Chapter 14 Flashcards
Who was Ilya Metchnikoff
A Russian born scientist
What did Metchnikoff hypothesize
He hypothesized that specialized cells in the body destroy invading organisms.
How did Metchnikoff come up with the idea that specialized cells in the body destroy invading organisms.
His ideas came about while he was studying the larval form of starfish.
As he looked at the larvae under the microscope, he could see amoeba like cells within the bodies.
How did Metchnikoff suggest the body fought disease
Metchnikoff reasoned that certain cells in animals are able to ingest and destroy foreign material.
What did Metchnikoff call the cells that are able to ingest and destroy foreign material
Phagocytes (cells that eat).
What did Metchnikoff say phagocytes do
He said phagocytes were primarily responsible for the body’s ability to destroy invading microbes.
What should the body’s defense system be doing
The system must maintain a delicate balancing act, destroying pathogens while maintaining relatively stable conditions within the human body-a state called homeostasis.
What are the two mechanisms of defense multicellular organisms have:
- Innate immunity
- Adaptive immunity
Innate immunity
Is the routine protection present at birth.
What are the protective features of innate immunity
The protective features include anatomical barriers, sensor systems that recognize patterns associated with microbes or tissue damage, phagocytes cells and inflammatory response.
Compared to innate immunity, adaptive immunity is
A more specialized defense system
Adaptive immunity
This develops throughout life as a result of exposure to microbes or certain other types of foreign material, and it substantially increases the host’s ability to defend itself.
Antigen
Substance that causes an immune response.
Molecule that reacts specifically with either an antibody or an antigen receptor on a lymphocyte
What happens each time the body is exposed to an antigen
Each time the body is exposed to an antigen, the adaptive defense system first “learns” and then “remembers” the most effective response to that specific antigen; it then reacts accordingly if the antigen is encountered again.
What is an important action of the adaptive immune response
- An important action of the adaptive immune response is the production of proteins called antibodies.
- The adaptive immune response can also destroy the body’s own cells that are infected with a virus or other invader.
Antibody
Y shaped protein that binds antigen
What do antibodies do
These bind specifically to antigens, thereby targeting them for destruction or removal by other host defenses.
Host cells or self cells
In immunology, one of the body’s own cells; also referred to as self cells.
The innate immune system has three general components
- First line defenses
- Sensor systems
- Innate effector actions
First line defenses
The barriers that separate and shield the interior of the body from the surrounding environment
What does the first line defenses do
The first line defenses prevent microbes and other foreign material from entering the body’s tissues.
What do the first line defenses include
First line defenses include the physical barriers provided by the skin and the mucous membranes, along with antimicrobial substances that bathe them.
Members of the normal microbiota residing on the surfaces also provide protection
Sensor systems
Sensor systems allow the immune system to recognize when the first line defenses have been breached.
What is perceived as an invader
Any microbe that passes through the first line defenses and into tissue is perceived by immune system as an invader.
Sentinel cells
Cells that help the immune system detect signs of invasion by producing cytokines when their pattern recognition receptors recognize an invading microbe.
How specifically do sentinel cells work
Sentinel cells (lookouts or guards), are certain host cells positioned at strategic sites in the body to detect invading microbes in blood or tissue fluids.
How do sentinel cells recognize microbes
Sentinel cells recognize microbes by detecting their unique components, such as peptidoglycan, using a special group of receptors called pattern recognition receptors (PRRs)
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.
Where can PRRS be located
Some PRRs are located surface of sentinel cells, others are within the sentinel cells’ endosomes or phagosomes
What do the PRRs located on the surface of sentinel cells allow the cells to do
Some PRRs located on the surface of sentinel cells allow cells to detect surrounding invaders
What do PRRs located within the sentinel cells’ endosomes or phagosomes allow the cells to do
Some PRRs within the sentinel endosomes or phagosomes allow cells to determine what they have engulfed.
Complement system
Series of proteins in blood and tissue fluids that can be activated to help destroy and remove invading microbes.
Why is the complement system named that
The complement system was named because it can complement ( act in combination with) the adaptive immune defenses.
Other than in sentinel cells, where can PRRs be present in the body
Many cell types have a different PRR set in their cytoplasm that allows the cells to recognize when a microbe has invaded them.
How are the series of proteins in the complement system before they see a stimuli
The complement system is a series of proteins that circulate in an inactive form but become activated in response to certain stimuli, setting off a chain of events that results in the removal and destruction of invading microbes
When do the series of proteins in the complement system become activated
The series of proteins become activated in response to certain stimuli, setting off a chain of events that results in the removal and destruction of invading microbes.
What do innate effectors do
Innate effector actions help eliminate invaders
Interferons
Cytokines that induce cells to resist viral replication; they also help regulate the immune response.
How do interferons work
When a host cell recognizes that it is infected by a virus, that cell produced as interferon, a type of protein that warns nearby cells about the virus. Those neighboring cells react by preparing to shut down their biosynthetic activities if they too become infected.
By shutting down their biosynthetic activities, what are host cells doing to viruses.
The cells can deprive the virus of a mechanism to replicate.
What happens in response to sensor signals that indicate a bacterial infection or tissue damage
Phagocytes are recruited to the site of invasion or damage.
Phagocytes
Cell type that specializes in engulfing and digesting microbes and cell debris
These cells specialize in engulfing and digesting microbes and cell debris
Phagocytosis
The process by which a phagocyte engulfs microbial invaders and debris.
What are some of the roles phagocytes play
- Destroying invaders
- Serving as sentinel cells
What makes it easier for phagocytes to engulf material
Certain activated complement system proteins recruit the phagocytic cells, and others bind to foreign material- an action that makes it easier for phagocytes to engulf the material.
Inflammatory response purpose
Coordinated innate response with the purpose of containing a site of damage, localizing the response, eliminating the invader and restoring tissue function.
What occurs part of the inflammatory response
As part of the response, changes to local blood vessels allow fluids to leak out into tissues; those fluids contain complement system components and other proteins. In turn, those proteins and other signals attract phagocytic cells, which move from the bloodstream to the tissues.
What is another innate response
Fever
Fever
A higher than normal body temperature.
An increase in internal body temperature to 37.8 C or higher.
What does a fever interfere with
Fever interferes with the growth of some pathogens and can enhance the effectiveness of other responses.
What is a short summary of the defenses
First line defenses prevent microbes from entering tissues.
Sensor systems recognize invading microbes.
Innate effector actions eliminate the invader.
What do the body’s borders do
These borders separate the interior of the body from the surrounding environment
They are the initial obstacles microorganisms must overcome to invade tissues.
What are all exposed surfaces of the body line with
Epithelial cells
How are the epithelial cells packed in the body
These cells are tightly packed together and rest on a thin layer of fibrous material, the basement membrane.
What are the two general types of barriers
- Skin
- Mucous membranes
What is the most difficult barrier for microbes to penetrate
Skin
What are the two main layers of the skim.
- Epidermis
- Dermis
Epidermis
The surface layer of skin
What is the epidermis composed of
The epidermis is composed of many sheets of epithelial cells.
What are the outermost sheets of the epidermis made from
The outermost sheets are made up of flattened dead cells filled with a water repelling protein called keratin, resulting in a dry surface environment; those dead cells continually flake off, taking with them any microbes that might be adhering.
What does the dermis layer of the skin contain
The dermis contains tightly woven fibrous connective tissue, making it extremely tough and durable
What do the mucous membranes line
The mucous membranes line the digestive tract, respiratory tract and genitourinary tract
What are the mucous membranes bathed in
They are constantly bathed with mucus or other secretions that help wash microbes from the surface.
What do the mucous membranes do
Most mucous membranes have mechanisms that move microbes toward areas where they can be eliminated.
What are examples of mucous membranes moving microbes toward areas where they can be eliminated
- Peristalsis
- Mucociliary escalator.
Peristalsis
The contractions of the intestinal tract propels food and liquid toward the anus and also helps remove microbes.
How does the respiratory tract remove materials from the lungs
The respiratory tract is lined with ciliated cells; the hairlike cilia constantly beat in a synchronized manner, moving materials away from the lungs to the throat, where they can then be swallowed.
This movement is referred to as mucociliary escalator.
Mucociliary escalator
Layer of mucus moved by cilia lining the respiratory tract that traps bacteria and other particles and moves them away from the lungs.
What is the purpose of sweat on skin
The salty residue that accumulates on skin as perspiration (sweat) evaporates is inhibitory to all but salt tolerant microbes.
What are some antimicrobial substances
- Lysozyme
- Peroxidases
- Lactoferrin
- Antimicrobial peptides (AMPs)
Lysozyme
This is an enzyme that degrades peptidoglycan of the bacterial cell wall.
Where is lysozyme found
It is in tears, saliva, mucus.
It is also found in phagocytes cells, blood, and the fluid that bathes tissues.
Peroxidases
Enzymes found in neutrophil granules, saliva, and milk that react with hydrogen peroxide to form antimicrobial compounds.
Where are peroxidases found
Enzymes found in Neutrophil granules, saliva, and milk.
What microorganisms are less susceptible to effects of peroxidases system
Microorganisms that produce the enzyme catalase are less susceptible to the lethal effects of peroxidase systems.
Why are microorganisms that produce the enzyme catalase less susceptible to the lethal effects of peroxidase systems
Microorganisms that produce the enzyme catalase are less susceptible to the lethal effects of peroxidase systems because they can potentially convert hydrogen peroxide to water and O2 before peroxidase systems have a chance to use it.
Where is lactoferrin found
This is an iron binding protein in saliva, mucus, milk and some types of phagocytes.
What do lactoferrins do
By binding to iron, these proteins make it unavailable to microorganisms.
What is one of the major elements required by organisms
Iron is one of the major elements required by organisms, so withholding it prevents microbial growth.
Transferrin
An iron binding protein found in blood and tissue fluids
What can some microorganisms do when the host captures iron
Some microorganisms can capture iron from the host, however, counteracting the iron withholding defense.
Antimicrobial peptides (AMPs)
These are short chains of amino acids (15-20 amino acids long) that have antimicrobial activity and are produced by a wide range of organisms.
A group of positively charged AMPs are called
Defensins
Defensins
Short antimicrobial peptides produced naturally by a variety of eukaryotic cells to fight infections.
What do defensins do
Defensins insert into microbial membranes, forming pores that damage cells.
What types of cells produce defensins
Certain epithelial cells produce and release defensins.
Defensins are also produced by phagocytes.
What do the defensins produced and released by certain epithelial cells do
Certain epithelial cells produce and release defensins , preventing the invasion of the skin and mucous membranes.
When would production of defensins increase
Production increases when microbial invasion is detected, thereby helping the body to eliminate the infection.
What do phagocytes do with the defensins they produce
Defensins are also produced by phagocytes, which use them to destroy the microorganisms, they have ingested.
What plays a role in regulating the expression of some AMPs
Vitamin D.
Normal microbiota (flora)
Is the population of microorganisms that routinely grow on the body surfaces of healthy humans but do not usually cause disease.
How do the normal microbiota provide protection
They prevent pathogens from adhering to host cells by covering binding sites that might otherwise be used for attachment.
The population also consumes available nutrients that could otherwise support the growth of less desirable organisms.
Some members of the normal microbiota produce compounds toxic to other bacteria.
What is an example of normal microbiota producing substances toxic to other bacteria in hair
In the hair follicles of the skin, Cutibacterium species degrade lipids, releasing fatty acids that inhibit the growth of many pathogens.
What is an example of normal microbiota producing toxic substances to bacteria in GI tract
In the gastrointestinal tract, some strains of E.coli synthesize colicons, a group of proteins toxic to certain bacteria.
What is an example of normal microbiota producing toxins to bacteria in genitals
Lactobacillus species growing in the vagina produce lactic acid as a fermentation end product, resulting in an acidic pH that inhibits the growth of some pathogens.
When can disruption of normal microbiota occur
Disruption of normal microbiota occur when antibiotics are used, which can predispose a person to various infections.
What can an inability to tolerate harmless microbes lead to
An inability to tolerate harmless microbes can result in chronic inflammatory conditions such as Crohn’s disease.
What does normal microbiota promote
Promotes immune system development.
Hematopoiesis
The formation and development of blood cells.
Where do all blood cells, including those important in the body’s defenses, originate from
The hematopoietic stem cell.
Hematopoietic stem cell
Bone marrow cells that give rise to all blood cells.
What are some qualities of hematopoietic cells
They are capable of long term self renewal, meaning they can divide repeatedly.
They given rise to red blood cells, platelets and white blood cells.
Red blood cells or erythrocytes
Carry O2 in the blood .
Platelets
Fragments arising from large cells called megakaryocytes, are important for blood clotting.
White blood cells or leukocytes
Are important in all host defenses.
What three groups can leukocytes be divided into:
- Granulocytes
- Mononuclear phagocytes
- Lymphocytes
Latter two groups are sometimes referred to as agranulocytes
Colony stimulating factors (CSFs)
A group of cytokines that direct the development of various types of blood cells from hematopoietic stem cells.
Granulocytes
Are a group of leukocytes that contain cytoplasmic granules filled with various compounds important for the cells’ protective functions
Degranulation
When Granulocytes release the granule contents, the process is degranulation.
What are the three types of Granulocytes named based on
The three types of Granulocytes are named based on the staining properties of their granules.
What are the three types of Granulocytes
- Neutrophils
- Eosinophils
- Basophils/ mast cells
Neutrophils
These are phagocytes that have multiple mechanisms for destroying microbial invaders.
There granules contain many destructive enzymes and antimicrobial substances.
What happens when a neutrophil engulfs microbes
When a neutrophil engulfs microbes, the granule contents then help destroy the microbes as part of the usual phagocytic process
Other than phagocytosis what can neutrophils do in the presence of microbes
Neutrophils can also degranulate to kill nearby microbes, or they can behave like mobile grenades, bursting in an area of infection to release not only the contents of their granules, but also cellular DNA.
Neutrophil extracellular trap (NET)
When neutrophils burst, releasing cellular DNA.
The DNA strands ensnare microbes so that they can be more easily destroyed by the granule contents.
What are the most numerous and important Granulocytes of the innate responses
Neutrophils
When do neutrophil populations increase
Their numbers typically increase during bacterial infections.
What are neutrophils also known as
Polymorphonuclear leukocytes
How do neutrophils stain
Their granules stain poorly
Eosinophils
Type of white blood cell.
Thought to be primarily important in expelling parasitic worms from the body.
Also involved in allergic reactions, causing symptoms associated with allergies, but reducing others.
What do the granules of eosinophils contain
Their granules contain various antimicrobial substances that can be released by degranulation.
How do eosinophils stain
Their granules stain red with the acidic dye eosin.
Basophils
Are involved in allergic reactions and inflammation.
What do the granules of basophils contain
Their granules contain histamine and other chemicals involved with inflammation.
How do basophils stain
Their granule stain dark purplish blue with the basic dye methylene blue.
What happens when basophils granules are released
When released, the chemicals increase capillary permeability.
What cells are similar in appearance and function to basophils
Mast cells
Mast cells
Tissue cells
They are an important sentinel cell that detects tissue damage and degranulate in response, an action that induces inflammatory response.
Mononuclear phagocytes are and include
Monocytes and macrophages
Monocytes
Are mononuclear phagocytes of the blood.
They circulate in the bloodstream.
They can move into tissues, but as they do so they develop into macrophages and dendritic cells.
What happens as monocytes move into tissues
Monocytes can move into tissues, but as they do so they develop into the macrophages and dendritic cells.
Macrophages
An important type of phagocyte.
Type of phagocytic cell that resides in tissues and has multiple roles, including scavenging debris and producing pro inflammatory cytokines.
What are the two names macrophages are referred to as
- Wandering macrophages
- Resident macrophages
Wandering macrophages
Macrophages that move around in tissues
Resident macrophages
Macrophages that live permanently in tissues
Where do resident macrophages live in abundantly
Liver, spleen, lymph nodes, lungs and peritoneal (abdominal) cavity.
What do macrophages do
In addition to phagocytosis, they are important type of sentinel cell, detecting tissue invaders and then alerting other components of the host defenses.
Dendritic cells
Antigen presenting cells that play an essential role in the activation of naive T cells.
They engulf material in the tissues and then bring it to the cells of the adaptive immune system for inspection.
Where do dendritic cells reside
Dendritic cells reside in the tissues where they function as scouts.
What do dendritic cells do
An important sentinel cell
They engulf material in the tissues and then bring it to the cells of the adaptive immune system for inspection
Where do dendritic cells develop from
Most dendritic cells develop from monocytes, but some develop from other cell types.
What leukocytes are responsible for adaptive immunity
Lymphocytes
Lymphocytes
A group of white blood cells involved in adaptive immunity
What of the two major groups of lymphocytes are
- B cells
- T cells
Where do B cells and T cells reside
These cells generally reside in lymph nodes and other lymphatic tissues
Innate lymphoid cells (ILCs)
A group of lymphocytes that lack specificity in their mechanism of antigen recognition
Where are ILCs commonly found
They are common near mucous membranes and appear to have multiple roles that can promote a balanced inflammatory response.
What is one type of ILC
Natural killer (NK) cell
Natural killer cells
Type of lymphocyte that induces apoptosis in cells to which antibody has bound or that lack MHC class 1 molecules on the surface and are stressed.
Why do immune cells need to communicate with each other
Immune cells must communicate with each other in order to mount a coordinated response to microbial invasion.
How do immune cells communicate with each other
They do this through surface receptors, cytokines, and adhesion molecules.
Surface receptors
Eyes and ears of the cell.
Proteins in the membrane of a cell to which certain signal molecules bind; they allow the cell to sense and respond to external signals.
Ligand
A molecule that specifically binds to a given receptor.
What happens when a ligand binds to its surface receptor
When a ligand binds to its surface receptor, the internal part of the receptor is modified.
Cytokines
Can be viewed as voices of a cell
They are proteins that function as chemical messengers, allowing cells involved in host defenses to communicate.
Cytokines include:
- Chemokines
- Colony stimulating factors (CSFs)
- Interferons
- Interleukins (ILs)
- Tumor necrosis factor (TNF)
Chemokines
These are important in chemotaxis of immune cells.
Colony stimulating factors (CSFs)
A group of cytokines that direct the development of various types of blood cells from hematopoietic stem cells.
They direct immature cells into the appropriate maturation pathways.
Interferons (IFNs)
Cytokines that induce cells to resist viral replication; they also help regulate the immune response.
Are important in a number of regulatory mechanisms, stimulating the responses of some cells and inhibiting others.
Interleukins (ILs)
Cytokines produced by leukocytes; they have diverse overlapping functions.
Tumor necrosis factor (TNF)
A cytokines that plays an important role in the inflammatory response and other aspects of immunity.
What does the tumor necrosis factor help initiate
It helps initiate the inflammatory response and it triggers one process of cell suicide a programmed cell death called apoptosis.
Pro inflammatory cytokines
Any of a group of cytokines that contribute to the inflammatory response.
Cytokine storm
A potentially deadly overproduction of cytokines during an immune response to infection.
Adhesion molecules
Molecule on the surface of a cell of the body that allows that cell to adhere to other body cells.
Why would cells use adhesion molecules
Cells use adhesion molecules to attach to other cells so that one cell can deliver cytokines or other molecules directly to another cell.
Pattern recognition receptors (PRRs)
Are sensors that allow the body’s cells to see signs of microbial invasion.
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.
Microbe associated molecular patterns (MAMPs)
Molecules that characterize invading microbes.
MAMPS are also called
PAMPS pathogen associated molecular patterns.
Damage associated molecular patterns (DAMPs)
Molecules that characterize damaged tissues.
Molecules that indicate host cell damage
What do PRRs help the body’s cells recognize
PRRs help the body’s cells recognize the general category of an infectious agent, thereby playing an important role in shaping the overall response to that agent.
What are the three distinct locations of PRRs on or in cells
- The cell surface
- In endospores and phagosomes
- Free in the cytoplasm
Why is it important that PRRs are located in different places
Because of these location, PRRs provide cells with information about not only which microbes are present but also whether the microbes are inside or outside a host cell.
What are the most well characterized of these PRRs on the surface of cells are
Toll like receptors (TLRs)
What do sentinel cells such as phagocytes and cells that line blood vessels and other sterile body sites have
PRRs anchored on their cell surface to detect invaders in the surrounding environment.
Toll like receptors (TLRs)
A group of pattern recognition receptors located on the surface of cells and within endosomes.
What do TLRs on the cell surface (anchored in the cytoplasmic membrane) detect
TLRs on the cell surface generally detect components of the outermost layers of microbial cells, including LPS, lipoproteins, and flagellin.
Phagocytic cells have what kind of PRRs
Phagocytic cells have PRRs that allow them to inspect material ingested by the cell
How to the PRRs in phagocytic cells allow them to inspect material ingested
Specific TLRs are anchored in phagosome and endosomal membranes, facing the lumen of the organelle. These TLRs typically recognize characteristics of nucleic acids that indicate a microbial origin.
What are the several features that distinguish normal host nucleic acid from microbial nucleic acid
Certain nucleotide sequences are much more common in bacterial DNA than in normal host cell DNA .
The genome of RNA viruses is often double stranded during the viral replication cycle
Example of cytoplasmic PRRs include
- Rig like receptors (RLRs)
- NOD like receptors (NLRs)
Rig like receptors
These cytoplasmic proteins detect viral RNA and are found in most cell types.
They represent a very important early warning system for viral infections.
NOD like receptors
These cytoplasmic proteins detect either microbial components or signs of cell damage; they are found in a variety of cell types but are particularly important in macrophages and dendritic cells.
What happens when certain NLRs in macrophages and dendritic cells detect invasion
When certain NLRs in macrophages and dendritic cells detect invasion, they combine with other proteins in the cytoplasm to form a structure called an inflammasome.
Inflammasome
Protein complex in macrophages that activates a potent pro inflammatory cytokine, thereby initiating an inflammatory response.
What happens when a cells cytoplasmic PRRS detect viral RNA
The cell responds by synthesizing and secreting a type of interferon that diffuses to nearby cells and induces them to develop an antiviral state.
How do IFNs diffuse to nearby cells
The IFN molecules attach to specific receptors on cells, causing the cells to express what can be viewed as in active suicide enzymes.
What enzymes are part of the suicide enzymes
Inactive antiviral proteins
How are Inactive antiviral proteins (iAVPs) activated
These iAVPs can be activated by viral dsRNA.
How are Inactive antiviral proteins (iAVPs) activated
These iAVPs can be activated by viral dsRNA.
What happens once iAVPs are activated
Once activated, the antiviral proteins (AVPs) degrade mRNA and stop protein synthesis, leading to apoptosis of that cell.
A key feature of iAVPs
A key feature of this response if that the iAVPs are activated by long dsRNA, which is typically found only in virally infected cells.
Complement system
Series of proteins in blood and tissue fluids that can be activated to help destroy and remove invading microbes.
In what form are the proteins in the complement system produced
The proteins are produced in an inactive form, but certain signals that indicate the presence of microbial invaders start a reaction cascade that rapidly activates the system.
How are each of the major complement system proteins labeled
The proteins are labeled with the letter C (for complement) along with a given number.
What are the nine major proteins labeled
The nine major proteins, C1 through C9 were labeled in the order of their discovery and not the order in which they react.
How are complement proteins that split into two fragments distinguished
When a complement protein is split into two fragments, those fragments are distinguished by adding a lowercase letter to each name.
For example, C3 splits into C3a and C3b.
What are the three pathways complement system can be activated by
- Alternative pathway
- Lectin pathway
- Classical pathway
Alternative pathway when is it triggered
The alternative pathway is triggered when C3b binds to foreign cell surfaces. That binding allows other complement proteins to the attach, eventually forming the C3 convertase.
What role does C3b play in the alternative pathway
C3b is a product of complement activation yet it also triggers the alternative pathway.
Why might C3b be a product and a trigger
This can occur because C3 is somewhat unstable, and at a low rate spontaneously splits even when the complement system has not been activated.
Lectin pathway
Activation of the complement system via this pathway involves pattern recognition molecules called mannose binding lectins (MBLs).
What do mannose binding lectins bind to in Lectin pathway
These bind to certain arrangements of mannose, a monosaccharide commonly found on the surface of bacteria and fungi.
What happens when MBL attaches to a surface
Once an MBL attaches to a surface, it can interact with other complement system components to form a C3 convertase.
Classical pathway
Complement system activation by this pathway requires antibodies.
What activates classical pathway
When multiple antibody molecules bind to an antigen (forming an antigen antibody complex), they interact with the same complement system component involved with lectin pathway to form a C3 convertase.
Activation of the complement system eventually leads to what three major protective outcomes
- Opsonization
- Inflammatory response
- Lysis of foreign cells
When does the concentration of C3b increase substantially?
The C3b concentration increases substantially when the complement system is activated.
What do C3b molecules bind to?
These molecules bind to microbial cells or other foreign particles.
What are the two effects of C3b binding to microbial cells or other foreign particles?
- Continued complement activation via the alternative pathway
- Opsonization
Opsonization
Coating of an object with molecules for which phagocytes have receptors, making it easier for phagocytosis to occur.
Opsonins
Molecule such as the complement system component C3b and certain antibody classes that binds to invading particles, making it easier for phagocytes to engulf them.
Activation of the Complement System lead to Inflammatory response, what happens?
The complement component C5a draw phagocytes to the area where the complement system has been activated.
C3a and C5a induce changes in the endothelial cells that line the blood vessels, contributing to the vessel leakiness associated with inflammation.
They also cause mast cells to degranulate, releasing various pro inflammatory cytokines and other chemicals that contribute to inflammation.
Effect of complement system activation: Lysis of foreign cells
Complexes of complement system proteins spontaneously assemble in cell membranes, forming donut shaped structures called membrane attack complexes (MACs).
These create pores in the membrane, causing cells to lyse.
What kind of cells do membrane attack complexes (MACs) damage?
MACs damage both the outer and cytoplasmic membranes of gram negative bacteria.
Why is phagocytosis important medically?
Because most pathogens have evolved the ability to evade one or more of them.
Six steps of phagocytosis
- Chemotaxis
- Recognition and attachment
- Engulfment
- Phagosome maturation and phagolysosome formation
- Destruction and digestion
- Exocytosis
Chemotaxis step of phagocytosis:
Phagocytes are recruited to the site of infection or tissue damage by chemicals that act as chemoattractants.
What chemicals act as chemoattractants in phagocytosis?
- products of microorganisms
-materials released by damaged tissue
-chemokines
-complement system component C5a
Recognition and attachment step of phagocytosis:
Receptors on phagocytes bind invading microbes either directly or indirectly.
Direct binding of phagocytes
Direct binding occurs when a phagocyte’s receptors bind mannose molecules on the microbe’s surface
Indirect binding
Indirect binding happens when a phagocyte binds opsonins that have attached to the invader.
Engulfment step of phagocytosis
Once phagocyte has attached to a particle, it sends out pseudopods that surround and engulf the material. This action beings the material into the cell, enclosed in a phagosome.
If phagocyte encounters an invader too large to engulf, it may release its toxic contents as a means of destroying it.
Phagosome
Membrane bound vacuole that contains the material by a phagocyte.
Phagosome maturation and phagolysosome formation
A phagosome matures to develop antimicrobial capabilities.
Mature stages are highly regulated and depend on type of material ingested.
Eventually, the mature phagosome fuses with enzyme filled lysosomes (and granules, in the case of neutrophils), forming a phagolysosome.
Phagolysosome
Membrane bound vacuole generated when a phagosome fuses with lysosomes.
Destruction and digestion step of phagocytosis
The many enzymes contributed by the lysosomes (or granules) degrade various bacterial cell components, including peptidoglycan.
Antimicrobial peptides damage the invader’s membranes, and lactoferrin limits microbial growth by binding iron.
Special pumps move protons into the phagolysosome, further lowering pH, and an enzyme converts O2 to toxic reactive oxygen species (ROS).
Another enzyme makes nitric oxide, which reacts with ROS to make more toxic compounds.
The net outcome of these actions is very toxic environment for any ingested microbes.
Exocytosis step of phagocytosis
The phagolysosome releases undigested debris to the outside of the cell by fusing with the phagocyte’s cytoplasmic membrane.
What do macrophages do?
- Phagocytosize dead cells and debris
- Destroy invaders and call in reinforcements when needed
How do macrophages maintain their killing power?
By continually regenerating their lysosomes
What happens as wandering macrophages die?
As wandering macrophages die, circulating monocytes leave the blood and migrate to the tissues replace them.
When does monocyte migration increase?
Monocyte migration increases in response to invasion and tissue damage.
Activated macrophages
Macrophages stimulated by cytokines to enlarge and become metabolically active, with greatly increased capability to kill and degrade intracellular organisms and materials.
What happens when activated macrophages fail to destroy microbes
The phagocytes form giant cells.
Giant cells
Very large cell with many nuclei, formed by the fusion of many macrophages during a chronic inflammatory response; found in granulomas.
What cells make up granulomas
Macrophages
Giant cells
T cells
Granulomas
Collections of lymphocytes and macrophages that accumulate in certain chronic infections;
an attempt by the body to wall off and contain persistent organisms and antigens.
Granulomas, which are part of the disease process in Tb and other illnesses, prevent the microbes from escaping to infect other cells.
Inflammation
Set of signs and symptoms (swelling, heat, redness, and pain) that characterizes an innate immune response to infection or injury.
What happens when mast cells detect tissue damage
When a mast cell detects tissue damage, it degranulates to release histamine and various inflammatory mediators.
Inflammatory mediators
Chemicals such as histamine that trigger an inflammatory response when released from cells.
Many of the mediators released by mast cells induce changes in local blood vessels
What happens when a macrophage detects microbial products
Its produces various pro inflammatory cytokines.
One of these tumor necrosis factor (TFN), induces the liver to synthesize acute phase proteins, a group of proteins that facilitate phagocytosis and complement activation.
If blood vessels are injured, two enzymatic cascades are activated. What are they?
- Coagulation cascade, which results in blood clotting
- The other produces several molecules that increase blood vessel permeability.
What does the inflammatory response involve?
The inflammatory response involves a series of events that result in dilation of small blood vessels, leakage of fluids from those vessels, and the migration of leukocytes out of the bloodstream and into the tissues.
Two general changes that occur during inflammation:
- Vascular changes
- Cellular changes
Vascular changes involved in inflammation:
The diameter of local blood vessels increases due to the action of histamine and other inflammatory mediators.
This results in greater blood flow to the area, causing heat and redness associated with inflammation. It also slows the blood flow in the capillaries.
Changes in the endothelial cells that line the capillaries create small gaps in the normally tight junctions between the cells, allowing more fluid to leak from blood vessels and into tissues.
What is the protein rich fluid that leaks from blood vessels into the tissues during vascular changes associated with inflammation? What does this fluid contain?
This protein rich fluid, referred to as exudate, contains transferrin, complement system proteins, antibodies and other substances that help counteract invading microbes.
What causes the swelling and pain associated with inflammation?
The accumulation of exudate in the tissues causes the swelling and pain associated with inflammation.
Pain also results from the direct effect of certain inflammatory mediators on sensory nerve endings.
Cellular changes associated with inflammation
Some of the pro inflammatory cytokines cause endothelial cells of the local blood vessels to produce adhesion molecules that loosely “grab” phagocytes in the bloodstream.
The phagocytes normally flow rapidly through the vessels but slowly tumble to a halt as the adhesion molecules attach to them. The phagocytic cells themselves begin producing a different type of adhesion molecule that strengthens the attachment. Then, in response to various chemoattractants, the phagocytes leave the blood vessels and move into the surrounding tissues.
What cells are first to arrive to site of infection
Neutrophils are the first to arrive at the site of infection and they actively phagocytize foreign material.
Monocytes (which mature into macrophages at the site of infection) and lymphocytes arrive later
What do clotting factors in exudate do during inflammation
Clotting factors in the exudate initiate clotting reactions in the surrounding area, walling off the site of infection.
What accumulates as the inflammatory process continues
Large quantities of dead neutrophils accumulate
What makes up pus
Dead neutrophils, along with tissue debris.
Abscess
A localized collection of pus within a tissue.
Acute inflammation
Short term inflammatory response, characterized by an abundance of neutrophils.
What happens as the infection is brought under control
Resolution of inflammation begins
Neutrophils stop entering the area, and macrophages clean up the damage by ingesting dead cells and debris.
As the area heals, new capillaries grow, destroyed tissues are replaces and scar tissue forms.
Chronic inflammation
Long term inflammatory response, marked by the prevalence of macrophages, giant cells and granulomas.
Damaging effects of inflammation
Some enzymes and toxic products contained within phagocytic cell are inevitably released, damaging tissues.
If process occurs in a delicate system, consequences can be severe.
Apoptosis
A programmed cell death that does not trigger an inflammatory response.
What are the cellular changes that occur during apoptosis
- The cell shape changes
- Enzymes cut the DNA
- Pieces of the cell bud off- shrinking the cell.
Pyroptosis/ necroptosis
A type of programmed cell death that elicits an inflammatory response.
What is the results of apoptosis, pyroptosis and necroptosis?
The outcome is the same: The infected cell is sacrificed so that it cannot play host to an invader and its death releases DAMPS and cytokines.
How does a higher body temperature result?
A higher body temperature results when macrophages release pro inflammatory cytokines in response to microbial products.
What does the rise in temperature do during infection?
The rise in temperature prevents microbes with lower optimum temperatures from growing, giving the immune system time to eliminate the microbes before they cause too much harm.
Pyrogens
Fever inducing substances
Androgenous pyrogens
Fever inducing substances the body makes
Exogenous pyrogens
Microbial products that induce fever and are introduced from external sources.
