10/6/22, 1:05 PM Laboratory Simulation

Student: Karen Joy Magbanua

Apply What You Have Learned

Imagine a genetic defect where positive selection of thymocytes occurs normally, but
negative selection does not occur. Which of the following is a likely detrimental result?
Mature thymocytes will be produced that are self-reactive, recognizing self-antigen with their TCRs

Bacteria invading a wound are clumped together by antibodies. The exposed Fc regions
are bound by a macrophage and the entire clump of cells is engulfed. Which two effector
functions of antibodies does this example describe?

Agglutination
Opsonization

Summary of Adaptive Processes

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Critical Concepts

Overview of Lymphocyte Formation and Migration

B-lymphocytes (B-cells) and T-lymphocytes (T-cells) form and develop in primary lymphoid
structures.

B-lymphocytes complete their development in the red bone marrow, whereas pre-T-
lymphocytes leave the marrow and finish development in the thymus.

Fully developed lymphocytes migrate to secondary lymphoid structures (e.g., lymph nodes,
spleen) where they are likely to encounter foreign antigens.

Development of B-Lymphocytes in the Red Bone Marrow

B-lymphocytes express unique B-cell receptors (BCRs) through a gene shuffling process called
somatic recombination.

The BCR is a Y-shaped immunoglobulin molecule projecting from the surface of the cell. Each
BCR is capable of binding to an antigen at its antigen-binding sites.

All BCRs on a single B-lymphocyte are identical, so each B-lymphocyte is only capable of
responding to a single antigen.

Movement of T-Lymphocytes in the Thymus

Pre-T-lymphocytes migrate from the red bone marrow to the thymus to complete their
development. Once in the thymus, they are called thymocytes.

Thymocytes begin in the thymic cortex and progress to the medulla. The hormone thymosin,
produced in the thymus, stimulates this process.

Formation of T-Cell Receptors and CD Coreceptors

Each thymocyte expresses an antigen-specific T-cell receptor (TCR) through the gene shuffling
process of somatic recombination.

Coreceptor proteins called CD4 and CD8 are also expressed at this time. The resulting
thymocyte is CD4+ and CD8+, also referred to as "double-positive."

Positive Selection of Thymocytes

During development in the thymus, thymocytes undergo stringent screening processes called
positive and negative selection. Only about 2% of cells make it to maturity.

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Positive selection involves testing the ability of double-positive thymocytes to bind major
histocompatibility complex (MHC) class I or MHC class II proteins displayed by thymic
epithelial cells.

Double-positive thymocytes with either CD8 proteins that bind MHC class I, or CD4 proteins
that bind MHC class II, survive this process.

Negative Selection of Thymocytes

Thymocytes that survive positive selection next undergo negative selection.

Negative selection tests the ability of double-positive thymocytes to "tolerate" (not bind
strongly to) self-antigens. This screening is important to avoid producing self-reactive T-
lymphocytes that cause autoimmune diseases.

Thymic dendritic cells display self-antigens on MHC complexes. Thymocytes that bind self-
antigens with their TCRs are induced to undergo apoptosis, while surviving thymocytes
continue maturing.

Outcome of Thymic Selection Processes

Double-positive thymocytes that survive the selection processes become single-positive

thymocytes that express only one type of CD protein (i.e., CD4 or CD8, but not both).

CD8+ cells are called naive cytotoxic T-lymphocytes.

CD4+ cells are called naive helper T-lymphocytes.

Presentation of Endogenous Antigen with MHC Class I

Cytotoxic (CD8+) T-lymphocyte activation depends upon binding to endogenous antigens

presented with MHC class I on the surface of an APC.

Endogenous antigens are those that originate from within the cell, such as a peptide from a
virus, which is an intracellular pathogen.

Presentation of Exogenous Antigen with MHC Class II

Helper (CD4+) T-lymphocyte activation depends upon binding to exogenous antigens

presented with MHC class II on the surface of an APC.

Exogenous antigens are those that originate from outside the cell, such as a peptide from an
extracellular bacterium, which is engulfed and processed by the APC.

Helper T-Lymphocyte Activation

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Helper T-lymphocyte activation depends upon binding to exogenous antigen presented with
MHC class II on the surface of an APC.

The T-cell receptor of the T-lymphocyte binds to the presented antigen, while its CD4 protein
binds to the MHC class II molecule displaying the antigen.

Helper T-Lymphocyte Proliferation

In addition to the physical interaction with an APC, an activated helper T-lymphocyte releases
interleukin-2 (IL-2), a cytokine that stimulates proliferation of itself.

IL-2 binds to IL-2 receptors on the helper T-lymphocyte, causing its replication and
differentiation into memory and effector helper T-lymphocytes.

Effector cells release specific cytokines to coordinate and activate other immune cells,
whereas memory cells stand by for quick activation upon future exposure to the same antigen.

Cytotoxic T-Lymphocyte Activation

Cytotoxic T-lymphocyte activation depends upon binding to endogenous antigen (e.g., a viral
peptide) presented with MHC class I on the surface of an APC.

The T-cell receptor of the T-lymphocyte binds to the presented antigen, while its CD8 protein
binds to the MHC class I molecule displaying the antigen.

Cytotoxic T-Lymphocyte Proliferation

In addition to the physical interaction with an APC, an activated cytotoxic T-lymphocyte

releases interleukin-2 (IL-2), a cytokine that stimulates proliferation of itself. IL-2 is also
released from activated helper T-lymphocytes nearby.

IL-2 binds to IL-2 receptors on the cytotoxic T-lymphocyte, causing its replication and
differentiation into memory and effector cytotoxic T-lymphocytes.

Cytotoxic T-Lymphocyte Effector Response

Effector cytotoxic T-lymphocytes contain TCRs specific for the antigen that caused their
activation. These cells seek out and recognize any body cell displaying that same antigen,
such as an infected or otherwise "unhealthy" cell.

Upon binding to the infected cell, cytotoxic T-lymphocytes release perforin and granzymes,
which facilitate apoptosis of the target.

Antibody Structure

Antibody-mediated immunity depends upon the action of antibodies.

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An antibody monomer is a Y-shaped protein with two main parts:

A "stem" called the Fc region, which determines the antibody class and its effector
functions.

Two "arms," each containing an antigen-binding site; these sites are identical on a single
antibody, but vary between antibodies.

Antibody Functions: Antigen-Binding Sites

The antigen-binding sites interact with antigens to cause neutralization, agglutination, or

precipitation.

During neutralization, the antibody binds biologically active antigens on a microbe so it is no

longer harmful.

Agglutination occurs when antibodies cross-link foreign cells, clumping them together.

Antibodies can also cross-link small, soluble particles such as viruses or toxins. This causes
them to become insoluble - a process called precipitation - and more easily removed by
immune cells.

Antibody Functions: Fc (Stem) Region

Once the antigen-binding sites are bound to antigen, the exposed Fc region interacts with other
immune structures.

Complement is activated by the classical pathway.

NK cells are activated and release cytotoxic chemicals (perforin, granzymes).

Opsonization occurs as macrophages bind to Fc region of antibody, initiating phagocytosis

of the entire immune complex.

B-Lymphocyte Activation

A naive B-lymphocyte contains B-cell receptors (BCRs) capable of directly binding to a specific
antigen. This initiates phagocytosis, processing, and presentation of the antigen with MHC
class II.

An activated helper T-lymphocyte produces cytokines (e.g., IL-4, IL-21, and others) that aid in
activation and differentiation of the B-lymphocyte.

B-Lymphocyte Proliferation and Differentiation

An activated B-lymphocyte proliferates, forming many copies of itself.

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These clones differentiate into memory cells capable of responding to future encounters with
the same antigen, and plasma cells that secrete antibodies.

The secreted antibodies are all identical and target the same antigen that activated the original
B-lymphocyte.

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