Nonspecific Defenses of the Host Innate Immunity.

Nonspecific Defenses of Nonspecific Defenses of the Hostthe Host

Innate ImmunityInnate Immunity

Nonspecific defenses of the hostNonspecific defenses of the host

The ability to ward off disease through our The ability to ward off disease through our defenses is called defenses is called resistance.resistance.

Vulnerability or lack of resistance to disease is Vulnerability or lack of resistance to disease is called called susceptibilitysusceptibility..

Non-specific defenses are also called innate Non-specific defenses are also called innate defenses and they protect us from infections by defenses and they protect us from infections by pathogens in general.pathogens in general.

This type of This type of innate immunity which one is born innate immunity which one is born with with is distinguished from is distinguished from adaptive immunity adaptive immunity which protects one from infection against a which protects one from infection against a specific organism and which develops after specific organism and which develops after exposure to that specific organism.exposure to that specific organism.

Innate versus adaptive immunityInnate versus adaptive immunity

As will be seen, the innate and As will be seen, the innate and adaptive immune systems adaptive immune systems do notdo not operate independently of each other, operate independently of each other, but are very inner-connected in their but are very inner-connected in their activities.activities.

Innate immunityInnate immunity

The first line of defenseThe first line of defense is intact skin and is intact skin and mucous membranes. Both mechanical and mucous membranes. Both mechanical and chemical factors are involved in this first chemical factors are involved in this first line of defense:line of defense: Mechanical factorsMechanical factors

Intact skin – consists of the connective tissue the inner Intact skin – consists of the connective tissue the inner dermis and the outer epidermis which is a continuous dermis and the outer epidermis which is a continuous sheet of closely packed epithelial cells. The top layer sheet of closely packed epithelial cells. The top layer contains a waterproofing protein called contains a waterproofing protein called keratinkeratin. This . This all provides a formidable physical barrier to the all provides a formidable physical barrier to the entrance of microorganisms. When the epithelial entrance of microorganisms. When the epithelial surface is broken, a subcutaneous infection may surface is broken, a subcutaneous infection may develop, frequently by develop, frequently by Staph. aureusStaph. aureus..

Intact skinIntact skin


Intact mucous membranes – also consists of Intact mucous membranes – also consists of outer epithelial and inner connective tissue outer epithelial and inner connective tissue layers. layers.

Mucous membranes line the digestive, Mucous membranes line the digestive, respiratory, urinary, and reproductive tracts. respiratory, urinary, and reproductive tracts.

Goblet cells in the epithelial layers secrete Goblet cells in the epithelial layers secrete mucous to prevent the tracts from drying out and mucous to prevent the tracts from drying out and the mucous may act to trap microorganisms that the mucous may act to trap microorganisms that enter. enter.

Some pathogens (Some pathogens (T. pallidum, M. tuberculosis, S. T. pallidum, M. tuberculosis, S. pneumoniaepneumoniae), however, actually survive in these ), however, actually survive in these moist secretions and, if present in sufficient moist secretions and, if present in sufficient numbers, are able to penetrate the membranes.numbers, are able to penetrate the membranes.


Cilia – the cells of the mucous membranes of Cilia – the cells of the mucous membranes of the respiratory tract contain cilia which the respiratory tract contain cilia which move synchronously to propel inhaled dust move synchronously to propel inhaled dust and microorganisms that have become and microorganisms that have become trapped in the mucous, upward toward the trapped in the mucous, upward toward the throat.throat.

Ciliated mucous membranesCiliated mucous membranes


The lacrimal apparatus of the eye The lacrimal apparatus of the eye manufactures and drains away tears. By its manufactures and drains away tears. By its continual washing action it helps keep continual washing action it helps keep microorganisms from settling on the surface microorganisms from settling on the surface of the eye. If something irritates the eye, of the eye. If something irritates the eye, the lacrimal glands will secrete heavily to the lacrimal glands will secrete heavily to wash away the irritating substance.wash away the irritating substance.

Lacrimal apparatusLacrimal apparatus


In a similar cleansing action, saliva produced by the In a similar cleansing action, saliva produced by the salivary glands, washes microorganisms from the salivary glands, washes microorganisms from the teeth and mucous membranes of the mouth.teeth and mucous membranes of the mouth.

The mucous membranes of the nose has mucous The mucous membranes of the nose has mucous coated hair that filter inspired air and trap coated hair that filter inspired air and trap microorganisms, dust and pollutants.microorganisms, dust and pollutants.

The epiglottis, which covers the larynx during The epiglottis, which covers the larynx during swallowing, helps to prevent microorganisms from swallowing, helps to prevent microorganisms from entering the lower respiratory tract.entering the lower respiratory tract.

The flow of urine through the urethra provides a The flow of urine through the urethra provides a mechanical cleansing of the urinary tract.mechanical cleansing of the urinary tract.


Chemical factorsChemical factors Sebum produced by the oil glands of the skin provides a Sebum produced by the oil glands of the skin provides a

protective film over the surface of the skin. It contains protective film over the surface of the skin. It contains unsaturated fatty acids which inhibit the growth of unsaturated fatty acids which inhibit the growth of certain bacteria and fungi and contribute to the low pH certain bacteria and fungi and contribute to the low pH of the skin which is also inhibitory to the growth of of the skin which is also inhibitory to the growth of microorganisms. What also contributes to the low pH? microorganisms. What also contributes to the low pH? What is the relationship between sebum and the acne What is the relationship between sebum and the acne that sometimes occurs, particularly in adolescents?that sometimes occurs, particularly in adolescents?

Perspiration produced by the sweat glands contributes Perspiration produced by the sweat glands contributes to the high salt content of the skin that is osmotically to the high salt content of the skin that is osmotically unfavorable for the growth of many microorganisms. unfavorable for the growth of many microorganisms.


Perspiration, tears, saliva, nasal secretions and tissue Perspiration, tears, saliva, nasal secretions and tissue fluids all contain lysozyme. What is the activity of fluids all contain lysozyme. What is the activity of lysozyme?lysozyme?

Gastric juice produced by the stomach is very acidic Gastric juice produced by the stomach is very acidic and will destroy most bacteria and bacterial toxins. and will destroy most bacteria and bacterial toxins. Food particles, however, may protect enteric Food particles, however, may protect enteric pathogens from the effects of the acid.pathogens from the effects of the acid.

Defensins - are cysteine rich peptides produced by Defensins - are cysteine rich peptides produced by the skin that have antibacterial activitythe skin that have antibacterial activity

Cryptocidins – are antimicrobial peptides produced by Cryptocidins – are antimicrobial peptides produced by the epithelium of the intestinethe epithelium of the intestine

The presence of normal flora may protect from The presence of normal flora may protect from colonization by potentially pathogenic bacteria. colonization by potentially pathogenic bacteria. How?How?


The second line of defense:The second line of defense: Phagocytosis – cells in the human body Phagocytosis – cells in the human body

that counter infection by phagocytosing that counter infection by phagocytosing microorganisms are called microorganisms are called phagocytesphagocytes and they are all either types of white and they are all either types of white blood cells (WBCs) or derivatives of blood blood cells (WBCs) or derivatives of blood cells.cells. Blood= plasma + the formed elements:Blood= plasma + the formed elements:

RBCs are called RBCs are called erythrocyteserythrocytes Platlets are called Platlets are called thrombocytesthrombocytes WBCs are called WBCs are called leukocytesleukocytes


During a bacterial infection, there is often an During a bacterial infection, there is often an increase in the number of leukocytes and increase in the number of leukocytes and this is called a this is called a leukocytosis.leukocytosis.

Some diseases cause a decrease in Some diseases cause a decrease in leukocytes and this is calledleukocytes and this is called leukopenia. leukopenia.

The source of the increase or decrease of of The source of the increase or decrease of of leukocytes can be determined by performing leukocytes can be determined by performing a a differential countdifferential count. The percentage of each . The percentage of each type of WBC is determined by counting 100 type of WBC is determined by counting 100 WBCs. The normal values are:WBCs. The normal values are:

Formed elements of the Formed elements of the bloodblood


Note that the WBCs are divided into two Note that the WBCs are divided into two basic types, granulocytes, which contain basic types, granulocytes, which contain granules and agranulocytes which lack granules and agranulocytes which lack granules, both of which may be phagocytic:granules, both of which may be phagocytic:


What are the basic functions of the various WBCs?What are the basic functions of the various WBCs? PMNs are highly phagocytic and can leave the blood to PMNs are highly phagocytic and can leave the blood to

enter infected tissues to destroy foreign substancesenter infected tissues to destroy foreign substances Basophils release histamine and heparin in the Basophils release histamine and heparin in the

inflammatory response and in hypersensitivity reactionsinflammatory response and in hypersensitivity reactions Eosinophils are somewhat phagocytic. They ingest Eosinophils are somewhat phagocytic. They ingest

antigen-antibody complexes and are increased during antigen-antibody complexes and are increased during parasitic infections and hypersensitivity reactions.parasitic infections and hypersensitivity reactions.

Lymphocytes are found mainly in lymphoid tissue, but Lymphocytes are found mainly in lymphoid tissue, but some are in circulating blood. They are important in some are in circulating blood. They are important in antibody production and in modulating the immune antibody production and in modulating the immune response.response.

Monocytes are poorly phagocytic until stimulated by Monocytes are poorly phagocytic until stimulated by infection. Then they move into the tissues and infection. Then they move into the tissues and differentiate into macrophages which are highly differentiate into macrophages which are highly phagocytic.phagocytic.


During an infection both PMNs and monocytes, which During an infection both PMNs and monocytes, which become macrophages, migrate to the infected area. become macrophages, migrate to the infected area. Neutrophils are the first cell type to arrive at the Neutrophils are the first cell type to arrive at the infected site and are the predominant cell found infected site and are the predominant cell found during the initial stage of the infection. In the latter during the initial stage of the infection. In the latter stages of the infection monocytes will predominate stages of the infection monocytes will predominate (more on this later).(more on this later).

Phagocytosis occurs in two stages:Phagocytosis occurs in two stages: AdherenceAdherence – this refers to the attachment of the phagocytic cell – this refers to the attachment of the phagocytic cell

with the surface of the invading microorganism via a receptor with the surface of the invading microorganism via a receptor on the phagocytic cell that recognizes structures that are on the phagocytic cell that recognizes structures that are characteristic of microbial pathogens and are not present on characteristic of microbial pathogens and are not present on mammalian cells (mammalian cells (pathogen associated molecular patterns or pathogen associated molecular patterns or PAMPsPAMPs). The receptors are called ). The receptors are called pattern recognition receptors. pattern recognition receptors.

PAMPsPAMPs


The pattern recognition receptors are also called The pattern recognition receptors are also called toll-toll-like receptorslike receptors because they resemble, both in structure because they resemble, both in structure and function, receptors, called toll receptors, that were and function, receptors, called toll receptors, that were originally identified in the innate immune response of originally identified in the innate immune response of Drosophila.Drosophila.

Binding of a PAMP to a toll-like receptor triggers a Binding of a PAMP to a toll-like receptor triggers a signaling cascade in which a transcription factor is signaling cascade in which a transcription factor is translocated into the nucleus leading to the expression translocated into the nucleus leading to the expression of genes involved in the innate response.of genes involved in the innate response.

When this occurs it is said that the phagocytic cell has When this occurs it is said that the phagocytic cell has been activated.been activated.

LPS is an example of a PAMP which binds to a toll-like LPS is an example of a PAMP which binds to a toll-like receptor to trigger a subsequent signal transduction receptor to trigger a subsequent signal transduction pathway that leads to expression of genes involved in pathway that leads to expression of genes involved in the innate response.the innate response.

TLRs and signal transduction TLRs and signal transduction pathwayspathways

LPS activation of innate immunityLPS activation of innate immunity


The process of adherence is facilitated by The process of adherence is facilitated by chemotaxis chemotaxis which is the attraction of phagocytes to the which is the attraction of phagocytes to the microorganisms via chemical factors (cytokines) released microorganisms via chemical factors (cytokines) released by certain WBCs, damaged tissues, microbial products or by certain WBCs, damaged tissues, microbial products or peptides derived from the complement cascade (more on peptides derived from the complement cascade (more on this later).this later).

Adherence of encapsulated microorganisms is difficult and Adherence of encapsulated microorganisms is difficult and may occur by two mechanisms:may occur by two mechanisms:

Non-immune or surface phagocytosis – the phagocyte Non-immune or surface phagocytosis – the phagocyte traps the microorganism against a rough surface traps the microorganism against a rough surface which the microorganism cannot slide away from.which the microorganism cannot slide away from.

OpsonizationOpsonization – the microorganism is first coated by an – the microorganism is first coated by an opsonin which can be either an antibody or a opsonin which can be either an antibody or a component of the complement cascade. Phagocytic component of the complement cascade. Phagocytic cells may contain receptors for these opsonins which cells may contain receptors for these opsonins which serve to act as a bridge to promote the attachment of serve to act as a bridge to promote the attachment of the microorganism to the phagocyte.the microorganism to the phagocyte.

OpsonizationOpsonization


Ingestion is the second stage of phagocytosis and it Ingestion is the second stage of phagocytosis and it follows adherence and activation of the phagocytic follows adherence and activation of the phagocytic cell. cell.

The microorganism is engulfed by pseudopods. The microorganism is engulfed by pseudopods. Once the microorganism is surrounded, the phagocytic Once the microorganism is surrounded, the phagocytic

membrane will fold inward enclosing the microorganism membrane will fold inward enclosing the microorganism in a sac called a phagosome or phagocytic vacuole.in a sac called a phagosome or phagocytic vacuole.

The phagosome will pinch off and enter the cytoplasm The phagosome will pinch off and enter the cytoplasm where it will fuse with a lysosome.where it will fuse with a lysosome.

The digestive enzymes present in the lysosome may kill The digestive enzymes present in the lysosome may kill the bacteria. the bacteria.

It should be noted that not all bacteria are killed by It should be noted that not all bacteria are killed by lososomal enzymes.lososomal enzymes.

Phagocytosis and Phagocytosis and intracellular destructionintracellular destruction

Mechanism of phagocytosisMechanism of phagocytosis


In addition to killing bacteria via the digestive enzymes In addition to killing bacteria via the digestive enzymes present in lysosomes, phagocytic cells have two other present in lysosomes, phagocytic cells have two other mechanisms by which they might kill bacteria (both mechanisms by which they might kill bacteria (both intra and extracellular):intra and extracellular):

Present in the plasma membrane of the phaocytic Present in the plasma membrane of the phaocytic cell and in the membrane of the phagosome is a cell and in the membrane of the phagosome is a phagocytic oxidase enzyme that is activated to phagocytic oxidase enzyme that is activated to produce produce reactive oxygen intermediates (ROIs)reactive oxygen intermediates (ROIs) such such as the superoxide radical which may be toxic to as the superoxide radical which may be toxic to bacteria. The process by which ROIs are produced bacteria. The process by which ROIs are produced is called the respiratory or oxidative burst.is called the respiratory or oxidative burst.

There is also a nitric oxidase synthase that may be There is also a nitric oxidase synthase that may be activated to produce activated to produce nitric oxide (NO)nitric oxide (NO) which can which can interact with the ROIs to generate a highly toxic interact with the ROIs to generate a highly toxic peroxynitrite radical.peroxynitrite radical.

Microbicidal mechanisms of Microbicidal mechanisms of phagocytesphagocytes

PhagocytosisPhagocytosis


In addition to killing phagocytosed microbes, In addition to killing phagocytosed microbes, activated macrophages serve many other activated macrophages serve many other functions in defense against infections including functions in defense against infections including leukocyte recruitment and tissue remodeling. leukocyte recruitment and tissue remodeling.

Many of these functions are mediated by Many of these functions are mediated by cytokines.cytokines. Cytokines are chemicals produced Cytokines are chemicals produced by in innate immunity, mainly by PMNs, by in innate immunity, mainly by PMNs, macrophages and NK cells (discussed later). macrophages and NK cells (discussed later).

Endothelial cells and epithelial cells may also Endothelial cells and epithelial cells may also produce cytokines. produce cytokines.

Cytokines serve to communicate information Cytokines serve to communicate information among inflammatory cells and between among inflammatory cells and between inflammatory cells and responsive tissue cells.inflammatory cells and responsive tissue cells.

More second line defense…More second line defense…

InflammationInflammation – damage to the bodies’ tissues – damage to the bodies’ tissues will trigger an inflammatory response. The will trigger an inflammatory response. The four fundamental symptoms of inflammation four fundamental symptoms of inflammation are are redness, pain, heat, and swelling. redness, pain, heat, and swelling. There is There is also sometimes loss of function.also sometimes loss of function. Inflammation Inflammation has the following three functions:has the following three functions: To destroy the injurious agent, if possible, and to To destroy the injurious agent, if possible, and to

remove it and its by-products from the body.remove it and its by-products from the body. If destruction is not possible, to wall off the injurious If destruction is not possible, to wall off the injurious

agent and its by-products.agent and its by-products. To repair or replace damaged tissue.To repair or replace damaged tissue.

More second line defenseMore second line defense

Inflammation occurs in three stages:Inflammation occurs in three stages: Damage to the tissues causes a release of histamine, Damage to the tissues causes a release of histamine,

kinins, and prostoglandins. The release of these kinins, and prostoglandins. The release of these substancees causes substancees causes vasodilation and increased vasodilation and increased permeability of the blood vessels. permeability of the blood vessels.

Vasodilation (increase in the diameter of blood vessels) Vasodilation (increase in the diameter of blood vessels) in the area of injury causes an increase in blood flow to in the area of injury causes an increase in blood flow to the injured area. This causes the injured area. This causes rednessredness and and heat.heat.

Increased vascular permeability permits defensive Increased vascular permeability permits defensive substances normally present in the blood to enter the substances normally present in the blood to enter the injured area resulting in edema and injured area resulting in edema and swelling. Pain swelling. Pain from from the pressure of swelling as well as from nerve damage the pressure of swelling as well as from nerve damage and irritation by toxins will occur.and irritation by toxins will occur.


Clotting elements are also delivered to the injured area. Clotting elements are also delivered to the injured area. The clots that form prevent the spreading of the The clots that form prevent the spreading of the microorganisms and result in a localized collection and microorganisms and result in a localized collection and pus in a cavity formed by the breakdown of body tissues pus in a cavity formed by the breakdown of body tissues (an abscess forms).(an abscess forms).

Phagocytic migration occurs. Within one hour Phagocytic migration occurs. Within one hour phagocytes appear on the scene. phagocytes appear on the scene.

As the blood flow decreases, the phagocytic cells begin to As the blood flow decreases, the phagocytic cells begin to stick to the lining of the blood vessels (stick to the lining of the blood vessels (marginationmargination), and ), and then the cells squeeze through the walls of the vessels to then the cells squeeze through the walls of the vessels to move to the damaged area (move to the damaged area (diapodesisdiapodesis). ).

PMN’s arrive first and are attracted to the area by PMN’s arrive first and are attracted to the area by chemotactic factors. chemotactic factors.

Leokocytosis promoting factorLeokocytosis promoting factor released from inflamed released from inflamed tissues causes the production and release of additional tissues causes the production and release of additional PMNs from the bone marrow. PMNs from the bone marrow.


As the inflammatory response continues monocytes As the inflammatory response continues monocytes enter the inflamed area and differentiate into enter the inflamed area and differentiate into macrophages which are much larger than and macrophages which are much larger than and several times more phagocytic than the PMNs.several times more phagocytic than the PMNs.

After PMNs and macrophages engulf large numbers After PMNs and macrophages engulf large numbers of microorganisms and tissue, they, themselves, of microorganisms and tissue, they, themselves, die. A collection of dead cells and various tissue die. A collection of dead cells and various tissue fluids is called pus. Pus formation will continue until fluids is called pus. Pus formation will continue until the infection subsides.the infection subsides.

Repair is the last stage of the inflammatory Repair is the last stage of the inflammatory process. This is the process by which tissues process. This is the process by which tissues replace dead or damaged cells.replace dead or damaged cells.

InflammationInflammation


Fever – fever is a systemic response to Fever – fever is a systemic response to infection. infection. Body temperature is controlled by the Body temperature is controlled by the

hypothalamus. hypothalamus. Certain antigens such as the LPS can cause Certain antigens such as the LPS can cause

the phagocytic cells to release leukocyte the phagocytic cells to release leukocyte pyrogen (IL-1) that causes the hypothalamus pyrogen (IL-1) that causes the hypothalamus to release prostoglandins that reset the to release prostoglandins that reset the hypothalmic thermostat at a higher hypothalmic thermostat at a higher temperature. temperature.


Blood vessel constriction, increased rate of Blood vessel constriction, increased rate of metabolism and shivering will all help to increase the metabolism and shivering will all help to increase the temperature of the body. Thus shivering is a definite temperature of the body. Thus shivering is a definite sign that body temperature is rising.sign that body temperature is rising.

As the infection subsides, heat losing mechanisms As the infection subsides, heat losing mechanisms such as vasodilation and sweating will occur.such as vasodilation and sweating will occur.

Up to a certain point, a fever is beneficial because it Up to a certain point, a fever is beneficial because it inhibits bacterial growth, intensifies the effects of inhibits bacterial growth, intensifies the effects of interferon (discussed later), and may help the body interferon (discussed later), and may help the body tissues to repair themselves more quickly. However, tissues to repair themselves more quickly. However, if body temperature gets too high (>45if body temperature gets too high (>4500 C) this may C) this may be lethal.be lethal.


Antimicrobial substancesAntimicrobial substances Interferon (IFN) – interferons are substances Interferon (IFN) – interferons are substances

produced and released from virally infected cells. produced and released from virally infected cells. Interferons bind to receptors on neighboring cells Interferons bind to receptors on neighboring cells and, though a signal transduction pathway, induce and, though a signal transduction pathway, induce them to produce anti-viral substances that interfere them to produce anti-viral substances that interfere with viral multiplication and thus protect the cell from with viral multiplication and thus protect the cell from viral infection.viral infection.

IFN is host specific, but not viral specific, i.e., IFN is host specific, but not viral specific, i.e., interferon in humans will not work in dogs (why?), interferon in humans will not work in dogs (why?), and when made, IFN is made to protect the and when made, IFN is made to protect the neighboring cells from viral infections in general. It neighboring cells from viral infections in general. It doesn’t protect only against a specific virus.doesn’t protect only against a specific virus.

IFN production and activityIFN production and activity


Complement and properdinComplement and properdin – complement and – complement and properdin are a group of proteins found in normal properdin are a group of proteins found in normal blood serum. blood serum. They are important in both non-specific and specific They are important in both non-specific and specific

antigen-antibody defenses against microbial infection. antigen-antibody defenses against microbial infection. They function to attack and destroy invading They function to attack and destroy invading

microorganisms and to help stimulate the inflammatory microorganisms and to help stimulate the inflammatory response. response.

The proteins act in an ordered sequence or cascade of The proteins act in an ordered sequence or cascade of reactions. In an ordered sequence of steps, the proteins reactions. In an ordered sequence of steps, the proteins activate one another usually by cleaving the next protein activate one another usually by cleaving the next protein in the series. in the series.

The fragments of the cleaved proteins have new The fragments of the cleaved proteins have new enzymatic or physiological functions. enzymatic or physiological functions.


There are three different, interconnected There are three different, interconnected pathways of complement activation:pathways of complement activation: The The classical pathwayclassical pathway is activated via an antigen- is activated via an antigen-

antibody complex which activates the complement antibody complex which activates the complement components C1 to an activated C1 complex which components C1 to an activated C1 complex which then activates C4, and C2 to form another activated then activates C4, and C2 to form another activated complex. This complex next activates C3 which is complex. This complex next activates C3 which is cleaved into C3a and C3bcleaved into C3a and C3b

The The lectin pathway lectin pathway is initiated by the binding of a is initiated by the binding of a serum protein, mannose-binding lectin (MBL) that is serum protein, mannose-binding lectin (MBL) that is produced during inflammation. MBL binds to produced during inflammation. MBL binds to mannose residues on glycoproteins or carbohydrates mannose residues on glycoproteins or carbohydrates that are on the surface of microorganisms. It that are on the surface of microorganisms. It functions like an activated C1-like complex.functions like an activated C1-like complex.


The The alternate or properdin pathwayalternate or properdin pathway is activated is activated by cell wall polysaccharides that interact with by cell wall polysaccharides that interact with properdin factors B, D, and P as well as properdin factors B, D, and P as well as circulating C3b to create a complex that also circulating C3b to create a complex that also activates C3 by cleavage into C3a and C3b.activates C3 by cleavage into C3a and C3b.

C3b produced by all three pathways involves C3b produced by all three pathways involves components C5 through C9 in a membrane attack components C5 through C9 in a membrane attack complex that punches a hole in an invading complex that punches a hole in an invading microorganism leading to its cytolysis (microorganism leading to its cytolysis (a process a process called complement fixationcalled complement fixation))

C3b, when bound to the surface of a microorganism, C3b, when bound to the surface of a microorganism, can interact with receptors on the surface of can interact with receptors on the surface of phagocytes to promate phagocytosis (phagocytes to promate phagocytosis (opsonizationopsonization))


C3a and cleavage products from C5, C6, and C3a and cleavage products from C5, C6, and C7 can contribute to the development of an C7 can contribute to the development of an acute inflammatory response via their acute inflammatory response via their activity on mast cells, platlets and basophils activity on mast cells, platlets and basophils (leads to increased permeability of blood (leads to increased permeability of blood vessels) and their ability to act as vessels) and their ability to act as chemotactic factors for phagocytic cells.chemotactic factors for phagocytic cells.

Once activated the destructive Once activated the destructive capabilities of the complement system capabilities of the complement system are quickly inactivated.are quickly inactivated.

Complement activationComplement activation

Lectin pathway

Complement fixationComplement fixation

Results of complement Results of complement fixationfixation

Complement stimulation of Complement stimulation of inflammationinflammation


Natural killer (NK) cells – NK cells are large, granular Natural killer (NK) cells – NK cells are large, granular lymphocytes that are activated by three types of lymphocytes that are activated by three types of targets:targets: Antibody coated cellsAntibody coated cells Cells infected by viruses and some intracellular bacteriaCells infected by viruses and some intracellular bacteria Cells lacking class I MHC molecules (more on this later). NK Cells lacking class I MHC molecules (more on this later). NK

cells express inhibitory receptors that recognize class I MHC cells express inhibitory receptors that recognize class I MHC molecules, and therefore NK cells are inhibited by class I molecules, and therefore NK cells are inhibited by class I expressing cells and activated by target cells lacking class I expressing cells and activated by target cells lacking class I molecules. Some viruses are known to down regulate molecules. Some viruses are known to down regulate expression of class I molecules.expression of class I molecules.

Activated NK cells lyse the target cells by releasing granules Activated NK cells lyse the target cells by releasing granules that contain perforin that creates pores in the target cells and that contain perforin that creates pores in the target cells and granzymes that enter the target cells through the pores and granzymes that enter the target cells through the pores and induce apoptosis of the target cell.induce apoptosis of the target cell.

NK activityNK activity

NK activity with normal cellNK activity with normal cell

NK activity with cell lacking NK activity with cell lacking MHC class I moleculesMHC class I molecules

Summary of components of innate immunity Summary of components of innate immunity – note how inner-connected these – note how inner-connected these components arecomponents are

Innate stimulation of adaptive Innate stimulation of adaptive immunityimmunity

Innate defenses play a major role in Innate defenses play a major role in stimulating adaptive defenses:stimulating adaptive defenses:

Nonspecific Defenses of the Host Innate Immunity.

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Transcript of Nonspecific Defenses of the Host Innate Immunity.