1 & 2- Introduction & Primary lymphoid organs Flashcards
Why is immunology important?
- 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
What is immunology?
The study of the physiological mechanisms we use to defend our bodies against other organisms. Particularly microorganisms.
What is the very basic principle of the immune system?
To recognise non-self material and respond to it if necessary.
What are the 2 mechanisms the immune system uses to recognise non-self material?
- Limited number of germ-line encoded receptors in individuals that recognise molecular patterns not found in health self tissue.
- 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.
What is autoimmunity?
Immune responses against self tissue
What is innate immunity?
- Immunity that uses the germ-line encoded receptors.
- Works rapidly, minutes to hours
- Broad specificity
What is adaptive immunity? (acquired immunity)
- Immunity that used antigen-specific receptors
- Takes longer to work, days to weeks
- Has exquisite specificity
Antigen defintion
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.
What is an immunogen?
An antigen which CAN induce an immune response
Antibody definition?
- 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.
Lymphocyte definition?
- 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.
Naïve lymphocyte definition?
Those that have never encountered the antigen to which their cell surface receptor is specific for, and thus have never responded to it.
Memory lymphocyte definition?
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.
Active immunity definition?
The induction of an immune response within an individual by the introduction of antigen.
Passive immunity definition?
Immunity gained without antibody induction of a response.
e.g. Transfer of an antibody, immune serum, or activated lymphocytes into a naïve recipient.
Primary immune response definition?
The response made by naïve lymphocytes when they first encounter their specific antigen.
Secondary immune response definition?
The response made by memory lymphocytes when they re-encounter their specific antigen.
T lymphocyte definition?
- 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).
B lymphocyte defintion?
- 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.
Where are T and B lymphocytes produced and where are they released?
Produced in the primary lymphoid organs.
Are released into the peripheral lymphoid pool.
What is clonal selection?
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.
What happens to lymphocytes that do not meet their antigen?
Those that do not meet their antigen die.
The overall size of the total peripheral lymphoid pool is regulated by homeostatic mechanisms.
How does primary immune response work?
- 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.
How does secondary immune response work?
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.
How does natural selection link to the immune system?
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.
How is the immune system physically organised?
- 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.
What are primary lymphoid organs?
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.
What shape is the thymus and where is it located?
Bi-lobed in mammals
Located in the thorax
How are the lobes of the thymus arranged? How do T cells mature?
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.
What does the bone marrow do?
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.
What are secondary lymphoid organs?
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).
Human lymph node function?
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)
Shape of human lymph nodes?
1-15 mm across,
- Round or kidney shaped
- Have an indentation at the hilus where the blood vessels enter and leave the node
What 2 types of tissue does the spleen contain?
Red pulp and white pulp
What does the red pulp do?
Acts as a general filter for the blood.
What does the white pulp do?
The lymphoid tissue and constitutes the major initiator of responses to blood-borne antigens
What is found around the central arteriole in the spleen?
- 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.
What does MALT stand for and what does it do?
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.
How do lymphocytes recirculate?
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.
In the presence of infection, where are the cells that recognise the infectious agent held?
The lymphoid tissue where they proliferate and differentiate.
What is the CD system?
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.
Differences between T and B cells
RECOGNITION
T cells…
Recognise processed antigen presented at the cell surface by MHC molecules
B cells…
Recognize intact, free antigen (not presented by MHC molecules)
Differences between T and B cells
ANTIGEN RECEPTOR
T cells…
Antigen receptor is either αβ or γδ TCR
B cells…
Antigen receptor includes cell surface antibody
Differences between T and B cells
CDs EXPRESS
T cells…
All T cell express CD3: T cells express CD4 or CD8, but not both
B cells…
Express CD19 and CD20 at surface
What are antigen presenting cells?
Cells that can present antigen to lymphocytes in an immunogenic form are collectively termed antigen presenting cells, or APCs.
Name the 4 APCs
Dendritic cells
Follicular dendritic cells
B cells
Activated macrophages
Where are dendritic cells located?
What do they present to?
Widespread e.g. skin and mucosal tissue; migrate to draining lymph nodes
Present to…
T cells
Where are follicular dendritic cells located?
What do they present to?
Lymphoid follicles
Present to…
B cells
Where are B cells located?
What do they present to?
Lymphoid tissue
Present to….
T cells
Where are activated macrophages located?
What do they present to?
Lymphoid tissue, peripheral tissues
Present to…
T cells
