Development of immune cells Flashcards by Aditi Mukherjee

What are the cells of the immune system divided into?

Antigen presenting cells
Lymphocytes (B and T cells)
Effector cells

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What are APCs?

dendritic cells
macroghages
B cells when activated
follicular dendritic cells

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Where are follicular dendritic cells active?

in lymph nodes involved in B cell-T cell interaction

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What is difference between B and T cell immunity?

B cells are mediators of humoral immunity (produce Ig)

T cells are mediators of cell-mediated immunity (are involved in elimination of infected cells)

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What are the different effector cells?

T effector lymphocyte- Activates phagocytes
Macrophage- phagocytosis
Granulocyte- mast cell, basophil, eosinophil
Natural Killer Cells

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Where are immune cells made?

bone marrow

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How many lineages are there in the bone marrow? What are they?

Myeloid and Lymphoid

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What is made in the myeloid lineage?

the phagocytes (neutrophils, macrophages, and dendritic cells) 
mast cells, eosinophils (wbc), and basophils (wbc)

function: identify, ingest, and destroy pathogens

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What is made in the lymphoid lineage?

natural killer cells, B cells and T cells

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How are white blood cells formed FROM THE MYELOID PROGENITOR?

bone marrow has stem cells
stem cells converted to 2 multipotent progenitors:
a. common myeloid progenitor
b. common lymphoid progenitor
thecommon myeloid progenitor is converted to committed precursors
committed precursors are converted to late precursors
they then mature INTO: erythrocytes•platelets•basophils•eosinophils•monocytes•dendritic cells•neutrophils

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How are white blood cells formed from the lymphoid progenitor?

bone marrow has stem cells
stem cells converted to 2 multipotent progenitors:
a. common myeloid progenitor
b. common lymphoid progenitor
the common lymphoid progenitor gives rise to two types of cells
a. pro-B cell
b. common T/NK cells

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What happens to the Pro-B cells?

mature into 3 types of B cells:

follicular B cell
marginal zone B cell
B-1B cells

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What happens to the common T/NK cells?

can become natural killer cells

2, convert to Pro- T cells

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What are types of Pro-T cells?

alpha delta T, gamma delta T

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What happens to granulocytes and monocytes?

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

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What happens to lymphocytes?

undergo maturation

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Where do T and B lymphocytes undergo maturation?

T= thymus
B= bone marrow

they are both generated in the bone marrow, T cells go to the thymus via blood and B cells stay where they are

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What are the peripheral lymphoid organs?

spleen, lymph nodes, mucosal and cutaneous lymph tissues

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Explain the maturation of lymphocytes:

common lymphoid precursors produce immature B cells and T cells
B cells remain in the bone marrow to mature and T cells mature in thymus
after B and T cells are mature, they enter the blood or the lymph circulation
they go to peripheral lymphoid organs (spleen, lymph nodes, mucosal and cutaneous lymph tissues)
get recirculated in the blood

What do the checkpoints do in the maturation of lymphocytes?

if lymphocytes pass the checkpoints they continue maturing

if they dont pass, they die by apoptosis (T cells) or go through maturation again (B cells)

What happens at the pro B/T cell proliferation stage?

they start to rearrange their genes to make antigen receptors

B cells will normally have a single IgM surface receptor= FIRST heavy chain made, then light chain made

T cells will have the T cell receptor= FIRST beta chain made, then alpha chain

What happens at the pre B/T cell stage?

cells now express first receptor chaings (heavy Ig chain for B cell, beta chain for T cell)
the first chains are self antigen receptors (they detect their environment)

When can the precursor cells get eliminated?

If B or T cells are unable to express this pre-antigen receptor (unable to make the chains)
If the receptors bind too weakly to the self antigens in the bone marrow or thymus
If receptors bind too strongly to the self antigens in the bone marrow or thymus

What do the checkpoints check for?

if the lymphocytes express antigen receptors that can recognize antigens sufficiently
if the lymphocytes are able to express antigen receptors
if the lymphocytes are recognizing self antigens too strongly.

What are the 3 rules to complete maturation?

eliminate/control microbes no damage to the host they should be able to discriminate between self antigens and foreign antigens (self-non self discrimination)

What are the 2 main mechanisms to self tolerance?

central (in bone marrow and thymus) and peripheral mechanisms (in blood and cells)

What is the aim of central tolerance?

eliminate cells that recognize self antigens too strongly in the central lymphoid organs (thymus and bone marrow)

What are thymocytes?

immature T cells in the thymus

What is the process for central tolerance in T cells called?

clonal deletion (negative selection)

What is the process of clonal deletion?

1. initally thymocytes dont express CD4+ or CD8+ receptors 2. after some development they express both (called double positive thymocytes) 3. test the thymocytes - can the thymocytes recognise the self antigens? if no= apoptosis - do they react too strongly to self antigens= this is bad so apoptosis - react too weekly to self antigens- this is what we want= so positively selected

What happens if cells reacto to MHCI antigens?

they become CD8+ T lymphocytes (become single positive)

What happens if th T cells react to MHC II antigens?

they become CD4+ T lymphocytes (become single positive)

What happens to thymocytes that dont react too strongly or weakly?

becomes CD4+ T lymphocytes

Why does the body have peripheral tolerance mechanisms?

some self-reactive T cells escape central mechanism

What cells do the peripheral tolerance mechanisms work on?

MATURE T lymphocytes

How are T cells activated?

1. t cell recognizes antigen on dendritic cell/ macrophage- T CELL gets signal that there is a problem somewhere 2. dendritic/ macrophage gives signal to T cell telling them the antigen is presented bc of infection 3. this sign upregulates co stimulatory molecules that ligate CD28 to T CELL RECEPTORS 4. cytoking release 5. leads to proliferation

What mechanisms are involved in peripheral tolerance?

anergy deletion (apoptosis) suppression by regulatory T cells

What is anergy?

when no infection, if T cell binds to healthy self antigen, then no co stimulation (no ligation of CD28) it cells become anergic (cant react to antigen)

Why does a T cell become anergic?

bc self cells express inhibitory receptors when T cell binds to a healthy self cell in the body, these inhibitory receptors bind to the T cell as well thus deactivating them (making them anergic)

What happens in the suppression by regulatory T cells?

can stop T cells that recognize self antigens from becoming activated

What happens if a B cell recognises an antigen too strongly?

delete - apoptosis cell deactivates- becomes anergic get second chance to rearrange light chain & express new receptor to recognize the antigen

What is receptor editting?

get second chance to rearrange light chain & express new receptor to recognize the antigen

What are the mechanisms of tolerance in B cells?

anergy deletion suppress by regulatory T cells blockade of activation by inhibitory receptors

What do B effectors do?

produce antibodies that can neutralize microbes, allow phagocytosis, and activate complement proteins

What do T helper cells do?

produce cytokines that activate macrophages, T cells, and B cell

What do cytotoxic T cells do?

involved in lysis of infected cells

What do regulatory T cells do?

involved in suppression of the immune response