Lecture 2 Flashcards
What are 2 adaptive immunity cells that are derived from lymphoid progenitor cells?
T cells and B cells
Delineate the Primary and secondary lymphoid organs
Primary:
Thymus
Bone Marrow
Secondary:
Spleen
Lymph nodes
mucosa associated lymphoid tissue
Describe where T cells and B cells are generated
T cells are generated in the Thymus and become functionally mature there
B cells are generated in the Bone Marrow and functionally mature there
Both T and B cells will then enter the secondary lymphoid organs in order to become “activated” by foreign antigens. (if they are not activated, they remain naive lymphocytes and return to the blood via lymphatic drainage)
How long to Naive lymphocytes typically survive if they do not recognize an antigen?
1 to 3 months
The Hassall’s corpuscles in the thymus appear to be involved in the generation of what specific type of cell?
T regulatory cells
During their maturation process in the Thymus, explain the process that T cells undergo in order to stimulate selection and differentiation. (include what type of interactions are occurring during this process)
T cells make contact with epithelial cells, Dendritic cells (DC’s), and resident tissue macrophages while in the thymus
Cell-to-cell interactions with these cells are what carries out the selection and differentiation of T cells
State the cytokines that are known to play an important role in the development of T cells in the thymus. (4 of them)
IL-1
IL-2
IL-6
IL-7
The majority of T cells are produced ______ in human lives. Where can these naive T cells be found dormant, before it is their turn to undergo proliferation?
early
Naive t cells are maintained (dormant) in the periphery of the thymus until it is their time to proliferate.
What happens to B and T cells that are reactive to self antigens?
they are deleted via apoptosis in order to prevent autoimmune issues
Compare T helper cells and Cytotoxic T cells (include what CD they express)
T helper cells express CD4 and provide help for B cell growth and differentiation
Cytotoxic T lymphocytes (CTL’s) express CD8 and (“screen”) recognize and kill cells infected with intracellular pathogens (such as viruses)
The development of B cells involves contact with stromal cells and what 3 cytokines?
IL-1
IL-6
IL-7
Describe where the production site of B lymphocytes is through all phases of life
While it occurs in the fetal liver in the womb, the bone marrow is the lifetime production site of B lymphocytes (B for bone)
Where can mature lymphocytes be found?
they circulate the secondary lymphoid organs
Supposed an antigen is captured ,via antibody binding, at a site of infection, and brought to a lymph node. Where is the immune response intiated?
The immune response is initiated in the lymph node (aka secondary lymphoid organ)
Name the 3 body parts that lymphocytes DONT circulate.
Eyes
Brain
Testicles
Describe the process how/why lymphocytes enter secondary lymph organs and include the name of the structure that mediates this entrance.
Lymphocytes enter secondary lymph organs via a specialized endothelium of postcapillary venules called High Endothelium Venules (HEV’s)
HEV cells are much taller than normal endothelial cells AND express much higher levels of adhesion proteins than normal endothelium (these adhesion proteins serve as a type of “homing” receptor)
Lymphocytes attach via adhesion proteins to the HEV’s and enter the secondary lymphoid organ via “Diapedesis”
What usually happens to naive lymphocytes after they enter a secondary lymphoid organ? what if that doesn’t happen?
Upon entering the secondary lymphoid organ, Lymphocytes may be activated by foreign Antigens (if this does not occur, then they remain as naive lymphocytes).
Lymphocytes then leave the secondary lymphoid organ via efferent lymph vessels.
Beginning with an antigen entering the body (not the blood), walk through the basic steps that occur in order to activate a naive B cell with the antigen. (5 steps ; step 4 and 5 occur at the same time)
- the antigen is collected in a lymph node (or other secondary lymphoid organ)
- A naive B cell joins the antigen in the lymph node and becomes activated by it
- Ag-activated B cells proliferate in the germinal centers of the lymph node (around the border of the node) and become either memory B cells or plasma cells
- Memory B cells persist for years to aid in adaptive immune responses in the future
- Plasma cells produce and secrete large amounts of Abs, which explains why they die in about 5 days (“stressed out plasma cells”)
Describe the activation of naive B cells (include where this happens) if there is an antigen in the blood that corresponds to it’s receptors
The spleen collects the antigen from the blood
Naive B cells (and some T cells) join the antigen in the spleen and are activated by it
The B cell initiates it’s adaptive immunity response (Memory B cells and plasma cells)
Effector B cells (Plasma cells) secrete antibodies which are delivered to the site of the infection via the blood
Where are plasma cells usually found? where are they rarely found?
they are usually in the bone marrow (0.2% to 2.8% of the bone marrow)
They are rarely found in the blood
What makes up the white pulp of the spleen?(2 types of cells) be specific about where these cells are found (what they may be near)
B cells are found in the germinal center of a lymphoid follicle (of the spleen) ; near the marginal sinus
T cells are found in the periarteriolar lymphoid sheath (PALS) ; near a central arteriole of the spleen
Name the one thing that T cells can recognize (if they can’t recognize it, that means they can’t react to it, duh) and why this is significant.
peptides
This is why APC’s are necessary! if the antigen is not a peptide, a T cell may not even detect it until an APC hand’s it to the T cell
Describe the steps in the activation of T cells (include where this happens, what cells they become, and where they end up)
Naive T cells migrate to a secondary lymphoid organ (usually a lymph node) in search of foreign antigens
After T cells are activated there, the differentiate into effector or memory T cells
Some of the effector and memory T cells migrate back into the peripheral sites of infection (leave the node)
Some of the effector and memory T cells remains in the Lymph node to help activated B cells become plasma cells (make lots of antibodies
Explain how Lymph nodes are “filtering devices” for the lymph
Lymph nodes basically collect antigens from the lymphatic fluid so that lymphocytes can interact with the antigens
The basically provide an area with a high concentration of antigens so lymphocytes can “study” them and prepare to combat them elsewhere in the body
In terms of lymph nodes, describe how antigens enter, how naive B cells enter, and how naive T cells enter
Antigens enter the Afferent lymphatic vessel, having been escorted there by a dendritic cell (DC)
naive T and B cells enter the lymph node through an artery, however they must pass through an HEV in order to leave the blood and enter
Describe what area’s of a lymph node T and B cells migrate to
T cells rendezvous with DC’s in the “t cell zone” in the medulla (middle) of the lymph node
B cells migrate to the periphery of the lymph node, and cluster around “follicles”
How do B and T cells know where to migrate to, after they have entered the lymph node?
They are directed by chemokines that are produced in certain areas by stromal cells
Compare primary and secondary follicles in lymph nodes (include why these form and why each contains)
In the absence of Ag stimulation, follicles are primary follicles composed of naive B cells or recirculating memory B cells
If there is Ag stimulation, B cells proliferate/differentiate, forming secondary follicles
(only secondary follicles have germinal centers)
Name the 3 professional APC’s. why are these needed?
DC’s (dendritic cells)
Resident Tissue Macrophages
Activated B cells
T cells can’t see shit, unless a professional APC spoon feeds it to them
Describe how DC’s are different than the other 2 professional APC’s
only DC’s are able to activate naive T cells in the Lymph nodes
Resident tissue macrophages and activated B cells can only present antigens for activated T cells (NOT naive T cells)
Explain what it means for resident tissue macrophages and DC’s to be “cells of innate immunity”
they provide a link between innate and adaptive immunity
DC’s can be divided into classical DC’s, myeloid (mDC’s), and plasmacytoid (pDC’s), and Langerhan’s cells (LC’s). which of these are derived from monocytes and which are derived from stem cells?
mDC’s are derived from monocytes
Classical DC’s, pDC’s, and LC’s develop directly from stem cells
DC’s express receptors that recognize Ags typically made by ____, NOT mammalian cells
Microbes
State the 3 ways by which DC’s acquire Ags. After DC’s aquire an Ag and are activated, what do they secrete?
Phagocytosis, Receptor-mediated endocytosis, and pinocytosis
Upon activation, DC’s secrete cytokines
Compare classical DC’s and Plasmacytoid DC’s. (compare their functions)
Classical DC’s: reside in skin, mucosa, and organ parenchyma
Upon activation, the migrate to LN’s where they display microbial protein Ags to T cells
Plasmacytoid DC’s are early cellular responders to viral infection, which they recognize by the nucleic acids that intracellular viruses produce.
After recognizing these viruses, plasmacytoid DC’s produce soluble (cytokines) interferons (such as IFN-alpha/beta) which have potent antiviral activities
What type of cells do Langerhan’s cells develop from?
embryonic cells
State the main function of inflammatory DC’s
They stay at the site of infection and restore the DC’s in that area (sort of the precursor for the newly generated DC’s that fight the infection)
Compare clonal selection with clonal expansion
Clonal selection: what occurs when B cells are being made with a large amount of diverse receptors for each B cell
Clonal expansion: When a specific B cell is selected to be rapidly proliferated because it is responding to an antigen
If there is a germinal center present in a lymph node (this only occurs if the lymph node is currently fighting a pathogen), describe the locations of primary follicles and secondary follicles in relation to one another
Primary follicles would be on the periphery of the lymph node while the secondary follicles will be found near the central arteriole
