabolic change accompanied by a transient increase in oxygen consumption that occurs in neutrophils and macrophages when they have taken up opsonized particles. It leads to the generation of toxic oxygen metabolites (free radicals) and other anti-bacterial substances that attack the phagocytosed material.

What follows after neutrophils during phagocyte mobilization?

Monocytes

Macrophages are derived from what white blood cell? (2) When do these cells become macrophages?

Monocytes (2) Monocytes become Macrophages once they leave the bloodstream & enter tissues.

Which immune cells kill by forcing target cells to undergo apoptosis? (2) Which of these 2 can also secrete chemicals that enhance the inflammatory process?

NK cells & cytotoxic T cells (2) NK cells

How do NK cells kill infected cells?

NK cells (and cytotoxic T cells) use perforins (create pores in the cell membrane) and granzymes (induce apoptosis).

When phagocytes are unable to ingest their targets (because of size, for example) they can do what to destroy a pathogen?

they can release their toxic chemicals into the extracellular fluid

Soon after inflammation begins, phagocytes are mobilized to the injured site. Which phagocytes arrive at the injured area first?

Neutrophils lead, followed by macrophages.

Dia

through, across

How do Opsonins help phagocytic immune cells recognize pathogens that have adapted to conceal their carbohydrate signatures?

Our immune system coats the pathogens in Opsonins, which provide "handles" so that the phagocyte receptors can bind to the Opsonins.

phag

to eat

Pathogens that get through the skin or mucosae (First line of innante defense) into the underlying connective tissue are confronted by

Phagocytes

soon after inflammation begins _____ are mobilized & flood the area of tissue damage. (2) What is this called?

Phagocytes (2) Phagocyte Mobilization

The inflammatory response enlists, _____, ______, all types of ____ ____ cells & dozens of chemicals that kill pathogens & repair tissue. (2) How do these identifty potentially harmful substances?

Phagocytes, Macrophages, White Blood Cells (2) by recognizing (binding to) molecules with specific shapes that are part of infectious organisms (bacteria, viruses, fungi, and various parasites) but not normal human cells.

Phagocytosis

Process in which extensions of cytoplasm surround and engulf large particles via endocytosis and take them into the cell where it is enclosed within a membrane lined vesicle. The resulting Phagosome then fuses with a lysosome to form a phagolysosome

opsonized

Process where a pathogen is essentially coated with either antibodies or complement proteins (called Opsonins) to identify pathogens that have adapted to be able to mask their carbohydrate signatures on their cell surface, which is what macrophages & neutrophils use to identify & recognize (bind to) the pathogen. The Opsonins act as "handles" that allow the macrophages or neutrophils to bind to the pathogen. Resulting in the acceleration & enhancement of the phagocytosis.

Fatty Acid Molecules produced from arachidonic acid which is found in all cell membranes;

Prostaglandins

Hyperemia accounts for which of the cardinal signs of inflammation?

Redness & Heat

paracrine

Referring to a secreted molecule that acts on a neighboring cell.

Autocrine

Referring to a secreted molecule that acts on the cell that secreted it.

What are the physiological effects of Kinins? (2) What difference does it have compared to Histamine?

Same as Histamine (Vasodilation, increased blood flow, & increase capillary permeability). (2) induces Chemotaxis of Leukocytes & Promotes the release of lysosomal enzymes by neutrophils (thereby enhancing generation of more Kinins). Also induces pain [Shares these functions in common with prostaglandins.]

unlike lymphocytes of the adaptive immune system, NK cells are far less "picky". Explain why

Short Answer - Because they are nonspecific, Lymphocytes of the adaptive immune system are very specific. they can eliminate a variety of infected or tumorous cells. Lymphocytes of the adaptive immune system are Specific, they only recognize & react to specific infected or tumorous cells.

The influx of exudate into the tissue spaces caused by inflammatory chemicals leads to what materials being swept where?

The Exudate is a fluid contains Clotting factors & antibodies. The influx of it leads to the "sweeping" of foreign material into the lymphatic vessels (2) Once the foreign material has been swept into the lymphatic vessels, it is can be processed in the lymph nodes

Explain how a phagocyte engulfs & destroys a pathogen

The phagocyte has specialize receptors on its cytoplasmic extensions that allow it to bind to the pathogen/particle. Once it binds to the particle it pulls it into the cell via endocytosis & encloses it within a membrane-lined vesicle called a Phagosome. The Phagosome then fuses with a lysosome to from a phagolysosome . The Pathogen is then broken down & destroyed by Toxic compounds & Lysosomal enzymes contained within the phagolysosome. (Sometimes the the Phagolysosome is exocytosed out of the cell along with any remaining residual materials from the broken down pathogen.)

Diapedis

The process by which white blood cells flatten & squeeze between the endothelial cells of the capillary wall to enter the tissue spaces outside the blood vessel

endothelial cells

The thin layer of cells that line the interior surface of all blood vessels. Only one cell thick in capillaries.

What physiological effects/functions do all inflammatory chemicals share?

They all dilate local arterioles and make local capillaries leakier (Many also attract phagocytes to the injured area.) Note: Also increase permeability of Local capillaries & Local Venules. Note: Some have individual inflammatory roles, such as mobilizing lymphocytes & other elements of adaptive immunity.

What physiological effect do Kinins & Prostaglandins have in common?

They both induce chemotaxis of leukocytes & they both induce pain Note: They both share the same physiological effects as histamine.

Aside from phagocytosis, what is another way Neutrophils can destroy pathogens?

They can pierce a pathogens membrane by using defensins (Antimicrobial proteins)

How do NK cells identify virus-infected or cancerous cells?

They detect for general abnormalities such as the lack of "self" cell-surface protein receptors, called MHC's