I&I development of immune cells Flashcards
What are the main cells of the immune system?
-Granulocytes
–neutrophils, basophils, eosinophils, mast cells
-Monocytes & Macrophages
-Dendritic cells
-Lymphocytes (T cells, B cells)
-NK cells
What are the 2 specific lineages in immune cell development?
-Myeloid lineage
-Lymphoid lineage
What is the origin of phagocytes?
Myeloid lineage
What cells included as phagocytes?
Neutrophils, macrophages, dendritic cells and antigen presenting cells
What cells are derived from the myeloid lineage?
Mast cells, eosinophils and basophils
What cells are derived from the lymphoid lineage?
Natural killer cells
What multipotent progenitor does the myeloid lineage cells come from?
Common myeloid progenitor
What multipotent progenitor does the lymphoid lineage cells come from?
Common lymphoid progenitor
What does the common lymphoid progenitor branch into before the final cells of the lymphoid lineage?
- T, NK cells and Pro-B
–Give rise to NK cells, T cells and B cells
What is the fate of granulocytes and monocytes?
Circulate in the blood and are recruited at sites of infection/tissue damage
What is the fate of resident APCs(dendritic cells and macrophages)?
stationed in all
organs and especially at portals of pathogen entry (skin,
airways, gut, etc.) to detect invaders
Where do immature T cells mature?
Immature T cells enter thymus where they continue maturation until the stage of mature naive T cells
Where do immature B cells mature?
Immature B cells continue maturation in the bone
marrow until the stage of mature naive B cells
What are immature lymphocytes tested for?
Immature lymphocytes are ‘tested’ for ability to:
- recognise self MHC-I and II (T cells) -useful
- respond to self Ags - not useful & dangerous
What are the stages in T cell maturation?
- Stem cell
- Double negative(CD4-CD8-)Pro-T cell
- Pre-T cell with a Pre-TCR(receptor)
- Double positive(CD4+CD8+)immature T cell
- If there is weak recognition of class II MHC + peptide we get mature CD4+ T cell. This is positive selection.
- If there is weak recognition of class I MHC+ peptide we get mature CD8+ T cell. This is positive selection
- If there is no recognition of MHC+ peptide then leads to apoptosis. This is because of a failure of positive selection(death by neglect)
- If there is strong recognition of either class I or II MHC + peptide then leads to apoptosis. This is due to negative selection
Stages in B cell maturation and selection
See slide 19
What is self tolerance of immune cells?
Mechanisms that prevent immune responses to self antigens
What happens in failure of self tolerance?
- Autoimmunity
-Attach own tissues/organs
How is central tolerance achieved?
Induction of tolerance to self Ags during lymphocyte
development in central lymphoid organs
How is peripheral tolerance achieved?
tolerance to self Ags is induced when mature lymphocytes
respond to Ags in peripheral lymphoid organs or peripheral
tissues
How is self tolerance achieved through central tolerance?
- Lymphoid precursor
- Immature lymphocytes
- Recognition of self antigen
–Apoptosis(deletion)
–Change in receptors(receptor editing: B cells only)
–Development of regulatory T lymphocytes(CD4+ T cells)
How is self tolerance achieved through peripheral tolerance?
- Immature lymphocytes
- Mature lymphocytes
- Recognition of self antigen
–Anergy
–Apoptosis
–Suppression by regulatory T lymphocytes(CD4+ T cells)
What is positive selection in T cell development?
When only T cells that express Ag receptors that can recognise self MHC+self antigens mature & are retained in repertoire
What is death by neglect in T cell development?
T cells that express Ag receptors that do not recognise self MHC+self antigen are eliminated (do not receive survival signals through their Ag receptors and die by apoptosis
What is negative selection in T cell development?
T cells with Ag receptors that recognise MHC+self Ags too strongly are eliminated (die by apoptosis)
What do maturing T cells that are double positive become and what does this depend on?
-During positive selection maturing T cells (thymocytes) that are double-positive (co-express CD4 and CD8) become either CD4+ T cells or CD8+ T cells (single-positive)
-This choice depends on whether their randomly generated TCR recognise Ag presented by MHC II+ the CD4 coreceptor (become CD4+ T cells) or Ag presented by MHC I + the CD8
coreceptor (become CD8+ T cells)
What is the mechanism of peripheral tolerance in anergy?
Functional unresponsiveness
What is the mechanism of peripheral tolerance in suppression?
Block inactivation
What is the mechanism of peripheral tolerance in deletion?
Apoptosis
What lymphocytes do central mechanisms of self tolerance work on?
Work on immature B lymphocytes
What lymphocytes do peripheral mechanisms of self tolerance work on?
Work on mature B lymphocytes
Overview of central tolerance mechanism for B cells
- Eliminate B cells recognising self antigens
- Occurs in bone marrow
- Occurs with immature B lymphocytes
- It occurs by deletion(die by apoptosis; negative selection)
-Ag receptor editing
-Anergy
What are the steps involved in receptor editing in B cell central tolerance?
- Immature B cells that recognise self Ags with high
avidity (strongly) in bone marrow can change specificty of their Ag receptors so that they no longer recognise strongly self Ags - This is done by rearranging the genes for the light chain
What happens in apoptosis in B cell central tolerance?
Immature B cells that recognise self Ags with high
avidity (strongly) in bone marrow can:
- die by apoptosis (deletion) = negative selection
What happens in anergy in B cell central tolerance?
Immature B cells that recognise self Ags with low
avidity (weakly) in bone marrow can:
- become anergic (functional inactivation)
What is the basic overview of peripheral tolerance in B cells?
- It eliminate/inactivate B cells recognize self antigens
- Occurs in peripheral lymphoid organs
-lymph node
-Spleen - Occurs on mature B lymphocytes
- Occurs by deletion
-Anergy
-Blockade of activation by inhibitory receptors
-Suppression by regulatory T(Treg) cells
What are the life stages of mature B and T lymphocytes?
- Naive cell (antigen recognition)
- Activated or effector lymphocyte (Proliferation)
- Memory lymphocyte (Differentiation)
What is the effector function of B lymphocytes?
-Neutralisation of microbes
-Phagocytosis
-Complement activation
What is the effector function of helper T lymphocyte?
-Activation of macrophages
-Inflammation
-Activation(proliferation and differentiation) of T and B lymphocytes
What is the effector function of cytotoxic T lymphocyte?
Killing of infected cell
What is the effector function of regulatory T lymphocytes?
Suppression of immune response
