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Defence > Development of immune cells > Flashcards

Development of immune cells Flashcards

1
Q

What are the main functions of lymphocytes?

A
  • Specific recognition of antigens
  • B - mediators of humoral immunity - produce Abs
  • T - mediators of cell-mediated immunity
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2
Q

What are the main functions of APCs?

A
  • Capture Ags to display to lymphocytes
  • Dendritic cells - initiation of T cell responses
  • Macrophages - effector phase of cell-mediated immunited
  • Follicular dendritic cells - display ags to B-cells in humoral immune responses
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3
Q

What are the main functions of effector cells?

A
  • Elimination of antigens
  • T-cells - activation of phagocytes, killing infected cells
  • Macrophages - phagocytosis and killing of microbes
  • Granulocytes - killing microbes
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4
Q

What are the main cells in the immune system?

A
  • Granulocytes - neutrophils, baso, eosino, mast cells
  • monocytes - differentiate into macrophages when they enter the tissue
  • Dendritic cells
  • NK cells
  • Lymphocytes
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5
Q

What is the myeloid lineage?

A
  • Stem cells proliferate, but also produce progenitors (committed stem cells)
  • Common myeloid and common lymphoid progenitors
  • Myeloid progenitors differentiate into committed precursors, which further differentiate into late precursors
  • These are blasts, which can proliferate and regenerate
  • then have the mature form (erythrocyte, platelets, baso, eosino, neutrophils, DCs, monocytes)
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6
Q

What do the granulocytes do?

A
  • Granules contain mediators. Once they have been generated in marrow, they leave and go into the blood
  • They’ll stay there nd circulate until they find infection then release their mediators and reactive oxygen species to eliminate the infection
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7
Q

What are dendritic cells?

A
  • Sentinel cells - sample the area around them - dendrites form a vast network to detect pathogens
  • Have them in skin, mucosa and other tissue
  • Capture microbes by phagocytosis, process the pathogen and present Ags to T cells
  • link innate and adaptive immune response
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8
Q

What happens once DCs have captured a microbe?

A
  • They process it and express its Ags on MHC II on their surface to be detected by CD4 T-cells
  • They also change, expressing membrane bound co-stmulatory molecules
  • Also release cytokines and express chemokine receptors - receptors allow them to migrate to lymph nodes
  • In the lymph nodes, they can present the Ag to naive T cells and activate them
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9
Q

What are the 3 different signals T-cells need in order to be activated?

A
  • Need Ag recognition by TCR
  • Need costimulation - APC expresses CD80/CD86 to say they have found an infection, which will activate CD28 on T cell
  • T cells starts to proliferate, then needs cytokine signal from APC, which tells the T cell what sort of cell to become
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10
Q

What is the lymphoid lineage?

A
  • From the common lymphoid progenitor, there are two common progenitors
  • Pro-B and one that can turn into T/NK cells
  • Pro-B -> FOB (follicular B cells), B-1B (peritoeum), MZB (marginal zone B cells in spleen)
  • T/NK -> NK cells, or to alpha-beta T cells (majority) or gamma-delta T cells
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11
Q

What do NK cells do?

A
  • Kill virus-infected cells
  • kill malignantly transformed cells (cancer)
  • Express cytotoxic enzymes to lyse target cells
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12
Q

What are the different types of T cells?

A
  • Th cells (Th1,2,17 etc) - express CD4, activate macrophages, help B cells produce Abs
  • Cytotoxic (CTLs) - express CD8, kill cells infected with microbes, kill tumour cells
  • T reg cells - make sure we respond to microbes in a proportionate way, inhibit function of other T cells and immune cells
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13
Q

Why do B and T cells look similar?

A
  • Similar morphology - big nucleus, small cytoplasm

- But have different functions

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14
Q

What are the different types of B cell?

A
  • FOB - spleen, lymph nodes. Produce mainly high-affinity IgG class/switched antibodies - directed against protein Ags
  • MZB - spleen, lymph nodes. Produce mainly IgM class antibodies - directed against polysaccharide, lipid Ags
  • B-1 cells - peritoneal cavity, mucosal tissues. Produce mainly natural low-affinity IgM Abs - directed against polysaccharide, lipid Ags
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15
Q

How do innate and adaptive immune cells work together?

A

Both work together
If the epithelial barriers are breached by microbes, the innate cells can capture microbes and process their antigens, or mast cells release their mediators such as histamine, and attract neutrophils to help fight
- If the microbe is eliminated here, then fine
- But if not, then the adaptive immune system will have to be brought in

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16
Q

What happens to immune cell after they are generated?

A
  • Most cells are released in the bood and are ready to work
  • Granulocytes and monocytes circulate
  • resident APCs (DCs and macrophages) in all organs and especially portals of entry (skin, airways, gut etc)
  • Lymphocytes need to be educated
  • Immature T cells go to thymus where they mature until mature naive T cells
  • Immature B cells continue maturation in BM until mature naive B cells
17
Q

What happens in the maturation process of lymphocytes?

A
  • Tested for their ability to recognise foreign ags (useful) and response to self ags (not useful and dangerous)
18
Q

What are the checkpoints in lymphocyte maturation?

A
  • Various checkpoints to make sure that cells are useful and not dangerous
  • Pro-t/b cells -> pre B/T cell (still immature, but they start rearranging one of the chains of their antigen receptor and express it on the surface, heavy chain if B cell, beta chain if T cell precursor)
  • They then get a test to see if they are able to recognise their own antigens
  • If they fail, they’ll die through apoptosis
  • If they pass, theyre tested again - They proliferate thanks to survival factors
  • If they can still recognise self-antigens, they are saved
  • They then rearrange the other chain so that they can present the complete antigen receptor – tested again
  • Weak binding (not too weak) – useful and so go to positive selection
  • If it recognises self antigen too strongly, it isn’t useful and so goes to negative selection
  • The ones that make it are still naïve as they haven’t been exposed to foreign antigens
19
Q

What are the 4 outcomes in T cell maturation and selection?

A
  • At first they are double negative immature T cells (CD4-CD8-) - then get tested with pre-TCR
  • Afterwards become double positive immature cells
  • Weak recognition of MHCII and co-peptide = positive selection and cell matures to CD4+ T cell
  • Weak recognition of MHCI and co-peptide = positive selection, to mature to CD8 T cell
  • If there is no recognition of either MHC, there is no positive selection = death by neglect
  • If there is strong recognition of either MHC, then there is negative selction, and the cell apoptoses
20
Q

Why are some cells produced that recognise too strongly?

A
  • Random generation of Ag receptors of T and B cell- Some self-reactive lymphocytes are generated
  • We need to be able to get rid of these
  • If we cant, then they can attack our own tissue/organs
21
Q

What are the 2 tolerance mechanisms?

A
  • Central tolerance - induction of tolerance to self Ags during lymphocyte development in central lymphoid organs
  • Peripheral tolerance - tolerance to self ags is induced when mature lymphocytes respond to ags in peripheral lymphoid organs (lymph nodes or spleen) or peripheral tissues (site of infection)
22
Q

What is central tolerance for T cells?

A
  • Want to eliminate cells recognising self ag
  • Happens in thymus
  • Double positive cells that undergo positive selection will become eithe CD4+ or CD8+
  • Negatively selected cells will apoptose
  • Some wont recognise Ags at all and die by neglect
  • Some CD4+ cells will become T reg cells
23
Q

What is peripheral tolerance in T cells?

A
  • Some self-reactive T cells escape central tolerance
  • Want to eliminate these in the lymph nodes, spleen and peripheral tissues
  • 3 ways to do this are by anergy, apoptosis and suppression
24
Q

What usually happens in an immune response to non-self ags?

A
  • APC presents ag to TCR AS WELL AS costimulatory molecule (B7) to CD28
  • This starts the generation of effector and memory T cells
25
Q

What happens in peripheral tolerance induction of T cells>

A
  • T cell will bind to self-Ag on APC, however as there isnt actually an infection, there will be no co-stimulatory signal, or in some cases an inhibitory receptor (CTLA-4) - T cell will become anergic and functionally unresponsive
  • There may be a DC that is able to actuvate the T-cell, in this case a Treg cell will come along and suppress it using the TF FOXP3, stopping its activation
  • Some cells will recognise the ag, and without a costim signal, will apoptose, via apoptotic proteins from mitochondria, or expression of death receptor ligand.
26
Q

How does central tolerance work in B cells?

A
  • Happens in bone marrow
  • Deletion - apoptosis from negative selection
  • Anergy - reduced receptor expression
  • receptor editing - expression of new V region on Ig (light chain rearrangement) - if the new one is non-self-reactive, they can live
27
Q

How does peripheral tolerance work for B cells?

A
  • Happens in lymph nodes and spleen
  • Anergy
  • Deletion
  • Suppressoin by Treg
  • Inhibitory receptors that block their activation
28
Q

What are the main life stages for lymphocytes?

A
  • Naive cell - antigen recognition -> proliferation
  • Activated or effector lymphocyte - differentiation
  • Memory lymphocyte

Defence (11 decks)

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