Transcript Genetic Disorders

University of Tabuk
Faculty of Applied Medical Science
Department of Medical Laboratory Technology
Basic Immunology
Mr.AYMAN.S.YOUSIF
MSc.Medical Microbiology &
Immunology
Academic Year: 1433-1434 (2012-2013)
Acquired Immunity
Lecture 5:
Mr.AYMAN.S.YOUSIF
10- 11/03/2013
Objectives
1
At the end of this lecture, you should be able to:
1. To compare and contrast antigens recognized by
the TCR and BCR.
2. To describe the pathways involved in processing
endogenous and exogenous antigens.
3. To discuss self MHC restriction in antigen
presentation to T cells.
4. To describe the major antigen presenting cells.
Comparison of BCR and TCR
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


B cells and T cells recognize different substances as
antigens and in a different form.
The B cell uses cell surface-bound immunoglobulin as a
receptor and the specificity of that receptor is the same as
the immunoglobulin that it is able to secrete after activation.
B cells recognize the following antigens in soluble form:
 Proteins.
 Nucleic acids.
 Polysaccharides.
 Some lipids.
 Small chemicals (haptens).
Comparison of BCR and TCR
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

1.
2.
In contrast, the overwhelming majority of antigens for T
cells are proteins, and these must be fragmented and
recognized in association with MHC products expressed on
the surface of nucleated cells, not in soluble form.
T cells are grouped functionally according to the class of
MHC molecules that associate with the peptide fragments of
protein:
Helper T cells recognize only those peptides associated
with class II MHC molecules, and
cytotoxic T cells recognize only those peptides associated
with class I MHC molecules.
Antigen Processing and Presentation
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



Antigen processing refers to the. ability of APCs to break
down antigen into peptides and to associate those peptides
with MHC molecules
Antigen presentation is he process of displaying peptide
antigens associated with MHC molecules to a T cell.
MHC class I molecules present degradation products
derived from intracellular (endogenous) proteins in the
cytosol.
MHC class II molecules present fragments derived from
extracellular (exogenous) proteins that are located in an
intracellular compartment.
I. Class I MHC Pathway.
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
1)
2)
3)
4)
All nucleated cells express class I MHC.
Proteins are fragmented in the cytosol by proteosomes or
by other proteases.
The fragments are then transported across the membrane of
the endoplasmic reticulum by transporter proteins (TAP).
Synthesis and assembly of class I Within the endoplasmic
reticulum .
The partial folded MHC class I complex binds to the TAP
complex, and, after binding of peptide . The peptide/MHC
complex is transported through the Golgi apparatus to
the cell surface.
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I. Antigen Processing and Presentation Class I MHC Pathway.
(Transporter Antigen Processing (TAP) in the endoplasmic reticulum)
I. Antigen Processing and Presentation Class I MHC Pathway.
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proteosomes (complex of proteins having proteolytic activity)
Activation of naïve CTL cell (CD8)
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II. Class II MHC pathway
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Whereas all nucleated cells express class I MHC,
only a limited group of cells express class II
MHC, which includes the professional Antigen
Presenting Cells (APC).
 The principal APC are Macrophages, Dendritic
cells (Langerhans cells) ,and B cells.
 The expression of class II MHC molecules is
either constitutive or inducible ( especially by
interferon-gamma (INF) in the case of
macrophages ).

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1)
2)
3)
4)
5)
II. Antigen Processing and Presentation
- Class II MHC Pathway.
Exogenous proteins taken in by endocytosis are fragmented by
proteases in an endosome.
The alpha and beta chains of MHC class II, along with an invariant
chain, are synthesized and assembled in the endoplasmic reticulum.
The invariant chain prevents endogenous peptides from the cytosol
from associating with class II MHC molecules.
The class II MHC molecules with the associated invariant chain are
transported through the Golgi and trans-Golgi apparatus to reach
the endosome
where the invariant chain is digested, and the peptide fragments
from the exogenous protein are able to associate with the class II
MHC molecules, which are finally transported to the cell surface.
Invariant chain
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II. Antigen Processing and Presentation
- Class II MHC Pathway.
Activation of naïve T helper cell (CD4)
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III. Self MHC Restriction
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In order for a T cell to recognize and respond to a
foreign protein antigen, it must: Recognize the MHC on the presenting cell as self
MHC. This is termed self MHC restriction.
 Helper T cells recognize antigen in context of
class II self MHC.
 Cytotoxic T cells recognize antigen in context of
class I self MHC.
Antigen Presenting Cells (APCs)
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The three main types of antigen
presenting cells are : Dendritic cells.
 Macrophages.
 B cells.
 although
other cells, that
express class II MHC
molecules,
(e.g.,
thymic
epithelial cells) can act as
antigen presenting cells in
some cases.
Dendritic
Cell
Macrophage
B cell
I. Dendritic cells
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Are found in skin and other tissues.
 Ingest antigens by pinocytosis and transport
antigens to the lymph nodes and spleen.
 Are the most effective antigen presenting cells and
can present antigens to naïve (virgin) T cells.
 They
can present internalized antigens in
association with either class I or class II MHC
molecules (cross presentation).
 The predominant pathway for internalized antigen
is the class II pathway.

I. Dendritic cells
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Constitutively express MHC I and MHC II (can
stimulate both CD4+ and CD8+ T cells) as well as
B7 (the co-stimulatory signal)
 Antigen presentation appears to be the sole purpose
of dendritic cells, and these cells can be infected by
a wide variety of viruses.
 They can present some viral peptides on their
MHC II, and contribute to the induction of antibody
against viruses.
 Very efficient at stimulation of cytotoxic responses.

II. Macrophages
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Are not as effective in presenting antigen to naïve
T cells but they are very good in activating
memory T cells.
 Express little MHC II or B7, but have receptors for
bacterial cell wall components which, upon
binding, activate the macrophage to express high
levels of B7 and MHC II.
 Once activated, macrophages are efficient at
stimulating CD4+ T cells, both for inflammatory
responses and helper (antibody) responses.

III. B cell
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B cells express high levels of MHC II, but not B7
 These cells bind antigen via their surface Ig and
ingest antigens by pinocytosis. Like macrophages
 These cells are Not as effective as dendrite cells in
presenting antigen to naïve T cells.
 B cells are very effective in presenting antigen to
memory T cells, especially when the antigen
concentration is low because surface Ig on the B
cells binds antigen with a high affinity.

Capture of circulating T cells in lymph nodes
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T cells enter lymph node across
the walls of venules
T cells monitor antigen
presented by macrophages and
dendritic cells
T cells that do not encounter
specific antigen leave the
lymph node through lymphatic
vessels
T cells that encounter specific
antigen proliferate and begin to
differentiate into effector cells
Thank You