PHARM 310 - LEC 4 - Lymphocytes and Immune Response

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Questions and Answers

What determines whether lymphocytes become B cells or T cells?

The type of antigen they encounter

The secretion of antibodies initially

The number of receptor gene rearrangements

Their location during development (correct)

Which structural feature is unique to T cell receptors compared to antibodies?

Rearrangement of immunoglobulin genes

Presence of a constant region

Combination of an alpha and beta chain (correct)

Two binding sites for antigen

What is a key difference between the antigens that B cell antibodies and T cell receptors recognize?

T cells can bind soluble toxins without MHC

B cells only bind carbohydrates

B cells recognize only lipid antigens

T cells recognize peptide antigens presented by MHC (correct)

What is the major histocompatibility complex (MHC) crucial for?

Presenting peptide antigens to T cell receptors Signup and view all the answers

Why are MHC molecules important for tissue compatibility?

They have diverse variation in populations. Signup and view all the answers

Which statement regarding antibodies is incorrect?

Antibodies exclusively recognize peptide antigens. Signup and view all the answers

What occurs in T cells as they rearrange genes in the thymus?

They develop a unique variable region for antigen interaction. Signup and view all the answers

What is a likely consequence of MHC incompatibility?

Tissue graft rejection and graft versus host disease Signup and view all the answers

What can occur when a bone marrow graft containing leukocytes is received by a recipient?

Graft versus host disease Signup and view all the answers

What is the significance of the RAG enzyme complex in T cell receptor diversity?

It aids in the fragmentation of T cell genes. Signup and view all the answers

Which accessory proteins are essential for T cell receptor signaling?

CD3 complex Signup and view all the answers

How do T cells differentiate between T cell receptors after gene rearrangement?

By selecting either alpha beta or gamma delta receptors Signup and view all the answers

What role do MHC molecules play in T cell activation?

They present antigen in peptide form. Signup and view all the answers

Why are gamma delta T cells considered to play a role in cancer surveillance?

They can recognize and eradicate mutated cells. Signup and view all the answers

What happens if a lymphocyte chooses to express an alpha chain during T cell receptor development?

The delta chain locus cannot be expressed. Signup and view all the answers

What signals through the CD3 complex upon antigen binding?

Transduction of activation signals to the lymphocyte Signup and view all the answers

In what form can the T cell receptor recognize antigens?

As peptides bound to MHC molecules Signup and view all the answers

What characteristic distinguishes the gamma delta T cell from the alpha beta T cell?

Composed of different chain proteins Signup and view all the answers

What distinguishes CD4 from CD8 in structure?

CD4 has one stalk with four domains, CD8 has two stalks Signup and view all the answers

Which antigen-presenting cells express MHC class 2?

Dendritic cells, macrophages, and B cells Signup and view all the answers

What type of immune response is primarily activated by T helper 2 cells?

Antibody secretion by B cells Signup and view all the answers

What is the role of the beta-2 microglobulin in MHC class 1?

It stabilizes the MHC class 1 molecule Signup and view all the answers

What feature is unique to MHC class 2 compared to MHC class 1?

It binds CD4 coreceptors Signup and view all the answers

What is the primary role of cytotoxic T cells (CD8 T cells)?

To directly destroy infected or cancerous cells Signup and view all the answers

What mechanism does a CD8 T cell utilize to induce apoptosis in a target cell?

Directly triggering cell death pathways Signup and view all the answers

What does the term 'cluster of differentiation' (CD) refer to?

A molecular biology term for cell surface markers Signup and view all the answers

Which feature is characteristic of professional antigen-presenting cells (APCs)?

They can present antigens to all types of lymphocytes Signup and view all the answers

What role do CD8 coreceptors play in T lymphocyte interactions?

They stabilize presentation to the T-cell receptor. Signup and view all the answers

Which cells are classified as professional antigen-presenting cells?

Macrophages, B lymphocytes, and Dendritic cells. Signup and view all the answers

What is meant by 'degenerate peptide binding specificity' of MHC molecules?

MHC can accommodate various peptide shapes and charges. Signup and view all the answers

What identifies the primary function of MHC class 1 molecules?

They present endogenous antigens from the cytosol. Signup and view all the answers

How are antigens presented to T cells by professional antigen-presenting cells?

By loading onto MHC class 1 or 2 and presenting them. Signup and view all the answers

What is the main role of helper T cells activated by MHC class 2 molecules?

Help B cells synthesize specific antibodies. Signup and view all the answers

What are the primary compartments involved in antigen sampling and MHC loading?

Cytosol and vesicular system. Signup and view all the answers

Which characteristic distinguishes MHC class 2 molecules?

They are expressed by professional antigen-presenting cells. Signup and view all the answers

What cellular structure facilitates the synthesis of proteins that will be subsequently presented by MHC molecules?

Endoplasmic reticulum. Signup and view all the answers

What is the significance of endocytic vesicles in antigen processing?

They help in taking up extracellular antigens for processing. Signup and view all the answers

Which statement accurately reflects the function of CD4 coreceptors during T cell activation?

They enhance the interaction between MHC class 2 and T-cell receptors. Signup and view all the answers

What happens when a T lymphocyte recognizes a viral antigen presented by an antigen-presenting cell?

The T lymphocyte becomes activated to destroy the infected cell. Signup and view all the answers

Why is the ability of MHC molecules to present diverse peptides important?

To provide the immune system with a broader range of antigen detection. Signup and view all the answers

What is an essential function of macrophages activated by helper T cells?

They become effector cells responsible for phagocytosis. Signup and view all the answers

What is the primary function of MHC class 1 molecules?

Present endogenous antigens to CD8 cytotoxic T lymphocytes Signup and view all the answers

Which cells primarily express MHC class 2 molecules?

Professional antigen-presenting cells Signup and view all the answers

What is the role of the proteasome in the antigen processing pathway?

Degrading cytosolic proteins into peptide fragments Signup and view all the answers

What is the function of the invariant chain in the context of MHC class 2 processing?

Blocking premature binding of peptides in the MHC class 2 cleft Signup and view all the answers

Which process involves the loading of peptide fragments onto MHC class 1?

Peptide editing Signup and view all the answers

In which organ do T cells undergo negative selection to prevent autoimmunity?

Thymus Signup and view all the answers

How do MHC class 2 molecules acquire exogenous antigens?

Through processes like endocytosis and phagocytosis Signup and view all the answers

What is the fate of proteins derived by self-peptides carried by MHC class 1 in healthy cells?

They are ignored by the immune system Signup and view all the answers

What happens to MHC class 2 molecules when they are acidified in phagolysosomes?

The invariant chain is cleaved Signup and view all the answers

What is the initial purpose of CD4 co-receptors during T cell activation?

Binding to MHC class 2 molecules during antigen presentation Signup and view all the answers

What role does HLA-DM play in the MHC class 2 antigen presentation process?

Facilitating the release of the invariant chain Signup and view all the answers

Which of the following correctly describes the relationship between MHC class molecules and T lymphocytes?

MHC class 1 presents to CD8 T lymphocytes, while MHC class 2 presents to CD4 T lymphocytes Signup and view all the answers

Which component specifically blocks the binding of peptides to MHC class 2 in the ER?

Invariant chain Signup and view all the answers

What role does the invariant chain play in the assembly of MHC class 2 molecules?

It prevents peptides from binding to the MHC until transported to the surface. Signup and view all the answers

Which cell types are known to express MHC class 1 molecules?

All nucleated cells including T cells and B cells. Signup and view all the answers

What happens during the progressive acidification of the endocytic vesicle containing MHC class 2?

It activates proteases that cleave the invariant chain. Signup and view all the answers

How does the specialized MHC class 2-like molecule HLA-DM function?

It facilitates the removal of the clip peptide from class 2 molecules. Signup and view all the answers

What is primarily responsible for generating peptides that bind to MHC class 1 molecules?

The proteasome. Signup and view all the answers

What mechanism is employed by MHC molecules to create genetic variability?

Polymorphism of isotypes. Signup and view all the answers

What is the difference in antigen sampling between MHC class 1 and class 2 molecules?

Class 1 samples proteins from within the cell while class 2 samples from extracellular sources. Signup and view all the answers

Why can some peptides not bind to MHC molecules immediately?

The clip peptide occupies the peptide binding groove. Signup and view all the answers

Where does the folding and assembly of MHC class 1 molecules primarily take place?

In the lumen of the endoplasmic reticulum. Signup and view all the answers

What is the fate of red blood cells in relation to MHC class 1 molecules?

They have MHC class 1 during their nucleated stage but lose it when mature. Signup and view all the answers

What is the primary function of the TAP transporter in relation to MHC class 1?

It transports stable peptides into the endoplasmic reticulum. Signup and view all the answers

What is a significant difference between necrotic and apoptotic cells?

Necrotic cells release pro-inflammatory molecules, while apoptotic cells do not. Signup and view all the answers

Which effector molecule is primarily associated with CD8 cytotoxic T cells?

Lytic Granules (Perforin and Granzymes) Signup and view all the answers

How do CD4 T helper 1 cells primarily assist macrophages?

By providing pro-inflammatory cytokines which activates macrophages Signup and view all the answers

Which T helper cell type is known to activate antibody-secreting cells?

T helper 2 Signup and view all the answers

Which cell type is known as the 'master' antigen presenting cell?

Dendritic cells Signup and view all the answers

What role do selectins play in lymphocyte circulation?

They help in the capturing and rolling of lymphocytes along the endothelium. Signup and view all the answers

What is a characteristic outcome of necrosis in cells?

Spillage of cellular enzymes and pro-inflammatory molecules Signup and view all the answers

How do antigen presenting cells interact with lymphocytes in lymphoid tissues?

By presenting processed antigens bound to MHC molecules Signup and view all the answers

What key factor distinguishes mature antigen presenting cells from immature ones?

The presence of co-stimulatory molecules like B7 Signup and view all the answers

What is the primary function of intracellular adhesion molecules (ICAMs) in the lymph nodes?

To make endothelial vessels leakier and facilitate lymphocyte movement Signup and view all the answers

Which statement accurately describes the process of lymphocyte homing?

Lymphocytes utilize adhesion molecules to exit blood vessels and enter lymphoid tissues. Signup and view all the answers

CD2 is classified as what type of molecule in the immune response?

An adhesion molecule Signup and view all the answers

What process allows T cells to squeeze between endothelial cells to enter lymph nodes?

Diapedesis Signup and view all the answers

What is the role of vascular addressins in lymphocyte migration?

To facilitate interactions with lymphocyte selectins during homing Signup and view all the answers

What happens to naive T cells when they effectively encounter antigens?

They proliferate and differentiate into various effector T cells. Signup and view all the answers

How do dendritic cells enhance their antigen presenting capabilities?

By developing extensive dendritic processes to increase surface area Signup and view all the answers

What is the primary mechanism through which genetic diversity is generated in MHC molecules?

Meiotic recombination and inter-allelic conversion Signup and view all the answers

Which of the following pairs represents the MHC class I isotypes?

A, B, C, E, F, G Signup and view all the answers

What is a key characteristic of MHC class II isotypes?

They are highly polymorphic and bind many exogenously derived antigens. Signup and view all the answers

Which statement about T-cell receptor recognition is true?

Recognition requires matching both the peptide antigen and MHC isotype. Signup and view all the answers

Which of the following statements about alleles is accurate?

Alleles are different forms of the same gene. Signup and view all the answers

What does MHC restriction refer to?

The specific recognition of both peptide and MHC edges by T-cell receptors. Signup and view all the answers

Which MHC class II isotypes start with the letter 'D'?

DM, DQ, DR Signup and view all the answers

How does meiotic recombination contribute to MHC diversity?

It facilitates the exchange of segments between parental chromosomes. Signup and view all the answers

Which class of MHC molecules has a higher range of polymorphism in their binding region?

Class I A, B, and C isotypes Signup and view all the answers

What role does HLA-DM play in relation to MHC class II molecules?

It assists in peptide loading by dislodging the CLIP. Signup and view all the answers

What could result from MHC class II molecules creating a false recognition of self?

Development of autoimmune diseases Signup and view all the answers

What genetic mechanism allows for the shuffling of MHC diversity similar to a deck of cards?

Meiotic recombination Signup and view all the answers

How many total MHC class I and class II isotypes are mentioned?

11 Signup and view all the answers

What role do co-stimulatory molecules play in T cell activation?

They provide necessary signals in addition to antigen recognition. Signup and view all the answers

What event triggers the expression of B7 co-stimulatory molecules on antigen-presenting cells?

Presence of microbial surface components. Signup and view all the answers

What is the consequence of a T cell recognizing an antigen without receiving costimulation?

The T cell enters a state termed anergy. Signup and view all the answers

What initiates the upregulation of MHC molecules on antigen-presenting cells?

Recognition of foreign materials by innate immune receptors. Signup and view all the answers

What is the primary function of interleukin-2 in T cells?

It activates T cell proliferation and differentiation. Signup and view all the answers

Which cells are primarily responsible for upregulating B7 molecules after phagocytizing bacteria?

Macrophages. Signup and view all the answers

In the context of T cell activation, what does the term 'promiscuity of MHC haplotype' refer to?

The ability of MHC to present diverse peptides. Signup and view all the answers

What process allows B cells to internalize and present antigens via MHC class II?

Endocytosis. Signup and view all the answers

What is required for B cells to successfully activate T cells?

Costimulatory signals such as B7. Signup and view all the answers

Which of the following statements best describes how T cell activation occurs?

Involves both antigen recognition and a second costimulatory signal. Signup and view all the answers

What is the relationship between IL-2 receptor affinity and T cell activation?

Higher affinity receptors develop only after T cell activation. Signup and view all the answers

What role does CTLA4 play in T cell activation?

Inhibits T cell activation by binding B7 with higher affinity than CD28. Signup and view all the answers

How does a cytotoxic T cell induce apoptosis in a target cell?

By triggering membrane-bound ligands like FAS and releasing perforins. Signup and view all the answers

Which mechanism is responsible for CD8 T cell activation with help from CD4 T helper cells?

Costimulatory signaling through B7. Signup and view all the answers

What is the main function of CD4 T helper cells in the immune response?

To activate B cells for antibody production. Signup and view all the answers

What is a major consequence of CTLA4 binding to B7 on antigen-presenting cells?

Decreased T cell proliferation. Signup and view all the answers

In the context of T cell immunity, what does paracrine signaling refer to?

T cells signaling to adjacent cells using cytokines. Signup and view all the answers

What triggers the activation of cytotoxic T cells during a viral infection?

Binding of CD8 T cell to viral peptides presented by MHC class I. Signup and view all the answers

Which mechanism allows a CD8 T cell to produce IL-2 after its activation?

Through autocrine signaling. Signup and view all the answers

How does CD28 contribute to T cell activation?

By competing with CTLA4 for B7 binding. Signup and view all the answers

What is the result of a T cell experiencing a lack of costimulatory B7 during activation?

Inhibition of T cell activation. Signup and view all the answers

Study Notes

Lymphocyte Development

Lymphocytes, specifically B and T cells, originate from the same lineage in the bone marrow.
B cells are formed in the bone marrow and responsible for antibody production; T cells migrate to the thymus to develop further.

Structure and Function of T Cell Receptors

T cell receptors (TCR) consist of an alpha chain and a beta chain, linked by disulfide bonds.
TCR has a single binding site for antigens, unlike antibodies, which have two binding sites.
TCRs recognize peptide antigens presented by major histocompatibility complex (MHC) molecules.

Major Histocompatibility Complex (MHC)

MHC molecules are present on almost all nucleated cells but not on erythrocytes.
MHC molecules play a crucial role in tissue compatibility; MHC incompatibility can lead to graft rejection and graft-versus-host disease during transplants.

T Cell Diversity

T cell receptor gene diversity is generated through a rearrangement process involving the RAG enzyme complex.
Gene segments for TCRs are scattered across specific chromosomes (e.g., 14, 7, 2, 22).
Each T cell ultimately expresses a unique TCR due to gene rearrangement.

Accessory Proteins in T Cells

TCRs require accessory proteins called the CD3 complex to facilitate signaling upon antigen binding.
The CD3 complex consists of gamma, delta, epsilon, and zeta chains, critical for T cell activation.

Types of T Cells

TCRs are classified as either alpha-beta TCRs or gamma-delta TCRs.
Gamma-delta T cells form less than 5% of the total T cell population and are involved in cancer surveillance.

Antigen Processing and Presentation

TCRs can only recognize antigens as peptide fragments presented by MHC molecules.
Pathogen-derived proteins are processed inside cells to generate peptide fragments that bind to MHC molecules for display.

MHC Classes

MHC Class I is present on all nucleated cells and interacts primarily with CD8 cytotoxic T cells.
MHC Class II is found only on professional antigen presenting cells (APCs) such as dendritic cells and B cells and interacts with CD4 helper T cells.

T Cell Activation

The interaction between TCRs and MHC-peptide complexes is stabilized by co-receptors: CD4 for T helper cells and CD8 for cytotoxic T cells.
Helper T cells (CD4) assist in activating macrophages and B cells, while cytotoxic T cells (CD8) directly target and kill infected cells.

Professional Antigen Presenting Cells (APCs)

Dendritic cells are the most efficient APCs, followed by macrophages and B cells.
APCs load antigens onto MHC Class I or II for presentation to T cells.

Degenerate Binding Specificity of MHC

MHC molecules exhibit degenerate specificity, enabling them to bind various peptide shapes and charges.
This broad binding capability allows MHC to present a diverse array of antigens to T cells.

Intracellular Compartments and Antigen Loading

Cells have two main compartments: the cytosol (internal fluid) and the vesicular system (membrane-bound structures).
Antigens are sampled via endocytic vesicles, which then merge with lysosomes or the endoplasmic reticulum for MHC loading.

Summary of MHC and TCR Interactions

MHC class I presents endogenous antigens to CD8 T cells; MHC class II presents exogenous antigens to CD4 T cells.
This interaction is crucial for the immune response, determining whether T cells will help other immune cells or directly kill infected cells.### Antigen Presentation and T Cell Activation
Infected cells express viral or cancer antigens on their surface to signal cytotoxic T lymphocytes for destruction.
MHC Class I molecules, present on all nucleated cells, present endogenous antigens (self or viral) to CD8 T cells.
MHC Class II molecules, found only on professional antigen-presenting cells (APCs) like dendritic cells and macrophages, present exogenous antigens to CD4 T helper cells.

Lymphoid Organs

Primary lymphoid organs: bone marrow and thymus.
Secondary lymphoid organs: lymph nodes, spleen, and other aggregates of lymphoid cells.
APCs sample exogenous antigens, process them, and present them via MHC Class II in the lymphoid tissues.

MHC Class I Mechanism

Viral proteins in infected cells are degraded by the proteasome into peptide fragments, which are transported to the endoplasmic reticulum (ER).
Peptide editing occurs to ensure only high-affinity peptides bind to MHC Class I before being presented on the cell surface to CD8 T cells.

MHC Class II Mechanism

Extracellular pathogens are internalized through endocytic vesicles, which then fuse with lysosomes containing enzymes to degrade them into peptides.
Invariant chain blocks premature peptide binding in the ER and guides MHC Class II to lysosomal compartments where it eventually binds to pathogen-derived peptides after HLA-DM activity.

Diversity of MHC Molecules

MHC genes exhibit polymorphism, generating diversity among individuals through genetic variations and mechanisms like meiotic recombination.
Six MHC Class I isotypes: A, B, C, E, F, G.
Five MHC Class II isotypes: DM, DP, DQ, DR, DO.

MHC Restriction

T-cell receptors recognize both the presented peptide and the MHC molecule, necessitating congruence for T cell activation.
Failure to match either the peptide or the MHC receptor results in no T cell activation.

Antigen-Processing Cells and Homing

Dendritic cells and macrophages transport processed antigens to secondary lymphoid tissues via lymphatics, allowing interaction with T lymphocytes.
Adhesion molecules facilitate the movement of lymphocytes into lymph nodes from the bloodstream, allowing targeted immune responses.

Key Vocabulary

Cytotoxic T lymphocytes: Immune cells that kill infected cells.
CD4/CD8 T cells: Subtypes of T lymphocytes that interact with Class II/Class I MHC molecules, respectively.
Peptide editing: Process of ensuring stable peptide-MHC binding.
Invariant chain: Protein that prevents premature peptide binding to MHC Class II in the ER.### Lymphocyte Migration and Activation
Lymphocytes migrate into lymphoid tissues by rolling on endothelial cells and adhering tightly through adhesion molecules.
Professional antigen-presenting cells (APCs) like dendritic cells sample antigens in infected tissues and transport them to lymph nodes.
In lymph nodes, dendritic cells present antigens to naive T cells on Major Histocompatibility Complex (MHC) class II molecules.

Antigen Presentation and Costimulation

Dendritic cells, macrophages, and B cells act as APCs, with dendritic cells being the most effective at antigen presentation.
Costimulatory molecules, like B7, on APCs are essential for T cell activation alongside MHC molecule binding.
Immature APCs express few MHC and costimulatory molecules, limiting their ability to activate T cells.

T Cell Activation Process

T cell activation requires two signals: specific recognition of the antigen by the T cell receptor and a costimulatory signal from the APC.
Activated T cells proliferate and differentiate; Interleukin-2 (IL-2) plays a crucial role in this process by promoting T cell growth and survival.
Absence of costimulation leads to an anergic state, rendering T cells unresponsive to antigens.

Mechanisms of T Cell Activation

B cells also present antigens: they bind specific antigens, internalize them, and present them on MHC class II molecules to activate T cells.
Three activation mechanisms for cytotoxic T cells include autocrine IL-2 signaling, costimulatory signals from helper T cells, and paracrine signaling from adjacent activated cells.

Cytotoxic T Cell Function

Cytotoxic T cells induce apoptosis in infected target cells using death-domain ligands (e.g., FAS) and release perforin and granzymes.
Perforin creates pores in target cell membranes, while granzymes initiate the degradation of cell structures to promote cell death.

Distinctions in Cell Death

Apoptotic cells undergo a clean, non-inflammatory process, contrasting with necrotic cells that release pro-inflammatory signals due to cellular lysis.
Apoptosis is characterized by chromatin condensation and vesicle formation, allowing for a tidy disposal of the dying cell without triggering inflammation.

T Helper Cell Functions

CD4 T helper cells differentiate into subsets (e.g., Th1 and Th2).
Th1 cells primarily activate macrophages and promote pro-inflammatory responses.
Th2 cells are involved in B cell activation and antibody production.

Immune Regulation Mechanisms

CTLA-4, an important receptor on T cells, competes with CD28 for binding to B7, downregulating T cell activation after an immune response.
Effector T cells produce varied effector molecules, with CD8 T cells focused on cytotoxic functions and CD4 T cells on helper roles for macrophages and B cells.

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Description

This quiz explores the development and function of lymphocytes, focusing on the differentiation of B and T cells from their common lineage in the bone marrow and thymus. Understand the processes of gene rearrangement and receptor expression that are crucial for immune response.