1 & 2- Introduction & Primary lymphoid organs

Question 1

Why is immunology important?

Answer 1

• Immune system is crucial to human survival
• Without the immune system (immunodeficiency), small infections can be fatal
• Manipulation of the immune system can improve health. e.g. vaccinations
• 10% of human genes are immune system related

Question 2

What is immunology?

Answer 2

The study of the physiological mechanisms we use to defend our bodies against other organisms. Particularly microorganisms.

Question 3

What is the very basic principle of the immune system?

Answer 3

To recognise non-self material and respond to it if necessary.

Question 4

What are the 2 mechanisms the immune system uses to recognise non-self material?

Answer 4

1. Limited number of germ-line encoded receptors in individuals that recognise molecular patterns not found in health self tissue.
2. Large amount of antigen-specific receptors in individuals generated during lymphocyte development. by recombination of gene segments. These receptors can recognise self tissue so lymphocytes must be regulated to avoid autoimmunity.

Question 5

What is autoimmunity?

Answer 5

Immune responses against self tissue

Question 6

What is innate immunity?

Answer 6

• Immunity that uses the germ-line encoded receptors.
• Works rapidly, minutes to hours
• Broad specificity

Question 7

What is adaptive immunity? (acquired immunity)

Answer 7

• Immunity that used antigen-specific receptors
• Takes longer to work, days to weeks
• Has exquisite specificity

Question 8

Antigen defintion

Answer 8

Molecules which react with (are recognized and bound by) antibodies or T cells.
However not all antigens can induce an immune response in the host: those that can are termed immunogens.

Question 9

What is an immunogen?

Answer 9

An antigen which CAN induce an immune response

Question 10

Antibody definition?

Answer 10

• Proteins (immunoglobulins) found in the blood and body fluids produced in response to a foreign molecule (antigen) and bind specifically to that particular antigen.
• They are the adaptive component of the humoral (soluble, non-cellular) immune response.

Question 11

Lymphocyte definition?

Answer 11

• Mononuclear cells that are part of the leukocyte (white blood) cell lineage.
• The main cell type found in lymph.
• All cells of the immune system are derived from stem cells in the bone marrow: lymphocytes are subdivided into two main subsets.
• B lymphocytes (develop in Bone marrow)
• T lymphocytes (develop in Thymus).
• Each lymphocyte expresses a single specificity of antigen receptor on their surface to enable recognition of a specific antigen.

Question 12

Naïve lymphocyte definition?

Answer 12

Those that have never encountered the antigen to which their cell surface receptor is specific for, and thus have never responded to it.

Question 13

Memory lymphocyte definition?

Answer 13

A product of an immune response, ensuring that the specificity of their antigen receptor remains in the pool of lymphocytes in the body, and that an efficient response can be made after re-exposure to the same antigen.

Question 14

Active immunity definition?

Answer 14

The induction of an immune response within an individual by the introduction of antigen.

Question 15

Passive immunity definition?

Answer 15

Immunity gained without antibody induction of a response.

e.g. Transfer of an antibody, immune serum, or activated lymphocytes into a naïve recipient.

Question 16

Primary immune response definition?

Answer 16

The response made by naïve lymphocytes when they first encounter their specific antigen.

Question 17

Secondary immune response definition?

Answer 17

The response made by memory lymphocytes when they re-encounter their specific antigen.

Question 18

T lymphocyte definition?

Answer 18

• Develop in the thymus from bone marrow-derived precursors.
• They only recognize processed antigen (peptides) presented at the cell surface by major histocompatibility complex (MHC) molecules.
• Surface markers found on T lymphocytes are…
  CD3 (all T cells),
  CD4 (a subset of T cells),
  CD8 (a different subset of T cells).

Question 19

B lymphocyte defintion?

Answer 19

• Develop in the bone marrow.
• They recognize free antigen in the body fluids, or intact antigen directly on cell surfaces.
• Surface markers found on B lymphocytes are…
  CD19, CD20 and surface immunoglobulin.

Question 20

Where are T and B lymphocytes produced and where are they released?

Answer 20

Produced in the primary lymphoid organs.

Are released into the peripheral lymphoid pool.

Question 21

What is clonal selection?

Answer 21

Lymphocytes that meet their specific antigen proliferate and produce effector and memory cells.
i.e. cells with an appropriate antigen receptor are selected for by antigen, and expand to produce a clone of cells, each with the same antigen receptor.

Question 22

What happens to lymphocytes that do not meet their antigen?

Answer 22

Those that do not meet their antigen die.

The overall size of the total peripheral lymphoid pool is regulated by homeostatic mechanisms.

Question 23

How does primary immune response work?

Answer 23

• Naïve lymphocytes are activated by antigen to ensure proliferation of lymphocytes with the appropriate receptors for that antigen.
• This is at the centre of an adaptive immune response.
• After the antigen has been removed relatively few lymphocytes with the appropriate receptors specific for that antigen remain (the rest die).
• These are memory lymphocytes and immune memory of a specific infection can last for years or even decades.

Question 24

How does secondary immune response work?

Answer 24

Some years later, upon re-exposure to the same antigen there can be a secondary response which is more effective than the primary response.
This greater effectiveness is due to its greater magnitude and more rapid onset than the primary response.

Question 25

How does natural selection link to the immune system?

Answer 25

Principal function of the immune system is defence against infection, and during evolution exposure of human populations to infectious agents has shaped the human immune system. There is a constant pressure from pathogens on the immune system: many pathogens develop ways to block or subvert the immune response.

Question 26

How is the immune system physically organised?

Answer 26

- The lymphatic system drains body fluid from between tissue cells via lymph nodes, through which lymphocytes recirculate. - The tissues are patrolled by lymphocytes, antibodies and antigen-presenting cells. - Gut-associated lymphoid tissue controls responses in the intestinal tract. - Antigens present in the blood are taken to the spleen.

Question 27

What are primary lymphoid organs?

Answer 27

The major sites of lymphopoiesis, the generation of lymphocytes. Here lymphoid stem cells differentiate into mature functional lymphocytes. The primary lymphoid organs are the thymus and bone marrow.

Question 28

What shape is the thymus and where is it located?

Answer 28

Bi-lobed in mammals | Located in the thorax

Question 29

How are the lobes of the thymus arranged? How do T cells mature?

Answer 29

Each lobe is organised into lobules and in each lobule are the histologically defined regions of cortex and medulla. The cortex contains the immature thymocytes, some of which are selected to become mature thymocytes in the medulla. There is a great deal of cell death of developing lymphocytes in the thymus and only a small percentage of the cells (about 5%) exit the thymus into the peripheral T cell pool. The mammalian thymus atrophies with age and areas of active T cell production are replaced with adipose tissue, however the total size of the mature T cell pool does not decline substantially with age.

Question 30

What does the bone marrow do?

Answer 30

In the foetus, the liver is an active site of haematopoiesis prior to most bones becoming active sites of production. In later life active sites may include spongy regions at the end of long bones; also vertebral bones, sternum, ribs, flat bones of the cranium and pelvis. Bone marrow produces stem cells and B lymphocytes. Those stem cells destined to be T lymphocytes migrate to the thymus throughout life. For B cells, differentiation is centripetal with the stem cells under the bone and the most mature phases of the B cell pathway found nearer the centre of the marrow.

Question 31

What are secondary lymphoid organs?

Answer 31

Provide an environment in which lymphocytes can interact with antigen and with other lymphocytes: they are the sites at which antigen, antigen presenting cells and mature lymphocytes come together to initiate an adaptive immune response. They have special vascular adaptations to recruit lymphocytes from the blood. Secondary lymphoid tissue includes... spleen, lymph nodes, mucosa associated lymphoid tissues (MALT).

Question 32

Human lymph node function?

Answer 32

Lymph arrives at the lymph node through several AFFERENT vessels and leaves through one EFFERENT vessel at the hilus. During passage of lymph through the node there is removal of particulate antigens by the phagocytic cells and then this is transported to the lymphoid regions of the node. The cortex is a B cell area and the paracortex is a T cell area. (Cortex, paracortex, medulla - from outside to inside)

Question 33

Shape of human lymph nodes?

Answer 33

1-15 mm across, - Round or kidney shaped - Have an indentation at the hilus where the blood vessels enter and leave the node

Question 34

What 2 types of tissue does the spleen contain?

Answer 34

Red pulp and white pulp

Question 35

What does the red pulp do?

Answer 35

Acts as a general filter for the blood.

Question 36

What does the white pulp do?

Answer 36

The lymphoid tissue and constitutes the major initiator of responses to blood-borne antigens

Question 37

What is found around the central arteriole in the spleen?

Answer 37

- Around the central arteriole are concentric areas of lymphoid tissue = the periarterial lymphatic sheath (PALS). - The region nearest the arteriole is a T cell zone. - Periodically, there are B cell follicles, either primary or secondary and around this is the marginal zone which seems to be the primary site of entry of B and T cells into the white pulp.

Question 38

What does MALT stand for and what does it do?

Answer 38

Mucosa Associated Lymphoid Tissue Aggregates of lymphoid tissue which do not have a tough outer capsule. They are found especially in the lamina propria, and sub-mucosal areas of the gastrointestinal, respiratory and genito-urinary tracts. Typical examples of MALT are tonsils and appendix. Other examples include Peyer’s patches. These are organised regions of lymphoid tissue found in the wall of the gut.

Question 39

How do lymphocytes recirculate?

Answer 39

Naïve lymphocytes circulate constantly from the blood into the secondary lymphoid organs, and leave the vasculature through a specialised section of the post capilliary venule known as the high endothelial venule (HEV). They move from the lymph node to the lymphoid vessels and eventually return to the blood via the thoracic duct.

Question 40

In the presence of infection, where are the cells that recognise the infectious agent held?

Answer 40

The lymphoid tissue where they proliferate and differentiate.

Question 41

What is the CD system?

Answer 41

The cluster of differentiation system is a way of identifying cell surface molecules present on leukocytes (and other cell types). CD numbers are assigned to particular cell surface molecules. The CD system is commonly used as cell markers, there are more than 350 CD numbers assigned. Of course, they are not just markers but important functional molecules. It is important to remember that some CD markers are present on cell types other than immune system cells, e.g. certain adhesion molecules.

Question 42

Differences between T and B cells | RECOGNITION

Answer 42

T cells... Recognise processed antigen presented at the cell surface by MHC molecules B cells... Recognize intact, free antigen (not presented by MHC molecules)

Question 43

Differences between T and B cells | ANTIGEN RECEPTOR

Answer 43

T cells... Antigen receptor is either αβ or γδ TCR B cells... Antigen receptor includes cell surface antibody

Question 44

Differences between T and B cells | CDs EXPRESS

Answer 44

T cells... All T cell express CD3: T cells express CD4 or CD8, but not both B cells... Express CD19 and CD20 at surface

Question 45

What are antigen presenting cells?

Answer 45

Cells that can present antigen to lymphocytes in an immunogenic form are collectively termed antigen presenting cells, or APCs.

Question 46

Name the 4 APCs

Answer 46

Dendritic cells Follicular dendritic cells B cells Activated macrophages

Question 47

Where are dendritic cells located? | What do they present to?

Answer 47

Widespread e.g. skin and mucosal tissue; migrate to draining lymph nodes Present to... T cells

Question 48

Where are follicular dendritic cells located? | What do they present to?

Answer 48

Lymphoid follicles Present to... B cells

Question 49

Where are B cells located? | What do they present to?

Answer 49

Lymphoid tissue Present to.... T cells

Question 50

Where are activated macrophages located? | What do they present to?

Answer 50

Lymphoid tissue, peripheral tissues Present to... T cells