Immunology sheet # 2 - Noor 5ammash

بسم الله الرحمن الرحيم

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Dendritic cell:

 Dentritic cell is called so due to the presence of dendrites.
 It originates from the bone marrow, and its lineage is not fully understood.
 Dendritic cells are present in small quantities in tissues that are in contact with the external environment, mainly the skin, under the squamous epithelium (where it's called Langerhans cells).
 Their main function is:
Dendritic cells are not phagosytic cells, they don't engulf whole cells, instead they in-bite small molecules by a process called pinocytosis.
They take foreign antigens into their cytoplasm and then migrate (the cells) to the local lymph nodes and display these antigens on their surfaces for the sake of lymphocytes.
So we don’t describe dendritic cells as phagosytic cells, we describe them as antigen presenting cells.
Their main function is presenting antigens on their surfaces.

Antigen presentation is in contact with lymphocytes.
Lymphocytes are divided into:
1. B-lymphocytes
2. T-lymphocytes
B-lymphocyte: can recognize any antigen through their specific receptor.
T-lymphocyte: As far as T-lymphocytes are concerned, this is not the case:
Native antigens(antigens that haven't been processed or broken) are not recognized by T-lymphocytes, and the only way the T-cells can recognize foreign antigens is through antigen presenting cells.(antigen presenting cells break antigens down and display its parts on the their surfaces, to help T-cells to function).
Follicular dendritic cell:
 Follicular dendritic cell is called so, due to its location and ofcourse the presence of dendrites. They are found in the lymph nodes follicles.
 We don’t know from where it originates.
 It has CR2 complement receptor2, which retains foreign antigens on cell surface for long duration.
 They assist in B cell maturation by the presentation of intact antigen to the B cells.
Almost all antigens are disposed or get lost rapidly upon their entrance to the body; as a result B-lymphocytes fail to detect their presence. So what these cells do is keeping antigen for a period of time as to activate the B-cells.
 It's believed that they play a role in immune system memory, by getting the B-cells challenged, and then form memory cells.

Lymphoid lineage:

B-lymphocyte:
 B-lymphocyte develops among certain line, and then goes to circulation as a mature B-cell.
 Why we call it B-cell!!
Some say that the name comes from "Bursa of fabricius" in birds, where B-cells were first defined.
Later, from its origin, that is the bone marrow in human.
 B-cells are produced and matured in bone marrow. Then they migrate through circulation until they are challenged by antigens, then they are activated into plasma cells or memory cells.

 B-cell types:
Plasma B cells (also known as plasma cells) are secretory B cells that have been exposed to antigen and produce and secrete large amounts of antibodies.
Memory B cells are formed from activated B cells that are specific to the antigen encountered during the primary immune response. These cells are able to live for a long time, and can respond quickly following a second exposure to the same antigen.

 B-cell receptor (BCR):

B-cells have receptors on their surface; it's a specific receptor that recognizes only one type of antigen.
Each b-cell has a certain type of receptor that recognizes certain antigen, and that’s what we call receptor specificity.

In the last lecture we talked about macrophages and neutrophills, we said that they recognize foreign bodies indiscriminately, so they lack specificity unlike the B-cells.

(BCR): is an antibody molecule
Antibodies molecules divide into:
1. Secreted antibodies: are found in the serum as immunoglobulin.
2. Fixed antibodies: are fixed on the surface of cells.(like the B-cells).

(BCR): antibody molecule
It consists of four polypeptide chains
1. Two small sized chains: known as light chains.
2. Two over sized chains: known as heavy chains.

 Development of B cells:

# Before talking about b-cell development, we must know its identification.
# Two certain molecules identify the cells in the bone marrow as cells that are going to be B-cells. These two molecules are CD10 and CD19.like once you find a cell in the bone arrow with CD10 and CD19 on their surface, there is no doubt that this cell is going to develop and become a B-cell.
# CD10 and CD19 are markers for the B-cell.

Stages:
1. Pro B-cell stage:
B-cell in the bone marrow, with CD10 and CD19 on its surface.

2. Pre B-cell stage:
B-cell in the bone marrow, with CD10 and CD19 on its surface, plus appearance of the heavy chains in its cytoplasm.

3. Immature B-cell stage:
B-cell in the bone marrow, with CD10 and CD19 on its surface, plus appearance of the heavy and light chains in its cytoplasm.

# Once the cell forms the heavy and light chains, it can produce an immunoglobulin molecule, and displays it on its surface.
# There are different classes of immunoglobulin, which differs in their structures more specifically their heavy chains, not in their binding site.
So the specificity of the receptor is preserved.
# Once the immunoglobulin (M) appears on the cell surface, we call it immature B-cell.

4. Mature B-cell stage:

# The next step is the production of another Ig class and displays it on the surface, and this Ig is IgD.
# So a mature B-cell displays two Ig, IgM and IgD.
# Once we have a mature cell, it leaves the bone marrow and goes into circulation to the secondary lymphoid tissues.
# The mature cell then sits and waits until it's exposed to antigen of their specificity then it's activated.

First exposure of antigen:

o Antigen X enters the body; B cells are exposed to it.
o Only the B-cell with the "antigen" receptor is activated, and it's called the MOTHER CELL.
o Once this cell is activated, it forms clone
o Clone: is a group of identical cells that share a common ancestry, meaning are derived from the same mother cell.
o MOTHER CELL proliferates to form clone.
o Clone divides into: Plasma cells and memory cells.
Let's say we have one million cells in one clone, half of this number becomes plasma the other half memory cells.

Plasma cells are effecter cells; they produce antibodies to get rid of antigens. And once they finish their job they die. (Limited life time).

On the other hand, the memory cells which are passive cells spread around the body and hide in lymph tissues until they are recalled.(long life time).

In the second exposure of antigen X:
o Instead of having one mother cells, we will have half million of mother cells (memory cells).each cell form its own clone. So the immune response becomes fast in the second exposure and there are merely any signs or symptoms of illness.
o Same story goes with vaccines and measles.

# If the mature b-cells are not exposed to any antigen in duration of five weeks, they die.

T-lymphocyte:
We have two types of T-cells:
1. Cytotoxin T-cell: recognized by CD8 on its surface, it kills cells.
Cytotoxic can act against foreign cells or virus infected cells by means of two main mechanisms.
 Cell lyses: CD8 cells attach to the virally infected cells, and release proteins called perforins that creates holes in the cell membrane of the target cell.
 Apoptosis: CD8 cells induce programmed cell death, by granzymes.

2. Helper T-cell: recognized by CD4 on its surface.,it plays a very important roles in the immune response:
 Being responsible for cytokines production.
 Interacting with B-cells to promote their differntiation into plasma cells.
 Activating the macrophages to phagocyteose.
 Induction of inflammatory reaction.

 T-cell receptor (TCR):

T-cells have receptors on their surface; it's a specific receptor that recognizes only one type of antigen.
Each T-cell has a certain type of receptor that recognizes certain antigen, and that’s what we have receptor specificity.

(TCR):
It consists of two chains:
1. alpha chain: represents the light chain in BCR
2. beta chain: represents the heavy chain in BCR

Development of T cells:
T-cells leave the bone marrow in a very early stage; enter the circulation to find their way to the thymus. Thymus has specific receptors for the immature circulated T-cells.
Stages:
1. Pro T-cell stage:
T-cell has left the bone marrow with CD4 and CD8 on its surface.

2. Pre T-cell stage:
T-cell has left the bone marrow with CD4 and CD8 on its surface, found it way to the thymus and linked to its receptors. The maturation process starts, and T-cell expresses part of its receptor.(beta chain).

3. Double positive T-cell:
The T-cell receptor is fully expressed (alpha and beta chains), with displayed CD4 and CD8.
This T-cell can't leave the thymus unless one of the CD is no longer presented on it surface.

4. Single positive T-cell
Once CD4s or CD8s are eliminated, T-cell (either cytotoxic or helper) enter the circulation, and it's called Single positive T-cell.

First exposure of antigen:

o Antigen X enters the body, T-cell are exposed to it.
o Only the T-cell with the antigen receptor is activated. And it's called the MOTHER CELL.(T-cell here is either cyto. Or helper)
o Once this cell is activated, it forms clone
o Clone: is a group of identical cells that share a common ancestry, meaning are derived from the same mother cell.
o MOTHER CELL proliferates to form clone.
o Clone divides into: effecters and memory cells.
For example:
Helper T-cell is activated. It will form a clone that will be divided into:
 Effecter Helper T-cell: releases chemicals like cytotoxins to help other T-cells in functioning. or other cells in general.
 Memory Helper T-cell: for feedback.

# If a cytotoxic T-cell is activated same story, memory and effecters cells.
# Here the effecters cells attack the cancers and virally infected cells, since the antibodies of the B-cell act only extra cellular.

Interferon-gamma cytokine:
# # There is something called interferon-gamma cytokine, that is critical for innate and adaptive immunity against viral and intracellular bacterial infections and for tumor control.
# # IFN-γ is produced by CD4 and CD8 cytotoxic T lymphocyte.
# # IFN-γ Activate and increase lysosome activity in macrophages .
# # For example in tuberculosis, where cells are resistible.
IFN causes:
 Respiratory burst.
 Increase in free radicals production.
 Eventually, elimination of the infected cells.

Immune system tissues:

Bone marrow:
 Is the flexible tissue found in the interior of bones.
 It's responsible of blood cells production. It contains the stem cells or the precursor of blood cells.
 The only way to differentiate cells in the bone marrow is by the CD molecules.

Thymus:
 It's located anatomically in the anterior superior mediastirnum, in front of the heart and behind the sternum. In one word retrosternum.
 Thymus continues to grow between birth and puberty then begins to atrophy, so the T-cell output is most active before puberty.
 What will be happened after puberty?
It's not really known. Some people say that by the time you reach puberty, your body has already produced so many memory T-cell.
Others say that thymus functions or roles are taken over by other types of tissues.
 Histologically, thymus is divided into central medulla and peripheral cortex.
1. Central medulla consists of macrophages and dendritic cells.
2. Peripheral cortex consists of epithelial cells and dendritic cells. These two types of cells interacts with T-cells and help in the maturation process. Eventually when T-cells mature, they leave the cortex and go into medulla.

The cells of the immature T-cells leave the bone marrow and enter the thymus, go through cortex. In the cortex they mature, some of these cells are CD8 cytotoxic T-cells, and some are CD4 helper T-cells

Lymph nodes:
 Surrounded by capsule.
 Consists of cortex and medulla.
 Cortex consists of follicles: primary and secondary follicles.
1. Primary follicle contains the inactivated B-cells. It's organized. And in histological view appears BLUE.
2. Secondary follicle contains the activated B-cells. Less bluish and less dense.
 T-cells are found in the paracortex, which is the area around the follicles

MALT: mucosa associated lymphoid tissue.
 Same as the lymph nodes.
 It's free of capsule.
 No medulla or cortex.
 Mixture of follicles (B-cells and T-cells).

Spleen:
 It has an important role in immune system and in blood cells filtration.
 It has white pulp and red pulp.
 Each pulp has its own function and its own composition.
 Concerning immune system, spleen synthesizes antibodies in its white pulp.
 White pulp is a lymphoid tissue that is presents around central arteriole, we call it PALS.
 PALS stands for Periarteriolar lymphoid sheaths (PALS), and it's rich in T-lymphocyte.
 The PALS is surrounded by lymphoid follicles that are rich in B-lymphocytes.




DONE BY: Noor Khammash
Lecture #: 2ed lecture of immunology.
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