Transcript Cell Mediated Immunity

Cell Mediated Immunity
Cell Mediated Immunity (CMI)
– Involves specialized set of lymphocytes called T cells that
recognize foreign antigens on the surface of cells,
organisms, or tissues:
– T cells regulate proliferation and activity of other cells of
the immune system:
• B cells, macrophages, neutrophils, etc.
– Defense against:
• Bacteria and viruses that are inside host cells and are
inaccessible to antibodies.
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Fungi, protozoa, and helminths
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Cancer cells
•
Transplanted tissue
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Cell Mediated Immunity is Carried Out by T Lymphocytes
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Antigens that stimulate cellular response are mainly
intracellular.
Requires constant presence of antigen to remain effective.
Unlike humoral immunity, cell mediated immunity is not
transferred to the fetus.
In addition to direct cytotoxicity, T cells produce cytokines
that activate macrophages.
Cytokines:
– Chemical messengers of immune cells.
– Over 100 have been identified.
– Stimulate and/or regulate immune responses.
• Interleukins: Communication between WBCs.
• Interferons: Protect against viral infections.
• Chemokines: Attract WBCs to infected areas.
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T Cells and Cell Mediated Immunity
Cellular Components of Immunity:
– T cells are key cellular component of immunity.
– T cells have an antigen receptor that recognizes
and reacts to a specific antigen (T cell receptor).
– T cell receptor only recognize antigens combined
with major histocompatability (MHC) proteins on
the surface of cells.
• MHC Class I: Found on all nucleated cells.
• MHC Class II: Found on phagocytes.
– Clonal selection increases number of T cells.
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Clonal selection of lymphocytes:
1) a hematopoietic stem cell
undergoes differentiation and
genetic rearrangement to produce
2) immature lymphocytes with
many different antigen receptors.
Those that bind to 3) antigens
from the body's own tissues are
destroyed, while the rest mature
into 4) inactive lymphocytes. Most
of these will never encounter a
matching 5) foreign antigen, but
those that do are activated and
produce 6) many clones of
themselves
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T Cells Only Recognize Antigen Associated with
MHC Molecules on Cell Surfaces
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Types of T cells
1. T Helper (TH) Cells:
 Central role in immune response.
 There are three subpopulations of Th cells:
1. Th0 (naïve)
2. Th1 (imflammatory)
3. Th2 cells (helper).
 Most are CD4+
 Recognize antigen on the surface of antigen
presenting cells e.g.: macrophage (MHC class II)
 Activate macrophages
(inflammatory)
 Induce formation of cytotoxic T cells
 Stimulate B cells to produce antibodies.(helper)
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Central Role of Helper T Cells
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Types of T cells (Continued)
2. Cytotoxic T (Tc) Cells:
• Destroy target cells.
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CD8+ (CD4 -).
Recognize (MHC class I) antigens on the surface of
all cells:
– Kill host cells that are infected with viruses or bacteria.
– Recognize and kill cancer cells.
– Recognize and destroy transplanted tissue.
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Release two types proteins:
1)perforin which forms pores in target cells, causing
lysis of infected cells.
2)Granzymes (serine proteases)
Undergo apoptosis when stimulating antigen is gone.
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Cytotoxic T Cells Lyse Infected Cells
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Types of T cells (Continued)
3. Delayed Hypersensitivity T (TD) Cells:
Mostly T helper and a few cytotoxic T cells
that are involved in some allergic reactions
and rejection of transplanted tissue.
4. T Suppressor (Ts) Cells:
 may shut down immune response.
 are a specialized subpopulation of T cells
that act to suppress activation of the immune
system and thereby maintain:
 immune system homeostasis and
 tolerance to self-antigens.
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Nonspecific Cellular Components
1. Activated Macrophages: (Stimulated phagocytes)
• Stimulated by ingestion of antigen
• Larger and more effective phagocytes.
• Enhanced ability to eliminate intracellular bacteria,
virus-infected and cancerous cells.
2. Natural Killer (NK) Cells:
•Lymphocytes that destroy virus infected and tumor
cells.
•Not specific. Don’t require antigen stimulation.
•Not phagocytic, but must contact cell in order to lyse it.
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Relationship Between Cell-Mediated and
Humoral Immunity
1. Antibody Production
T-Dependent Antigens:
– Antibody production requires assistance from T helper cells.
– Macrophages ingest antigens and present them to TH cell.
– TH cells stimulate B cells specific for that antigen to become
plasma cells.
– Antigens are mainly proteins on viruses, bacteria, foreign red
blood cells, and hapten-carrier molecules.
T-Independent Antigens:
– Antibody production does not require assistance from T
cells.
– Antigens are mainly polysaccharides or lipopolysaccharides
with repeating subunits (bacterial capsules).
– Weaker immune response than for T-dependent antigens.
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Humoral Response to T Dependent Antigens
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Relationship Between Cell-Mediated and Humoral
Immunity
2. Antibody Dependent Cell Mediated Cytotoxicity
– Target cell is covered with antibodies, leaving Fc
portion sticking outwards.
– Natural killer and other nonspecific cells that have
receptors for Fc region are stimulated to kill targeted
cells.
– Target organism is lysed by substances secreted by
attacking cells.
– Used to destroy large organisms that cannot be
phagocytosed.
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TCR
• TCR is a heterodimer composed of two
transmembrane polypeptide chains, either:
a and b chains or
of g and d chains.
• The ab receptors account for 90% of T-cell helper
function and cytotoxic activity.
• The gd T cells receptors, its physiologic role is still
unclear.
• The biochemical signals that are triggered in T cells by
antigen recognition are transduced not by the T cell
receptor itself but by the invariant proteins called CD3
• CD3 are noncovalenlty linked to the antigen receptor
to form the TCR complex.
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TCR
2/9/04
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What are the similarities/differences between
T-cell receptors and B-cell receptors?
Similarities:
Differences:
1. Antibodies can be both soluble and
membrane bound, TCR only membrane Bound
2.Both have their variabilities 2. TCR has one binding site, Ab has two
3. TCR is shorter and wider than Fab portion of
located in one part of the
Ab.
molecule that bind antigen
(V-region)
4. B-cells/antibodies recognize circulating
antibodies. T-cells require antigen to be
3.Three dimensional structures presented by MHC-molecules
5. All energy of antigen-antibody focus on foreign
are remarkably similar
antigens whereas a substantial fraction of the
energy of the TCR-peptide-MHC is directed
against self.
6. Antibodies have higher affinity than TCRs
1.Both bind antigen
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Overview of the Immune Response
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