Lecture 3 Flashcards
What stem cell underlies all immune cells.
Hemtopoetic stem cell in the bone marrow
What are the immune cells of the myeloid lineage?
Red blood cells, platelets, myeloid dendritic cells, macrophages, neutrophils, eosinophiles, Basophils, mast cells
What are the immune cells of the lymphoid lineage?
B1 and B2 cells B-cell subpopulations natural killer cells plasmacytoid dendritic cells
Describe the myeloid lineage.
So white blood cells of the immune system originate in the bone marrow. Cells will then migrate to guard peripheral tissue circulating in the blood in special vessels called the lymphatic system. During this time cells receive signals via their receptors that contribute to their survival. The hermit are poetic stem cell Gives rise to the common lymphoid precursor and the common myeloid precursor. The common myeloid precursor gives rise to granulocyte macrophages and Dendritic cells of the innate system. Mono sites are located in the circulation and can last up to about a day where they continually differentiate into macrophages located in the tissues. Dendritic cells are specialised myeloid cells that can take up antigen process it and present it to T lymphocytes and are therefore The prototypic antigen presenting cells. Other specialised my Lloyd cells include mast cells eosinophiles and Basophils.
Describe the lymphoid lineage.
The common lymphoid progenitor gives rise to lymphocytes and natural killer cells of the innate immunity the CLP can also give rise to plasmacytic Dendrid cells.
There are two main classes of lymphocytes B lymphocytes which are activated into plasma cells that secrete antibodies and T lymphocytes that are involved in killing infected cells and regulating adaptive immunity.
Lymphocytes are remarkable and being able to mount a specific immune response against virtually any foreign antigen. This is because each individual lymphocyte mature bearing a unique variant of a prototypic antigen receptor so that the population of B and T lymphocytes collectively there’s a huge repertoire of receptors that are highly diverse in their antigen binding sites. On the lymphocytes the antigen receptor or B cell receptor is a membrane bound form of Antibody. Taylan for sites however have an antigen receptor that is the T-cell.
What are the key haematopoetic sites?
Meto poetic stem cells can first be detected in embryonic structures such as the AGM region, aorta-gonad-mesoneohros where they differentiate from haemogenic endothelial cells in the embryonic dorsal aorta. HSCsMigrate to the human feet all over at five weeks. Liver haematopoiesis replaces embryonic haematopoiesis by 12 weeks. At 12 weeks and hematopoetic stem cells are found in the spleen and the bone marrow of long bones. Long bones are the major sight of Haematopoiesis during the second half of gestation.
Describe Haematopoiesis in the bone marrow.
Bone marrow is the primary sites of haematopoiesis in adults. Bone marrow sell population is about 60 to 70% my Lloyd, 20 to 30% erythroid, 10% lymphoid. Yellow marrow is usually hematopoetically inactive, While red marrow is active tissue. Cytokines and growth factors regulate blood cell maturation.
Describe all of the cells in the blood system
Neutrophils are the most abundant Leucocytes. With a lifespan of up to 5 days they are activated by the binding of pattern recognition receptors to DAMP/PAMPs. After this activation they immediately phagocytose foreign entities.
Eosinophiles and basophils can phagocytose microbes. D granulation is the primary effective mechanism important in allergy.
Monocytes are 10% of circulating leucocytes which into tissues and differentiate into macrophages. Macrophages a long lived (2/4 months) powerful phagocytes activated by PAMPS/D aMPs. They produce chemical lines that attract other innate and adaptive leucocytes that can function as antigen-presenting cells.
Natural killer cells are capable of cytolytic killing of target cells that are often cancer or virally infected cells. They carry FCRS enabling the lysis of cells coated in Ab. Natural killer T cells are similar to both alpha beta– T cells and nk cells.
Dendritic cells activate naive T cells. They are the prototypic APC.
Mast cells along left sells important for defence against worms and other parasites. They are a key cellular mediater of type one immune hypersensitivities reactions (allergy).
Describe the poles of states of macrophages.
Functionally heterogenous, morphologically diverse
M1/classically activated (I FN – why and for LPS stimulated) or M2/alternatively activated (IL – 4 stimulated)
M1 and M2 are polls of a spectrum of functional states.
Described Dendritic cells.
Stineman discovered a new cell type called the DC. DC can activate T cells. Prototypic antigen-presenting cells. Couples innate and adaptive immunity.
A PC that bridges innate and adaptiveImmunity. DAMPS/PAMPS activate immature Dendrid excels to elevate surface expression of MHC and costim molecules (b7 which binds to CD 28 on T cells). Cells become more motile and migrate to the lymph nodes presenting antigen to T cells.
Compare plasmocytoid DC and conventional DC.
Conventional DC: mini dendrites with prominent finger like protrusions, found and all tissues, short lived, broad range PPR expression, high MHC class 2 expression, main function to present antigens too naive T cells, links to adaptive immunity by direct T-cell activation
Plasmacytoid DC: no dendrites rounded plasma cell appearance, found where lymphocytes reside, long-lived lifespan, narrow range of PRR expression, Low expression of MHC Class I I. Main function is to secrete cytokines effective against viruses, recruits and activates many leucocytes subsets.
Describe the primary and secondary lymphoid tissues.
The primary lymphoid organs are the bone marrow and thymus. The secondary lymphoid organs: lymph nodes, spleen, bronchi associated lymphoid tissues, nasopharynx, Skin associated lymphoid tissue, gut
Where do b lymphocytes originate and migrate to.
B cells develop from lymphoid progenitors. In the bone marrow. These then rearrange their Ig/BCRS. It’s depends on the interactions with stromal cells. Generates immature cells with surface I GM bCell receptors. If B-cell receptors can recognise self antigen they are removed by negative selection and are apoptosed.
B lymphocytes migrate to lymphoid organs. First immature B cells are released into the periphery through circulation into the lymphoid organs. Mature, expressing I GD and IgM. They can now be activated and proliferate in the lymphoid organs differentiating into Ab secreting plasma cells or memory cells.
So early development of b cells requires the interaction with bone marrow stromal cells. Interleukin seven is produced by the bone marrow and required for B-cell development. CLPs bind to VCAM On stromal sales via the integrin VLA4 along with other cell adhesion molecules. This adhesion promotes the binding of Que IT to stem cell factor leading to the progenitor bcell proliferation
Describe the architecture of the thymus.
Lymphoid organs are located above the heart, each love you has its own medullar and cortex. This is where immature T cells complete their development, where they enter as thymocytes and undergo the process of thymic selection (positive and negative).
Describe how T cells develop in the thymus.
T-cell pre-curses migrate from the bone marrow to the timers. T-cell receptor jeans are rearranged. A: be T-cell receptors undergo positive and negative selection. Mechanisms to develop T cells bearing T-cell receptors that are best equipped to recognise foreign antigen presented on MHC molecules.
(from diagram)
Pre-curses commits to the T-cell lineage following notch signalling, and initiate T-cell receptor gene rearrangements. Immature T cells that recognise self MHC Receive signals for survival. Those that interact to strongly with self antigen are removed from the repertoire.
