Week 6: Bacterial and Viral Infections Flashcards

1
Q

How are extracellular pathogens eliminated?

A
  1. Innate humoral response complement
  2. Adaptive humoral response antibodies
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2
Q

How are intracellular infections addressed?

A
  1. Pathogen is protected against the humoral response from complement and antibodies
  2. NK cell and cytotoxic T cells can induce apoptosis of infected cell
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3
Q

What are the steps of an acute infection being cleared of adaptive immunity?

A
  1. Microbe colonizes and its number increase as it replicates (Innate detects pathogen)
  2. Pathogen numbers increase producing antigen to initiate adaptive
  3. 4-7 days, effector cells and molecules of the adaptive response start to clear infection
  4. Infection is cleared by antibody and effect cells, and memory cells remain to protect against reinfection
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4
Q

What are the characteristics of bacteria?

A
  1. Prokaryotic
  2. 1 chromosome consisting of circular DNA
  3. Lack membrane enclosed organelles
  4. Cell wal
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5
Q

What does a bacterial cell-wall consist of?

A

Cross linked polysaccharides (peptidoglycan)

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6
Q

What are the major groups of bacteria?

A

Gram positive and negative

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7
Q

What are gram classifications based on?

A
  1. Location and amount go peptidoglycan
  2. Gram staining
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8
Q

What are the characteristics of G+?

A
  1. Thick layer of peptidogylcan
  2. No periplasmic space
  3. Teichoic acid
  4. Non outer membrane
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9
Q

What are the characteristics of G-?

A
  1. Thin layer of peptidoglycan
  2. Periplasmic space
  3. No teichoic acids
  4. Outer phospholipid membrane
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10
Q

What are the immune response of bacterial infection?

A
  1. Physical and chemical barriers to infection
  2. Cellular responses to infection
  3. Activation of adaptive immune responses
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11
Q

What are the cell functions of eliminating bacteria?

A
  1. Complement (alt and lectin)
  2. Phagocytosis by neutrophils and macrophages
  3. Inflammation and acute phase response
  4. DCs take antigen to draining lymph node
  5. T cells -> effector and help B cells with GC response
  6. B cells generate high affinity antibodies that travel to infection site
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12
Q

How do sentinel cells respond to bacteria?

A

Located in tissues they have PRRs (TLRs) that recognize PAMPs on cell walls of bacteria flagellum leading to cell activation

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13
Q

How are DCs the bridge between innate and adaptive immunity?

A
  1. Internalize extracellular antigens using endocytic processes of PRRs, phagocytosis, and mincopinocytosis
  2. Transports antigens to draining lymph node and APC through MHCII
  3. Present antigens from infection site to T cell that can stimulate B cells
  4. T and B cells activated by antigen, expand, and differentiate into effector cells
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14
Q

What are the humoral responses of extracellular bacterial infections?

A
  1. Neutralization
  2. Opsonization
  3. Classical complement activation
  4. Agglutination (aid with clearance)
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15
Q

What are the types of bacterial infections?

A
  1. Toxigenic
  2. Encapsulated
  3. Intracellular
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16
Q

What is a toxigenic bacterial infection?

A
  1. Exotoxins and endotoxins produced by these bacteria play an important role in the pathogenesis of specific diseases
  2. Toxins damage or disrupt the function of host cells
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17
Q

What is encapsulated bacterial infection?

A
  1. Organism evades phagocytosis by coating themselves with polysaccharide
  2. Can be G+ or -
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18
Q

What is intracellular bacterial infection?

A

Able to avoid host defenses by growing inside the cell

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19
Q

What are virulence factors?

A

Microbial component that can damage the host

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20
Q

What is the difference between exo and endotoxins?

A

Exo: Polypeptides secreted by bacteria
Endo: Lipopolysaccaride-protein complexes on the bacterial cell surface

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21
Q

What are the characteristics of exotoxins?

A
  1. Most bac. produces more than 1
  2. Some are superantigens
  3. Targeted by IgG and A
22
Q

What are enterotoxins?

A

Type of exotoxin release by a bacteria that targets the intestine

23
Q

What are the characteristics of endotoxins?

A
  1. Non secreted toxin located on all G- bacteria
  2. Shed when bacteria dies
  3. Recognized by surface TLRs
24
Q

What is exotoxin neutralization?

A
  1. Toxins exert their effects by binding to cell receptors and entering cells and poisoning their host
  2. Ig are able to bind to antigens on toxins and prevent the toxins from binding to the cell surface receptors
  3. IgM, IgG, and IgA
25
Q

What are encapsulated bacteria?

A

Have polysaccharide capsules that help them hide from phagocytic destruction by macrophages and neutrophils

26
Q

Describe the capsules of a bacteria?

A
  1. Viscous and sticky polysaccharides that coat the outside of the bacteria promoting adherence to tissue
  2. Can’t be recognized by phagocytic receptors
27
Q

How are encapsulated bacteria eliminated?

A
  1. MBL can bind to capsule and activate the lectin complement pathway that leads to C3b deposition on bacterial surface
  2. IgG bound to pathogen surface can also activate the classical complement pathway leading to C3b deposition
  3. Phagocytes can recognize C3 b by their complement receptors or Fc receptors and destroy the pathogen by opsonization
28
Q

What causes an intracellular bacterial infection?

A

Bacteria grow inside macrophage phagosomes by inhibiting the acidification and fusion of the phagolysosome

29
Q

Describe the cytotoxic responses of intracellular bacterial infection?

A
  1. NK cells recognize intracellular infection in macrophages
  2. Macrophages secrete IL12 and 5 to activate NK cells
  3. NK cells secrete IFN-y to activate macrophages
  4. Later, T cells activate macrophages through IFN-y
30
Q

Describe the T cells response to intracellular bacterial infections?

A
  1. Bacteria live within the endosomes formed during cell entry
  2. Peptide antigens present in the endosome are processed and loaded in MHCII molecules
  3. TH1 cells recognize their antigen on MHCII molecule become activated and secrete IFN-y and TNF
  4. IFN-y activates macrophages and causes then to increase phagocytosis and secrete inflammatory cytokines
31
Q

Describe the characteristics of viruses?

A
  1. Infectious agents of prokaryotic and eukaryotic cells
  2. Most numerous microbe on the planet
  3. Minute particle containing DNA or RNA surrounded by a protein coat
  4. Has an extracellular and intracellular state
  5. Requires a host cell to replicate (obligate intracellular pathogens)
32
Q

What is the extracellular state of a virus?

A
  1. Virion
  2. Nucleic acid is surrounded by protein and other macromolecules
  3. Metabolically inert
  4. Transports viral genome from host cell to new cell
  5. Susceptible to humoral immune response
33
Q

What is the intracellular state of a virus?

A
  1. Occurs once the viral genome is introduced in a new cell
  2. Viral replication occurs
  3. Virus utilizes the host cells machinery to replicate and assemble new virions
34
Q

What is a virion?

A

Virus particle

35
Q

What are the major functions of type I interferons produced by virally infected cells?

A
  1. Induce resistance to viral replication
  2. Increase MHC I expression
  3. Activate NK cells to target infected cells
36
Q

How do type 1 IFN induce resistance to viral replication?

A
  1. Activate genes that cause destruction of mRNA
  2. Inhibit translation of viral proteins
37
Q

How do type 1 IFN increase MHC I expression?

A
  1. Activate CTLs by viral peptides
  2. Inhibit NK cell killing of non-infected cells
38
Q

How much of NK cells make up circulating lymphocytes?

A

5-10%

39
Q

What is the role of NK cells for viral infection?

A
  1. Induced innate response
  2. Recognize and kill virally infected cells and tumor cells by their absence of MHC I
  3. Lack specific antigen receptors
40
Q

What are the NK regulations?

A
  1. NK cells must make contact with a target cell to release their granules contents (limits cell killing to 1 cell at a time)
  2. Multiple cell receptor interactions need to happen before the NK cell can kill the target cell
  3. These receptor interactions have to be activating interactions and not inhibitory
41
Q

What is a NK-cell synapse?

A

NK cells making a strong connection with an infected cell

42
Q

What are the functions of IFN-y?

A
  1. Activates NK cell to become IFN-y secreting effector cells (IL15 causes NK cell proliferation)
  2. Polarizes CD4 T cells into becoming TH1 effector cells that secrete IFN-y
  3. IFN-g increases phagocytic activity of macrophages. (Macrophages will filter viral particles from the blood)
43
Q

Describe the NK cell cytotoxicity activation from viral infection?

A
  1. Infected epithelial cells respond to infection by secreting type I interferon (IFN-a and IFN-b)
    2 . induce NK cells to proliferate and differentiate into cytotoxic NK cells that will then kill the virally infected cells.
  2. NK cells induce infected cells to undergo apoptosis by releasing the contents of their granules containing lytic enzymes that cause the infected cell to undergo apoptosis.
  3. The apoptotic cell will eventually be cleaned up by macrophages.
44
Q

What are the role and signals of cytotoxic T cell of viral infection?

A
  1. Effector CTLs are generated from CD8+ T cells
    Signal 1: TCR binds to peptide presented by APC on MHC I
    Signal 2: Costimulatory signal transmitted (CD28 on T cell and CD80/B7 on APC)
    Signal 3: The cytokine IL2 and IL12 induces proliferation and differentiation into a CTL
45
Q

What is the role of helper T cells of viral infection?

A
  1. Intracellular pathogens are taken in by APCs are recognized by endosomal TLRs resulting in the production of IL12
  2. Viral pathogen is broken down in the endosome and its peptide antigens are loaded into MHC II molecules
  3. Naive CD4+ helper T cells recognize the peptide and are polarized into the TH1 effector T cells by the polarizing cytokine IL12
46
Q

What is the role of TFH of viral infection?

A

work directly with B cells to induce B cell proliferation and differentiation into plasma cells in a GC response

47
Q

What is the role of TH1 of viral infection?

A

Enhance CTL activation

48
Q

How does CTL kill virus infected cells?

A

Forms an immunological synapse with TCR and MHC class I and costimulatory molecules then releases perforin and granzymes on infected cells

49
Q

Describe the role of virus-neutralizing antibodies?

A
  1. Formed against adhesion proteins on virus
  2. High-affinty, class switched antibodies that prevent the virus from adhering to and entering a host cell (neutralization)
50
Q

When can neutralization occur?

A

When the virion is outside the host cell

51
Q

What is resolution?

A

Requires elimination of free virions and virus producing cells by cell mediated lysis by CTLs or NK cells

52
Q

What is the function of memory B and CTLS?

A

Formed to inhibit subsequent infections