Bacterial infection Flashcards
What are the general stages in an immune response to a bacterial infection?
- 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 ????
What works well for extracellular pathogens?
- 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
What works well for intracellular bacterial/viral infections?
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
What receptors on macrophage dendritic cells recognize Candida infection?
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
What receptors on the macrophage dendritic cell recognize Mtb?(mycobacterium tuberculosis)
complement receptors - TLR1,2,6 - which make IL1, TNF and IL12
What receptors on a marophage dendritic cell recognize the schistosomiasis mansonii?
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
How to dendritic cells/macrophages shape the immune response?
they present antigen - and produce specific cytokines to shape the immune response
APCs present antigen to T cells, but what promotes T helper cell differentiation?
the cytokines that the APCs secrete promote T helper cell differentiation
what happens when T helper cells are stimulated by cytokines?
when the naive T cells are stimulated, they differentiate into different T helper subsets - each of which has different effector functions
what is the effector function of Th1 subset of Thelper cells?
macrophage activation and IgG production
(intracellular bacterial infections - autoimmunity)
what is the effector function of Th2 subset of Thelper cells?
mast clle, eosinophil activation, IgE production, alternative macrophage activation
(extracellular helminth infections, asthma and allergies)
what is the effector function of Th17 subset of Thelper cells?
Neutrophilic monocytic inflammation
(extracellular bacterial/yeast infections and autoimmunity)
describe the reaction to an Mtb infection
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*
How does IFN-gamma activate macrophages to kill Mtb?
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
what drives the Th17 cells?
IL 1 and IL23
IL23 secreted from naive CD4 T cells-
*Th17 cells are really important in mucosal sites, skin
What effect does IL17 have?
IL17 - drives production of antimicrobial peptides
chemotaxis of neutrophisl
promotes bacterial clearnace
drives production of IgG antibodies and
drives inflammation
Describe the bodies innapropriate response to allergens in the environment
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
what cells are important in ridding the body of extracellular infection?
mast cells, eosinophils, and basophils - all give off cytotoxic granules
Describe the function of T helper 2 cells in immunity
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
What is the importance of the Th1 vs. Th2 balance?
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
What is the role of T reg cells / Supressor T cells?
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
