Bacterial infection Flashcards

1
Q

What are the general stages in an immune response to a bacterial infection?

A
  • Macrophages and dendritic cells site of infection first line defence
  • B cells and circulating antibodies specific to outer coat proteins lipids also important
  • Antigen presentation to T cells
  • Activation of Th and Tc cells
  • Extracellular ????
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2
Q

What works well for extracellular pathogens?

A
  • Drive inflammation, complement
  • Neutrophils and

phagocytes for clearance

  • Activate T helper cells
  • Antibody – will neutralise, activate complement, promote opsonisation *opsonization is super important b/c it makes the bacteria more attractive to the macrophages
  • IgG excellent at promoting all aspects
  • IgE for clearing helminths
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3
Q

What works well for intracellular bacterial/viral infections?

A

Extracellular phase

  • Antibodies from previous encounter
  • Complement activation
  • Macrophage uptake and presentation on MHC II

Intracellular phase

  • Activate the cells that are infected so can halt infection
  • Presentation on MHC I
  • Activate Cytotoxic T cells
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4
Q

What receptors on macrophage dendritic cells recognize Candida infection?

A

TLR2/4 and C type lectin receptor

TLR2/4 = makes IL1, TNF, IL23, and IL6

C type lectin receptor = makes IL1, TNF, IL23, and IL6

pattern recognition receptors are able to recognize the various

antigens it experineces - when a receptor encounters its antigen it

activates an immune response pro-inflammaotry in nature

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5
Q

What receptors on the macrophage dendritic cell recognize Mtb?(mycobacterium tuberculosis)

A

complement receptors - TLR1,2,6 - which make IL1, TNF and IL12

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6
Q

What receptors on a marophage dendritic cell recognize the schistosomiasis mansonii?

A

TLR2 recognizes it and produces IL10, and IL4

IL10 is inhibiting to the inflammation response?

IL4 primes the B cells to class switch to produce

the IgE used to fight worms

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7
Q

How to dendritic cells/macrophages shape the immune response?

A

they present antigen - and produce specific cytokines to shape the immune response

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8
Q

APCs present antigen to T cells, but what promotes T helper cell differentiation?

A

the cytokines that the APCs secrete promote T helper cell differentiation

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9
Q

what happens when T helper cells are stimulated by cytokines?

A

when the naive T cells are stimulated, they differentiate into different T helper subsets - each of which has different effector functions

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10
Q

what is the effector function of Th1 subset of Thelper cells?

A

macrophage activation and IgG production

(intracellular bacterial infections - autoimmunity)

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11
Q

what is the effector function of Th2 subset of Thelper cells?

A

mast clle, eosinophil activation, IgE production, alternative macrophage activation

(extracellular helminth infections, asthma and allergies)

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12
Q

what is the effector function of Th17 subset of Thelper cells?

A

Neutrophilic monocytic inflammation

(extracellular bacterial/yeast infections and autoimmunity)

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13
Q

describe the reaction to an Mtb infection

A

Mtb is an intracellular bacteria that normally infects phagocytes (like many intracellular bacteria) - therefore it is hard to get rid of b/c antibodies to not enter the cell.

Mtb is internalised into phagosomes and it starts to replicate in there- it prevents fusion of lysosomes, so macrophages have a hard time getting rid of them

BUT… the Mtb is recognized by the IL1 TNF and IL12 - causes secretion of IFNy which primes the immune response to take place so the macrophages can’t do much on their own but they can produce cytokines to prime the body for a proper response

cytokines stimulate the Th1 cells which produce IFN-gamma- this activates macrophages to kill Mtb *IFN-gamma is a potent activator of macrophages*

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14
Q

How does IFN-gamma activate macrophages to kill Mtb?

A

the Interferon gamma is produced by helper T cells -

it upregulates costimulatory molecules CD80/86 on macrophages and CD40 ligand as well

With the IFN gamma, you also get an increase in MHC class 1 and 2 as well as antigen presentation - so it primes the macrophage to get rid of the bacteria in a way that it wouldn’t have naturally.

get activation of Nitric oxide synthase and production of ROS - all work together to enhance microbiocidal activity f macrophage and activate other Th and cytotoxic Tcells

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15
Q

what drives the Th17 cells?

A

IL 1 and IL23

IL23 secreted from naive CD4 T cells-

*Th17 cells are really important in mucosal sites, skin

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16
Q

What effect does IL17 have?

A

IL17 - drives production of antimicrobial peptides

chemotaxis of neutrophisl

promotes bacterial clearnace

drives production of IgG antibodies and

drives inflammation

17
Q

Describe the bodies innapropriate response to allergens in the environment

A

TH2 cells induced by IL10 from antigen presenting cells and produces IL4/IL5 to drive responses

so once you’ve got IgE cell you have mass cells which cause hay fever - if you have a body infected with a worm thhen the APC will secrete IL10 which causes the Th2 cell to dominate…. IL4 and IL5 are produced which drive the production of IgE from B cells

18
Q

what cells are important in ridding the body of extracellular infection?

A

mast cells, eosinophils, and basophils - all give off cytotoxic granules

19
Q

Describe the function of T helper 2 cells in immunity

A

Mast cells, eosinophils and

basophils all good at getting rid of

extracellular infection – cytotoxic

granules

•Antibodies – great at fighting

extracellular infections - helminths

•IL4 and IL5: drive recruitment

and activation

  • Also drive IgG and IgE production
  • So potential role if imbalanced

Th2 in allergy

20
Q

What is the importance of the Th1 vs. Th2 balance?

A

High Th2 levels are associated with an increased susceptibility to asthma and allergies b/c high levels of IgE and high levels of mast cell activity

we don’t have 100% Th1 or Th2 response for any given infection, it’s just a shift in balance between the two. However, those who lean more towards Th2, tend to experience asthmas

21
Q

What is the role of T reg cells / Supressor T cells?

A

they arise during development - their main function is supression of autoreactive T cells - they work by secreting inhibitory cytokines (TGF-beta)

deficiency of these can lead to autoimmunity