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Pathogenic Microbiology > Lecture 4 > Flashcards

Lecture 4 Flashcards

1
Q

What is the first line of defense for the immune system?

A 
Physical barriers (skin) that viruses, bacteria must cross
Mucous membranes that line digestive, respiratory, and reproductive tracts
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2
Q

What is the second line of defense for the immune system?

A

Innate immune system (germline-encoded receptors) – no adaptation to specific pathogens
Cellular barriers: Macrophages, neutrophils, natural killer (NK) cells
Cytokines – hormone-like proteins that mediate inflammation, and Complement proteins
Chemokines – chemotactic cytokines

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3
Q

What is the third line of defense for the immune system?

A

Adaptive immune system adapts to defend against specific pathogens using variable receptors
B cells make antibodies that vary – can make an antibody specific for any new antigen
T-cells mediates cellular responses using variable receptors (T-cell receptors; TCRs)

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4
Q

What are chemokines?

A

particular kind of cytokines that have chemical defense with chemotactic properties

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5
Q

What constitutes the compliment system?

A

consist of circulating proteins and enzymes in the blood that are inactive unless a pathogen is encountered

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6
Q

What is mucus?

A

vicus fluid that helps trap microbes and particles to prevent them from spreading everywhere in the body

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7
Q

What do skin secretion provide as a physical barrier?

A

Provide an environment that is often hostile to microbes (a pH between 3 and 5, which is acidic enough to prevent colonization of many microbes)
proteins such as lysozyme digest cell walls of many bacteria

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8
Q

What are the characteristics of innate immunity?

A

rapid receptor binding
does not generate immunologic memory
dependent upon germline encoded receptors recognizing structures common to many pathogens

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9
Q

What are the 3 functions mediated by innate immunity?

A
  1. phagocytic receptors to stimulate pathogen uptake
  2. chemotactic receptors that guide phagocytes to site of infection
  3. stimulates the production of effector molecules and cytokines that induce innate responses, and also influence downstream adaptive immune responses
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10
Q

What are the chemical barriers of inflammatory response?

A

Tissue damage by a wound or by invading pathogen leads to inflammatory response

  • Leukocytes
  • invading microbe
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11
Q

What are the capillary barriers of inflammatory response?

A

Redness of tissue increase
Tissue temperature increase
Capillary permeability Influx of fluids increases
Influx of phagocytes into tissues

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12
Q

What is fever?

A

a systemic inflammatory response triggered by substances released by macrophages and by toxins from pathogens

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13
Q

What is septic shock?

A

a life-threatening condition caused by an overwhelming inflammatory response

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14
Q

What can leukocytes produce in immune response?

A

Neutrophils and macrophages can produce oxygen reactive species that can destroy the bacterial protein/membrane, and are part of signaling inside the cell to fight infection

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15
Q

What is PAMP?

A

express repeating patterns of molecular structures recognized by pattern recognition receptors (PRR) on effector cells via the innate immune system

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16
Q

What are some Examples of Pattern Recognition Receptors?

A 
Mannose-Binding Lectin (MBL)
Macrophage Mannose Receptor
Scavenger Receptors
Toll-like Receptors (TLRs); e.g., fro LPS recognition
Nod-like Receptors (NLRs)
RNA helicases (RIG-I, MDA-5)
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17
Q

What are NLRs?

A

NLRs Are Cytoplasmic Bacterial Sensors that Activate IL-1B “Inflammasomes”

  • Typically multi-protein made of Capse-1 interacting with ASC and NAPL3
  • Once activated, and NMR recognizes specific path leading to the protection of cytokine Beta
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18
Q

What is Pyrosis?

A

form of cell death that is inflammation mediated via Capase-1

19
Q

What are the characteristics of Cytokines?

A

induce response by binding to specific receptors
can function in autocrine or paracrine manner
cytokines (and their receptors) are clustered according to structural similarities and their expressions are tightly regulated
a number of critical cytokines are secreted by macrophages following activation to stimulate inflammation and phagocytosis/killing

20
Q

What are the characteristics of Chemokines?

A

diverse family of chemotactic cytokines that induces directed chemotaxis of cells
all related in amino acid structure
certain chemokines induce cell activation in addition to cell recruitment
promiscuous in receptor usage, each can bind more than one receptor, and likewise, receptors are promiscuous

21
Q

What are the steps of bioassay of cytokines in vitro?

A
  1. activation of macrophages in vitro
  2. cytokine secretion
  3. remove cytokine containing supernatant
  4. test for the characteristic and effect of other cells (IL-1 –> induces proliferation of thymocytes)
  5. include an antibody that blocks interleukin-1
22
Q

How are TNFa, IFNaB and IL-1B produced?

A

Activation of TLRs, NLRs and RIG-I type molecules results in production of TNFa, IFNaB and IL-1B

23
Q

What is the importance of inflammatory cytokines?

A

TNFa, IFNaB and IL-1B are critical for host defense

24
Q

What is the role of TNFa?

A

activates macrophage and PMN phagocytosis and killing

25
What is the role of IFNaB?
activates anti-viral mechanisms
26
What is the role of IL-1?
stimulates inflammation and fever
27
Describe the innate viral interfering activity discovered in cell culture (1950)
1. When you infect these cells initially, they release something that has anti-viral immunity, 2. and when they then took these cells and put it into cultural media added it to new cells 3. and now they couldn’t infect these cells anymore. They realized that they produce molecules called interferons which has the ability to stop viral replication
28
What are the characteristics of immune IFN/Type 2 IFN?
a.k.a IFN-y critical for adaptive Immune, and only 1 member made by T-cells; NK cells
29
What are the characteristics of Type 1 IFN?
Fibroblast IFN, a.k.a IFN-b: - very potent - made by all cells - only one member Leukocyte IFNs, a.k.a IFN-a’s: -most prevalent -made by all cells > 10 members
30
What are the steps of IFN-alpha and beta in virus-infected host cells?
1. induce resistance to viral replication in all cells 2. increase MHC class 1 expression and antigen presentation in all cells 3. activate NK cells to kill virus-infected cells
31
How does Natural killer NK cells work?
First identified by having the ability to lytically kill certain tumor cell lines without prior sensitization Kill target cell by release of cytotoxic granules containing granzymes, and perforin which penetrate target cell membrane and induce programmed cell death Can mediate Antibody-Dependent Cellular Cytotoxicity (ADCC) Kill virally-infected cells with missing MHC class I
32
How are NK cells activated, and what happens once they are activated?
Activated by IFN-a/b or IL-12 (produced rapidly by activated macrophages) Activated NK cells secrete IFNy, acts on macrophages to increase microbial phagocytosis and killing -Fc receptors on NK cells recognized the antibody to be killed
33
What are the roles of he inhibitory and activating NK cell receptors?
Inhibitory Receptors: - inhibit cytotoxicity to prevent killing of normal host cells - specific for MHC class I alleles - binding to class I, and sends inhibitory signal to NK cells Activating Receptors: recognize carbohydrate structures on self proteins
34
Describe the NK cell cytotoxicity in tumor cells.
``` In tumor cells or virus-infected cells, reduced expression or alteration of MHC molecules interrupts the inhibitory signals, allowing activation of NK cells and lysis of target cells. Normal cells are not killed because inhibitory signals from MHC class I molecules override activating signals ```
35
What are dendritic cells?
DCs link innate and adaptive immunity When inactive/immature - they are highly phagocytic, but not good stimulators of adaptive T-cell responses Once they are activated by pathogens and activation of their PRRs - they secrete cytokines to initiate inflammation and then they migrate to lymph nodes and mature. they make excellent APC but cannot phagocytose
36
What are the characteristics of immature DC?
principal function is antigen capture highly phagocytic low T-cell stimulating potential low MHC class II low CD80/86 expression
37
What are the characteristics of mature DC?
principal function is antigen presentation low phagocytic capacity high T-cell stimulating potential high MHC class II high CD80/86 expression
38
What is the compliment system?
proteins that can recognize some pathogen surfaces intrinsically, or can recognize Ab molecules bound to pathogen-infected cells
39
What occurs upon the activation of the complement system?
The recognition by and activation of the complement system results in pore-forming complexes being created on infected cells which results in lysis of infected cells Other byproducts of complement activation are the recruitment of more immune effector cells by the C3a and C5a components
40
What are the 3 ways the complement system is activated?
1. Classical – antibody binds to the pathogen forming a complex which is recognized by complement system to be attacked. Found in vertebrates 2. Alternative – one of the components of complement system binds directly the surface of the pathogen 3. MB-lectin – lectin binds on surface of the pathogen, then the complement system binds the MBL and get activated
41
What is the role of MBL?
MBL discriminates self carbohydrates from non-self carbohydrates by recognition of a particular pattern of sugar residues
42
What are the steps of activating the complement system?
1. C3 can binds to surface of bacteria directly 2. Complement protein B comes and binds to C3b, then protein D cleaves B to yield C3Bb 3. Convertase can covert another C3b protein to create more C3b molecules, and it can also cleaved another complement protein called C5 to create C5A and C5B 4. C5b has c6,7,8, and c9….all together produce MAC-C-channel causes the whole in the bacteria
43
What is a lysozymes?
an enzyme that digests the cell walls of many bacteria

Pathogenic Microbiology (12 decks)

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