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Flashcards in Immunity to Infection Deck (53):
1

How would you classify the following:

Streptococcus pneumoniae
Clostridium tetani
Tryanosoma brucei
Pneumocytis jrovecii

What disease may they cause?

extracellular:

bacteria (gram pos. and neg)
parasites
fungi

pneumonia
tetanus
sleeping sickness
pneumocytsis pneumonia

2

How would you classify the following:

Mycobacterium leprae
Leismania denovani
Pasmodium falciparum

What disease may they cause?

Intracellular:

bacteria
parasites

Leprosy, leismaniasis, malaria

3

How would you classify the following:

Variola
Influenza
Varicella

What disease may they cause?

viruses (intracellular)

smallpox
flu
chickenpox

4

How would you classify the following:

Ascaris
Schistosoma

parasitic worms

5

Under most circumstances, microorganisms cannot cause disease unless there exists a breach in the protective barriers that normally prevent the pathogen from entering a foreign ecological niche (our body). The most notable barriers to infection have both Physical and Chemical
properties.

Describe physical barriers.

Skin:
Thick, multilayered
Low moisture
Acidic

(physical)
The skin serves as a major barrier to a variety of noxious insults, including infection (bacterial, fungal, parasitic). The multiple layers of keratinocytes act as an
impasse to pathogen invasion.
Thus, infection via skin first
requires direct tissue damage.

(physical)
Perhaps even more so than skin, mucosal surfaces are a primary site of infection (viral,
bacterial, fungal, parasitic).
Some mucosal surfaces (GI tract) secrete a thick mucus layer that acts as a physical barrier to cell surface interaction by microbes.
The movement of the ciliated epithelium of the lung expels particulate matter and foreign
material and prevents microorganisms from establishing an infectious niche.
Resistance to invading pathogens at mucosal surfaces is partially imparted by antibodymediated processes (e.g. secretory dimeric IgA).

Mucosal Surfaces:
Major site of infection
Mucus secretion (GI)
Ciliated epithelium (Lung)
Secretory IgA

6

Under most circumstances, microorganisms cannot cause disease unless there exists a breach in the protective barriers that normally prevent the pathogen from entering a foreign ecological niche (our body). The most notable barriers to infection have both Physical and Chemical
properties.

Describe chemical barriers.

Lysozyme - secreted in saliva/tears. A potent antimicrobial of Gram positive
(Staphylococcus aureus, Streptococcus pyogenes, Clostridium difficile) and
Gram negative (Salmonella,
Pseudomonas aeruginosa, Escherichia coli) bacteria. Degrades the
peptidoglycan layer that is unique to bacterial surfaces and is required for their survival.

Mostly Gram positive bacteria, some Gram negative. No Others!!

Antimicrobial peptides (AMPs), secreted by epithelial cells and phagocytes (Defensins, Cathelicidins, Histatins) +Defensins and Cathelicidins can act broadly, on bacteria, fungi,
viruses.
+Histatins act dominantly on pathogenic fungi (e.g Cryptococcus neoformans). +All AMPs are believed to function by perturbing pathogen membranes

7

What are Defensins, Cathelicidins and Histatins?

Antimicrobial peptides- small peptides prod. by immune and epithelial cells that bind directly to membrane surface of pathogens. form pore on membrane of pathogen that leads to lysis of that microorganism.

Defensins and Cathelicidins – Broad acting ( can act on bacteria and fungi)

Histatins – Pathogenic fungi (Cryptococcus neoformans)

8

What can kill Cryptococcus neoformans

Histatins

opportunistic pathogen that usually causes disease in already immunocompromised individuals - generally manifests as disease of CNS. colonizes in brain or lung. when it enters infectious niche, histatins-prod to kill it.

9

Which TLR recognizes:

lipoteichoic acid, lipoproteins (GRAM POSITIVE and GRAM NEGATIVE bacteria)

TLR2

10

Which TLR recognizes:

Flagellin (BACTERIAL motility component)

TLR5

11

Which TLR recognizes:

Single-stranded RNA (VIRUSES)

TLR7/8

12

Which TLR recognizes:

lipopolysaccharide - LPS (GRAM NEGATIVE bacteria)

TLR4

13

Which TLR recognizes:

Bacterial/Viral DNA (BOTH bacteria and herpesviruses)

TLR9

14

Which TLR recognizes:

Double-stranded RNA (VIRUSES)

TLR3

15

Which, TLR/NOD recognizes extracellular
bacteria and viral pathogens vs intracellular?

NOD-like receptors – recognition of INTRACELLULAR bacteria

Toll-like receptors – recognition of extracellular
bacteria and viral pathogens

16

Which receptor would likely recognize Salmonella (gram negative, intracellular?

NOD1 – Peptidoglycan of GRAM NEGATIVE intracellular bacteria (eg Salmonella).

17

Which receptor is found highly enriched within cells of the gut?

NOD2 – Peptidoglycan of GRAM POSITIVE/GRAM NEGATIVE intracellular bacteria, AND Mycobacterium tuberculosis). NOD2 is found highly enriched within cells of the gut.

18

Which NOD receptor binds gram negative bacteria, which gram positive?

NOD1 - gram negative
NOD2- gram positive/gram negative

19

Listeria monocytogenes, Mycobacterium tuberculosis both potently induce what receptor?

both potent NOD2 inducers

20

What will a NOD2 mutation possibly induce clinically?

Clinical correlate –NOD2 mutation and Crohn’s disease

-Chronic inflammatory disorder of the GI tract.
-Typically ileal, ilealcolic, and colonic.
-Abdominal pain and diarrhea most common symptoms.
-No cure, treatments aim to alleviate symptoms and promote remission.

-NOD2 – maintains intestinal homeostasis and healthy microbiota.

-NOD2 mutations - Linked to the intestinal permeability and inflammation associated with disease due to improper recognition of bacterial by-products and dysbiosis.

21

Which receptor recognizes β-glucans that comprise the FUNGAL cell wall (e.g. acapsular Cryptococcus neoformans)?

Glucan receptor

22

Which receptor recognizes bacterial cell wall components?

Scavenger receptors – Recognize BACTERIAL cell wall components.

23

Describe the responses that PAMP receptors promote.

**Together, these PAMP receptors promote a number of critical responses including: induction
of inflammatory cytokine secretion, mobilization of immune cells (recruitment of inflammatory monocytes and neutrophils), initiation of adaptive immunity via T cell activation, and promote
bactericidal killing by activation of antibacterial functions [antimicrobial peptide (AMP) production, reactive oxygen species (ROS) production].

24

What kind of bacteria can MAC act on?

The membrane attack complex (MAC). The pore-forming activity of the membrane attack complex is able to act on GRAM NEGATIVE bacteria, but not Gram positive.

FUNGI are also highly resistant to the MAC, but are efficiently opsonized by C3 to
promote phagocytosis.

25

What type of bacteria can be opsonized?

Opsonization with C3 and recognition by the C3 receptor (C3R) can effectively
opsonize GRAM POSITIVE/NEGATIVE and most other foreign pathogens (i.e.
the mechanism is broad and generalizable), which promotes phagocytosis by immune cells.

FUNGI are also highly resistant to the MAC, but are efficiently opsonized by C3 to
promote phagocytosis.

26

How might a complement deficiency affect a patient? Specifically.

Complement deficiencies render patients significantly more susceptible to bacterial infection, in particular meningococci (Neisseria meningiditis) and pneumococci (Streptococcus
pneumonia)

27

What is a respiratory burst? Describe.

C3 coated bacteria are phagocytosed and reside in phagosomal compartments.
The phagosome fuses with lysosomes containing bacterial damaging reactive oxygen species.

Upon induction of phagocytosis by PAMP receptors or complement mediated opsonization, innate immune cells (macrophages and neutrophils) are activated to kill the pathogen. In most circumstances this is facilitated by the production of reactive oxygen species, which consist of peroxides and free radicals that cause
significant damage to the microorganism – known as Respiratory Burst

when respiratory bursts occur they mostly occur through action of NADPH oxidase which is responsible for generating reactive oxygen species that can directly perturb the viability of infectious microbes

28

What migh recurrent infections (Pneumonia, Abscess formation, osteomyelitis, etc.) indicate?

Chronic Granulomatous Disease – Defective enzyme (NADPH oxidase) involved in respiratory burst leads to significant susceptibility to bacterial and fungal infections.

Recurrent infections (Pneumonia, Abscess formation, osteomyelitis, etc.)
Staphylococcus aureus and other catalase positive bacteria are key infectious microorganisms.
Fungal infections, primarily Aspergillus and Candida.

29

What immune function are Type I Interferons specific for? Describe their functions.

Specific anti-viral
Viral single-stranded (TLR7) and double stranded RNA (TLR3) is recognized by TLRs leading
to the induction of Type I interferons

Interferon-α/Interferon-β Act on cells surrounding the infected cell and induce Interferon Stimulated Genes (ISGs) that prevent viral synthesis and contain viral spread.

they increase MHC Class I expression and antigen presentation in all cells. expression of MHC I critical for immune system to recogn. infection by virus. without MHC I cant recognize cell infected by virus.

DC and macrophages also recruit NK cells. (major innate viral eradicator) one of dominant roles is prevent virally infected cells continuing to prod progeny virus

30

How do type I and type II interferons differ?

Type I Interferons differ from Type II interferon (Interferon-γ) in that they are traditionally considered specific to
antiviral immunity. Interferon-γ, on the otherhand, can be induced in response to bacterial and viral pathogens (often associated with Th1
cell-mediated immune responses that lead to significant macrophage
activation).

31

Describe the virus titer and how it changes over days.

Slide 15
see is early on during virus infection in first few days, immediate spike in interferon alpha and beta levels. as result of that spike, increased prod. of major pro inflammatory cytokines and cytokines that active T cells and macrophages like TNF alpha and IL12. response to that induction of type I interferons is this rapid influx of NK cells. this occurs v early on in viral infection and is critical for restricting ability of virus to escalate its titer. titer of virus begins to plateau (due to recogn. and killing of infected cells by NK cells)

as NK cells reach peak, the induction of cytokine recruitment leads to additional recruitment of effector T cells that come in and can further recognize MHC I - critical for most viruses to be eradicated.

alpha defensins- key in functioning as eradication of other microbes.
bc they make this NK cells can behave in anti-microbial function as well
(think of them as major player in VIRAL eradication)

32

Specific antibody directed against all pathogens is crucial to effective protective immunity.
Specific antibodies facilitate:

Opsonization - Extracellular bacteria and Fungi are opsonized by antibodies recognizing microbial cell surface determinants.
extracellular bacteria: Staphylococcus aureus, Vibrio Cholera,
Streptococcus pyogenes, Streptococcus
pneumoniae)

Toxin Neutralization – Specific to bacterial pathogens and not viruses. Antibodies with
specificity to a bacterial-produced toxic factor

Complement Activation and cell lysis by MAC (e.g. Neisseria meningiditis). *Some bacteria are
opsonized less efficiently due to the production of capsular polysaccharides that interfere with C3 recognition

33

What is the significance of Protein A of Staphylococcus aureus?

*Some bacteria produce toxins
that can perturb antibody binding

34

How can the body fight cholera toxin of Vibrio Cholera?

Cholera toxin of Vibrio Cholera can be neutralized by toxin-specific IgA in the gut – the
site of V. cholera infection).

gram neg. extracellular bacterial pathogen
(Toxin Neutralization)

35

How do Th1 cells activate macrophages?

Intracellular bacteria (e.g. Mycobacterium tuberculosis and Listeria monocytogenes).

Th1 cells serve to activate macrophages via the production of Interferon-γ and other pro-inflammatory cytokines

Th1 dep. responses critical for eradicating and inducing macrophages to kill intracellular bacteria

36

How might the following be killed:

Intracellular bacteria (e.g. Mycobacterium tuberculosis and Listeria monocytogenes).

Th1 cells serve to activate macrophages via the production of Interferon-γ and other pro-inflammatory cytokines

Th1 cells that interact w peptide loaded receptors that prod IFNgamma that activates intracellular bacterial immune cells.. respiratory burst

37

Defects in superoxide production leading to ineffective respiratory bursts are known as Chronic Granulomatous Disease. In TB, granuloma formation occurs as well, describe.

leads to infectious condition in lungs. granuloma formation occurs; it is highly dep. on Th1 cells causing induction of macrophage killing of TB, leading to damage w/in central region of tissue, that then leads to granuloma formation.

38

CD8 T cells are important for clearing what type of infection?

Clearance of viral infection is highly dependent on the induction of cytotoxic CD8 T cells in conjunction with antibody and NK cell-mediated responses

39

What TLR would recognize Staphylococcus aureus? (gram positive)

aureus- THICK cell wall. recogn. by TLR2 as a result of being gram positive and having lipoproteins being prod. prod. grape like clusters on gram stains.

40

Parasitic infections are a unique case when it comes to immune-mediated clearance. Describe control of parasitic infections like Schistosoma mansoni.

Control of parasitic infections (e.g. Schistosoma mansoni) can be mediated by complement activation,
but is also mediated by an IgE-dependent process known as antibody dependent cellular
cytotoxicity (ADCC).

During ADCC parasite specific IgE, bound to eosinophils via their Fc regions, recognize the invading parasite and induce eosinophil-dependent killing.

41

In what situation might you have eosinophil dependent killing?

parasitic infections (ADCC)

42

Consider sensitivity to barrier functions, recognition by PAMPs, innate immune cell responses, and the roles of humoral and cell-mediated immunity involved in pathogen clearance.

Influenza virus.

TLR critical to recognition of number of viral pathogens. occurs thru TLR3 and 7. downstream effects are induction of type I interferons which include interferon alpha and interferon beta (these alpha and beta are prod by viral infected cell by recognition by variety of motifs, induce prod. of genes known as interferon stimulated genes or ISG.. these are critical for preventing viral synthesis and ability of virus to spread their cells…specific and defined antiviral mechanism -importance of interferon alpha and beta- info box…events occur that lead to eradication of virus…

expression of MHC I critical for immune system to recogn. infection by virus. without MHC I cant recognize cell infected by virus.

DC and macrophages also recruit NK cells. (major innate viral eradicator) one of dominant roles is prevent virally infected cells continuing to prod progeny virus

43

Consider sensitivity to barrier functions, recognition by PAMPs, innate immune cell responses, and the roles of humoral and cell-mediated immunity involved in pathogen clearance.

Candida albicans, an extracellular fungal pathogen.

AMP- (antimicrobial peptides- small peptides prod. by immune and epithelial cells that bind directly to membrane surface of pathogens. form pore on membrane of pathogen that leads to lysis of that microorganism. antimicrobial peptides, dep. on specific activity have have functions on diff organisms- histatins- specific for individual pathogens, high affinity for pathogenic fungi.)
Histatins – Pathogenic fungi

Defensins and Cathelicidins – Broad acting ( can act on bacteria and fungi)

opsonization
FUNGI are also highly resistant to the MAC, but opsonized by C3.

44

Consider sensitivity to barrier functions, recognition by PAMPs, innate immune cell responses, and the roles of humoral and cell-mediated immunity involved in pathogen clearance.

Staphylococcus aureus, a Gram positive extracellular bacterial pathogen.

(TLR2)
Lysozyme
AMP- Defensins and Cathelicidins – Broad acting ( can act on bacteria and fungi)

NO MAC

opsonization - recognition of conserved motifs on bacteria. Ab binds to these motifs. then bacterium tagged w signature that makes them prone to be taken up by immune cells. bc most phagocytic immune cells have Fc receptors on surface…they recognize Fc region on antibody and it leads to opson-phagocytosis …bacteria taken up into macrophage (in this case) and downstream effects of respiratory bursts and bacteria killing occurs.

45

Consider sensitivity to barrier functions, recognition by PAMPs, innate immune cell responses, and the roles of humoral and cell-mediated immunity involved in pathogen clearance.

Neisseria meningitides, a Gram negative extracellular bacterial pathogen.

TLR 2, TLR4

A. The membrane attack complex (MAC). GRAM NEGATIVE bacteria, but not Gram positive.

lyzozyme (mostly gram positive, so gram negative NO OTHERS)

46

Consider sensitivity to barrier functions, recognition by PAMPs, innate immune cell responses, and the roles of humoral and cell-mediated immunity involved in pathogen clearance.

Vibrio cholera, a Gram negative extracellular bacterial pathogen that produces a potent toxin (Cholera Toxin) during infection of the gut.

toxin neutralization (specific for bacterial pathogens and NOT viruses)
cholera can be neutralized by toxin specific IgA in the gut.

47

Consider sensitivity to barrier functions, recognition by PAMPs, innate immune cell responses, and the roles of humoral and cell-mediated immunity involved in pathogen clearance.

Mycobacterium tuberculosis, an intracellular bacterial pathogen.

NOD2 – Peptidoglycan of GRAM POSITIVE/GRAM NEGATIVE intracellular bacteria, AND Mycobacterium tuberculosis). NOD2 is found highly enriched within cells of the gut.

Th1 cells serve to activate macrophages via the production of Interferon-γ and other pro-inflammatory cytokines

Th1 dep. responses critical for eradicating and inducing macrophages to kill intracellular bacteria

relies on recruitment and induction of Th1 cells that interact w peptide loaded receptors that prod IFNgamma that activates intracellular bacterial immune cells.. respiratory burst… but occurs in a way that allows intracellular recognition of that pathogen.

48

Consider sensitivity to barrier functions, recognition by PAMPs, innate immune cell responses, and the roles of humoral and cell-mediated immunity involved in pathogen clearance.

Schistosoma mansoni, a parasitic trematode.

Parasitic infections are a unique case when it comes to immune-mediated clearance. Control of parasitic infections (e.g. Schistosoma mansoni) can be mediated by complement activation,
but is also mediated by an IgE-dependent process known as antibody dependent cellular
cytotoxicity (ADCC). During ADCC parasite specific IgE, bound to eosinophils via their Fc regions, recognize the invading parasite and induce eosinophil-dependent killing.

49

Toxin neutralization is specific for what type of invasion?

bacterial pathogens NOT viruses

Cholera toxin- can be neutralized by toxin specific IgA in gut

50

Neisseria meningidits is what type of pathogen?

How to kill it?

gram negative, extracellular bacteria

51

Describe the type of pathogen:

Candida albicans
Staphylococcus aureus

Candida albicans, an extracellular fungal pathogen.

Staphylococcus aureus, a Gram positive extracellular bacterial pathogen.

52

Describe the type of pathogen:

Neisseria meningitides
Vibrio cholera

Neisseria meningitides, a Gram negative extracellular bacterial pathogen.

Vibrio cholera, a Gram negative extracellular bacterial pathogen that produces a potent toxin (Cholera Toxin) during infection of the gut.

53

Describe the type of pathogen:

Mycobacterium tuberculosis
Schistosoma mansoni

Mycobacterium tuberculosis, an intracellular bacterial pathogen.

Schistosoma mansoni, a parasitic trematode.