1. Case Study 2 Streptococcus Pneumoniae

Front 1

How do pathogens avoid phagocytosis?

Back 1

Many pathogens evolved surface components that prevent the attachment and engulfment of macrophages and other host cellular immune responses

Front 2

What specific components do pathogens use to avoid phagocytosis?

Back 2

1) Membrane bound proteins
2) Slimy polysaccharide capsules
3) LPS (Gram-Negative Only)
-These factors prevent the deposition of antibodies and complement on the bacterial surface, avoiding complement-mediated killing and reducing phagocytosis

Front 3

What's so special about Streptococus pneumoniae?

Back 3

It is an exmaple of a pathogen that uses a capsule to avoid phagocyotsis by the host's macrophages

Front 4

Describe some general characteristics of S. pneumoniae

Back 4

-Non-motile
-Non sporulating
-Gram Positive cocci
-It can be seen as pairs of cocci under microscope, may also occur in singly and short chains
-Is transient member of normal flora that colonizing the nasopharynx of 40% of healthy adults and children with no adverse effects
-Sensitive to heat, cold and drying
-Transmission requires close person to person contact via respiratory droplets

Front 5

What are the major virulence factors of S. pneumoniae

Back 5

-Anti-phagocytic polysaccharide capsule
-Several adhesins
-Pneumolysin (a toxin that binds to chloesterol in the host cell membrane and disrupts them by forming pores)
-Lipoteichoic acid (LTA)

Front 6

What are the major symptoms associated with S. pneumoniae?

Back 6

1) Pneumonia (inflammation of lungs)
2) Bactermia (bacteria in the blood)
3) Meningitis (inflammation of the membranes surrounding the brain and spinal column)
4) Otitis media (ear infection)

Front 7

What type of pathogen is S. pneumoniae?

Back 7

-It is an opportunistic pathogen
-Present in the normal flora of healthy individuals but only causes disease in debilitated hosts

Front 8

Which groups are at risk of S. pneumoniae infections?

Back 8

1) Infants and young children - because their immune systems have not fully developed
2) Elderly patients - because their immune systems do not function as efficently as younger adults (elderly do not develop fevers in response to bacterial infections)
3) Smokers (and those exposed to 2nd hand smoke)
4) Alcohol abuses

Front 9

Why are smokers prone to S. pneumoniae infections?

Back 9

Smoke injures the airways and damage the cilia
-General inability to clear microorgansims from the lungs will grealty increase risk (Ie, decrease in mucociliary transport, decrease in the cough reflex)

Front 10

Why are alcohol abusers more prone to S. pneumoniae infections?

Back 10

Alcohol acts as a sedative and can diminish the reflexes that trigger coughing and sneezing
-Alcohol also interferes with the actions of macrophages (the white blood cells that destroy bacteria and other microbes)

Front 11

What is the most common form of pneumonia?

Back 11

Pneumococcal pneumona
-Divided into two forms bronchial pneumonia and lobar pneumona

Front 12

Bronchial pnemonia

Back 12

-Most prevalent in infants, young children and aged adults and involves the alveoli contected to larger bronchioles of the bronchial tree

Front 13

Lobar pneumonia

Back 13

Likely to occur in younger adults and involves all of a single lobe of the lungs

Front 14

If bacteria manage to evade the mucociliary system and reach the lung. How do they protect themselves from the macrophages in the lung from gulfting them?

Back 14

-Capsule prevents macrophages in the lung from engulfing the bacteria
-Some bacteria will lyse releasing pneumotoxin and damaging the host mucosal cells
-Toxin impairs host ability to clear bacteria trapped in mucus and facilitates in the colonization of the bacterial in the lungs

Front 15

What else does pneumotoxin do?

Back 15

It initiates a localized inflammatory response in the lung which attracts more phagocytic cells to the area
-Due to the damage in the lung, the gas exchange mechansism are impaired and the person becomes cyantoic (skin appears blue) due to lack of oxygen

Front 16

What does pneumococcal pneumonia follow?

Back 16

Upper respiratory tract infection

Front 17

How does bacteremia occur?

Back 17

-Bacteria enter the bloodstream and lyse and the cell wall components trigger a massive cytokine release resulting in fever and septic shock

Front 18

How does meningitis occur?

Back 18

Meningitis occurs when bacteria from the bloodstream attach to the membranes that cover the brain and spinal column

Front 19

How do we diagnose S. pneumoniae infections/

Back 19

1) Minimum criteria for identification of S. pneumoniae from sputum, blood or cerebrospinal fluid include Gram-poistive staining, hemolytic activity and bile sensitivity
-While growing on blood agar plates in aerobic conditions, S. pneumoniae causes alpha emolysis (partial or greening hemolysis from a reduction in the red blood cell hemoglobin)
-In anaerobic conditions bacteria switch to beta hemolysis (complete lysis of the red blood cells surrounding the colony)
-But bacteria can be difficult to grow so a negative result does not rule out pneumonococcal pneumonia
-Positive culture from sputum samples may be the result of contaimination from bacteria in the mouth of a colonized patient

Front 20

Tell me about the capsule of S. pneumoniae.

Back 20

-Capsule composed of polysaccharide completely envelops the pneumoncococal cells
-90 different capsule types have been identified
-Polysaccharide is non-toxic and does not include an inflammatory response
-Antibody-mediated response to polysaccharide can be induced

Front 21

How can different capsular types be identified?

Back 21

By serological testing
-To determine the capsular type, a sample of the bacteria colony is mixed with a specific monoclonal antibodiy
-Positive test is indicated by swelling of the capsule which can be viewed under a phase constrat microscope (known as quellung reaction)

Front 22

How does S. pneumoniae evade host defences?

Back 22

-Encapsulated organisms are pathogenic for humans and experimental animals, whereas mutant derivatives without polysaccharide capsules are not
-Therefore the capsule is essential determinant of the virulence of the bacterium
-S. pneumoniae invade and grow primarily due to their resistance to the host phagocytic response
-Capsule can hide bacterial components such as peptidoglycan which can incude the alternate complement pathway and prevents formation of C3b complex
-Capsule interferes with phagocytosis by preventing C3b opsonization of bacteria

Front 23

How do we treat S. pneumoniae infections?

Back 23

-Penicillin and penicillin derivatives used to work well
-Erythromycin or tetracycline is an alternative treatment but resistance is showing
-Therefore it is best to prevent infections

Front 24

Is there a vaccine for S. pneumoniae?

Back 24

Yes
-It contains purified, capsular polysaccharide antigens of 23 types of S. pneumoniae
-In addition, cross reactivity occurs for several of the capsular types
(Cross reactivity is where an antibody against one serotype will bind to another serotype because of a shared epitope)

Front 25

How effective is the vaccine for S. pneumoniae?

Back 25

First understand that vaccine is given to high-risk persons such as elderly, immunosuppressed patients (those with aids) and patients with pulmonary disease
-Since polysaccharides are less immunogenic than proteins the vaccine does not elicit a strong antibody response
-This is true in the high risk groups such as infants and the elderly

Front 26

What are the recent developments in S. pneumoniae vaccination?

Back 26

Conjugate vaccine consisting of polysaccharide antigens covalently bonded to proteins to make the vaccine more immunogenic has been introduced
-This vaccine covers only 7 of the capsular types and is used primarily for prevention of ear infections