Cell Mediated Immunity

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Immune team
Cell Mediated Immunity (CMI)
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Cell-Mediated Immunity (CMI)
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Cell Mediated Immunity

• Cell-mediated immunity (CMI).
• Remember -
• CD4 ( T helper ) is attracted to MHC II
• CD8 ( T cytotoxic ) is attracted to MHC I
• T cells (lymphocytes) bind to the surface of
  other cells (Antigen Presenting Cells) that
  display the antigen and trigger a response

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Antigen Presenting cells that has MHC II
MCQ
Monocytes Peripheral blood Macrophages
Tissues Dendritic cells Lymphoid tissues
Langerhans cells Epidermis B-cells Lymphoid
tissue, Blood
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Lymphocyte
Macrophage
Lymphocyte
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Cell Mediated Immunity
The T helper cell need the help from ( antigen
presenting cell ) to recognize an antigen and
produce an effect against that antigen The APC (
antigen presenting cell ) hold the foregin
antigen in one hand , and hold its MHC class in
the other hand Then it present both his MHC
class and the foregin antigen to T helper cell in
the same time So T helper cell first recognize by
MHC II that this is a normal body cell , then it
recognize by the antigen that there is a foregin
antigen having fun in the body that need to
be killed so it produce a response against it
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6
2
5
3
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Invariant chain(Ii)
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In The Previous Picture
In ( 1 ) you can see a foreign body in red color
havind a dark black part called the most
antigenic part and that what stimulate T cells In
( 2 ) the foreign body get endocytosed into an
endosome In ( 3 ) the endosome then fuse with the
lysosome to degrade the antigen into small parts
to separate the most antigenic part from the rest
of it In ( 4 ) the ER produce the MHC in vesicles
that fuse with the endosome In ( 5 ) the MHC
work as a hand that hold the most antigenic part
and present it to the T cell In ( 6 ) the MHC
and most antigenic part go to the surface of the
cell and do the presentation to T cell this
process happen in both MHC class I and II cells

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T cell ActivationAntigen Presentation
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T cell Activation Antigen Presentation
CD4 ( T helper ) is the brain of the immune
system All effector cells work under its command
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If the antigen wes intracellul-ar the ( CMI )
will work , but if the antigen wes extracellu-lar
the ( HI ) work
T lymphocytes
HI
CMI
Other cells
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In viral infections like ( HIV ) , because the
virus will inter the cell and force it to produce
endogenous proteins for the virus so the foreign
protein ( antigen ) come from inside the cell and
thats way it is called endogenous
1. Endogenous antigen
2. Exogenous antigen
Like microbes
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Virus
Target cell
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Target cell
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The virus can not make its own proteins (
antigens ) so it need a host cell to produce its
proteins ( endogenous antigens ) , the endogenous
antigen will bind with ( MHC I ) of the effected
cell and appear on the surface to be recognized
by CD8 ( T cytotoxic ) to kill it
Target cell
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Target cell
Host cell
Transcription Translation
Viral protein
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MCQ
Type of antigen
Type of MHC
Type of T cell
Exogenous
MHC II
CD4
Endogenous
MHC I
CD8
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Exogenous antigen like
Microbes Proteins
Cell-mediated immunity
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MCQ
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1
5
4
2
3
Invariant chain(Ii)
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TCR-MHC interaction
T cells
T cells
T cells
TCR
TCR
TCR
Y
X
X
MHC
MHC
MHC
APC
APC
APC
Recognition
No Recognition
1
2
3
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In the previous figure ( there is an interaction
between T cell receptor and MHC )
In ( 1 ) the MHC class is the right class for
that T cell receptor and the picked up part of
the foreign antigen is the most antigenic part ,
so there will be recognition and response to that
antigen In ( 2 ) the picked up part of the
antigen is the most antigenic part , but the MHC
class is not right for that T cell receptor , so
there will not be a recognition and of course no
response In ( 3 ) the MHC class is right for
that T cell receptor , but the picked up part of
the antigen is not the most antigenic part , so
no recognition and no response So to have a
recognition and response to an antigen by
effected cells you need ( the right type of MHC ,
the right part of antigen ) to the TCR
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CD4-MHC class II interaction
Antigen presenting cell
Antigen presenting cell
Antigen presenting cell
CD4
CD4
MHC class II
CD4
TCR
T cell
T cell
T cell
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Cell-Mediated Immunity

• Lymphocytes (B T lymphocytes)
• B lymphocytes ("B cells") These are responsible
  for making antibodies (humoral immunity)
• T lymphocytes ("T cells") CMI
• Subsets include
• CD8 cytotoxic T lymphocytes (CTLs) that kill
  virus-infected and tumor cells
• CD4 helper T cells enhance CMI and production of
  antibodies by B cells

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Cell-Mediated Immunity

• Examples of Cell-Mediated Immunity
• Delayed-Type Hypersensitivity (DTH) the
  tuberculin test (or Mantoux test)
• Tuberculosis a chronic disease, caused by
  Mycobacterium tuberculosis
• The response to tuberculin is called "delayed"
  because cells take long time to arrive to site of
  infection
• in contrast to the "immediate" responses
  characteristic of many antibody-mediated
  sensitivities like an ( allergic response to a
  bee sting)
• So immediate hypersensitivity is mediated by
  humoral immunity , but delayed hypersensitivity
  and chronic diseases is mediated by cell mediated
  immunity

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Cell Mediated Immunity
MCQ

• DTH is a cell-mediated response
• Anti-tuberculin antibodies are rarely found in
  tuberculin-positive people
• The T cells responsible for DTH are members of
  the CD4 subset

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Cell-Mediated Immunity

• Contact Sensitivity
• Many people develop rashes on their skin
  following contact with certain chemicals such as
  nickel, certain dyes, and the active ingredient
  of the poison ivy plant
• The response takes some 24 hours to occur, and
  like DTH, is triggered by CD4 T cells
• The actual antigen is probably created by the
  binding of the chemical to proteins in the skin
• The fragments of antigen are then presented to
  CD4 T cells by phagocytic cells in the skin by
  antigen presentation

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Activation of helper T cells

• Requires recognition of MHC - antigen complex on
  the surface of antigen-presenting cells eg,
  macrophages consisting of both antigen and class
  II MHC proteins
• Viral antigens are recognized in association with
  class I MHC proteins
• The activation of T cell in general by
  interaction between MHC antigen complex and T
  cell receptor is called MHC restriction

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Cellular Basis of Immune Response

• To activate T helper cell and initiate a response
  you need two signals ( 2 interactions )
• First signal
• Interaction between ( Class II MHC antigen )
  with TCR
• mediated by IL-1, LFA-1 with ICAM (
  Inter-Cellular Adhesion Molecule 1)
• Second signal (Co - stimulatory signal)
• Interaction between B7 on APC with CD28 on T
  lymphocyte
• The two reactions must happen to initiate the
  immune response

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T helper cell
CD28
TCR
antigen
B7
MHC
APC
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T cell Activation

• In the absence of co-stimulatory signal , state
  of unresponsiveness called anergy develops
• Production of co-stimulatory protein depends on
  activation of the toll like receptor on antigen
  presenting cell
• Foreign antigens such as bacterial proteins
  induce B7 protein where as self proteins do not

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T cell Activation

• After antigen recognition by TCR, signal is
  transmitted through CD3 molecule ( receptor )
• This results in influx of calcium into the cell
• Calcium activates calcineurin
• Calcineurin activates gene for IL-2 and its
  receptor

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Out come of T helper cell activation

• Production of IL-2 and its receptor
• IL-2 is also know as T cell growth factor
• Proliferation of antigen specific T cells
• Effector and regulatory cells are produced along
  with memory cells
• IL-2 also stimulates CD8 cytotoxic cells

MCQ
T helper cell
Retain memory for different pathogens and
proliferate in later exposure to that pathogen
Produce cytokines and activate other cells
Proliferate
into
memory
effector
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Out come of T helper cell activation
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• Production of Gamma Interferon (IF?)
• ( IF? is an antiviral substance that will kill
  cell infected by viruses and will make the cells
  resistant to viruses so virus can not enter to
  cells , ( used in hepatitis )
• It increases expression of Class II MHC proteins
• It enhances the ability of APC to present antigen
  to T cells
• It enhances the microbicidal activity of
  macrophages
• Enhances immune response

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Out come of T helper cell activation

• Memory T cells
• Respond rapidly for many years after initial
  exposure to antigen
• A large number of memory cells are produced so
  that the secondary response is greater than the
  primary
• Memory cells live for many years and have the
  capacity to multiply
• They are activated by smaller amount of antigen
• They produce greater amounts of interleukins

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Effector functions of T cells

• Delayed type of hypersensitivity mediated by Th-1
  type of CD4 positive cells
• Cytotoxicity mediated by CD8 ve cells.
• Directed against virus infected cells, tumor
  cells and allografts

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Killing by cytotoxic cells

• Perforins ( a chemical makes wholes in cell
  membrane
• Granzymes degrading enzymes
• Fas-Fas Ligand interaction - apoptosis
• Antibody dependent cellular cytotoxicity
• Immune surveillance
• Allograft rejection

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The mechanism by which CD8 cell deal with cells
that have strange antigen on their surface is -
1- secrete perforin which is a peptide thats
make wholes in cell membrane 2- secrete enzymes
which lyse the cell membrane 3- secrete cytokines
like ( TNF ) which destroy cell membrane
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Killing Mechanisms of Cytotoxic T cells
perforin
enzymes
cytokines
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Activation of B cells

• B cell functions as APC
• Multivalent antigen binds to surface IgM
• Cross links adjacent Ig molecules
• Igs aggregate to form patches and migrate to
  one pole to form a cap
• Capped material is endocytosed
• Antigen is processed and epitopes appear on the
  cell surface in association with Class II MHC
  proteins

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