Lec 19-Immunity To Bacterial Infection Flashcards
When microbe enters body:
- Microbe is in intracellular space, gets detected by patrolling innate immune cells via PRRs
- First response: Phagocytic receptors invaginate PM and form phagosome—>phagosome and lysosome fuse—>lysosome proteolytic enzymes destroy contents of phagosome
What happens if some microbial peptides escape phagosome?
They get captured in Golgi vesicles containing MHC2 receptors. MHC2 heterodimer receptor holds peptide in groove. Vesicle memb fuses w/ PM, exposing MHC2 receptor and expels microbial peptide. Peptide then goes to activate T cell to launch adaptive immune response
Antigen processing—converting proteins into peptides
- Viral or bacterial protein can enter cytoplasm
- PRRs respond to immune signalling OR protein can be further degraded into peptides by proteosomes. Peptides can diffuse to ER
- Once peptide reaches ER, its mounted onto MHC1 and vesicle is created. Vesicle goes from ER—>golgi—>PM, exposing MHC1 with microbial peptide attached, initiating attention of CD8
MHC1 vs MHC2
- If MHC 1, peptide travels to PM to interact with CD8 T cells. If MHC2 is exposed, has to travel to lymph node to activate CD4 T-cells.
- MHC1 can be presented by any cell. MHC2 is only presented by antigen presenting cells and B cells
Do erythrocytes have MHC1 or MHC2?
- Erythrocytes don’t have a nucleus
- They don’t have class 2 because they aren’t antigen presenting or B cells
- They also don’t have class 1 bc now their only job is to carry oxygen, no normal cell functions
Why do antigens go to lymph nodes?
Once our innate immune cells have detected and loaded pathogen, sometimes they cant respond. So, antigen presenting cell with loaded MHC2 goes to lymph node to present in T-cell area to CD4 to activate immune response
Antigen itself can travel to lymph nodes thru lymphatic system to activate B cells in B-cell area.
They go to lymph nodes bc we may not have B or T cells in that area, so they go right to the source
Delivery of antigen to T and B cells overview
- PRR activates dendritic cell
- Dendritic cell is loaded with antigen, activates TLRs
- TLRs release cytokines
- Cytokines call on other innate immune cells to start fighting infection
- Loaded dendritic cell is taken to lymph node
- Dendritic cell reaches T-cell zone and interacts with CD4 T-cell. With MHC2, dendritic cell activates clones active T cell specific to that antigen. Clone T cell leaves lymph node and goes to infection site to get rid of infection. OR Antigen can move to B cell zone. Interaction of BCR and antigen causes B cell to engulf of antigen. B-cell will expose antigen on MHC2 and goes to talk to T-cell.
Step 1: Present antigen to T cells and activate them
- Dendritic cell presents antigen to T-cell on MHC2
- Antigen binds to specific TCR—this interaction is powered by CD4 and co-stimulatory factors. This interaction makes dendritic cell release IL-12.
- T cell activation causes cytokine release. Cytokine is a signal that makes CD4 produce IL-2 cytokine and IL-2 receptor—this is the key point, when T-cell finally has the message. IL-2 complex allows T-cell to clone itself.
- Clone will mainly be effectors to go kill, but some will be memory
How do we deal with a pathogen the second time?
Memory T-cells
CD8 activation in lymph node
CD8 are the killer cells
- Activated by interacting directly with antigen-presenting cell OR interaction of active CD4 and CD8—CD4 causes CD8 to divide and form effector killer clones (and memory cells) that hunts for a cell infected by that specific pathogen
Step 2: B cell-T cell interaction
- B cells are in lymph nodes
- Lymphatic vessel brings antigen
- When correct BCR meets antigen, B cell is activated and presents antigen to CD4 T cell
- CD4 T cell output help B cell produce best antibody for that specific antigen. CD4 T cell releases IL-4, allowing B-cell to clone itself to become plasma cells (antibody producing cells) and memory cells.
How do B-cells know what class of antibody to produce?
- T-cells also secrete other cytokines to show B cell what type of antibody it should produce
- Eg. IFN-Y signals IgG creation, IL-t signals IgA creation, IL-4 signals IgE creation
T-cell continues to instruct B-cell about what?
- T cell have told B cell to class switch and they do!
- Now T cell tells them to choose appropriate gene region to make the antibody with highest affinity and avidity to your antigen (IgM or class switch to smth diff)—B cell does this via somatic recombination, as well as making memory B cells
B-cell activity in germinal center, interaction with follicular T cells
- Most specificity for antibody happens with hypermutation in Diversity region of heavy chain
- Follicular T cells are CD4, they enter in follicle of B cell to make B cell better at producing plasma cells—B cells proliferate and hypermutate in their germinal center, and then meet with follicular T cells. If B cell affinity is good enough they go fight bacteria, if not good enough, they die.
What are extracellular bacteria?
Stay interstitial, around organs. Will kill the cell if they go inside, they dont go inside cells. These are the bacteria that innate immune sys kills
