I&I development of immune cells

Question 1

What are the main cells of the immune system?

Answer 1

-Granulocytes
–neutrophils, basophils, eosinophils, mast cells
-Monocytes & Macrophages
-Dendritic cells
-Lymphocytes (T cells, B cells)
-NK cells

Question 2

What are the 2 specific lineages in immune cell development?

Answer 2

-Myeloid lineage
-Lymphoid lineage

Question 3

What is the origin of phagocytes?

Answer 3

Myeloid lineage

Question 4

What cells included as phagocytes?

Answer 4

Neutrophils, macrophages, dendritic cells and antigen presenting cells

Question 5

What cells are derived from the myeloid lineage?

Answer 5

Mast cells, eosinophils and basophils

Question 6

What cells are derived from the lymphoid lineage?

Answer 6

Natural killer cells

Question 7

What multipotent progenitor does the myeloid lineage cells come from?

Answer 7

Common myeloid progenitor

Question 8

What multipotent progenitor does the lymphoid lineage cells come from?

Answer 8

Common lymphoid progenitor

Question 9

What does the common lymphoid progenitor branch into before the final cells of the lymphoid lineage?

Answer 9

• T, NK cells and Pro-B
  –Give rise to NK cells, T cells and B cells

Question 10

What is the fate of granulocytes and monocytes?

Answer 10

Circulate in the blood and are recruited at sites of infection/tissue damage

Question 11

What is the fate of resident APCs(dendritic cells and macrophages)?

Answer 11

stationed in all
organs and especially at portals of pathogen entry (skin,
airways, gut, etc.) to detect invaders

Question 12

Where do immature T cells mature?

Answer 12

Immature T cells enter thymus where they continue maturation until the stage of mature naive T cells

Question 13

Where do immature B cells mature?

Answer 13

Immature B cells continue maturation in the bone
marrow until the stage of mature naive B cells

Question 14

What are immature lymphocytes tested for?

Answer 14

Immature lymphocytes are ‘tested’ for ability to:
- recognise self MHC-I and II (T cells) -useful
- respond to self Ags - not useful & dangerous

Question 15

What are the stages in T cell maturation?

Answer 15

1. Stem cell
2. Double negative(CD4-CD8-)Pro-T cell
3. Pre-T cell with a Pre-TCR(receptor)
4. Double positive(CD4+CD8+)immature T cell
5. If there is weak recognition of class II MHC + peptide we get mature CD4+ T cell. This is positive selection.
6. If there is weak recognition of class I MHC+ peptide we get mature CD8+ T cell. This is positive selection
7. If there is no recognition of MHC+ peptide then leads to apoptosis. This is because of a failure of positive selection(death by neglect)
8. If there is strong recognition of either class I or II MHC + peptide then leads to apoptosis. This is due to negative selection

Question 16

Stages in B cell maturation and selection

Answer 16

See slide 19

Question 17

What is self tolerance of immune cells?

Answer 17

Mechanisms that prevent immune responses to self antigens

Question 18

What happens in failure of self tolerance?

Answer 18

1. Autoimmunity
   -Attach own tissues/organs

Question 19

How is central tolerance achieved?

Answer 19

Induction of tolerance to self Ags during lymphocyte
development in central lymphoid organs

Question 20

How is peripheral tolerance achieved?

Answer 20

tolerance to self Ags is induced when mature lymphocytes
respond to Ags in peripheral lymphoid organs or peripheral
tissues

Question 21

How is self tolerance achieved through central tolerance?

Answer 21

1. Lymphoid precursor
2. Immature lymphocytes
3. Recognition of self antigen
   –Apoptosis(deletion)
   –Change in receptors(receptor editing: B cells only)
   –Development of regulatory T lymphocytes(CD4+ T cells)

Question 22

How is self tolerance achieved through peripheral tolerance?

Answer 22

1. Immature lymphocytes
2. Mature lymphocytes
3. Recognition of self antigen
   –Anergy
   –Apoptosis
   –Suppression by regulatory T lymphocytes(CD4+ T cells)

Question 23

What is positive selection in T cell development?

Answer 23

When only T cells that express Ag receptors that can recognise self MHC+self antigens mature & are retained in repertoire

Question 24

What is death by neglect in T cell development?

Answer 24

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

Question 25

What is negative selection in T cell development?

Answer 25

T cells with Ag receptors that recognise MHC+self Ags too strongly are eliminated (die by apoptosis)

Question 26

What do maturing T cells that are double positive become and what does this depend on?

Answer 26

-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)

Question 27

What is the mechanism of peripheral tolerance in anergy?

Answer 27

Functional unresponsiveness

Question 28

What is the mechanism of peripheral tolerance in suppression?

Answer 28

Block inactivation

Question 29

What is the mechanism of peripheral tolerance in deletion?

Answer 29

Apoptosis

Question 30

What lymphocytes do central mechanisms of self tolerance work on?

Answer 30

Work on immature B lymphocytes

Question 31

What lymphocytes do peripheral mechanisms of self tolerance work on?

Answer 31

Work on mature B lymphocytes

Question 32

Overview of central tolerance mechanism for B cells

Answer 32

1. Eliminate B cells recognising self antigens 2. Occurs in bone marrow 3. Occurs with immature B lymphocytes 4. It occurs by deletion(die by apoptosis; negative selection) -Ag receptor editing -Anergy

Question 33

What are the steps involved in receptor editing in B cell central tolerance?

Answer 33

1. 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 2. This is done by rearranging the genes for the light chain

Question 34

What happens in apoptosis in B cell central tolerance?

Answer 34

Immature B cells that recognise self Ags with high avidity (strongly) in bone marrow can: - die by apoptosis (deletion) = negative selection

Question 35

What happens in anergy in B cell central tolerance?

Answer 35

Immature B cells that recognise self Ags with low avidity (weakly) in bone marrow can: - become anergic (functional inactivation)

Question 36

What is the basic overview of peripheral tolerance in B cells?

Answer 36

1. It eliminate/inactivate B cells recognize self antigens 2. Occurs in peripheral lymphoid organs -lymph node -Spleen 3. Occurs on mature B lymphocytes 4. Occurs by deletion -Anergy -Blockade of activation by inhibitory receptors -Suppression by regulatory T(Treg) cells

Question 37

What are the life stages of mature B and T lymphocytes?

Answer 37

1. Naive cell (antigen recognition) 2. Activated or effector lymphocyte (Proliferation) 3. Memory lymphocyte (Differentiation)

Question 38

What is the effector function of B lymphocytes?

Answer 38

-Neutralisation of microbes -Phagocytosis -Complement activation

Question 39

What is the effector function of helper T lymphocyte?

Answer 39

-Activation of macrophages -Inflammation -Activation(proliferation and differentiation) of T and B lymphocytes

Question 40

What is the effector function of cytotoxic T lymphocyte?

Answer 40

Killing of infected cell

Question 41

What is the effector function of regulatory T lymphocytes?

Answer 41

Suppression of immune response