Lecture #142: Immunogenetics, Lymphocyte Activation, Immune Reg. and Tolerance 2

What is the focus of immune responses after antigen recognition?

Expansion, differentiation, memory formation, regulation, and resolution determine whether immunity leads to protection or pathology.

What is clonal selection?

Only antigen-specific lymphocytes are selected for activation, ensuring specificity but creating a problem because these cells are initially rare.

Why is clonal expansion necessary?

It increases the number of antigen-specific lymphocytes to generate sufficient effector cells to control disease.

What is the danger of clonal expansion?

It is powerful but can cause tissue damage if not properly regulated.

What signals support lymphocyte expansion?

Costimulation promotes survival and proliferation, cytokines reinforce expansion, and context determines whether expansion occurs.

Why is antigen recognition alone insufficient?

Without costimulation and cytokines, lymphocytes will not expand effectively or may become inactive.

What is differentiation in immune responses?

The process by which activated lymphocytes develop specialized functional roles such as cytotoxic or helper functions.

Why is differentiation important?

It assigns appropriate immune functions tailored to specific threats, improving effectiveness and safety.

What are effector cells?

Differentiated lymphocytes that perform immune functions such as killing infected cells or coordinating immune responses.

Why is effector diversity important?

Different immune threats require specialized responses, so diversity improves effectiveness and minimizes damage.

What is immunologic memory?

A subset of activated cells becomes long-lived and allows faster, stronger responses upon re-exposure to the same antigen.

Why is memory formation important?

It enables rapid secondary responses and is a defining feature of adaptive immunity.

What must happen after immune activation to prevent damage?

Contraction must occur to terminate the immune response and restore balance.

What is contraction?

The process where effector cells undergo apoptosis after the immune response, restoring homeostasis.

Why is contraction not considered failure?

It indicates successful immune response and prevents prolonged tissue damage.

What happens if contraction fails?

Persistent effector cells can lead to chronic inflammation and disease.

How are effector and memory cell fates determined?

Early signals during activation influence whether cells become short-lived effectors or long-lived memory cells.

What factors influence memory formation?

Cytokine environment, antigen strength and duration, and metabolic and gene regulation changes.

What are advantages of memory cells?

Faster activation, reduced costimulation requirements, and stronger secondary immune responses.

How are memory cells maintained long-term?

They persist without antigen and are supported by survival cytokines and regulated homeostasis.

What is immune resolution?

An active coordinated process involving effector cell loss, memory preservation, and tissue repair.

What happens when immune resolution is poorly regulated?

It leads to persistent inflammation and disease.

Why is tolerance necessary?

Lymphocyte receptor specificity risks self-reactivity, so tolerance prevents immune attacks on self tissues.

What is tolerance?

Mechanisms that prevent immune responses against self antigens to maintain immune safety.

What are the two main types of tolerance?

Central tolerance during development and peripheral tolerance in mature lymphocytes.

Where does central tolerance occur for T cells?

In the thymus during T-cell development.

What is the purpose of central tolerance?

To eliminate nonfunctional or strongly self-reactive lymphocytes.

What is negative selection?

The process by which strongly self-reactive T cells are eliminated during development.

Why is central tolerance incomplete?

Not all self antigens are present during development, requiring peripheral tolerance as backup.

What is peripheral tolerance?

Mechanisms that control mature lymphocytes that encounter self antigens outside primary lymphoid organs.

What are mechanisms of peripheral tolerance?

Anergy, deletion, and suppression by regulatory cells.

What is anergy?

A state of functional inactivation where lymphocytes survive but cannot respond to antigen.

When does anergy occur?

When antigen is recognized without costimulation.

What is the role of regulatory T cells?

They suppress immune responses and maintain immune homeostasis.

What transcription factor defines regulatory T cells?

FOXP3 defines the regulatory T-cell program and is required for suppressive function.

What happens if FOXP3 is defective?

Loss leads to immune dysregulation and autoimmunity.

Why is immune regulation important?

It prevents excessive responses that could damage host tissues.

What are consequences of failed immune regulation?

Autoimmunity and chronic inflammatory disease.

How does tolerance integrate with immune responses?

It shapes responses to ensure they are appropriate and not harmful.

How do B cells maintain tolerance?

Through central tolerance in the bone marrow and peripheral mechanisms such as anergy and deletion.

What is receptor editing in B cells?

A process that alters antigen receptor specificity to reduce self-reactivity.

Why is receptor editing important?

It preserves useful B cells while preventing autoimmunity.

Why do B cells require T-cell help?

T-cell help acts as a checkpoint to prevent inappropriate or self-reactive antibody production.

What is transplantation immunology?

The immune response to foreign tissue introduced into the body.

What is allorecognition?

The recognition of donor MHC molecules by recipient T cells.

What are the two pathways of allorecognition?

Direct recognition of donor MHC and indirect recognition via processed donor antigens.

What are the types of transplant rejection?

Hyperacute, acute, and chronic rejection, each differing in timing and mechanism.

What is the purpose of immunosuppression in transplantation?

To prevent rejection by dampening immune responses.

What is the risk of immunosuppression?

Increased susceptibility to infections.

What is the central theme of immune regulation?

Balance between effective protection and prevention of tissue damage.

What is the overall sequence of adaptive immune response?

Activation, expansion, differentiation, regulation, contraction, and memory formation.