9. Adaptive Response: Where and When? Flashcards
Where do the lymphocytes and dendritic cells combine to activate T cells?
The secondary lymphoid tissue, then they may all go off and GSD (get shit done)
What are the secondary lymphoid organs?
Lymph nodes, spleen and mucosa associated lymphoid tissue (MALT)
What two pathways haematopoietic stem cells develop through? Which cells undergo which pathway?
Two pathways: myeloid, lymphoid
Myeloid: platelets, erythrocytes, dendritic cells, monocytes/macrophages, neutrophils, eosinophils, basophils
Lymphoid: B cells in bone marrow, T cells, NK cells, lymphoid dendritic cells
What is the role of the blood and lymphatic systems?
Method of carrying cells from one place to another
How do lymphocytes travel from the blood into the lymph nodes?
Through the high endothelial venues (HEV)
What happens if an antigen for a lymphocyte is present in the lymph nodes?
Antigen will be processed by dendritic cells, presented to T cells which activate B cells and produce plasma cells
Describe the structure of the lymph nodes
Consist of an outer capsule, cortex, paracortex, medulla
What is the cortex and paracortex mostly composed of?
Cortex is mostly B lymphocytes
Paracortex is mostly T lymphocytes
What occurs to the lymphocytes in the lymph nodes when antigen is present?
Lymphocytes divide and form primary follicles which then develop to secondary follicles then germinal centres
What happens to dendritic cells if it is activated by a pathogen (activation-lymph node)?
- Dendritic cell uses PRRs to recognises DAMPs or PAMPs of pathogen
- Recognition activates dendritic cell and it becomes phagocytic, taking up and processing pathogenic antigens
- Dendritic cell moves out of tissue and migrates through affluent lymphatics to the lymph node
- Dendritic cell also vastly increases the amount of MHCII, CD80 and CD86 on cell surface making it a more potent antigen presenting cell
- Reaches lymph node
- MHCII presenting peptides and CD80 interact with CD28 to provide costimulation of T cells which become activated and leave lymph node
How does the type of T cell activated affect the result?
If helper T cell activated then helps B cell differentiation
If cytotoxic T cell activated then goes to site of infection and murders
What are germinal centres?
Structures in lymphoid tissue responsible for the maturation of B cells
How do B cells mature through germinal centres?
Follicular dendritic cells show antigen to B cells
T follicular helpers also help B cell to differentiate
What is the structure of germinal centres?
3 distinct zones (surrounded by a mantle): dark zone, basal light zone and apical light zone
How does the names of the B cells vary as they travel through the germinal centre?
in dark zone = centroblast
in basal and apical light zone = centrocyte
Why are plasma cells not produced in the germinal centres?
Because they produce antibodies which would cover up antigens and prevent responses
What happens when the B cell mature?
Class switching, affinity maturation (proliferate and incorporate mutations), produce memory cells, produce plasma cell precursors
Describe the lymphoid follicle/node
White pulp present within red pulp, contains PALS (periarteriolar lymphoid sheath), mostly T cells
Which organ deals with blood infections?
The SPLEEEEEEEEEEEN
How do most infections occur?
Through mucosal tissues
How does IgA protect mucosal surfaces?
Present as a dimer (linked by J chain) and containing a secretory component (derived from poly Ig receptor) which protects mucosal surface, preventing pathogenic adhesion and infection
How does IgA travel from underlying mucosal to mucosal surfaces?
Plasma cells which release the IgA are underlying mucosal so IgA must travel through the epithelial cells.
Polymerised Ig recognises and binds to J joining chain of IgA and transports it to mucosal surface. It is then endocytose to the mucosal side. A specific enzyme cleaves the poly Ig, leaving a bit of receptor to protect IgA from digestion
What happens if pathogens get past IgA?
IgE ENTERS THE RING!
IgE activates Mast cells which cause neutrophils/eosinophils to leave blood and move to site of infection
What are the Peyer’s patches?
Organised lymphoid nodules present in the intestinal epithelium, pathogens present here may also initiate an immune response.
What is the role of the microfilm (m) cells in the Peyer’s patch?
transport antigen from outer mucosal surface and show it to lymphocytes underlying surface of gut (Peyer’s patch)
What happens after lymphocytes are activated?
Undergo further round of activation by leaving Peyer’s patch and going to local draining lymph nodes (mesenteric lymph nodes), then they move back to the gut using homing molecules (such as MAdCAM-1 - mucosal addressin cell adhesion molecule 1) which act as a postcode for the lymphocytes
What things are required for communication between cells?
Cell-to-cell contact, or release of soluble molecules (cytokines)
What are cytokines?
Small proteins which act as messengers, controlling haematopoiesis and up/down regulating immune response, each cytokine has it’s own receptor (e.g. interleukin 1)
What are the 6 groups of cytokines?
- Interleukins - messengers between lymphocytes
- Colony-stimulating factors
- Chemokines (chemotactic cytokines that attract cells to site of infection)
- Interferons (interfere with viral replication - stop viral spread)
- Tumour necrosis factors (pro-inflammatory cytokines)
- growth factors (cause growth of cells)
What is pleiotropy of cytokines? Give an example
Where a single cytokine can do multiple things e.g IL-4 can act on B cells, activating them and causing proliferation and differentiation
What is redundancy in cytokines? Give an example
Where different cytokines do exactly the same thing e.g. IL-2 may also cause B cells to proliferate
What is synergy in cytokines? Give an example
Where cytokines work better together than on their own e.g. IL-4 can cause class switching to make IgE but if IL-5 around then the effect is increased
What is antagonism in relation to cytokines?
If lots of gamma interferon around then it blocks the class switching of interleukin
What effect increases the amount of cytokines produced?
Cascade effect
What are the 6 functions of cytokines?
- stimulate inflammation - IL-1, IL-17
- immunosuppressive - IL-10, TGFbeta
- antiviral - IFNalpha, IFNgamma
- T cell proliferation/ differentiation - IL-2, IL-12
- haematopoiesis - IL-2, IL-13
- chemotaxis - IL-8, RANTES
Describe the two types of interferons
Type I: IFNalpha, IFNbeta, produced by most nucleated cells
Type II: IFNgamma, produced by NK/T cells, important in regulating production of Th1 cells and in macrophage activation
How else may cytokines be used (other than in the immune system)?
Therapeutically (e.g. IFNalpha for viral infections), or inhibited therapeutically (e.g. anti-TNFalpha for rheumatoid arthritis)
