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T-Cells and Cell-Mediated Immunity

Specific Defenses Of The Host: The Immune Response

Introduction

Antigens and Antibodies

B Cells And
Humoral Immunity

Monoclonal Antibodies

T-Cells And
Cell-Mediated Immunity

26. Describe the roles of T-cells in cell-mediated immunity.

27. List the nonspecific cellular components of the immune system.
18. Define major histocompatibility complex.
19. Explain the significance of the histocompatibility antigens.
28. Describe the cell-mediated response.
17. Differentiate between T-independent and T-dependent antigens and describe how the B-cell system deals with each one.

T-Cells and Cell-Mediated Immunity

Components: Cells (T Lymphocytes, Antigen Presenting Cells, Natural Killer Cells) and Chemicals

Chemical Messengers of Immune Cells: Cytokines

Interleukins 18 known, communicate between leukocytes.
Interferons - protect cells against viruses, stimulate macrophages and neutrophils to phagocytize bacteria, stimulate
macrophages and NK cells to attack tumor cells, and stimulate T H1 cells, which drive cell-mediated reactions.
Very high levels of gamma-IFN stimulates cytotoxic T-cells.

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Chemokines - chemotactic for leukocytes.

Cellular Components of Immunity

T-cells differentiate into effector T-cells when they are stimulated by their specific antigen. Some effector T-cells become
memory cells.
Types of T cells
Classified by function and cell surface antigens (cluster differentiation antigens, or CDs, which also act as receptors).
T-cells recognize their antigen only when it is bound to a Human Leukocyte Antigen (HLA molecule),on the surface of a cell.
Human Leukocyte Antigens, or tissue antigens, are glycoproteins that are present on almost every cell in the
body. There are two classes of HLA molecules, Class I and Class II.
Class I HLAs are coded for by three different genes, Class I A, Class I B, and Class I C. Class I molecules are
present on almost every cell in the body and are recognized by CD8 T-cells.
Class II HLAs are coded for by three different genes as well, the DR, DP, and DQ genes. Class II molecules are
present on antigen presenting cells (APCs), which include macrophages, dendritic cells, and B-cells. Class II
HLAs are recognized by CD4 T-cells.
Normally, HLA molecules have a small piece of self-peptide bound to their antigen binding site, and T-cells "dock"
with the HLA-peptide complex and recognize it as "self".
If a foreign peptide is bound to the antigen binding site of the HLA molecule the T-cell will recognize the complex
as "foreign" and become activated if it receives co-stimulation from a cytokine.
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The presence of peptide in the peptide binding site of an HLA molecule such that T-cells can bind to the HLApeptide complex is known as antigen presentation.
Class I HLAs present viral peptides when the cells are infected with virus. Tumor cells often have mutant peptides
that are presented to T-cells and recognized as "foreign" as well.
Antigen presenting cells phagocytize antigens, break them down in phagolysomes, and put peptide fragments in
the peptide binding site of Class II HLAs. The act of phagocytosis will stimulate macrophages to secrete Il-1,
which will co-stimulate CD4 T-cells when they bind to the HLA-peptide complex.

When CD4 T-cells are activated in this way they secrete Il-2, which stimulates the macrophage, stimulates the
CD4 T-cell, stimulates CD8 T-cells, and will stimulate B-cells.

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Helper T-cells (CD4)

T H1 secrete Il-2, gamma-IFN, TNF-
Drives cell-mediated responses (stimulates CD8 T-cells)
T H2 secrete Il-4, Il-5, Il-6, Il-10
Drives humoral responses (stimulates B-cells)
Cytotoxic T-cells (CD8)
Recognize Class I HLAs, kill virally infected cells and tumor cells when activated.

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Delayed hypersensitivity T-cells

Mostly T H1 cells, some CD8
Secrete Il-2, activate macrophages
Tuberculosis, allergic reactions to poison ivy, transplant rejection
Supressor T-cells
May be CD4 or CD8
Suppress immune responses (wind things down)

Nonspecific Cellular Components

Activated macrophages

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Natural killer cells

Uncertain lineage, no CD4 or CD8 antigens
Not HLA restricted but seem to be Class I mediated

The Interrelationship of Cell-Mediated and Humoral Immunity

T-dependent antigens are attacked by antigen-presenting cells and presented to helper T-cells (T H ).
T H -cells activate B-cells to produce IgG, IgA, or IgE.

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T-independent antigens directly activate B-cells to produce mainly IgM.

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T-Cells and Cell-Mediated Immunity

Antibody-dependent cell-mediated cytotoxicity - antibodies attached to target cells cause destruction by non-specific immune
system cells (NK cells, macrophages, eosinophils).

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Interrelationship

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