Transcript Adaptive Immune System

Immune System Part III:
Adaptive Immune System & Cell Mediated Immunity
1
Adaptive Immunity (Specific Immunity)
Third Line of Defense
• Develops after exposure to pathogens
• Involves very specific response to pathogens
• Much slower than innate immunity
• Requires support of innate immunity to function
• Two parts:
• humoral immunity and
• cell mediated immunity
2
Adaptive Immunity
Lymphocytes—Specialized Cells
•B cells- are synthesized and mature in the red bone
marrow with characteristic plethora of rough E.R.
•T cells- are synthesize in bone marrow but mature in
the thymus with an abundance of free floating
ribosomes
Immature B and T
cells are virtually
indistinguishable.
Adaptive Immunity and Primary Lymphatic Tissue
Primary lymphatic
tissue
All lymphocytes
originate in the red
bone marrow. T cells
then migrate to, and
mature in, the thymus.
B cells remain in the
marrow to mature.
4
T cell receptor sites
T cells have T cell
receptor (TCR) sites
that can attach to an
antigen that is
presented by
another cell such as
a macrophage or
dendritic cell.
5
B Cell Receptor Sites and Antibody Structure
B cell receptor (BCR) sites
• Each one can attach to two
antigens.
•
• Made of four poly-peptide
chains held in place by
covalent bonds known as
disulfide bridges.
Two identical heavy chains and two identical light
chains with variable and constant regions.
• Antibodies also have this same construction.
6
Secondary Lymphatic Tissue
Where Lymphocytes are Activated
Four Characteristics of Adaptive (Specific) Immunity
1. Self/Nonself Recognition - T cells and B cells have the
ability to recognize one’s own cells versus a pathogen
(invader).
2. Specificity - Lymphocytes are tailored to combat
specific antigens due to the great diversity of B cells
and T cells.
3. Diversity - There are potentially billions of different
antigen receptors on B cells and T cells that recognize
billions of different antigens.
4. Memory - Immune system is capable of “remembering”
a pathogen once exposed.
8
Self Versus Non-self
Major Histocompatibility Complex (MHC)
Major
Histocompatibility
Complex (MHC)
Proteins are cell
surface proteins that are
unique for each
individual (except for
identical twins).
• Three classes of MHC proteins - MHC I, II, and III.
• MHC I proteins are on ALL cells and MHC II proteins
are on antigen presenting cells (B cells, macrophages,
dendritic cells).
9
Major Histocompatibility Complex (MHC)
• Four polypeptide chains with cleft to attach to antigens
which are small polypeptide chains.
• Extremely polymorphic with some classes having as
many as 500 different alleles.
• Antigens can attach to the cleft.
10
Major Histocompatibility Complex (MHC)
•
MHC I and II proteins have the ability to attach to foreign
material (small polypeptides) and transport the foreign
polypeptides to the surface of the infected cell.
•
Antigen presenting cells (APC) are mostly phagocytes. As
APC are in the process of cleaning up an infection, bits and
pieces of the pathogens are displayed on the MHC proteins.
11
Recognizing Self from
Non-self for T cells
T cells migrate to
and mature in the
thymus with
interaction of
dendritic cells.
12
T Cells Recognizing Self
from Non-self
Three possible outcomes:
1.TCR binds to a dendritic cell
with body’s own proteins and
MHC protein. Apoptosis is
induced and T cell dies
2.TCR weakly binds to a
dendritic cell with MHC with no
proteins. T cell survives.
3.TCR does not bind to any
MHC protein. Apoptosis is
induced and the T cell dies.
13
T Cells Recognizing Self
from Non-self
Surviving T cells (called naïve
T cells) can recognize MHC
proteins that have some foreign
protein in the cleft. It must be a
double match.
T cells ignore MHC proteins
without any foreign material in
the cleft or healthy cells.
14
B cells Recognizing
Self from Non-self
• Mature in the bone marrow.
• If the receptor site on a B
cell matches a surface
protein found on bone
marrow cells, apoptosis
occurs.
• The B cells that survive
(naïve B cells) are those that
will ignore the body’s own
surface proteins but will
recognize foreign material.
15
A Few Self-Reactive B
and T Cells Do Survive
•
NOT all self-reactive B and T
cells are destroyed. Those few
that do survive, are suppressed to
insure that the self-reactive B and
T cells DO NOT react with the
body’s own tissue.
•
More on this later.
•
Once mature, naïve B and T cells
migrate out of the secondary
tissue to wait to be selected.
16
Specificity and Diversity of Immune System
The specificity and diversity of adaptive immunity
lies in the receptor sites on B and T cells and
production of free floating antibodies.
17
Structure of Antibodies Are Like B Cell Receptors
B cells produce proteins called antibodies that
interact with pathogens. The basic structure is
similar to that of the B cell receptors.
Antibodies are a part of the
humoral response
18
Genes of Receptor Sites and Antibodies
19
Adaptive Immune System (Specific Immune System):
Cell Mediated Immunity
Adaptive Immune System: Two Components
1. Cell Mediated Immunity- Selected T cells recognize
and destroy infected body cells and cancer cells.
2. Humoral Immunity- Selected B cells produce
copious amounts of antibodies to fight pathogens.
20
Cell Mediated Immunity-Needs the Support of Innate
Immunity (Nonspecific Immunity)
The cell mediated immunity needs
the support of the cells involved in
the innate immunity.
The dendritic cells and
macrophages are used to present
antigens to select and clone T cells
in the secondary lymph tissues.
The secondary lymph tissue
includes tonsils, adenoids lymph
nodes, etc.
21
Cell Mediated Immunity
1. Macrophages and
dendritic cells arrive at
the site of infection.
2. Phagocytosis occurs.
3. Both types of cells have
MHC I and MHC II
proteins.
22
Role of the Macrophage or Dendritic Cell
4. The antigen (AG)
combines with
either a MHC I or
MHC II protein
5. Complex migrates
to the cell surface
to become antigen
presenting cell.
Cytotoxic T cells are Selected and Cloned
• APC cell migrates
to secondary
lymphoid tissues.
• Begins searching for
a match with a T
cell.
• If the match is with
MHC I protein, the
T cell becomes
cytotoxic cell or
memory cell.
Helper T Cells
If the MHC II protein
makes a match with
the T cell, the T cell is
destined to become a
helper T cell and
memory helper T cells.
More on this later.
Dendritic Cells
• Dendritic cells
are found in skin
and other tissues
that interact with
the environment.
• Involved in being
APC to T cells
Pathogens Invade Body Cells
• While appropriate T cells
are being selected and
cloned, body cells are
becoming infected.
• Bits and pieces of the
pathogen end up on the
MHC I protein of the body
cell.
27
Matching T Cells with Infected Cells
• The body cell is tagged
as infected.
• Selected cytotoxic cell
recognizes the infected
body cell and attaches
to the cell.
Cytotoxic Cells Destroy Infected Cells
•
Once attached, the
cytotoxic cell secretes
perforin which makes
pores in the membrane
of the infected cell.
•
The cytotoxic cell also
secretes granzymes
which cause the infected
cell to die.
Cytotoxic Cells Destroy Infected Cells
This is another rendition of how a cytotoxic cell kills in infected cell.
Below is a cytotoxic cell (orange) killing a cancer cell (purple)
30
Homeostasis
• Regulatory T cells (Treg) help to halt the
immune response.
• Do not know how they are activated possibly through antigens.
• Thought to stop any further naïve B or T cells
from being activated. Then the immune
response stops because activated immune
cells die due to their short life span.