Lecture 5 Infectious process. Non-specific host defence. Immunity. Immune system.

Lecture 5

Infectious process. Non-specific host defence.Immunity. Immune system.

What Is Infection?

Our environment is full of microorganisms (microscopic organisms) referred to as microbes (bacteria, fungi, protozoa and viruses).

Microbes that are capable of causing disease (ie., pathogenic) are called pathogens/the infectious or causative agent.

The interaction between the pathogen microorganism, the environment and the host is defined as infectious disease process.

If a pathogen invades the body and the conditions are favorable for it to multiply and cause injurious effects or disease, the resulting condition is called an infection.

Infectious process

The process may be thought of as a circular chain with six links.

The following story illustrates the chain.

Horton & Parker: Informed Infection Control Practice

I. Chain of Infection

I. Microorganisms

Normal FloraNormal Flora

PathogensPathogens

Opportunistic PathogensOpportunistic Pathogens

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Types of microbes causing infectious disease

Type Branch Cellular? Genome Nuclear Example (Kingdom) membrane?

Metazoan Eucarya yes DNA yes Ascarisparasites (Animalia) lumbricoides

Protozoan Eucarya yes DNA yes Plasmodiumparasites (Protista) falciparum

Fungi/ Eucarya yes DNA yes Candidayeasts (Fungi) albicans

Bacteria Eubacteria yes DNA no Streptococcus (not Archaea) pyogenes

Viruses no DNA/RNA no Herpes simplex

Prions no no genes no BSE (Mad Cow Disease)

Phylogenetic Classification of Bacteria

Oxford Textbook of Medicine

Phylogenetic Classification of Viruses

Oxford Textbook of Medicine

Mabbott & MacPherson, Nat Rev Microbiol 2006

Prions

Two basic types of pathogens

- exogenous pathogen - aggressive pathogen, requires acquired immunity for host defense

- opportunistic (endogenous) pathogen - becomes a pathogen when host is compromised

• damage to epithelium• introduction of bacteria to sites where they are not normal flora - linked to presence of foreign body, catheters, biofilms• disruption of normal flora by antibiotics • suppression of immune system by drugs• insufficient host defenses due to infection


II. Chain of Infection

A host that carries a pathogen without injury to itself and serves as a source of infection for

other host organisms.

Reservoir of infection – ecological niche where the infectious agent survives and multiplies

ex. person, animal, arthropod, soil, or substance

(asymptomatic infective carriers)

Reservoirs

Humans{hepatitis}

Other Vertebrates{antrax, pesta}

Birds & Bats{chlamidia, leptospirosis}

soil, or substance{tetania}

NOT vectors

Reservoirs, examples


III. Chain of Infection

Portal of exit Portal of exit - the route by which the disease agent may

escape from the human or animal reservoir.

While many disease agents have only one portal of exit, others may leave by various portals.

The portals most commonly associated with human and animal diseases are:

• Respiratory • Genitourinary • Gastrointestinal• Skin

Superficial lesions Percutaneous

• Transplacental

Respiratory:

Respiratory:

the route of many disease agents that cause respiratory illnesses such as common cold, influenza, and tuberculosis.

the route used by many childhood vaccine-preventable diseases (measles, mumps, rubella, pertussis, Haemophilus influenzae type b (Hib) and pneumococcal disease).

the most important portal, but the most difficult to control.

Genitourinary:

Genitourinary:

This portal of exit is the route of sexually transmitted diseases, including syphilis, gonorrhea, chlamydia, HIV.

Schistosomiasis, a parasitic disease and leptospirosis, a bacterial infection, are both spread through urine released into the environment.

Gastrointestinal:

Gastrointestinal:

Examples include: Hepatitis A Salmonella, including typhoid Shigella Cholera Giardia Campylobacter

In general, enteric diseases may be controlled through good hygiene, proper food preparation and sanitary sewage disposal.

Skin:

Skin may serve as a portal of exit through superficial lesions or through percutaneous penetration. Superficial skin lesions that produce infectious

discharges are found in smallpox, varicella (chickenpox), syphilis, and impetigo.

Percutaneous exit occurs through mosquito bites (malaria, West Nile virus) or through the use of needles (hepatitis B and C, HIV).

Transplacental:

Transplacental:

This portal of exit from mother to fetus is important in the transmission of: rubella, HIV, syphilis, and cytomegalovirus (the most common infectious cause

of developmental disabilities).

It is, fortunately, not a factor for most diseases.

Some Pathogens that cross the Placenta


IV. Chain of Infection

Mode/means of transmission

A mode of transmission is necessary to bridge the gap between the portal of exit from the reservoir and the portal of entry into the host.

The two basic modes are:

direct indirect

Direct transmission

occurs more or less immediately. Many diseases are transmitted by direct contact with human, animal or environmental reservoir.

Ex. sexually transmitted diseases and enteric diseases such as shigella, giardia and campylobacter.

Ex. contact with soil - mycotic (fungal) diseases.

Droplet spread is also considered direct transmission. Infectious aerosols produced by coughing or sneezing can transmit infection directly to susceptible people up to 2 m.

Indirect transmission

May occur through:

1. animate or 2. inanimate mechanisms.

Animate mechanisms involve vectors.

Ex. flies may transmit infectious agents such as shigella in a purely mechanical way, by walking on feces and then on food.

Ex. mosquitoes, ticks or fleas may serve as reservoirs for the growth and multiplication of agents in malaria or Lyme disease.

Arthropod Vectors

Pathogen - Vector

Viruses (Arbovirus) - Mosquitoes

Bacteria (Yersinia) - Fleas

Bacteria (Borrelia) - Ticks

Rickettsias (R. prowazeki) - Lice, ticks

Protozoa (Plasmodium) - Mosquitoes

Protozoa (Trypanozoma) -Tsetse flies

Helminths (Onchocerca) - Simulium flies

Inanimate mechanisms:• involve environmental vehicles, including

objects, food, water, milk, or biological products.

Ex. Food - salmonella infections.

Water - cholera outbreaks.

Surgical instruments and implanted medical devices - staphylococcal infections.

Modes of Disease Transmission


V. Chain of Infection

Portal of entry The portal of entry into the host is usually the

same as the portal of exit from the reservoir.

In some diseases, however, the exit and entry portals may differ.

Ex.: staphylococcal bacteria may escape from one person’s respiratory tract to infect another person’s skin lesion.

If that person is a foodhandler, the staphylococcal bacteria may escape from the infected skin lesion, contaminate food where it can incubate, and cause “food poisoning” in people eating the food.


VI. Chain of Infection

Susceptible Host

The last essential component in the chain of infection is the susceptible host.

A person who cannot resist a microorganism invading the body, multiplying, and resulting in infection.

Susceptibility is affected by: Genetic factors Non-specific defence Specific acquired immunity

Genetic factors

The role of genetic factors in susceptibility to infectious diseases is not yet well understood.

Genes do seem to play a role in the progression of HIV disease, and perhaps in individuals’ susceptibility to meningococcal meningitis are described.

Host defense factors

Intact skin and mucous membranes help us resist disease.

So do the gastric acid in our stomachs, the cilia in our respiratory tracts and the cough reflex.

Specific acquired immunity

This immunity is specific to a particular disease agent, and it may be acquired

naturally or artificially

Summarize – 6 chains of infection

Infectious agent Reservoir Portals of exit Means of transmission Portal of entry Susceptible host


REVIEW - Chain of Infection

The Infectious Disease Spectrum

The impact of disease agents on human host populations is very different.

If a large number of individuals are equally exposed to an infectious agent, they do not all respond in the same manner.

It may be a broad range of responses.

No infection Clinical Sub-clinical Carrier

Death Carrier Immunity No immunity

Outcome

Exposure to Infectious Agents

Infectious agents

Host

Manifestations of infectious process (Infection spectrum)

a. Clearance of pathogenb. Subclinical infectionc. Clinical infection or apparent infectiond. Carrier state - Health carrier - after subclinical infection - Convalescent carrier - after clinical infection - Incubatory carrier - before onset of diseases According to carrier time: - acute (transient) carrier - chronic carrier.a. Latent infection

Iceberg Concept of Infection

Clinical features of infectious disease

Incubation period – the time between exposure to a pathogenic organism and when first symptoms apparent.

Prodromal period – the time during which a disease process has begun but is not yet clinically manifest. May appear some prodromal symptoms.

Period of apparent manifestation - the acute phase when specific symptoms appear.

Convalescent period - during this time the body systems return to normal.

Relapse - is the return of a disease after its apparent recovering. Recrudescence - the recurrence of symptoms after a temporary

abatement.

The distinction between a recrudescence and a relapse is the time interval. A recrudescence occurring after some days or weeks, a relapse after some weeks or months.

Dynamics of disease and infectiousness/contagiosity

Latent period Infectious periodContagious period

Non-infectious period

Incubation period Clinical disease Recovery

Infection

Time

Onset ofsymptoms

Resolutionof symptoms

Common symptoms and signs

Fever: Three stages: effervescence fastigium deffervescence

Five kinds of fever: sustained fever, remittent fever, intermittent fever, relapsing fever, saddle type fever. And irregular fever


Rash eruption Date of eruption

chickenpox scarlet feversmallpox measlestyphus typhoid fever

Location of eruption

Form of rash - Exanthema: maculo-papular rash petechia vesiculo-pustular rash urticaria - Enanthema


Toxemic symptoms Mononuclear phagocyte system

reactions Hepato-splenomegale Lymphonodus enlarged

Clinical types acute, subacute, mild, common, severe, fulminate, typical, atypical, abortive.

Types of Diseases

Diseases are given different names on the mode of their transmission, geographic area of distribution, or severity etc.

1. Communicable Diseases2. Noncommunicable Diseases3. Endemic Diseases4. Epidemic Diseases5. Pandemic Diseases6. Other type of Diseases

Disease occurrence in populations

Sporadic: occasional cases occurring at irregular intervals;

Endemic: continuous occurrence at an expected frequency over a certain period of time and in a certain geographical location;

Epidemic or outbreak: occurrence in a community or region of cases of an illness with a frequency clearly in excess of normal expectancy;

Pandemic: epidemic involves several countries or continents, affecting a large population.

Host

Agent Environment

Factors influencing disease transmission

Agent

Host

Environment

• Host defence

• Age, Sex• Genotype• Behaviour• Nutritional status• Health status

• Infectivity• Pathogenicity• Toxigenicity • Virulence• Immunogenicity

• Weather• Housing• Geography• Occupational setting• Air quality• Food

Factors influencing disease transmission:

InfectiInfectivityvity::Multiplication of an infectious agent within the body. Multiplication of an infectious agent within the body.

Multiplication of the bacteria that are part of normal flora Multiplication of the bacteria that are part of normal flora of gastrointestinal tract, skin, etc, is generally not of gastrointestinal tract, skin, etc, is generally not considered an infection.considered an infection.

On the other hand, multiplication of pathogenic bacteria On the other hand, multiplication of pathogenic bacteria (e.g. (e.g. Salmonella speciesSalmonella species), even if the person is), even if the person is asymptomatic, is deemed an infection.asymptomatic, is deemed an infection.

Basic terms frequently used in describing aspects of pathogen agents:

Basic terms frequently used in describing aspects of pathogen agents:

PathogenicityPathogenicity::The ability of an infectious agent to cause disease.The ability of an infectious agent to cause disease.

VirulenceVirulence::The quantitative ability of an agent to cause disease.The quantitative ability of an agent to cause disease. VirulentVirulent agents cause disease when introduced into the agents cause disease when introduced into the

host in small numbers. host in small numbers. Virulence involves invasiveness and toxigenicity.Virulence involves invasiveness and toxigenicity.

ToxigenicityToxigenicity::The ability of a microorganism to produce a The ability of a microorganism to produce a

toxin that contributes to the development of toxin that contributes to the development of disease.disease.

InvasionInvasion::The process whThe process whichich bacteria, parasites, fungi bacteria, parasites, fungi

and virusesand viruses enter the host cells or enter the host cells or tissues and spread in the body. tissues and spread in the body.

Basic terms frequently used in describing aspects of pathogenesis:

Bacterial virulence factorsBacterial virulence factors

Many factors determine the Many factors determine the virulence of bacteria, or their ability virulence of bacteria, or their ability to cause infection and disease.to cause infection and disease.

ToxinsToxinsEnzymesEnzymesAntiphagocytic factorsAntiphagocytic factorsAdherence factorsAdherence factors

ToxinsToxins

Toxins produced by bacteria are generally Toxins produced by bacteria are generally classified into two groups:classified into two groups:

EEndotoxinsndotoxins

EExotoxinsxotoxins

Endotoxins of gram-negative Endotoxins of gram-negative bacteriabacteria

The endotoxins of gram-negative bacteria are complex The endotoxins of gram-negative bacteria are complex lipopolysaccharides lipopolysaccharides derived from bacterial cell walls derived from bacterial cell walls and are often eliberated when the bacteria lyse. and are often eliberated when the bacteria lyse.

The substances are The substances are heat-stableheat-stable and and can be extractedcan be extracted (e.g. with phenol-water).(e.g. with phenol-water).

The presence of endotoxins in the blood is called The presence of endotoxins in the blood is called eendotoxemiandotoxemia. .

It can lead to It can lead to septic shock shock, if the immune response is , if the immune response is severely pronounced.severely pronounced.

EffectsEffects of endotoxinsof endotoxins

feverfever leukopenialeukopenia hypotensionhypotension acidosisacidosis activation of C3 and complement cascadeactivation of C3 and complement cascade disseminated intravascular coagulation (DIC)disseminated intravascular coagulation (DIC) deathdeath

ExotoxinsExotoxins

Many gram-positive and gram-negative Many gram-positive and gram-negative bacteria produce exotoxins of considerable bacteria produce exotoxins of considerable medical importance. medical importance.

Some of these toxins have had major role in Some of these toxins have had major role in world history (e.g. toxin of world history (e.g. toxin of Clostridium Clostridium tetanitetani).).

Exotoxin Excreted by a microorganism, including bacteria, fungi, algae, and

protozoa.

Can cause damage to the host by destroying cells or disrupting normal cellular metabolism.

Exotoxin may be secreted, or may be released during lysis of the cell.

Most exotoxins can be destroyed by heating.

They may exert their effect locally or produce systemic effects.

Exotoxins are susceptible to antibodies produced by the immune system, but many exotoxins are so toxic that they may be fatal to the host before the immune system has a chance to mount defenses against it.

Well-known exotoxins include the botullinum toxin produced by Clostridium botulinum.

Ex. Botulotoxin (toxin of Clostridium botulinum)

Clostridium botulinumClostridium botulinum is found in soil or water and is found in soil or water and may grow in foods if the environment is appropriately may grow in foods if the environment is appropriately anaerobic. anaerobic.

An An exceedingly potent toxin (exceedingly potent toxin (the most potent toxin the most potent toxin knownknown) is produced by ) is produced by Clostridium botulinumClostridium botulinum strains. It is strains. It is heat-labileheat-labile and is destroyed by sufficient heating. There and is destroyed by sufficient heating. There are are eighteight disctinct disctinct serological typesserological types of toxin. Types A, B of toxin. Types A, B and E are most commonly associated wih human disease. and E are most commonly associated wih human disease. Toxin is absorbed from the gut and carried to motor nerves, Toxin is absorbed from the gut and carried to motor nerves, where it where it blocksblocks the release of the release of acetylcholineacetylcholine at synapses at synapses and neuromuscular junctions. Muscle contraction does not and neuromuscular junctions. Muscle contraction does not occur, and paralysis results.occur, and paralysis results.

Ex. Tetanospasmin (toxin of Clostridium tetani)

Clostridium tetaniClostridium tetani is an anaerobic gram-positive rod that is is an anaerobic gram-positive rod that is widespread in the environment. widespread in the environment.

Clostridium tetaniClostridium tetani contaminates wounds, and the spores germinate in contaminates wounds, and the spores germinate in the anaerobic environment of the devitalized tissue. The vegetative the anaerobic environment of the devitalized tissue. The vegetative forms of forms of Clostridium tetaniClostridium tetani produce toxin produce toxin tetanospasmin.tetanospasmin.

Toxin reaches theToxin reaches the central nervous system central nervous system by retrograde transport by retrograde transport along axons and through the systemic circulation. along axons and through the systemic circulation.

The toxin acts by blocking release of an The toxin acts by blocking release of an inhibitory mediatorinhibitory mediator in motor in motor neuron synapses. The result is initially localized then generalized, muscle neuron synapses. The result is initially localized then generalized, muscle spasms. Extremely small amount of toxin can be lethal for humans.spasms. Extremely small amount of toxin can be lethal for humans.

Ex. Streptococcal erythrogenic toxin

Some strains of Some strains of hemolytic lysogenic hemolytic lysogenic streptococcistreptococci produce a toxin that results in a produce a toxin that results in a punctate maculopapular erythematous rash, punctate maculopapular erythematous rash, as in scarlet fewer. as in scarlet fewer.

Production of erythrogenic toxin is under the Production of erythrogenic toxin is under the genetic control of temperate bacteriophage. If genetic control of temperate bacteriophage. If the phage is lost, the streptococi cannot the phage is lost, the streptococi cannot produce toxin.produce toxin.

Ex. Toxic shock syndrom toxin - 1 (TSST-1)

Some Some Staphylococcus aureusStaphylococcus aureus strains growing on strains growing on mucous membranes (e.g. on the vagina in association mucous membranes (e.g. on the vagina in association with menstruation), or in wounds, elaborate TSST-1.with menstruation), or in wounds, elaborate TSST-1.

Although the toxin has been associated with Although the toxin has been associated with toxic shock toxic shock

syndrome,syndrome, the mechanism of action in unknown. the mechanism of action in unknown.

The illness is characterized by shock, high fever, and a The illness is characterized by shock, high fever, and a diffuse red rash that later desquamates; multiple other diffuse red rash that later desquamates; multiple other organs systems are involved.organs systems are involved.

Toxins associated with diarrheal diseases

Vibrio choleraeVibrio cholerae toxin toxin Staphylococcus aureusStaphylococcus aureus enterotoxin enterotoxin Other enterotoxins are also produced by some Other enterotoxins are also produced by some

strains of:strains of:Yersinia enYersinia entterocoliticaerocoliticaVibrio parahaemolyticusVibrio parahaemolyticusAeromonas speciesAeromonas species

EnzymesEnzymes

Many species of bacteria produce enzymes that are Many species of bacteria produce enzymes that are not intrinsically toxic but play important role in the not intrinsically toxic but play important role in the infectious process.infectious process.

Collagenase:Collagenase:degrades collagen, the major protein of fibrous degrades collagen, the major protein of fibrous

connective tissue, and connective tissue, and promotes spread of infection in tissue.promotes spread of infection in tissue.

CoagulaseCoagulase::Staphylococccus aureusStaphylococccus aureus produce coagulase, which produce coagulase, which

works in conjuction with serum factors to coagulate works in conjuction with serum factors to coagulate plasma. plasma.

contributes to the formation of fibrin walls around contributes to the formation of fibrin walls around staphylococcal lesions, which helps them persist in staphylococcal lesions, which helps them persist in tissues.tissues.

EnzymesEnzymes

HyaluronidasesHyaluronidases::hydrolyze hydrolyze hyaluronic acidhyaluronic acid, a constituent of the ground , a constituent of the ground

substance of connective tissuesubstance of connective tissueproduced byproduced by many bacteria (e.g. many bacteria (e.g. staphylococci, staphylococci,

streptococci and anaerobesstreptococci and anaerobes) ) aid in their spread through tissues.aid in their spread through tissues.

Streptokinase Streptokinase ((fibrinolysinfibrinolysin))::byby many hemolytic streptococci, many hemolytic streptococci, activates a proteolytic enzyme of plasma. activates a proteolytic enzyme of plasma. able to dissolve coagulated plasma and probably aids in able to dissolve coagulated plasma and probably aids in

the spread of streptococci through tissues.the spread of streptococci through tissues.used inused in treatment of acute myocardial infarction to treatment of acute myocardial infarction to

dissolve fibrin clots. dissolve fibrin clots.

EnzymesEnzymes

Hemolysins and leukocidinsHemolysins and leukocidins::Many bacteria produce substances that are Many bacteria produce substances that are cytolysinscytolysins - -

they dissolve red blood cells (hemolysins) or kill tissue cells they dissolve red blood cells (hemolysins) or kill tissue cells or leukocytes (leukocidins). or leukocytes (leukocidins).

Streptolysin O, for example, is produced by group A streptococci Streptolysin O, for example, is produced by group A streptococci and is letal for mice and hemolytic for red blood cells from many and is letal for mice and hemolytic for red blood cells from many animals.animals.

Antiphagocytic factorsAntiphagocytic factors

Many bacterial pathogens are rapidly killed by Many bacterial pathogens are rapidly killed by polymorphonuclear cells or macrophages. polymorphonuclear cells or macrophages.

Some pathogens evade phagocytosis by Some pathogens evade phagocytosis by adsorbing normal host componets to their adsorbing normal host componets to their surfaces. surfaces.

For example, For example, Staphylococcus aureusStaphylococcus aureus has surface has surface protein A, which binds to the Fc portion of IgG. Other protein A, which binds to the Fc portion of IgG. Other pathogens have surface factors that impede pathogens have surface factors that impede phagphagoocytosis, e.g. cytosis, e.g. Streptococcus pneumoniaeStreptococcus pneumoniae and and many other bacteria have polysaccharide capsules.many other bacteria have polysaccharide capsules.

Adherence factorsAdherence factors

Once bacteria enter the body of the host, they must Once bacteria enter the body of the host, they must adhere to cells of a tissue surface. If they do not adhere to cells of a tissue surface. If they do not adhere, they would be swept away by mucus and adhere, they would be swept away by mucus and other fluids that bathe the tissue surface. other fluids that bathe the tissue surface.

Adherence (which is only one step in the infectAdherence (which is only one step in the infectiious ous process) is followed by development of process) is followed by development of microcolonies and subsequent complex steps in the microcolonies and subsequent complex steps in the pathogenesis of infection.pathogenesis of infection.

Agent

Host

Environment

• Immunity

• Age, Sex, Genotype• Behaviour• Health status, Nutritional status

• Host defence

• Infectivity• Pathogenicity• Toxigenicity • Virulence• Immunogenicity

• Weather• Housing• Geography• Occupational setting• Air quality• Food

Factors influencing disease transmission

Lecture 5

Infectious process. Non-specific host defence.Immunity. Immune system.

The action of immune reaction of host in infectious process

Non specific host-defence

Specific immunity

HOST DEFENSE MECHANISMS

1st LINE OF DEFENSE - intact skinmucous membranes & their secretions

2nd LINE OF DEFENSE - phagocytic white blood cellsinflammation -complementfever -interferon

3rd LINE OF DEFENSE- B & T lymphocytes specificantibodies

nonspecific

1st LINE OF DEFENSE

1. PHYSICAL BARRIERS2. CHEMICAL BARRIERS3. GENETIC BARRIERS

PHYSICAL BARRIERS

First line of defense are barriers that shield interior of body from external surroundings

Anatomical barriers include skin and mucous membranes

Provide physical separation

Membranes bathed in antimicrobial secretions

PHYSICAL BARRIERS Physical barriers

Skin is most visible barrier.

Covers majority of surfaces in contact with environment.

Mucous membranes barrier that lines digestive tract, respiratory tract and genitourinary tract

Mucous protect these surfaces from infections.

Skin Provides the most difficult barrier to penetrate Composed of two main layers

Dermis Contains tightly woven fibrous connective tissues

Makes extremely tough Epidermis

Composed of many layers of epithelial cells As cells reach surface, they become increasingly flat

Outermost sheets of cells embedded with keratin Makes skin water-repellent

Outer layers slough off taking microbes with it

PHYSICAL BARRIERS

SKIN

Dermis Inner thicker portion

Epidermis Outer, thinner portion

Keratin (waterproofing)

SKIN INFECTIONS

Rare in unbroken skin

Sweat washes microbes off

Cuts and burns may get infected Subcutaneous infections Staphylococcus spp.

MUCOSAL MEMBRANE

Epithelial layer Connective tissue

Bronchi Intestine

MUCOSAL SURFACES (cont.)

1. Reproductive tract

2. Urinary tract

3. Gastrointestinal tract

4. Respiratory tract

1 2

43

PHYSICAL BARRIERS

Mucous membranes Constantly bathed with

mucus Helps wash surfaces

Some mucous membranes have mechanisms to propel microorganisms and viruses to areas where they can be eliminated

MUCOSAL SURFACES (cont.)

Mucosal irritation or damage facilitates infection (smoking)

Substances produced by pathogens Treponema pallidum

CHEMICAL BARRIERS

Sebaceous secretions

Lysozyme, an enzyme that hydrolyzes the cell wall of bacteria, in tears

High lactic acid & electrolyte concentration in sweat

CHEMICAL BARRIERS

Skin’s acidic pH

Hydrochloric acid in stomach

Digestive juices and bile of intestines

Semen contains antimicrobial chemical

Vagina has acidic pH

CHEMICAL FACTORS

Skin

Sebaceous glands

Unsaturated fatty acids pH 3-5

Antimicrobial substances Both skin and mucous membranes are protected by variety of

antimicrobial substances including Lysozyme

Enzymes that degrade peptioglycan Found in tears, saliva, blood and phagocytes

Peroxidase Found in saliva, body tissues and phagocytes Breaks down hydrogen peroxide to produce reactive oxygen

Lactoferrin Sequesters iron from microorganisms

Iron essential for microbial growth Found in saliva, some phagocytes, blood and tissue fluids

Defensins Antimicrobial peptides inserted into microbial membrane Found on mucous membranes and in phagocytes

SPECIALIZED CHEMICAL BARRIERS

Enzyme that degrades peptidoglycans Gram + are more susceptible than Gram -

Secreted in Sweat Saliva Tears Nasal secretions

LYSOZYME

GASTRIC JUICE

Hydrochloric acid (pH 1.2 to 3) Helicobacter pylori

Neutralizes acidic pH

Enzymes

Mucus

Normal flora Defined as microorganisms found growing on

body surfaces of healthy individuals Not technically part of immune system

However, provides significant protection Protects through competitive exclusion

Covers binding sites Pathogens can’t bind

Competes for nutrients Nutrients unavailable for pathogens

NORMAL FLORA

GENETIC IMMUNITY

Some hosts are genetically immune to the diseases of other hosts.

Some pathogens have great specificity.

Some genetic differences exist in susceptibility.

1st LINE OF DEFENSE - intact skinmucous membranes & their secretions

2nd LINE OF DEFENSE - phagocytic white blood cellsinflammation -complementfever -interferon

3rd LINE OF DEFENSE- B & T lymphocytes specificantibodies

nonspecific

2nd LINE OF DEFENSE

A HEALTHY IMMUNE SYSTEM IS RESPONSIBLE FOR:

1. Recognition of foreign material

1. Surveillance of the body

1. Destruction of foreign entities

SYSTEMS INVOLVED IN IMMUNE DEFENSE

The reticuloendothelial system

The blood

The lymphatic system

The extracellular fluids (ECF) - spaces surrounding tissue cells

SYSTEMS INVOLVED IN IMMUNE DEFENSE

RETICULOENDOTHELIAL SYSTEM

This system is formed of reticular fiber which form a support network for each cell.

This network connects one cell to another within a tissue or organ.

Provides phagocytic white blood cell (WBC) the ability to move within and between tissues

CELLS OF THE IMMUNE SYSTEM

Always found in normal blood Numbers increase during infection

Some cells play dual roles in both innate and adaptive immunity

Blood cell formation called hematopoiesis Blood cells including immune cells originate from

hematopoietic stem cells in bone marrow Blood cells stimulated to differentiate by colony-

stimulating factor

General categories of blood cells Red blood cells (RBC)

erythrocytes carry oxygen in blood

Platelets fragments of megakaryocytes important component in blood clotting

White blood cells (WBC) leukocytes important in host defenses divided into four categories

Granulocytes - Mononuclear phagocytes Dendritic cells- Lymphocytes


BLOOD CELLS


Granulocytes

Contain cytoplasmic granules

Divided into three types Neutrophils Basophils Eosinophils


Neutrophils Most abundant and important in

innate response Sometimes called

polymorphonuclear neutrophilic leukocytes (PMNs)

Basophils Involved in allergic reaction

Eosinophils Important in expelling parasitic

worms Active in allergic reactions


Mononulcear phagocytes Constitute collection of

phagocytic cells called mononuclear phagocyte system

Include monocytes Circulate in blood Macrophages

differentiate from monocytes

Present in most tissues Abundant in liver,

spleen, lymph nodes, lungs and peritoneal cavity


Dendritic cells Branched cells involved

in adaptive immunity Function as scout in

tissues Engulf material in

tissue and bring it to cells of adaptive immunity


Lymphocytes Involved in adaptive

immunity Two major groups

B lymphocytes B cells

T lymphocytes T cells

Another type Natural killer

Lacks specificity of B and T cells

LYMPHOCYTES

LEUKOCYTES Neutrophils- 55-90% - lobed nuclei with

lavender granules; phagocytes Eosinophils – 1-3% - orange granules & bilobed

nucleus; destroy eucaryotic pathogens Basophils, mast cells – 0.5% constricted nuclei,

dark blue granules; release potent chemical mediators

Lymphocytes – 20-35% - large nucleus B & T cells involved in the specific immune response

Monocytes, macrophages – 3-7%- large nucleus; phagocytic

CHARACTERISTICS OF LEUKOCYTES

Diapedesis – migration of cells out of blood vessels into the tissues

Chemotaxis – migration in response to specific chemicals which have passed through the 1st line of defense

Chemotaxis

Diapedesis

CHARACTERISTICS OF LEUKOCYTES

Group 1 - Toll-like receptors and NOD proteins Found on variety of

cells Recognize families of

compounds Enable cells to sense

invasion Send signal to body

to respond

LYMPHATIC SYSTEM

1. Provides an auxiliary route for return of extracellular fluid to the circulatory system

1. Acts as a drain-off system for the inflammatory response

1. Renders surveillance, recognition, and protection against foreign material

LYMPHATIC FLUID

Lymph is a plasmalike liquid carried by lymphatic circulation

Formed when blood components move out of blood vessels into extracellular spaces

Made up of water, dissolved salts, 2-5% proteins

Transports white blood cells, fats, cellular debris & infectious agents

LYMPH NODES

Small, encapsulated, bean-shaped organs stationed along lymphatic channels & large blood vessels of the thoracic and abdominal cavities

Contains both T and B lymphocytes

RESULTS OF A MICROBE PASSING THE 2ND LINE OF DEFENSE

In order for immune system to respond to trauma or invasion, cells must communicate with environment and with each other

Cell surface receptors are the “eyes” and “ears” of the cell

Cytokines are the “voice”

Adhesion molecules act as the “hands”

CELL COMMUNICATION

Surface receptors Membrane proteins to which signal molecules

bind Receptors specific to molecule to which it bonds

Binding molecules called ligands When ligand binds, receptor becomes modified

and sends signal to cell Cell responds by initiating some action like

chemotaxis

CELL COMMUNICATION

Cytokines are proteins made by certain cells as a mechanism to communicate with other cells. Cytokines bind to surface receptors; and regulate cell

function

Binding of a cytokine to its receptor induces a change in the cell such as growth, differentiation, movement, or cell death.

They can act locally, regionally, or systemically

CELL COMMUNICATION

CYTOKINES

Numerous cytokine classes Chemokines – important in chemotaxis

Enhance ability of cells to migrate to appropriate site in body Colony stimulating factors – Important in

multiplication and differentiation of leukocytes During immune response, directs immature leukocytes to

correct maturation pathway Interferons – important in control of viral

infections Also associated with inflammatory response

Interleukins – produced by leukocytes Important in innate and adaptive immunity

Tumor necrosis factor – kill tumor cells Instrumental in initiation of inflammation

Adhesion molecules Allow cells to adhere to each other

Responsible for the recruitment of phagocytes to area of injury

Causes phagocytes to slow and leak out of vessels to area of injury

CELL COMMUNICATION

SENSOR SYSTEMS

Systems within blood detect signs of tissue damage or microbial invasion

Responds to patterns associated with danger by Directly destroying invading microbe Recruiting other host defenses

SENSOR SYSTEMS

Toll-like receptors (TLR) and NOD proteins Pattern recognition receptors TLR allow cells to “see” molecules

signifying presence of microbes outside the cell

TLR found in variety of cell types Recognize distinct “danger”

compounds Signal is transmitted

Results in change of gene expression of cell

NOD proteins are intracellular receptors that recognize bacterial cell wall components within cytoplasm

Complement system Series of proteins circulating in blood and fluids

Circulate in inactive form Augment activities of adaptive immune response Stimulation of inactive proteins initiates cascade of reactions

Results in rapid activation of components

Complement system composed of nine proteins C1 – C9

Numbered as discovered, not order of activation Certain proteins split into “a” and “b” fragments after activation

C3 can spontaneously split to C3a and C3b Insures enough C3b for activation of alternative pathway

SENSOR SYSTEMS

Complement activation

Three pathways of activation of the complement system

Classical pathway

Alternative pathway

Lectin pathway

SENSOR SYSTEMS

Classical pathway Activation requires

antibodies Antibodies interact

complement C1 Activates protein

Leads to activation of all complex proteins

SENSOR SYSTEMS

Alternative pathway Quickly and easily initiated Relies on binding of

complement protein C3b to cell surface

Initiates activation of other complement proteins

Allows formation of complement complex

C3b always circulating in blood so nearly any cell automatically triggers the pathway unless the body’s own cells stop the process

SENSOR SYSTEMS

Lectin pathway Activation requires

mannose/mannan-binding lectins (MBL) on host cells

MBLs are pattern recognition molecules

Detect mannane Polymer of mannose

Found in microbial cells

MBL attaches to surface of the microbe if mannan is present

Activates complement proteins

Activation of complement leads to major protective outcomes

Inflammation

Opsonization

Lysis of foreign cells

SENSOR SYSTEMS

SENSOR SYSTEMS

Inflammation Complement components C3a and C5a

induce changes in endothelial cells Effects vascular permeability associated with

inflammation

Opsonization C3b binds foreign material

Allows phagocytes to easily “grab” particles

SENSOR SYSTEMS

Lysis of foreign cells

Complexes of C5b, C6, C7, C8 and multiple C9 spontaneously assemble

Forms donut-shaped structure called membrane attack complex (MAC)

Creates pores in membrane

Most effective on Gram + Little effect on Gram + cells

ACTIVITIES OF PHAGOCYTES

1. To survey tissue compartments & discover microbes, particulate matter & dead or injured cells

1. To infest and eliminate these materials

1. To extract immunogenic information from foreign matter

PHASES OF PHAGOCYTOSIS

PHAGOCYTOSIS

Process of phagocytosis Chemotaxis

Cells recruited to infection

Recognition/attachment Use receptors to bind

invading microbes Engulfment

Phagocyte engulfs invader forming phagosome

Phagosome lysosome fusion

Phagosome binds lysosome, forming phagolysosome

Destruction and digestionOrganism killed due to lack

of oxygen and decreased pH

ExocytosisPhagocyte expels material

to external environment

INFLAMMATION

STAGES OF INFLAMMATION1.Blood vessels dilate in response to chemical mediators and cytokines.

1.Edema swells tissues, helping prevent spread of infection

3. WBC’s, microbes, debris and fluid collect to form pus

4. Pyrogens may induce fever

5. Macrophages and neutrophils engage phagocytosis

INFLAMMATION

Inflammation occurs in response to tissue damage

Four cardinal signs Heat Pain Redness Swelling

Loss of function Fifth sign that can also be

present

INFLAMMATION

Factors that initiate inflammatory response Microbial products trigger toll-like receptors

of macrophages Causes release of pro-inflammatory cytokines

Microbial cell surface can trigger complement Leads to the production of C3a and C5a

Tissue damage results in enzymatic cascade Cascades initiate inflammation

INFLAMMATION

The inflammatory process Initiation leads to a cascade of

events Results in dilation of blood

vessels, leakage of fluid from vessels and migration of leukocytes and phagocytes

Leakage of phagocytes from blood vessels called diapedesis

Certain pro-inflammatory mediators cause the diameter of blood vessels to increase

Results in increased blood flow

Increased blood flow responsible for cardinal signs of inflammation

INFLAMMATION

Outcomes of inflammation Intent is to limit damage and restore function

Inflammation itself can cause considerable damage Release of toxic products and enzymes from phagocytic

cells is responsible for tissue damage

If inflammation is limited to area of injury, damage is usually nominal

If inflammation results in delicate systems, consequences are more severe

Inflammation around brain and spinal cord can lead to meningitis

FEVER

One of the strongest indicators of infection Especially of bacterial infection

Important host defense mechanism

Temperature regulation center of body responds to fever-inducing substances called pyrogens Fever-inducing cytokines termed endogenous pyrogens Microbial products termed exogenous pyrogens

Resulting fever inhibits growth of pathogens by Elevating temperature above maximum growth temperature Activating and speeding up other body defenses

Summary of Innate Immunity

External and mechanical barriers Receptors for pathogen Soluble antimicrobial proteins Pattern of cytokines produced

influences adaptive response

Natural immunity

“active natural immunity” - may be acquired by experiencing an infection. Many diseases confer immunity after a single infection, but many others do not. For ex. a single bout of measles or chickenpox, confers

lifelong immunity to that disease. Influenza and salmonella are examples of infections that do not confer immunity and therefore may recur.

“passive natural immunity” - the transfer of antibodies from the mother to the newborn child, via the placenta and/or breast milk. It is diminishes after varying lengths of time. It is very important in giving infants a good head start in life.

Artificial immunity

may be acquired through the use of vaccines, toxoids and immune globulins.

Active immunity: Receiving a vaccine or toxoid stimulates “active” immunity, since the recipient responds by producing his/her own antibodies.

Passive immunity: Receiving an antitoxin or immune

globulin confers “passive” immunity, essentially by borrowing the antibodies of other people.

Passive immunity lasts for only a short time, while activeimmunity usually lasts much longer, even for a lifetime.

Lecture 5 Infectious process. Non-specific host defence. Immunity. Immune system.

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Transcript of Lecture 5 Infectious process. Non-specific host defence. Immunity. Immune system.