Lymphoid Tissues

Why is the immune system considered more complex than many other body systems?

Because specialised immune cells and molecules are found in almost every tissue in the body and can act both locally and systemically.

Can non-specialised cells contribute to immunity?

Yes. Nearly all nucleated cells can mount immune responses and interact with professional immune cells.

Why is the immune system distributed throughout the body?

Because potential threats can enter through many different tissues and organs.

What is healthy tissue homeostasis?

Maintenance of normal tissue function and balance, a process in which the immune system plays an important role.

Why do B and T cells require specialised lymphoid organs?

Because the generation, selection and activation of highly specific adaptive immune cells requires specialised environments.

What is the major challenge faced by the adaptive immune system?

Finding extremely rare antigen-specific lymphocytes and bringing them together with their matching antigen.

Why are adaptive immune responses highly specific?

Each B cell and T cell expresses a unique antigen receptor.

What happens to a B-cell receptor when a B cell becomes activated?

It can be secreted as an antibody.

What is the role of antibodies after secretion?

They can bind antigens distant from the B cell that produced them.

What is the major difference between B-cell and T-cell responses?

B cells primarily produce antibodies, whereas T cells mediate cell-to-cell immune responses.

Where is the antigen-binding site of an antibody located?

At the tip of the heavy-chain and light-chain variable regions.

What is the purpose of the antibody constant region?

It provides distinct effector functions and structural support.

Why do antibodies contain both variable and constant regions?

The variable region binds antigen while the constant region determines biological function.

What is V(D)J recombination?

A genetic rearrangement process that creates unique antigen receptor sequences in B and T cells.

Why is V(D)J recombination necessary?

It generates enormous receptor diversity capable of recognising many different antigens.

What happens to unused V, D and J gene segments during receptor generation?

They are physically excised from the genome.

Why is receptor diversity important for survival?

It increases the likelihood that at least one lymphocyte can recognise a newly encountered pathogen.

What is a common lymphoid progenitor?

A precursor cell capable of differentiating into B cells, T cells, NK cells and several other lymphocyte populations.

What determines whether a common lymphoid progenitor becomes a B cell or T cell?

The developmental signals it receives.

What is a pre-B cell?

An early B-cell precursor committed to the B-cell developmental pathway.

What is a pre-T cell?

An early T-cell precursor committed to the T-cell developmental pathway.

Why do T-cell precursors leave the bone marrow?

To complete maturation and selection within the thymus.

Why do B-cell precursors largely remain in bone marrow?

B-cell receptor generation and much of B-cell development occur there.

What does the term repertoire mean in immunology?

The range of genetically distinct B-cell receptors or T-cell receptors present within a host.

What advantage does a larger immune repertoire provide?

It increases the range of threats that can potentially be recognised.

What are thymocytes?

Developing T cells located within the thymus.

What is the first stage of T-cell development in the thymus?

The double-negative stage, where cells express neither CD4 nor CD8.

Why are early thymocytes called double-negative cells?

Because they express neither CD4 nor CD8 surface proteins.

What characterises the double-positive stage of T-cell development?

The cells express both CD4 and CD8 as well as a T-cell receptor.

Why is positive selection necessary?

To ensure developing T cells possess a functional T-cell receptor capable of signalling.

What happens if a thymocyte fails positive selection?

It undergoes apoptosis.

Why can a thymocyte fail positive selection?

V(D)J recombination may generate a non-functional T-cell receptor.

What is the purpose of negative selection?

To eliminate T cells that strongly recognise self-antigens.

Why are self-reactive T cells dangerous?

They can trigger autoimmune disease.

What happens to thymocytes that react strongly against self-antigens?

They undergo apoptosis during negative selection.

What antigens are displayed during negative selection?

A broad range of self-antigens encoded by the body.

Why does the immune system deliberately test T cells against self-antigens?

To ensure harmful autoreactive cells are deleted before entering the circulation.

What happens after successful positive and negative selection?

T cells mature into CD4+ helper or CD8+ cytotoxic T cells.

What is the significance of central tolerance?

It prevents many autoreactive T cells from entering the peripheral immune system.

Why is central tolerance not perfect?

Additional peripheral tolerance mechanisms are required to control remaining autoreactive cells.

At what stage of life is T-cell production highest?

Early childhood.

Why is early life associated with high thymic output?

Many new T cells are needed to build a broad immune repertoire against environmental challenges.

How does the thymus change during ageing?

It becomes progressively smaller and increasingly replaced by fatty tissue.

Why do elderly individuals generate fewer new T cells?

Because thymic involution reduces thymic function.

Why are antigen-specific T cells rare?

The potential TCR repertoire is vastly larger than the total number of T cells in the body.

Why is a system required to concentrate antigens and lymphocytes together?

Because the chance of random encounters between rare antigen-specific lymphocytes and their antigen is otherwise extremely low.

What is the main function of secondary lymphoid organs from a systems perspective?

To maximise encounters between antigens and rare antigen-specific lymphocytes.

Why are secondary lymphoid organs highly organised?

Organisation increases the efficiency of immune-cell interactions and antigen recognition.

What is the functional purpose of separate T-cell and B-cell zones?

To organise immune cell interactions and optimise adaptive immune responses.

Why are germinal centres considered evidence of active immune responses?

They are sites where activated B cells proliferate and undergo affinity maturation.

What is affinity maturation?

The process by which B cells evolve higher-affinity antibodies during an immune response.

Why do germinal centres enlarge during immune responses?

Activated B cells rapidly proliferate and undergo selection within them.

Why does the spleen monitor blood rather than lymph?

Its specialised role is surveillance of blood-borne antigens.

Why are many secondary lymphoid tissues located near mucosal surfaces?

Because most foreign antigens enter the body through mucosal tissues.

Why are Peyer's patches particularly rich in germinal centres?

The gastrointestinal tract is constantly exposed to large amounts of foreign antigen.

Why is IgA the dominant antibody at mucosal surfaces?

It is particularly suited to protecting mucosal tissues while causing relatively little inflammation.

In which tissues is IgA especially abundant?

Gut, respiratory tract and reproductive tract mucosa.

Why is excessive inflammation undesirable at mucosal surfaces?

It could damage delicate barrier tissues exposed continuously to environmental antigens.

How does IgA help maintain a healthy microbiome?

It limits overgrowth of strongly stimulatory microbes and promotes microbial diversity.

Why does the immune system interact with the microbiome?

The microbiome influences health and requires regulation to maintain balance.

What is meant by common mucosal immunity?

Immune responses generated at one mucosal site can provide protection at other mucosal surfaces.

Why do tonsils contain prominent germinal centres?

They are continuously exposed to inhaled and ingested antigens.

What types of antigens are encountered by tonsils?

Microbial antigens, food antigens, fungal antigens and viral antigens.

Why do approximately 2-3 litres of lymph return to the circulation each day?

To return tissue fluid and transport molecules and immune-related material through the lymphatic system.

How does lymphatic flow contribute to immune surveillance?

It continuously transports antigens through secondary lymphoid tissues.

Why do naïve T cells recirculate continuously?

To increase their chance of encountering their specific antigen.

How do inflamed lymphoid tissues recruit additional lymphocytes?

By producing chemotactic signals that attract immune cells.

What is chemotaxis?

Directed movement of cells toward chemical attractants.

Why does inflammation increase lymphocyte recruitment?

It improves the likelihood of mounting a productive immune response.

What is the purpose of rolling during extravasation?

It slows lymphocytes so they can sample signals from endothelial cells.

What causes firm adhesion during extravasation?

Activation of adhesion molecules such as integrins.

What is transendothelial migration?

The movement of immune cells through the endothelial layer into tissues.

Why are dendritic cells called professional antigen-presenting cells?

They are particularly efficient at processing and presenting antigens to T cells.

Why do dendritic cells express high levels of MHC molecules?

To maximise their ability to present antigen to T cells.

What happens to dendritic cells after they capture antigen in tissues?

They migrate to secondary lymphoid organs.

Why is dendritic cell migration important?

It physically transports tissue-derived antigens to sites containing large numbers of lymphocytes.

What is a Langerhans cell?

A specialised dendritic cell found in the epidermis.

Why are Langerhans cells strategically positioned in the skin?

They can rapidly detect and capture invading antigens.

What is a cognate interaction?

A highly specific interaction between a T-cell receptor and its matching antigen-MHC complex.

What happens when a T cell encounters its cognate antigen on a dendritic cell?

The T cell becomes activated and begins proliferating.

Why do antigen-specific T cells slow down within lymph nodes during activation?

They form stable interactions with antigen-presenting dendritic cells.

What does expansion of antigen-specific T cells mean?

Activated T cells proliferate to increase the number of cells capable of responding to the antigen.

Why is clonal expansion important?

It generates enough effector cells to mount an effective immune response.

How do lymphoid tissues contribute to immunological memory?

They provide environments where antigen-specific lymphocytes can become activated and expand into long-lived memory populations.

What is the immune system?

A body-wide system that protects against foreign substances and helps maintain tissue homeostasis.

Why can immunology seem difficult to learn?

Immune cells and molecules are distributed throughout nearly every tissue in the body and interact both locally and systemically.

What is the major function of primary lymphoid tissues?

Production and development of lymphocytes (lymphopoiesis).

What is the major function of secondary lymphoid tissues?

Allow lymphocytes to encounter antigens and generate immune responses.

What are the three major lymphocyte classes produced during lymphopoiesis?

B cells, T cells and natural killer (NK) cells.

What are the two hallmarks of adaptive immunity?

Specificity and memory.

What does specificity mean in adaptive immunity?

B and T cells can recognise specific antigens through unique receptors.

What does immunological memory mean?

A faster and stronger response occurs upon re-encountering the same antigen.

What is an antigen?

A molecule recognised by B-cell receptors or T-cell receptors that can trigger an immune response.

How do B cells respond to antigen recognition?

They produce and secrete antibodies.

What is another name for the B-cell receptor?

Immunoglobulin (antibody).

How do T cells respond to antigen recognition?

They interact directly with cells presenting antigen and mediate cellular immune responses.

What is the antigen-binding region of an antibody?

The variable region at the tip of the heavy and light chains.

What is the function of the antibody constant region?

It determines the effector functions of the antibody.

What are the two major T-cell receptor forms?

αβ TCR and γδ TCR.

Where does antigen recognition occur on the TCR?

In a specialised antigen-binding pocket.