Immunity-L8- Adaptive Immune response to and evasion by bacteria- Adaptive Immune system recap

main components of host immune response and roles

1. innate- rapid/non specific- AMPs, complement, cytokine mediated responses

2. adaptive- slower, specific- B/T/Ab

3. bridge: phagocytes present antigens

main functions of the adaptive immune system

1. neutralise- Ab neutralise

2. eliminate- CD8/Phagocytes- remove infected cells and pathogens

3. memory: faster, stronger and more efficient response upon re-exposure

where do T/B cells arise and mature? key features?

• B cells- bone marrow, express Ig receptors and mature into plasma cells that secrete Ab

• T cells- arise from bone marrow, mature in the thymus- TCRs and have subsets CD4/CD8/Treg

DISCUSS major CD4 subsets and functions (5)

• Th1: DC makes IL-12- STAT4/TBET- makes IFN gamma for intracellular bacteria-TB and enhances phagosome maturation

• Th2: DC makes IL-4- STAT6/GATA3→IL-4/5/13- eosinophils for parasites, class switching

• Th17: DC makes IL-6/33- STAT3/RORgammaT- il-22/IL-17-recruits neutrophils and G-CSF, and AMP at mucosal sites

• Tfh: DC IL-6: STAT3/BCL6→ IL-21 helps B cell differentiate to plasma cells

• Tregs: IL-2→ FOXP3- suppress effector T cells

what evidence links CD4 T cells and infection susceptibility of S.aureus?

1. patients w/ B cell defects aren’t susceptible to S.aureus, Ab not as important

2. diabetes- CD4 T cells make it worse, more susceptible

3. STAT3 mutations- reduced Th17 and more S.aureus infections in skin/soft tissue NOT blood

what Th response is suitable for streptococcus pneumoniae and why: experiment? what was this tested against?

• mice infected with pneumonias and isolated memory T cells

• stimulated memory cells made IL-17, Th17 biased response

• transferred to naive mice and infected with pneumoniae and reduced balance load due to IL-17

• CD8 and IFN gamma from TH1 didn’t make a difference- extracellular bacteria!!!!!

what is the role of Th17/Th1 cells in s.aureus? evidence

• Th17 is critical for skin infections as it recruits neutrophils but not essential for bloodstream infection or survival

• need Th17 and il-17 for SKIN infections but doesn’t help for the blood

• Th1 cells protect against BLOODSTREAM S.aureus by making IFN-gamma for macrophages specifically

main CD8 effector functions

secrete cytokines for the immune response

kill cells via perforin and granzymes

and Fas-FasL ligand

how do CD8 cells control listeria? experimental

• Took immune T cells listeria specific from an animal

• Transferred to receipt animal and looked for bacterial burden post infection

• Took CD8 from perforin deficient mice- transferred the CD8 that were specific but couldn’t make perforin- burden went up

• CD4/CD8 specific for perforin- made no difference

• Proves CD4s weren't involved, specific CD8 reaction for this bacteria

what is antibody class switching and what are the key Ig functions?

activates B cells undergo DNA rearrangement in the constant region- changing the Fc effector function but not the specificty

• IgM- primary response for complement

• IgD- also seen with Igm

• IgA- mucosal and epithelial help

• IgE- in allergy and hypersensitivity

• IgG- main secondary Ab response for opsonisation, neutralisation

what are the main effector functions of antibodies?

1. neutralisation of toxins/pathogens

2. opsonisation for enhanced phagocytosis

3. ADCC- Fc of Ab binds to Fcgamma IIIA to kill infected cells

4. complement activation for microbial lysis, C3b, inflammation

protective role of antibodies and what do deficiencies show?

-        Recurrent infection of H.influenzae, clearance depends heavily on Ab and need opsonisation

-        People with B cell deficiencies show that they have impaired class switching of low IgG and IgM

-        Vaccines and immunoglobulin therapies are needed to help