Basic terms, organization of the immune system (first seminar) Flashcards
role of immune system
Maintenance of immune homeostasis
Self non-self versus dangerous harmless
Recognition immune response elimination
immunotolerance
ignorance
innate cells-
phagocytic cells- macrophages, neutrophils and dendritic cells nk cells, mast cells eosiniphils basophils
Main features of the adaptive immune response-
Main features of adaptive immune response
- Specificity
The answer is specific to the recognized molecule - Sensitivity
A very low amount of the specific molecule is enough to trigger an immune response - Memory
- Selectivity
There is a wide range of preformed receptors, and the cell clone that has the most appropriate receptor for a particular molecule (antigen) is selected
Antigen, epitope.
alloantigens, xenoantigens, autoantigens
Molecules which trigger immune response are antigens.
an epitope, also known as antigenic determinant is part of of an antigen that is recognized by the specific angtigen receptors (one antigen may have several epitops!)
alloantigens- An antigen that occurs in some but not all members of the same species. Used by the immune system to distinguish self from nonself.
Xenoantigen: An antigen that is found in more than one species. An antigen is something that is capable of inducing an immune response
autoantigens- an antigen that, despite being a normal tissue constituent, is the target of a humoral or cell-mediated immune response, such as in autoimmune disease.
what types of receptors can recognize antigens-
Pattern recognition receptors which detect general components of microboes like common cell wall structures.
Specific antigen receptors:
B cell receptors which recognize the Whole molecule= CONFORMATIONAL EPITOPE.
T cell receptors-which recognize processed peptides on mhc molecules (linear epitope)
Passive immunity vs active immunity.
Passive immunity: Immunity produced by the transfer of antibodies or activated T cells.
natural: pregnancy artificial: adoptive transfer
Active immunity: Immunity is induced in the host itself by antigens
natural: pathogen infection artificial: active vaccination
Lymphocyte recirculation
Specific immune response is based on the meeting of antigen-specific lymphocytes and invading
antigens. To this end, T and B cells circulate through peripheral tissues permanently. This is the so
called recirculation (homing).
Steps of lymphocyte recirculation:
1) Lymphocytes move from the primary to the secondary lymphoid tissues. They enter from the blood
via the HEVs (high endothelial venules). Lymphocyte traffic is regulated by selective expression of
adhesion proteins in peripheral lymphatic tissues.
2) In the absence of antigen exposition the virgin cells (that have not already been exposed to
antigens) go back to the blood through lymphatics, while memory cells selectively return to the tissues
where they were first stimulated by antigens. It is also regulated by adhesion proteins.
3) After activation by an antigen-presenting cell, lymphocytes proliferate and differentiate to effector
and memory cells. (Figure 1.2)
Lymph nodes-
Lymph nodes have two major functions:
1) elimination of foreign antigens (during the filtration of lymph
as it passes through the lymph nodes, the phagocytic cells eliminate the invading microbes and other
foreign substances);
2) antigen presentation (the professional APCs – macrophages and dendritic
cells – capture antigens and display them to T lymphocytes).
Regions-
Paracortex/interfollicular space- T cells and dendritic cells.
Cortex- B cells and Macrophages.
Centrum germinativum- Driving B cells, plasma cells, macropahges and follicular dendritic cells
Medulla- Plasma cells and macrophages.
Area of antigen presenting is the paracortex between dendritic cells and T cells.
Sentinal lymph nodes
The sentinel lymph node (SLN) is the first lymph
node in a lymph node bed to receive lymphatic drainage from a tumor. The new regional staging
system is based on the biopsy of senitel lymph nodes. There are two methods that can be used for
identifying SLNs:
1) injections of blue dye in the area immediately surrounding the cancer
2) injectionsof a radioactive substance in the area immediately encompassing the cancer. The injections are administered prior to surgery. During surgery the surgeon identifies the node(s) containing either the
blue dye (through direct visualization) or the radioactive substance (through a detector e.g. Geiger
counter), indicating the collection of drainage from the cancer. The nodes that collect the injected
substances are determined to be the SLN and are subsequently removed for a biopsy.
Advantages:
surgery decreases unnecessary lymph node dissections, thereby reduces the risk of
lymphedema
more effective in the demonstration of micro-metastasis
enables new staging strategies
helps to optimize the supplemental radiation therapy
Common myeloid and common lymphoid.
Pluripotential stem cells differentiate into committed progenitors. Two types of committed
progenitors are known:
1) common myeloid progenitor-
The common myeloid progenitors generate proerythroblasts (erythropoiesis),
myeloblasts (granulopoiesis),
monoblasts (monocytopoiesis)
megakaryoblasts (thrombopoiesis)
2) common lymphoid progenitor-
lymphoblasts (lymphopoiesis).
Myelopoiesis and B cell development are
localized in bone marrow but T cell maturation occurs in the thymus.
Thymus-
Cortex phases
Medulla phases.
Cells in the thymus can be divided into thymic stromal cells (epithelial cells, macrophages, dendritic cells) and cells of hematopoietic origin, derived from bone marrow (thymocytes).
The function of the thymus is to produce T lymphocytes.
The cortex is mainly composed of lymphoid cells (immature thymocytes) surrounded by a network of
cortical epithelial cells. The earliest phases in thymocyte development, T cell receptor gene
rearrangement and positive selection take place here.
The medulla consists of mature thymocytes,
medullary epithelial cells, macrophages and dendritic cells. The later phase of T cell development,
negative selection, takes place in the medulla.
positive selection
Positive selection: production of T cells whose receptors (TCR) can recognize antigens presented by
self MHC molecules. During this process, all other developing T cells (whose TCR cannot recognize
antigens presented by self MHC molecules) die by apoptosis before reaching maturity.
negative selection
Negative selection: the thymocytes that recognize self molecules (autoantigens) are deleted from the repertoire.
What happens if the bone marrow has a functional defect?
The amount of circulating blood cells is reduced (pancytopenia), severe and recurrent infections occur.
What happens if a baby loses his/her thymus in the course of a surgical procedure
It can affect the function of peripheral T cells and can lead to early senescence of the immune system.
M cells?
M cells (microfold cells): This is a specific cell type in the intestinal epithelium which can endocytose protein and peptide antigens. Instead of digesting these molecules, M cells transport them into the underlying tissue, where they are taken up by local dendritic cells and macrophages.
Immunophenotyping
Immunophenotyping is a technique used to study the protein expressed by cells. This technique is commonly used in basic science research and laboratory diagnostic purpose. This can be done on tissue section (fresh or fixed tissue), cell suspension, etc. An example is the detection of tumor marker, such as in the diagnosis of leukemia. It involves the labelling of white blood cells with antibodies directed against surface proteins on their membrane. By choosing appropriate antibodies, the differentiation of leukemic cells can be accurately determined. The labelled cells are processed in a flow cytometer, a laser-based instrument capable of analyzing thousands of cells per second. The whole procedure can be performed on cells from the blood, bone marrow or spinal fluid in a matter of a few hours.
multipotent hematopoietic stem cell- hemocytoblast
CD117 so called cKit.
