Immunology Exam 2 Final Set

The purpose of negative selection in B and T cells

To eliminate or neutralize B cells that recognize and react against the body's own self antigens.

The process negative selection in B cells establishes

Central tolerance

What central tolerance prevents

The immune system from attacking healthy tissues, which helps prevent autoimmune diseases.

Where clonal selection and activation of B and T cells is occuring

Secondary lymphoid organs (lymph nodes and spleen)

How the negative selection process is activated in T cells

Antigen presenting cells travel from infected tissues to the lymph nodes and present fragments (antigens) on MHC I proteins to T receptors

How the negative selection process is activated in B cells

Activated by binding directly to free-floating or membrane bound antigens via BCRs. Requires help from activated CD4+ helper T cells

How many polypeptide chains antibodies have

Four polypeptide chains (two heavy, two light)

What the polypeptide chains in antibodies are composed of

Constant and variable regions linked by covalent disulfide bonds

Hinge region

Allows flexibility in binding to multiple antigens

Constant region

Confers functional specialization on the antibody

Localized regions of hypervariable sequence (CDRs)

Form the immunoglobulin antigen-binding site

How antibodies bind to antigens

Via contacts in CDRs that are complementary to the size and shape of the antigen

Antibodies

Recognize linear or conformational determinants in folded proteins

T cells

Only recognize unfolded linear peptides when presented by an antigen presenting cell (ex. Dendritic cell)

Antigen recognition mechanisms

B-cells receptors bind directly to antigen. T-cells receptors bind a complex of antigen fragment and MHC found on the surface of the antigen-presenting cells

What is V(D)J recombination?

A process that generates diversity in antibodies at the genetic loci of immunoglobulin genes.

What type of genetic change does V(D)J recombination represent?

A permanent genetic change that occurs independently in each B cell

How B cell and T cell diversity is achieved

This huge diversity is achieved by combinatorial complexity from the random combination of segments from a large pool of possible segments. For the light chain, one random V segment recombines with one random J segment to form a unit light chain gene. For heavy chains, one random V segment recombines with one random D segment and then one random J segment to form a unit heavy chain gene.

How naïve B cells cells get activated by interacting with antigen

Signals required for B cells are antigens, the receptors needed are BCRs, B cells are involved, the activation occurs in secondary lymphoid organs/peripheral lymphoid organs

How naïve T cells cells get activated by interacting with antigen

Signals required for T cells are CD4+, T cell activates B cell, the receptor needed is TCR on T cell and MHC II on B cell, the cells involved are B cells, T cells (CD4+ helper), activation occurs in secondary lymphoid organs

Consequences to both steps required for B cells to secrete antibodies

B cells differentiate into plasma cells and clonal expansion occurs

How T cells recognize antigens through their unique T cell receptors (TCRs)

The T-cell receptor interacts with MHC class I and MHC class II molecules. The TCR simultaneously binds to both the alpha helices in the MHC that surround the peptide binding groove and the peptide bound inside the binding groove of the MHC.

MHC I on the APC binds to

TCRs on cytotoxic (killer) T cells (CD8+)

MHC II on the APC binds to

TCRs on helper (activating) T cells (CD4+)

Why CD4 and CD8 are known as co-receptors.

The CD4 or CD8 cell-surface proteins of T cells directly contact MHC molecules and are required to make an effective response to antigen

Why must T cells an B cells interact with antigen 2 times before they can perform their effector immune functions.

After encountering antigen, naïve b cells get activated and undergo clonal expansion and differentiation into effector b cells such as antibody secreting plasma cells. B cells directly bind to antigen that is delivered to secondary/peripheral lymphoid organs from circulation. In contrast, T cells are presented antigens by dendritic cells that migrate to the secondary/peripheral lymphoid organs through the lymphatic circulatory system. As a result of naïve B cells and T cells interacting with antigen for the first time, the B cells or T cells activate B cell receptor signaling or T cell receptor signaling, respectively. This leads to clonal expansion of the B cells or T cells specific for the antigen and differentiation into effector B or T cells. The second time B cells or T cells encounter antigen is when the effector B and T cells interact with antigen at the site of infection, injury, or tumor and perform their immune effector function to fight against the pathogen.

What is the role of MHC Class I in activating CD8+ T cells?

MHC Class I molecules present peptide antigens from intracellular pathogens to activate naïve CD8+ T cells, leading to their differentiation into effector cytotoxic T cells.

How are peptide antigens from intracellular pathogens presented on MHC Class I molecules?

Peptide antigens from intracellular pathogens are presented on MHC Class I molecules through the delivery of peptide fragments generated by the ubiquitin-proteasome system to the ER.

What is the function of TAP in the MHC Class I antigen presentation process?

TAP is a transporter that allows the passage of peptides from the cytosol to the endoplasmic reticulum for binding to MHC Class I.

What happens to MHC Class I + peptide complexes after they are formed?

MHC Class I + peptide complexes are delivered to the cell surface to present antigens to effector cytotoxic T cells.

How do dendritic cells cross-present antigens to CD8+ T cells?

Dendritic cells cross-present antigens by taking up dead infected cells through phagocytosis, allowing peptide fragments to bind to MHC Class I.

What is the role of chaperones in the MHC Class I pathway?

Chaperones bind to MHC Class I in the ER to ensure the stability of the MHC Class I molecule.

What is the outcome of CD8+ T cell activation by MHC Class I presentation?

The activation of CD8+ T cells leads to their clonal expansion and differentiation into effector cytotoxic T cells, which can kill infected cells.

What is the role of MHC Class II in activating CD8+ T cells?

MHC Class II presents peptide antigens from extracellular pathogens to CD4+ T cells.

How are peptide antigens from extracellular pathogens presented on MHC Class II?

Peptide fragments generated in endocytic/phagocytic vesicles are delivered to MHC Class II in secretory vesicles.

What happens when endocytic vesicles containing peptide antigens fuse with secretory vesicles?

Antigen binds to MHC Class II.

What is the role of chaperones in relation to MHC Class II?

Chaperones bind to MHC Class II in the ER to ensure its stability before binding to peptide antigens.

What occurs after antigen binding to MHC Class II?

MHC + peptide antigen complexes are delivered to the cell surface to present antigens to T cells.

How are peptide antigens from intracellular pathogens presented on MHC Class II?

Peptide fragments generated in autophagosomes are delivered to MHC Class II in secretory vesicles.

What happens when autophagosomes containing peptide antigens fuse with secretory vesicles?

Antigen binds to MHC Class II.

What is polymorphism in the context of MHC genes?

Polymorphism refers to the presence of many alleles of MHC class I and MHC class II genes within the human population.

Which genes have the most unique alleles in the human genome?

MHC class I and MHC class II genes have more unique alleles than any other genes in the human genome.

Where is most of the polymorphism in MHC genes concentrated?

Most of the polymorphism is concentrated in the peptide-binding groove.

What is the significance of the peptide-binding groove in MHC alleles?

The peptide-binding groove gives different peptide-binding specificity for each unique MHC I or MHC II allele.

What is the likelihood of an individual having two copies of the same MHC allele?

It is highly unlikely that any one person has two copies of the same allele due to the vast array of MHC gene alleles.

How are MHC alleles inherited?

Individuals have two distinct alleles of each MHC gene, one inherited from each parent.

What does genetic diversity in MHC alleles allow?

Genetic diversity allows MHC molecules to recognize a wider array of peptide antigen substrates.

What is polygeny in the context of MHC genes?

Polygeny refers to the presence of multiple genes for MHC class I and class II in the human genome.

How many distinct genes are there for MHC class I in humans?

There are three distinct genes for MHC class I in humans.

How many distinct genes are there for MHC class II in humans?

There are six distinct genes for MHC class II in humans.

What is the significance of having multiple MHC genes?

Having multiple MHC genes leads to genetic diversity and allows MHC molecules to recognize a wider array of peptide antigen substrates.

How T cell receptor binding to the MHC as well as the peptide antigen leads to MHC restriction of each T cell receptor for a specific MHC molecule. Understanding the implications of MHC polymorphism affecting MHC restriction

Since T cell receptors recognize both antigens of MHC molecules at the same time, recognition of an MHC I or MHC II molecule is restricted for each T cell receptor. This means that an individual T cell receptor may not recognize or bind to one of your MHC alleles, even if they are bound to the same peptide antigen. Each unique MHC allele has differences in the peptide-binding groove, which determine which peptide antigens it can present. However, unlike B cell and T cell receptors, unique MHC alleles can present multiple antigens as long as they share similar chemistry at key anchor residues.

What are the major classes of T cells?

CD8+ cytotoxic T cells and CD4+ helper T cells

What is the function of CD4+ Helper T cells?

They activate other immune cells and protect against intracellular and extracellular bacteria, viruses, and fungi.

What do CD4+ Helper T cells recognize?

Antigens via MHC II molecules on professional antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells.

What type of pathogens do CD8+ Cytotoxic T cells protect against?

Intracellular pathogens, including viruses and tumor/cancer cells.

What do CD8+ Cytotoxic T cells recognize?

Antigens via MHC I molecules on nucleated cells.

How are peptide antigens presented to CD4+ Helper T cells?

Peptide antigens from extracellular or intracellular pathogens are presented on MHC class II molecules to naïve CD4+ T cells.

How are peptide antigens presented to CD8+ Cytotoxic T cells?

Peptide antigens from intracellular pathogens are presented on MHC class I molecules after dendritic cells phagocytose dead infected cells.

What is the role of dendritic cells in T cell activation?

Dendritic cells present antigens to naïve T cells via MHC molecules, activating their clonal expansion and differentiation.

How somatic hypermutation of the variable regions of the immunoglobulin genes and selects for B cells that have B cell receptors (and antibodies) with enhanced affinity for their antigens

During clonal expansion and B cell differentiation, immunoglobulin genes (light chains) undergo somatic hypermutation to introduce additional diversity into the B cell repertoire. These mutations can further enhance antibody/antigen interactions. B cells can undergo class switching, in which the immunoglobulin heavy-chain RNA is alternatively spliced to produce antibodies with distinct constant (Fc) regions. These distinct constant (Fc) regions can interact with different immune effector cells to produce different immune responses.

Five classes of antibodies

IgA, IgD, IgE, IgG, IgM, Distinguished by the structure of their heavy chain constant regions

How antibody class switching affects opsonization

Enhances opsonization by shifting B cell production from low-affinity (IgM) to high affinity (igG) which binds more effectively Fc receptors on phagocytic cells

How antibody class switching affects activation

Maintains complement-fixing ability while adding tissue mobility and specialized receptor interactions

How antibody class switching affects neutralization

Allows for high-affinity mucosal defense or deep tissue/systemic production

How B cells take in antigens that bind to the B cell receptor, break these down into peptide antigens and present them on MHC II molecules to facilitate the interaction of the B cell with an activated CD4+ T helper cell and how the CD4+ T helper cell secretes cytokines to fully activate the B cell to undergo clonal expansion and differentiate into an effector B cell.

B cells require an initial activating signal which occurs when an antigen binds to their B cell receptors. After binding, B cells take in the antigens, break them down into peptide antigens, and present them on their surface using MHC II molecules. Presenting the antigen on MHC II molecules facilitates the B cell's interaction with an activated CD4+ helper T cell, which provides the necessary second activating signal. The CD4+ (helper T) cell secretes cytokines to fully activate the B cell. This causes the B cell to undergo clonal expansion and differentiate into an effector B cell.

How much combinatorial diversity contributes to the diversity of T cell and B cell receptors.

Rag 1 and rag 2 are unique to B cells and T cells and are exclusively involved in recombination. These recognize recombination signal sequences (RSSs) in the immunoglobulin genes.

The basis of the asymmetric 12/23 rule for RSS recognition by Rag1 and Rag2

The fidelity of recombination (meaning only v segments recombine with d segments) is ensured by the asymmetric spacer 12/23 rules imposed by rag1/rag2 structure.