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Flashcards in Exam 3 Deck (132):
1

Alveoli:

tiny sacs in lungs that allow oxygen and carbon dioxide to move between the lungs and bloodstream

2

mucociliary escalator

cilia are continually pushing mucus up and out into the throat- the mucociliary escalator is a major barrier against infection. Microorgs hoping to infect the respt tract get caught in the sticky mucus and are pushed upwards toward the throat

3

URT versus LRT

UTR: Sinuses, naspharyns, pharyns, oral cavity, larynx
LTR: trachea, bronchi, lungs
UTR damage may increase risk of LTR infection- LTR infections are most fatal
Respt tract is portal to elsewhere

4

Be able to list some antimicrobial defenses of the respiratory tract. What are some features of the environment of the respiratory tract?

Resp secretions in the nasal, airway surface, alveolar fluid- contain lysozymes, lactoferrin, antimicrobial peptides, surfactants, IgA, mucus, reactive nitrogen species
Mucociliary clearance- also sneezing and coughing’

5

What are some of the major genera of bacteria found in the upper respiratory tract? Which ones are considered commensal pathogens?

Aerobes and anaerobes
In the front of the UTR- s nasopharyns: firmicutes, mollicutes, actinobacteria
-such as staphylccocus spp, streptococcus spp
Rear of UTR: so pharynx/larynx: firmicutes and proteobacteira
-such as streptococcus spp, neisseria
Commensals include: staphylococcus, streptococcus

6

. What is the old and the new view about the population of microbes found in the lower respiratory tract? Why is this difficult to determine?

They help decrease allergic airway inflammation directly and indirectly- help promote health

7

What are some diseases of dysbiosis that may occur in the respiratory tract?

Asthma, COPD, cystic fibrosis- all caused by low microbial diversity
Asthma: caused when total proteobacteria increase, and the proportion of streptococcus within firmicutes increases
COPD: total proteobacteria increase, and proportion of staphylococcus and streptococcus within firmicutes increases
Cystic fibrosis: total proteobacteria increase, and actinobacteria increase

8

Transmission of respt tract microbes:

-acquire from environment
-self to self: aspiration from UTR to LTR, spread to hands, spread to bloodstream
-person to person: droplet size (smaller spread better), contamination of fomites, life of microbe outside host varies

9

Measles Reservoir:

humans only

10

Measles Basic biology and contribution of this to disease

: enveloped single stranded, negative strand RNA virus

11

Measles Mechanism of transmission

coughing, sneezing

12

Measles Major sites of colonization

resp tract, infects epithelial cells

13

Measles Major sites of disease – are they the same or different than colonization sites

spreads everywhere- resp tract, gi tract, skin, liver, small blood vessels, lymphatic system,

14

Measles Main diseases

sore throat, fever, rash, can cause complications such as secondary infections from immunosuppression and epithelial cell damage, pneumonia-most common cause of death, and diarrhea
Other complications: poor pregnancy outcomes, fever and seizures, ocular damage including blindness,

15

Measles Major virulence factors

transient but profound immunosupression

16

Measles Main disease symptoms

sore throat, fever, rash

17

Measles Main treatment and control

): live attenuated vaccine (doesn’t kill pathogen, just inactivates it)

18

What are the main features of the basic biology of measles virus?

Enveloped, singles stranded, negative strand RNA virus, has replicase enzyme (needed because only positive strand mRNA can be directly translated to make proteins, negative strands can’t be translated, so positive strands need to be made from this, which is what replicase does, and makes more negative strands from positive trand)

19

What are the main host receptors for measles virus and what types of cells are they found on?

CD150- found on dendritic, B and T cells
Nectin 4- also receptor, on epithelial cells

20

3. Why are significant complications associated with measles virus infection?

Because it is transient but causes profound immunosuppression
It causes local replication in respiratory dendritic cells, spreads to lymphatic system, causes viremia (presence of virus in blood) and wide dissemination (spread) to the respt tract, skin, gi tract, liver, small blood vessels, lymphatic system. Causes sore throat, fever, cough, rash- causes brief but profound immunosupression
And it exits via respiratory epithelial cells

21

Influenza Reservoir

birds, other animals, people. All types present within bird populations

22

Influenza Basic biology and contribution of this to disease

enveloped, negative single stranded RNA genome, many subtypes, has cap and RNA polymerase, has segmented pieces if RNA- allows it to affect different organisms due to genetic diversity, also makes it hard to create vaccines

23

Influenza Mechanism of transmission

within bird populations, respiratory and fecal-oral route in birds,
animal to human transmission of animal types: direct contact with animal,
human-human transmission of human types: spread through inhalation of virus-containing aerosols and droplets
virus is unstable and inactivated by heat, dryness, pH extremes and detergents

24

Influenza Major sites of colonization

infects local UTR
infects epithelial cells, infects cell receptors with sialic acids
SA-alpha-2,6-Gal preferred by human types
SA-alpha-2,3-Gal preferred by avian types

25

Influenza Major sites of disease – are they the same or different than colonization sites:

local upper respiratory tract infection, may spread to LTR, usually not elsewhere in body

26

Influenza Main diseases

vsymptoms caused by immune response, complications include secondary bacterial infections (by S. pneumoniae, S. aureus, S. pyogenese

27

Influenza Major virulence factors

envelope, ssRNA, capsid proteins

28

Influenza Main disease symptoms

fever, headache, nasal discharge, sore throat, vomiting, diarrhea

29

Influenza Main treatment and control

vaccines

30

Be able to describe the influenza A virus replication cycle, including the role of HA, NA, and replicase

NA: 11 major subtypes of neuraminidase- catalyze break down of glycosides containing neuraminic acid
HA: 18 major subtypes of hemagglutinin- causes hemagglutination- clumping together of RBCs

Initiation of virus infection involves multiple HAs binding to sialic acids
Adhesion to host cell using Has to bind to sialic acids occurs- entry into the host cell;
entry of vRNPs into the nucleus;
transcription and replication of the viral genome;
export of the vRNPs from the nucleus;
and assembly and budding at the host cell plasma membrane.
In order for the virus to be released from the cell, neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins.[

31

5. What is the biological basis for continuing annual influenza outbreaks?

Virus evolution is rapid- antigenic drift
Virus may reassert- antigenic shift

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6. What is the biological basis for pandemics caused by Influenza A virus?

Pigs are susceptible to both human and avian virus strands. They act as an intermediate step in combining avian, human, and swine influenza genetic material. This occurs when pigs become infected with both human and avian virus. The influenza RNA strands reassort while in the pig to form new combinations of avian, swine, and human strands. In turn, these new influenza viruses could possible infect humans and have surface proteins (H and N proteins) not previously seen by the human immune system, creating a pandemic strain that can spread worldwide.

33

Streptococcus pneumoniae Reservoir

humans only

34

Streptococcus pneumoniae Basic biology and contribution of this to disease

: gram positive, encapsulated, circular DNA, has extracellular toxins, surface adhesins

35

Streptococcus pneumoniae Mechanism of transmission

: person-person via resp secretions, aerosols

36

Streptococcus pneumoniae Major sites of colonization

: it is a normal part of the URT flora, but can become pathogenic under immune suppressed conditions using adhesins

37

Streptococcus pneumoniae Major sites of disease – are they the same or different than colonization sites

colonizes UTR- esp nose, but spreads to LRT (lungs- causes pneumonia) and other parts of body such as ear, brain (causes meningitis)

38

Streptococcus pneumoniae Main diseases:

pneumonia (lungs), brain(meningitis

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Streptococcus pneumoniae Major virulence factors

: has anticomplement invasion factors, extracellular matrix degrading protein, surface adhesins, extracellular toxins and enzymes

40

Streptococcus pneumoniae Main disease symptoms

chills, fever, cough. If left untreated can progress to septic shock, acute respirator failure and death

41

Streptococcus pneumoniae Main treatment and control

-antibiotics (however, is resistant to penicillin) macrolides and second generation beta-lactams- resistance is increasing.
-vaccines- PCV- polycalenin conjugated vaccine- improves antibody response

42

What is thought to be the role of biofilm formation and dispersal in colonization and disease caused by Streptococcus pneumoniae?

When S. pneumonia grows in biofilms, genes are specifically expressed that respond to oxidative stress
the host’s polymorphonuclear leukocytes produce an oxidative burst to defend against the invading bacteria, and this response can kill bacteria by damaging their DNA. Competent S. pneumoniae in a biofilm have the survival advantage that they can more easily take up transforming DNA from nearby cells in the biofilm to use for recombinational repair of oxidative damages in their DNA

43

What is the significance of autolysis for the bacterium s. pneumoniae and for the host?

Autolysis releases MAMPs, which activates the immune response, which causes damage

44

What is the basic sequence of events in pneumococcal pneumonia? What type of host response is responsible for much of the symptoms of disease?

UTR damage leads to it being introduced into the LRT which can either result in clearance or bacterial growth and then cell lysis. The capsule around pneumococcus prevents clearance, neutrophils are recruited, inflammation occurs at site of infection, and damage occurs.
Host inflammatory response is responsible for most of symptoms

45

Diphtheria- “the strangling angel”
Diphtheria Reservoir

humans

46

Diphtheria Basic biology and contribution of this to disease

: gram positive, diphtheria exotoxin, rod shaped

47

Diphtheria Mechanism of transmission

human contact through respiratory glands like coughing and sneezing, airborne transmission

48

Diphtheria Major sites of colonization

nasal in URT and skin, can colonize skin lesions of other origins, usually on lower legs, feet or hands

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Diphtheria Major sites of disease – are they the same or different than colonization sites:

URT and skin so same as colonization sites

50

Diphtheria Main disease

: causes thick coating to build up in the throat or nose making it hard to breath or swallow. causes cell death du to protein inactivation. The exotoxin causes damage to nervous system, heart, kidneys, causes enlarged lymph nodes and swollen neck

51

Diphtheria Major virulence factors

diphtheria exotoxin, AB type, receptor is heparin-binding epidermal growth factor precursor- present on many cell types, including heart and nervous tissue cells

52

Diphtheria Main disease symptoms

Causes sore throat, weakness, fever, swollen glands . if not treated, can lead to difficulty breathing, heart failure, paralysis, dath

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Diphtheria Main treatment and control

treatment involves antitoxin (horse antiserum) which has to be given ASAP, A toxoid vaccine is used to treat it- it has formaldehyde which inactivates the toxin, booster shots are needed. antibiotics are also used.

54

10. What is the role of diphtheria toxin in local and systemic disease in diphtheria?

Dtx- It is a secreted exotoxin, AB type, its receptor is a heparin-binding epidermal growth factor precursor which is present on many cell types, including heart and nervous tissue cells. The toxin causes cell death due to protein inactivation, it causes damage to the nervous system, heart and kidneys

55

Mycobacterium tuberculosis Reservoir

humans

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Mycobacterium tuberculosis Basic biology and contribution of this to disease

affects permeability to nutrients, antibiotic resistance and stress tolerance, persists under extreme conditions such as low nutrients, high temps, low pH, desiccation

57

Mycobacterium tuberculosis Mechanism of transmission

human-human, aerosol, small droplets lead to transmission/infection of LRT

58

Mycobacterium tuberculosis Major sites of colonization:

: LRT, intracellular pathogen that infects macrophages

59

Mycobacterium tuberculosis Major sites of disease – are they the same or different than colonization sites

LTR/Lungs (also site of colonization), mostly pulmonary disease but can cause disease in central nerveous system, GI tract, urogenital, military

60

Mycobacterium tuberculosis Main diseases

inflammation

61

Mycobacterium tuberculosis Major virulence factors

gets taken up by alveolar macrophages, prevents pagosome-lysosome fusion, may escape to cytoplasm. Affects macrophage function and survival-may induce or prevent apoptosis or necrosis, inhibit autophagy, inhibit antigen processing and presentation to T-cells, affects interferon-gamma (IFN-y) mediated signaling, delays adaptive immune response

62

Mycobacterium tuberculosis Main disease symptoms

causes fever, fatigure, weight loss, cough, significant damage to lung tissue

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Mycobacterium tuberculosis Main treatment and control (if applicable):

-Public health measures
-Vaccine- BCG- effective in preventing disseminated TB in infants, variable effectiveness in adolescents/adults.
-New vaccine development is ongoing- BCG boosters, vaccines that recognize dormant cell antigens
drug-treatment regimen- directly observed treatment- certain meds daily for 2 months, and then followed by certain others daily for 4 months.

64

Be able to describe the unique features of the mycobacterial cell wall and their impact on bacterial biology and disease.

Its cell wall has mycolic acid- makes the pathogen more resistant to chemical damage and limits the effectiveness of hydrophilic antibiotics and biocides. Mycolic acids allow bacterium to grow inside macrophages, hiding it from the host immune system, so mycolate biosynthesis is crucial for survival and pathogenesis of M. tuberculosis

65

Be able to describe the process involved in granuloma formation and the role of the granuloma in tuberculosis latency and disease.

1)stage 1: Mtb enters host, multiplies, delays host adaptive immune response, infects macrophages,
2) establishment of granuloma: promotes migration of macrophages, and causes aggregates of immune cells to form around the site of infection= granuloma formation,
3)stabilization: causes t-cell response, granuloma attracts other immune cells, causes differentiation of macrophages into epithelioid cells, giant cells, foamy macrophages- several types of granulomas may form,
4)latency: solid granulomas form that contain the pathogen- latent TB- live bacteria but no symptoms of disease (so not contagious), can persist for decades
5) progression to active disease: triggers are not well understood but caseous (cheese-like, soft) granulomas develop-central area of necrotic cell debris, these “cavitate”-open into lung spaces which causes dissemination to new sites or to new hosts

66

What is some evidence that the bacterium actively contributes to granuloma formation and caseation?

Scout hypothesis- active Mtb goes and activates other dormant Mtb, which then become scouts themselves and go and activate other dormant Mtb, contributing to granuloma formation.
Caseation: bacterial lipid vesicles induce foamy cholesterol rich macrophages, these cells burst and provide the nutrients for Mtb to grow extracellularly, and the cell debris form the caseum

67

What is the nature of the current tuberculosis vaccine?

Vaccine is BCG- 80% effective in preventing disseminated TB in infants, variable effectiveness in adolescents/adults
New vaccine development is ongoing- BCG boosters, vaccines that recognize dormant cell antigens
Currently there is a drug treatment regimen- isonized/rifampin etc daily for 2 months followed by isoniazid/rifampin daily for 4 months
-slowly becoming resistant

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Aspergillus fumigatus Reservoir

environment- soil or decaying vegitation

69

Aspergillus fumigatus Basic biology and contribution of this to disease

: opportunistic pathogen, has aerial hyphae (tree-like), hyphae produces spores

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Aspergillus fumigatus Mechanism of transmission

air

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Aspergillus fumigatus Major sites of colonization:

lungs, LTR

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Aspergillus fumigatus Major sites of disease – are they the same or different than colonization sites

LTR- same

73

Aspergillus fumigatus Main diseases

: allergic bronchopulmonary aspergillosis in people with asthma or cystic fibrosis- hypersensitive response, invasive aspergillosis in people with leukemia, organ transplant patients on prolonged corticosteroid treatment, people with HIV, people with genetic immune disorders

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Aspergillus fumigatus Major virulence factors

melanin, proteases, siderophores (binds and transports iron), gliotoxin

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Aspergillus fumigatus Main disease symptoms

allergic bronchopulmonary aspergillosis- wheezing, difficulty exercising, coughing, diagnosed by high levels of IgE, positive aspergillus skin test, Aspergillus-specific Ig
Invasive aspergillosis: fever, chest pain, coughing

76

Aspergillus fumigatus Main treatment and control

allergic bronchopulmonary aspergillosis: avoidance, antifungals and corticosteroids (supress inflammation)
Invasive aspergillosis: antifungals but not immunosuppressives

77

What is a unique feature of most systemic primary fungal pathogens?**

they stress the immune system
They are geographically restricted to one region of earth

78

What is the natural lifecycle of Aspergillus fumigatus and how might this contribute to human disease?

Hyphae release spores (conidia), they get into the body and germinate into hyphae which grow and spread. They spores are very small so easily get into the lungs, they are thermoresistant, and can easily survive in the body.
So immune compromised individuals fail to clear A. fumigatus

79

17. What types of occurrences predispose people to invasive Aspergillus infections

Immune compromised people, people with leukemia, organ transplant patients, patients on prolonged corticosteroid treatment, people with HIV, people with genetic immune disorders

80

1. HIV the basics characteristics of the microbes:

ssRNA-RT, 2 copies of single stranded + RNA, 9 genes enclosed by concial capsid, RNA bound to nucleocapsid protein, encodes reverse transcriptase, protease, ribonuclease and integrase

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2. HIV types of disease they cause

aids

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3. HIV major virulence factors

reverse transcriptase, protease, ribonuclease and integrase, infects CD4+ t lymphocytes, macrophages, mlymph node follicular dendritic cells, Langerhans cells

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4. Why was the AIDS epidemic such a shock to our society? What has been the human impact? A sentence or so would sum it up. You do not need to know exact numbers but roughly how many are HIV+, in US, in world

It suddenly appeared in the 80s
1.1 million people in US were living with HIV/AIDS (2015)
more prevalent in male-to-male sexual contact, especially in gay black men-most at risk
36.7 million people in world currently living with HIV/AIDS

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5. What is striking about the epidemiology of people who are diagnosed with HIV infections and then go on to AIDS?

AIDS defining conditions:
Can lead to infection, or carconomas (cancer in epithelial cells)
Infections: can be fungal, viral, parasitic or bacterial (Mtb, salmonella)
Carcinoma: invasive cervical (HPV), lymphoma,
By leading to the destruction and/or functional impairment of cells of the immune system, notably CD4+ T cells, HIV progressively destroys the body's ability to fight infections and certain cancers.
An HIV-infected person is diagnosed with AIDS when his or her immune system is seriously compromised and manifestations of HIV infection are severe.

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6. What are the three modes of person-to-person transmission? HIV

Sexual contact-homosexuals (MSM) and heterosexuals
Parenteral transmission: hemophiliacs, accidental needle sticks
Vertical transmission: mother to child during delivery

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7. What type of virus is Human Immunodeficiency Virus and the basics about its life cycle. If you see a diagram of a virus infecting a cell-know the steps


Infects CD+4 positive cells
CD4+ T cell lmphocyts
Macrophages
Lymph node follicular dendritic cells
Langerhans cels

Binding of CD4 by gp120
Entry into cell by fusion requires gp41 and co-receptos-CCR and CXCR (important!)
Envelope is lost and RNA is uncoated
DNA made from RNA using reverse transcriptase
DNA and integrase migrate to nucleus forming a provirus by integrating viral DNA to host DNA

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8. Make sure you know the three categories of HIV genes.

Category A: A1-A3-acute and asymptomatic HIV infection and persistent generalizes lymphadenopathy (disease affecting lymph nodes)
Category B: B1-B3-symptomatic but not conditions in C
Category C: C1-C3 AIDS defining conditions, severely symptomatic
AIDS: A3, B3 or C1-3
Acute phase has high level of viral production and mononucleosis-like symptoms like fever, sore throat, rash, malaise, lymphadenopathy, diarrhea

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9. What are the major structural genes in HIV, to what do they bind on host cells, and what type of cells? What role does the co-receptor play?

3 genes: gag, pol, and env (glycoprotein complex that allows virus to attach to and fuse with target cell to initiate infectious cycle) are the structural genes needed to directly new virus particles.
bind CCR co-receptor
The remaining genes are regulatory genes for proteins that control the ability of HIV to infect cells, produce new copies of virus/replicate, or cause disease
Encode reverse transcriptase, protease, ribonuclease and integrase

89

10. What are the roles of the non-structural genes in HIV

The nonstructural genes are regulatory genes for proteins that control the ability of HIV to infect cells, produce new copies of virus/replicate, or cause disease- reverse transcriptase and integrase are esp important

90

11. What is the recent-and surprising finding about HIV infection in CD4+ T cells how does this relate to the pathogenesis (or lack of) with SIV infections?

There is latency of HIV in resting CD4+ cells, infections in hematopoietic stem cells which explains why they are so hard to cue
There is latency of HIV in resting CD4+ cells, infections in hematopoietic stem cells which explains why they are so hard to cue
SIV infects African non-human primates, and likely transferred to humans through meat
Unlike HIV-1 and HIV-2 infections in humans, SIV infections in their natural African simian non-human hosts appear in many cases to be non-pathogenic due to evolutionary adaptation of the hosts to the virus. Extensive studies in sooty mangabeys have established that SIVsmm infection does not cause any disease in these African primates, despite high levels of circulating virus. However, if the virus infects an Asian or Indian rhesus macaque, these non-African simian primates will also develop simian AIDS (SAIDS), as they, like humans (despite being an African-origin simian primate species), have not had a prolonged history with the virus

91

12. What role does the GALT (Gut-Associated Lymphoid Tissue play)? Why is it nearly impossible to eradicate HIV from an individual and from populations?

Has a high concentration of CD4+ t cells which HIV infects, and virally suppressed HIV patients have persistant HIV infection in the gut t cells
If treatment for HIV is discontinued, the GALT refuels rebound viremia, providing evidence that gut is a HIV reservoir

92

13. What are the stages of HIV/AIDs? What defines AIDs and to what do patients ultimately succumb?

Recent findings on pathogenesis: HIV infects T cells, CD4 T cell death (pyropoptosis) which releases pro-inflammatory cytokines and cellular contents, causes inflammation which recruits healthy CD4T cells to the site, allowing them to get infected and the cycle to continue
So AIDS: HIV causes compromised immune system, allowing different fungal, bacterial, viral, parasitic infections and cancers to take advantage and occurr simultaneously

93

14. What are the prime targets of HAART? What is PrEP?

HAART: antiretroviral therapy- suppress HIV replication target reverse transcriptase and protease to delay disease progression- entry inhibitors
PrEP: pre-exposure prophylaxis- the taking of a prescription drug as a means of preventing HIV infection in an HIV negative person

94

Symptoms of malaria

headache, chills, sweating, fever, fatigue, pain, back pain, dry cough, enlarged spleen, nausea, vomiting

95

1. Make sure you know the basic phylogeny of this group, domain, phyla and main characteristics of plasmodium spp

Domain: Eukaryote
Phylum: apicomplexa
Main characteristics:
-obligate parasite
-non-motile in adult stages
-absorb soluble food across membranes
-sporozites (spore like stage in life cycle) function in transmission/infection
-contain apicoplasts which are degenerate chloroplasts, lack pigment and photosynthetic ability, contain own genome and express a few genes, carry out fatty acid, isoprenoid, and heme biosynthesis

96

2. What is the general status of malaria in the world? What has changed recently?

Global malaria increased by 5 million cases from 2015-2016, first time since 2000 that there has been an increase since we have backed off pressure for curing malaria. There is less acess to care for some populations, and spread of drug-resistance

97

3. What microbe causes malaria and which species is the biggest problem? Why is there a difference between the severity of infections caused by the different species?

Causative agent: plasmodium spp, obligate parasite
Is an apicomplexan which have a group of organelles found at one end called th apical end of the organism
6 species affect humans- 4 biggest threats, differ morphologically and in their preference for age of RBCs
-P. falciparum has no preference so is the biggest threat
-P. vivax and P. ovale like young RBCs
-P. malariae like old RBCs

98

4. What is the role of the insect vs. human being in the plasmoidium spp cycle?

Requires development in both insect and human
sexual occurs in mosquito

99

a. Where does sexual reproduction occur of plasmodium

In mosquito –vector is female anopheles mosquito- means good for nothing,

100

b. At which stage is in infectious

? Becomes infectious when the plasmodium gametocyte is fertilized into a zygot and it swims to the salivary glands, which is where it becomes infective

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5. Know the vector/transmission, target cells or anatomical area affected, and cause of pathology (why it causes problems), and impact.

Vector: female anopheles mosquito, target cells

102

a. What’s happening in the liver? Plasmodium spp

They access the liver by having proteins punch holes in the membrane, they traverse though cells by forming a vacuole- crosses sinusoidal barrier. They interact with liver cells and go into invasive mode, and the sporozoite transforms into merozioite (capable of sexual or asexual reproduction)

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b. What’s happening the RBCs? plasmodium/ malaria

The parasite renovates host cell by remodeling hundreds of proteins, exports these proteins from vacuole to different locations within RBC
Net effect:
-RBC tougher- can withstand parasite growth
-Heme and other nutrients become available so parasite can grow
-can switch expression of antigens on infected RBC so no longer recognized by antibodies-immune evasion
Sticky RBCs can also attach to vessels and each other and cause blockages

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c. What is schizogony?

in the plasmodium’s blood-stage schizogony, the nuclear membrane divides to separate daughter genomes and the cell does not divide until several cycles of mitosis have produced a multinuclear cell
Schizogony is the process of asexual reproduction during which the nucleus undergoes division preceding cell division. Schizogony produces daughter cells known as merozoites, which can develop in to gametocytes or enter new host cells and undergo another cycle of schizogony.
Asexual reproduction

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6. What causes symptoms and why are they cyclical in nature? What causes complicated malaria?

Merozoites stick to RBCs, apical organelle causes invagination and formation of vacuole, becomes young trophozoite (growing stage in life cycle, absorb nutrients from host). They feed on erytheocyte (RBC without nucleus- transport Oxygen and CO2) content and digest heme, forming food vacuoles. The deformed RBCs form knobs which makes them sticky. The bactierum needs access to nutrients as they consume a lot of glucose for energy. It enters the erythocytic schizogony stage. The knobs allow sequestration of infected cells. The RBCs burst and release merozoites, release pyrogens (induce fever). The merozites go and infect new cells.
When many cells burst at once, causes many symptoms, which is why this is cyclical- the cells get infected, all burst inducing symptoms, new cells get infected and then all burst at the same time, and so on

106

7. What is the relationship to sickle cell anemia and the Duffy antigen and human evolution?

Duffy is the antigen/receptor, located on RBCs that is important in plasmodium entry to RBC- missing on some people
Some Africans are Duffy ngative
People who have O blood group are at the most advantage since it is least adhesive on group O
Most adhesive- group A and/or B
Sickle cell anemia- even people who are heterozygous for HBB (hemoglobin in humans) gene are sickle cell resistant
People develop sickle-cell disease, a condition in which the red blood cells are abnormally shaped, if they inherit two faulty copies of the gene for the oxygen-carrying protein haemoglobin. The faulty gene persists because even carrying one copy of it confers some resistance to malaria.

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8. What are three ways “we” are trying to control malaria

1) Control vector
2) Prophylactic treatment (prevention)
3) Treat symptoms
Drugs:
Chloroquine- enters RBS and blocks biocrystallization of heme- some resistance in some geographic areas, drug combos required
Paraquine- effective against liver stage, binds plasmodial DNA
Antimalarial drugs: drugs which kill P. Vivax and P. falciparum and used for prophylaxis and treatment of malaria

108

1. What are the basic characteristics of Listeria monocytogenes

Intracellular (facultative) pathogen
Food born pathogen
Systemic and neurological pathogen, opportunistic
Gram-positive, firmicute, rod-shaped, psychrotolerant- optimal growth 30-37 degrees C, gros from 1-45 degrees C, salt tolerant, acid tolerant pH4.5
Ubiquitous in environment, mostly sensitive to antibiotics, requires aa and vitamins for growth
16 variations (serovars) based on O (somatic) and H (flagellar)
Uses aipper mechanism to get into cell, replicates, avoids host response

109

listeria monocytogens what type of diseases do they cause, for whom is it a major concern

Healthy people mostly not affected0 disease 1-7 days after ingestion, slight fever, abdominal cramps, diarrhea
In sensitive people, low infectious dose can cause GI symptoms, then septicemia, meningitis, encephalitis, endocarditis

110

3. Why has there been so much emphasis on studying listeria monocytogens

Because it is a rare but important foodborne pathogen that can have serious complications
Psychrotolerant- can grow in refrigerator, can live in water, plant matter, soil, animals,
Associated with cheese, unpasturized milk, deli foods

111

4. What are the major virulence factors Listeria monocytogenes?

inlA and InlB- host cell invasion, hly- pore-forming cytolysin needed for phagosome lysis
prfA needed for expression of virulence genes

112

a. Specifically know the roles of Internalins, Listerolysins (LLOs), Phospholipases in Listeria monocytogenes

Has internalins: cell attachment factors- internal uptake and internal survival
Has listeriolysin and 2 phospholipases: are hemolysins (destroys RBCs and liberates heme), they dissolve vacuole (single and double vacuole membrane) they are in for entry

113

5. How do they promote their own uptake, escape into the cytoplasm, survival within cells, and spread from cell to cell Listeria monocytogenes?

Use zipper mechanism to promote uptake, attach to cells and allow internal uptake and survival using internalins
Take control of many aspects of host- histone modifications, host immune response, host stress response
Adapt to host environment, able to grow at 4 degrees C
Use ActA to spread from cell to cell
Use InlA and InlB to promote uptake

114

6. What are roles of ActA and PrfA?

ActA- mediates actin mediated intracellular and intercellular motility
PrfA- regulates virulence genes- required for their expression

115


a. What signals PrfA to turn on genes

At low temps, ribosomes can’t bind the RBS, but at high temps, they can, which turns on transcription of PrfA, and turns on virulence gene expression

116

hat are some examples of how Listeria controls or effects the host

It inhibits maturation of phagosome, affects death of that cell by controlling apoptosis, affects death of cell by controlling pyropotosis
Have mechanisms to deal with life in GI tract: can enter vili
Can control host transcription and inflammation- controlling NF-kB realted to promoting inflammation, can induce histone modification, innate response, and interferon response
Has riboswitches and miniproteins for antibody efflux and host stress response
Control host innate response and affects adaptive response

117

Diseases caused by listeria

neonatal disease- early onset- granulomatous infantiseptica- acquired in utero, disseminated (spread) abscesses (swollen) and granulomas. Late onset acquired after birth- meningitis or meningeocephalitis
Healthy adults- influenza like illness with or without gastroenteritis
Pregnant women or immune suppressed- bacteremia, disseminated disease (spreads) or septicemia (blood poisoning)

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1. What are the natural hosts of B. anthracis and how do they come in contact with the bacteria, in what form is the bacterium infectious?

Natural hosts are herbivores, present in soil so herbivores come into contact with it while grazing
Sporozoite infectious- target host, when they germinate and grow is when they become infectious

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What is the importance of the spores in Bacillus anthracis life cycle

Sporulation is required part of life-cycle, not just for survival, spores are a means of transport

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3. Why is Bacillus anthracis considered a true and obligate pathogen

It infects almost all mammals=true pathogen
Obligate pathogen= has to cause disease to be transmitted- need this

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4. What are the three diseases in human beings by Bacillus anthracis -what happens in each?

Cutaneous anthrax: spores enter though breaks in the skin, germinate and grow, causes gelatinous edema, without treatment the infection can spread and cause lethal septicemia
-Gastrointestinal anthrax: caused by ingestion of spores from undercooked food similar to cutaneous anthrax except site of infection is intestinal tract. Normally not diagnosed due to hidden lesion, rare but almost always fatal
-Inhalation anthrax: spores enter lungs- 1 day to 6 week incubation period. Under natural infection spores are inhaled from animals hides or other tissue. Symptoms of malaise, fever cough and muscle aches. Abrupt onset of high fever and chest pain in 2 to 3 days and progresses rapidly to systemic infection with hemorrhaging. Inhalation anthrax is rapidly fatal without treatment and if not diagnosed early has high morbidity even with treatment

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Cutaneous anthrax

spores enter though breaks in the skin, germinate and grow, causes gelatinous edema, without treatment the infection can spread and cause lethal septicemia (blood poisoning)

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Gastrointestinal anthrax

caused by ingestion of spores from undercooked food similar to cutaneous anthrax except site of infection is intestinal tract. Normally not diagnosed due to hidden lesion, rare but almost always fatal

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Inhalation anthrax

spores enter lungs- 1 day to 6 week incubation period. Under natural infection spores are inhaled from animals hides or other tissue. Symptoms of malaise, fever cough and muscle aches. Abrupt onset of high fever and chest pain in 2 to 3 days and progresses rapidly to systemic infection with hemorrhaging (escape of blood from ruptured blood vessel). Inhalation anthrax is rapidly fatal without treatment and if not diagnosed early has high morbidity even with treatment

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5. Where are anthrax unique genes located? How do these relate to B. cereus and how does that complicate diagnosis?

Closely related to B. cereus
Unique genes are on pXO1 and pXO2 and 4 lysogenic phage. Mutation in plcR leads to no production of B. cereus associated virulence genes
Closely related to B. cereus, time consuming to figure out which it is- based on biochemical tests

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1. What happens after spores are taken up (the pathogenesis pathway)? anthrax

Spores enter host, are taken up by macrophages or dendritic cells, and taken to lymph nodes.
Spores germinate in macrophages, vegetative bacteria replicate and are released from phagocyte and replicate in lymph nodes.
They spread through the blood, can be very concentrated at time of death
Bacteria multiply extracellularly in later stages of infection

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1. What happens after spores are taken up (the pathogenesis pathway)? anthrax

Spores enter host, are taken up by macrophages or dendritic cells, and taken to lymph nodes.
Spores germinate in macrophages, vegetative bacteria replicate and are released from phagocyte and replicate in lymph nodes.
They spread through the blood, can be very concentrated at time of death
Bacteria multiply extracellularly in later stages of infection

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6. Be sure to know the main virulence factors of B. anthrax

Capsule: polyglutamic acid (polymer of glutamate), gives microbe a wet mucoid appearance on plates, mutants unable to make the capsule can’t cause disease- so required for pathogenesis, protects microbe against phagocytosis- important early on, capsule only made under a 5% CO2 atmosphere.

Toxins: 3 components make 2 toxins of AB type

- Protective antigen (PA),- B component binds to 2 receptors present on many host cell types, protective for toxin, elicits immune response, no toxic effect on host cell

lethal factor (LF) plus PA= LT; LF is protease- a Zn dependent metalloprotease, disrupts cell function, attacking specific kinases in the cell, prevents interaction with signaling pathways, blocks signals that would normally recruit immune cells to fights the infection, macrophages are a target of lethal toxin since they produce shock-inducing cytotoxins and may rupture, the flood of cytokines are the cause of morbidity

-edema factor (EF) plus PA= ET; EF has adenylate cyclase activity, making cAMP from ATP, causes changes in membrane permeability and an efflux of water out of the cell, also depletes ATP in neutrophils and macrophages

Toxins and capsule are regulated by AtcRA, which responds to temperature and CO2 concentration

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a. What are the activities of PA, LT and EF.

Protective antigen (PA),- B component binds to 2 receptors present on many host cell types, protective for toxin, elicits immune response, no toxic effect on host cell

lethal factor (LF) plus PA= LT; LF is protease- a Zn dependent metalloprotease, disrupts cell function, attacking specific kinases in the cell, prevents interaction with signaling pathways, blocks signals that would normally recruit immune cells to fights the infection, macrophages are a target of lethal toxin since they produce shock-inducing cytotoxins and may rupture, the flood of cytokines are the cause of morbidity

-edema factor (EF) plus PA= ET; EF has adenylate cyclase activity, making cAMP from ATP, causes changes in membrane permeability and an efflux of water out of the cell, also depletes ATP in neutrophils and macrophages

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b. What is the hypothesis for how vegetative cells are able to get a foot -hold and start growing anthrax

First LT and ET affect immune cells to clear body of response, this increases apoptosis, increases cytokine production and inhibits phagocytosis.
Second, vegetative cells can grow unimpeded
Third, toxin production by vegetative cells affects many cell types to produce lethal symptoms

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7. Treatment B. anthracis

susceptible to many antibiotics, with penicillin being a good choice, Cipro found widespread usage as a prophylactic treatment.
Early treatment is critical: after a high concentration of toxin and microbes build up in the body, antibiotics will do little to prevent death.
Early symptoms are often misdiagnosed. However, recent treatment attempts have shown that antibiotic therapy can sometimes be effective in humans even if started after symptoms appear

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8. For anthrax How has the vaccine strain been modified-how is it like the virulent strain?

Developed by Pastuer in 19th century
Modern animal vaccines have a nonencapsulated strain that is still able to produce toxin and the toxin made stimulates the induction of antibodies directed against it
Antibodies made are very protective
A component vaccine for humans is available that consists of protective antigen