CUMULATIVE micro exam 3

Pathogenicity

The overall ability of a microorganism to cause disease (either pathogenic/non-pathogenic)

Virulence

specific degree or intensity of pathogenicity

ID50 (Infectious dose 50%)

the infectious dose required to produce disease in 50% of test sample population (measures virulence)

LD50

(Lethal dose 50%) the lethal dose of a toxin required to kill 50% of a test sample population (measures potency of a toxin)

Adhesins/Ligands

surface molecules on a pathogen that bind specifically to complementary receptors on host tissue cells

Siderophores

specialized proteins secreted by pathogens to scavenge and bind iron (Fe-3) more tightly than host proteins

Exotoxins

toxic proteins synthesised inside bacteria (mostly gram-positive) and secreted into the surrounding environment during log or growth phase

soluble proteins (A-B subunits)

secreted metabolic products during growth phase

no fever induction

neutralized by antitoxins; convert to toxoids for vaccines

Endotoxins

Lipid A portion of lipopolysaccharide (LPS) residing in the outer membrane of Gram-negative bacterial cell walls, released upon cell death/lysis or division

Lipid A (lipopolysaccharide)

outer membrane component released upon cell death/lysis

Does induce fever (pyrogenic response)

not easily neutralized by antitoxin; cannot make effective toxoids

Toxoid

an inactivated exotoxin used in vaccines to stimulate immune protection

Antitoxin

an antibody that specifically neutralizes a particular exotoxin

Transformation

genetic transfer where a recipient bacterial cell takes up “naked” free DNA from its surrounding environment

Conjugation

plasmid transfer from a donor bacterial cell to a recipient via direct cell-to-cell contact through a sex pilus or mating bridge

Transduction

transfer of host bacterial DNA from a donor cell to a recipient cell mediated by a bacteriophage virus

Lysogenic conversion

a change in the physiological characteristics or virulence of a host bacterium following the incorporation of a prophage into its genome (ex. diphtheria toxin)

Transposons

segments of DNA (“jumping genes”) that can move from one locus in DNA to another

Portals of entry

pathogens enter hosts via Mucous membrane (respiratory, GI, genitourinary, conjunctiva) Skin, or the parenteral route (direct deposition into subcutaneous tissues via bites, cuts, punctures, or surgical wounds.)

most pathogens have a preferred portal of entry

Portals of exit

generally mirror the portals of entry

Capsules (glycocalax)

impair phagocytosis by host immune cells

S. pneumoniae, H. influenzae, B. anthracis, Y. pestis)

Cell wall components

M protein, Opa protein, Mycolic acid (waxy lipid)

M protein

resists phagocytosis (S. pyogenes)

Opa protein

facilitates attachment to host tissues (N. gonorrhoeae)

Mycolic acid (waxy lipid)

resists digestion within phagocytes (M. tuberculosis)

Enzymatic defenses

coagulases, kinases, hyaluronidase, IgA proteases

Coagulases

clot fibrinogen in blood to isolate bacteria

Kinases

digest fibrin clots formed by the host

Hyluronidase

digests connective tissue polysaccharides

Collagenase

breaks down collagen fibers

IgA protease

destroy host mucosal IgA antibodies

Cytoskeletal alterations

bacterial invasins rearrange host cell actin filaments, causing membrane ruffling to engulf the pathogen (salmonella). Others (like L. monocytogenes) use host actin to form “tails” to travel between adjacent host cells.

Mechanism of A-B exotoxins

the B (binding) subunit attaches to the outer host cell surface receptor, triggering entry via endocytosis. Once inside, the subunits separate, and the A (active/enzymatic) subunit alters cell function (ex. inhibiting protein synthesis)

Pyrogenic (fever) response of endotoxins

macrophage ingests Gram-negative bacterium - - endotoxin released in vacuole - - macrophage releases cytokines (IL -1 and TNF) into bloodstream - - travel to hypothalamus - - hypothalamus produces prostaglandins to raise temperature set-point, producing fever

Viruses

cause Cytopathic Effects (CPE) such as stopping host synthesis, releasing lysosomal enzymes, forming inclusion bodies, creating syncytia (fused cells), loss of contact inhibition (leading to cancer), or inducing interferon production

Fungi

produce toxic metabolic products, allergic reactions

Protozoa and Helminths

use host tissues for growth, block tissue passages, produce toxic metabolic waste, or alter surface antigens

Transformation (Griffith’s experiment)

demonstrated that non-encapsulated (anti virulent) S. pneumoniae transformed into virulent encapsulated strains when mixed with heat-killed encapsulated bacteria. Recipient cell integrated naked donor DNA via homologous recombination

Conjugation (E. coli)

F+ donor cells contain F factor plasmid and build a sex pilus

Transduction

a bacteriophage inadvertently packages bacterial host DNA instead of viral DNA during replication. Upon lysing and infection a new recipient cell, it delivers the donor bacterial DNA for genetic recombination

Plasmids

Circular, self-replicating extrachromosomal DNA molecules

Conjunctive plasmids: code for sex pilus and transfer

R factors (resistance plasmids): contain RTF (resistance transfer factor) and r-determinants encoding resistance to multiple antibiotics/heavy metals.

Streptococcus pneumoniae

Causes Pneumococcal pneumonia or Pneumococcal Disease

Cell structure of Streptococcus pneumoniae

polysaccharide capsule

Primary site of infection for Streptococcus pneumoniae

nasopharynx (top part of throat)

Secondary sites of infection of Streptococcus pneumoniae

Can spread to lungs, blood, ear, sinuses, and meninges

Role of pneumolysin (PLY) and pilus during respiratory epithelium receptors causing invasion

PLY attaches to cholesterol, weakening membrane and allowing better adhesion of pilus to respiratory epithelium cells.

Old Streptococcus pneumoniae vaccine vs. new vaccine

Old: uses unlinked bacterial sugars that trigger weak T-cell response, ineffective for children under 2

New: link sugars to carrier protein to trigger strong T-cell response

Why is conjugation to a protein carrier advantageous in Streptococcus pneumoniae vaccine

Attaching protein acts like a flag that the immune system responds to, the body creates long term memory antibodies.

What challenge does "selection for non-vaccine serotypes" pose to long-term pneumococcal vaccination strategies?

Due to serotype replacement (serotypes not affected by the vaccine become more common) the vaccine effectiveness is decreased.

Corynebacterium diphtheriae

Causes diptheria

Mode of transmission for Corynebacterium diphtheriae

Respiratory droplets and direct contact with someone who is infected

How does C. diphtheriae acquire the ability to produce diphtheria toxin?

lysogenic conversion - bacteriophage inserts its DNA carrying the TOX gene into the bacterial chromosome

B subunit of C. diphtheriae

binds to the host cell receptor, triggering uptake via receptor-mediated endocytosis inside a vesicle. Acidification of the vesicle allows the B subunit to form a pore, releasing the A subunit into the cytoplasm.

A subunit of C. diphtheriae

A subunit halts host protein synthesis, causing the cell to undergo apoptosis. 

What is the characteristic throat lesion observed in respiratory diphtheria, how does it form, and what airway complication can arise in young children? 

thick, grayish-white pseudomembrane in the throat.

forms when diphtheria toxin damages and kills throat epithelial cells, causing the dead tissue, fibrin, bacteria, and inflammatory cells to accumulate and form the pseudomembrane.

In young children, the pseudomembrane can obstruct the airway and cause difficulty breathing or suffocation. 

Does the diphtheria component of DTaP/Tdap target the bacterial cell itself or the exotoxin? How is this vaccine antigen prepared?

DTap/Tdap targets the exotoxin of diphtheria and not the bacterial cell itself.

The vaccine works to isolate the diphtheria toxin and make it into a toxoid using chemicals such as formalin. The vaccine contains components that will neutralize the toxicity of the toxin. 

Why are adults aged 40–70+ considered a primary high-risk demographic for diphtheria in populations with high childhood vaccination coverage?

because vaccine-induced immunity against diphtheria naturally wanes over decades if they do not receive recommended 10-year booster shots (Td or Tdap). Over time, circulating antitoxin antibody levels fall below protective thresholds, leaving the body unable to quickly neutralize the diphtheria toxin upon exposure. 

Clostridium tetani

Tetanus

Oxygen requirement for Clostridium tetani

It is anaerobic; These grow only without oxygen

Is Clostridium tetani communicable between humans

no

Primary modes of communication for Clostridium tetani

It enters through wounds like cuts, puncture wounds, umbilical stumps, lacerations, burns, and bites.

host protein targeted by tetanospasmin and how it leads to paralysis/lockjaw

• Synaptobrevin- a protein that helps nerve cells release chemical messengers called neurotransmitters

• Tetanospasmin breaks down synaptobrevin

• This prevents the release of 2 inhibitory neurotransmitters, GABA and Glycine, which normally tell muscles to relax; without those signals, muscles keep contracting and can’t relax properly 

• This causes spastic paralysis-muscles become stiff and contract uncontrollably

Why is the basic reproduction number (R0) for tetanus equal to 0? 

It is an environmental disease, meaning it is not transferable from person to person, the contagiousness would be 0. 

Also, tetanus is a toxin, meaning the clinical manifestation is caused by the endospores of the bacteria C. tetani; it is not a virus.

Identify three distinct clinical manifestations of tetanus involving skeletal muscle contraction.

Lockjaw, involuntary smile, severe aching of the spine

CDC recommended timing for tetanus toxoid-containing vaccines across a person’s lifespan

Infants: DTaP; 2, 4, 6 months; 4-6 years old

Preteens: Tdap

Adults: TD booster every 10 years

DTap

Diphtheria, tetanus, and acellular pertussis

Inactivated vaccine containing toxoids and antigens not the whole bacteria

Bordetella pertussis

Whooping cough

function of three key outer surface structures in Bordetella pertussis

Fimbriae and filamentous hemagglutinin play a role in attachment to host cells, while pertactin is an outer membrane protein that allows it to resist neutrophil-mediated clearance.

(Bordetella pertussis) how the AB-type pertussis toxin alters intracellular signaling (cAMP pathways) following endocytosis into host cells. 

It adds ADP-ribose from NAD+ onto inhibitory G proteins to inactivate them, which allows cAMP signaling to occur uninhibitedly. 

Catarrhal stage of pertussis

First stage, highly contagious with less obvious symptoms

Paroxysmal stage of pertussis

Second stage, less contagious but with more extreme symptoms

Why is Tdap administration recommended during the 27th-36th week of pregnancy?

Triggers the mother’s immune system to make antibodies that will be passed to the fetus and provide the baby with some immunity before their first vaccine

High risk individuals for Whooping cough

infants and young children

Who would work as a carrier for this disease

Elderly who didn’t receive booster shots and pass disease to their grandchildren

Adolescents, adults, and older siblings/parents

Neisseria meningitidis

Meningococcal / Meningococcal disease

primary mucosal colonization site of Neisseria meningitidis and clinical manifestation. 

Nasopharyngeal mucosa. can enter the bloodstream and meninges, causing fever, headache, and stiff neck.

(Neisseria meningitidis) Which surface structures serve as the target antigens for vaccines against Serogroups A, C, W, Y?

capsular polysaccharides found on the outer surface. targeted by MenACWY vaccines to help the immune system recognize and fight the bacteria.

How does the polysaccharide capsule help N. meningitidis survive in the human bloodstream

Capsule acts as a protective shield that prevents the immune system from destroying bacteria via phagocytosis, allowing it to survive and spread.

What is meningococcemia

when N. meningitidis enters and multiplies in the blood stream. It can cause sepsis that would possibly lead to septic shock.

Who is susceptible to N. meningitidis

young infants and children, teenagers and young adults, college students, soldiers in barrack, immunocompromised individuals

Describe the primary capsular component of Haemophilus influenzae type b (Hib), a target molecule in the current vaccine.

Polyribosylribitol-phosphate polysaccharide (PRP) capsule

Primary invasive disease of Haemophilus influenzae type Hb (Hib)

Meningitis

High fever, severe headache, altered mental status

High risk age demographics for Haemophilus influenzae type b (Hib)

5 and under

65 and older

How does Polyribosylribitol-phosphate (PRP) act as a virulence factor for Hib during infection

PRP capsule prevents the bacterium from being phagocytosed

Pure polysaccharide vaccine vs. conjugate vaccine for Hib

Pure polysaccharide: made only of purified polysaccharide

Conjugate: capsular PRP covalently bonded to carrier protein, tetanus toxoid.

Why is the conjugation to a carrier protein provide superior protection in infants under 18 months

Capsule alone doesn’t result in strong immune response, tetanus toxoid elicits better immune responses. It recruits T-cell help, enabling B cells to produce antibodies and long-term immunological memory

Hib R0 = 3.3 and requires 70% herd immunity threshold, what does that mean?

R0 means one person infected with Hib will pass the bacteria to 3.3 other people

Herd immunity threshold means at least 70 of 100 people in a community must be immune to Hib to prevent outbreaks

Mycobacterium tuberculosis

Tuberculosis/TB

What unique chemical component in the Mycobacterium tuberculosis cell envelope renders it acid-fast?

Waxy lipids (Mycolic Acid)

Target cells of Mycobacterium tuberculosis

In lungs: Alveoli (alveolar macrophages)

Difference between pulmonary TB and Miliary TB

Pulmonary TB: TB that affects the lungs

Miliary TB: TB that spreads to multiple organs in the body through blood 

Latent TB vs active TB

Latent: bacteria are present in the body but it’s controlled by the immune system- no system, not contagious.

Active: symptomatic disease, mainly spreads through pulmonary TB- airborne transmission, symptoms, contagious, 5-10% develop TB without treatment

What organism is used to create BCG vaccine for TB

live-attenuated Mycobacterium bovis (normally causes TB in cattle)

Which immune cells does BCG vaccine for TB train

induces memory cells and induces trained immunity

What is the major limitation of BCG TB vaccine for adults

provides strong protection against severe disseminated TB in children, shows poor efficacy against adult pulmonary TB

Measles Virus

Rubeola

two main surface glycoproteins on the Measles virus envelope

• Hemagglutinin (H) Protein→ binds to the host-cell receptors

• Fusion (F) Protein→ facilitates viral entry and cell-to-cell spread

classic symptoms of measles

High fever, cough, runny nose, conjunctivitis (inflammation of membrane covering white part of eye), rash from head to toe

Main transmission route of measles

Droplet trasmission

Basic reproduction number for measles, why is immunity threshold particularly high

12-18

it spreads through airborne transmission, 90% SAR

What platform is used for licensed measles vaccines, what efficacy rates are achieved after 1 vs 2 doses

MMRI- Measles, mumps, rubella; live attenuated vaccine

1st- 93% effective

2nd- 97% effective

Which Poliovirus capsid protein is the major antigenic target for neutralizing antibodies?

VP1, VP2, VP3 BUT —> VP1 is the major antigenic target

path of poliovirus through the host body from entry site to central nervous system.

Poliovirus attaches to the host-cell receptor, then replicates and produces viral proteins that cause the infection.

Initial replication is in the throat or intestine, then may travel through the bloodstream to the central nervous system and damage motor neurons.