Download Adaptive Immune System Chapter 16

Adaptive Immune System
Chapter 16
Overview of Adaptive Immunity
• Adaptive immunity is the body’s ability to
recognize and defend itself against distinct
invaders and their products
• Five attributes of adaptive immunity
– 1. _______________
• Any adaptive response acts against only one particular
molecule shape and not others.
– Specific pathogens
– 2. _______________
• Activation of adaptive cells only in response to specific
pathogens
Five attributes of adaptive immunity
continued..
• 3. _____________
– Once induced cells of the adaptive system proliferate
(expand) to form many generations of nearly identical
cells (clones).
• 4. _____________________________
– The adaptive system does not act against normal body
cells.
• 5. __________________________
– An adaptive immune response has memory which
allows a quick response if you encounter the
pathogen again
Innate vs. adaptive
• Innate
– Nonspecific response
• A fever is a fever whether
triggered by a cold virus
or Ebola
– Always ready and fast
acting
• Born with these systems
• Adaptive
– Specific immune
response to a pathogen
• If you have a cold virus
antibodies are produced
specifically for that virus
– Slower
– Not born with an
adaptive system
• Antibodies can be
transferred through
breast milk
Types of Acquired Immunity
• Specific immunity acquired during an
individual’s life
– _________________
•
– Distinguished as either active or passive
• Active- normal exposure and response to pathogen
• Passive immunity
– Receive antibodies from another individual
» Newborns respond slowly to antigen
» IgG crosses the placenta providing protection
– IgA in breast milk-
– ____________________
•
Dual Nature of Adaptive Immunity
• T and B cells develop from stem cells in red bone
Stem cells develop in bone marrow
marrow
Red bone
marrow of
adults
Thymus
Differentiate to B cells in adult
red bone marrow
Differentiate to T cells in thymus
Migrate to lymphoid
tissue such as
spleen, but especially
lymph nodes
Dual Nature of Adaptive Immunity
• Two types of adaptive immune responses
–
•
–
•
Where does the Adaptive Immune
response take place?
– The Tissues and Organs of the Lymphatic
System
• Act as a surveillance system that screens the
tissues of the body for foreign antigens
• Composed of lymphatic vessels and lymphatic
cells, tissues, and organs
The Nature of Antigens
•
• Include various bacterial components as well as proteins of
viruses, fungi, and protozoa
• Food and dust can also contain antigenic particles
Extracellular
microbes
Types of antigens
•
•
Exogenous
antigens
– Toxins and other secretions
– Components of cell walls, membranes, flagella
•
Endogenous
antigens
•
– Endogenous antigens are not accessible to immune
cells
– Immune cells will respond if the endogenous
antigen is incorporated into the bodies cells
cytoplasmic membranes (external display)
•
Intracellular
virus
Virally
infected
cell
Autoantigens
(normal cell antigens)
–
– Derived from normal cell processes
Normal
(uninfected)
cell
The Nature of Antibodies
• Globular proteins called immunoglobulin's
• Secreted by _____________________
• Antibodies (Ab) interact with________________
_______________
Epitopes (antigenic determinants).
Antibody A
antigenic determinants on
antigen
Antigens:
components
of cell wall
Binding sites
Bacterial cell
Antibody B
Antibodies
• Classes of antibodies
– ____–first antibody produced
– ____–most common (80% of serum antibodies) and
longest-lasting antibody
– ____– associated with body secretions, provides nursing
newborns some protection against foreign antigens, newborn
receives antibodies against antigens that have infected their
mothers
– _____–involved in response to parasitic infections
and allergies
– _____–exact function is not known
Humoral Response
• The introducing the players:
– Extra cellular antigen
– B cells
• BCRs
– T helper cells (T-dependent humoral immunity
only)
• CD4
– MHC class II proteins
– Exogenous antigen processing
– Cytokines (chemical signalling)
B Cells and Antibodies
• Arise and mature in the red bone marrow
– Found primarily in the spleen and lymph
nodes
– Small percentage of B cells circulates in the
blood
–
B Cells and Antibodies
• The process leads to the secretion of antibodies
starts when B cells are exposed to extracellular
antigens.
• B cells carry immunoglobulin's on surface of cell
– Called B cell receptors (BCRs)
• Each B lymphocyte has multiple copies of the same B cell
receptor
• Each B cell generates a single BCR
– ~500,000 identical copies per cell
– Billions of different BCR’s in a human
Figure 16.4 B cell receptor (BCR)
Epitope
Antigenbinding
sites
Heavy chain
Variable
region
Light chain
Cytoplasmic
membrane of
B lymphocyte
Transmembrane
portion of BCR
B cell receptor
(BCR)
Cytoplasm
T Cells
• T cells mature in the thymus
– Have T cell receptors (TCRs) on their cytoplasmic
membrane
• TCRs do not recognize epitopes directly
• TCRs only bind epitopes associated with a MHC protein
• Have either CD 4 or CD 8 protein (to recognize MHC)
– T Helper lymphocyte
•
– T helper cells require ______________________
_____________________
The Roles of the Major
Histocompatibility Complex (MHC)
– Major histocompatibility antigens are proteins
found in the membranes of most cells of vertebrate
animals
–
The Roles of the Major
Histocompatibility Complex (MHC)
• Antigens bind to MHC molecules
• Two classes of MHC proteins
• _______________Found on every nucleated cell
• _______________Found only on B cells and
antigen presenting cells (APC)
Antigen-binding grooves
Cytoplasmic
membrane
Class I MHC
on every
nucleated
cell
Class II MHC
on B cell or other
antigen-presenting
cell (APC)
Antigen Presenting Cells (APC) and
Antigen Processing
– Digest antigen
– Display antigen fragments on APC surface with
MHC
– Exogenous Antigen processing
• Antigen presenting cells internalize the antigen and
digest the in the phagolysosome
• A vesicle containing MHC II fuses with the
phagolysosome and the antigens can bind to its
complementary MHC II molecule
Role of CD4
• T helper cells recognize antigens presented
with their ______and _____protein on T
helper recognizes _____________
• T helpers become activated when antigen is
presented on a MHC II and matches its ______
Exogenous Processing
An APC encounters, in this case a B cell, and ingests a
microorganism. The antigen is enzymatically processed
into short peptides, which combine with MHC class II
molecules and are displayed on the surface of the APC.
A receptor (TCR) on the surface of the T helper cell
(TH cell) binds to the MHC–antigen complex. The
APC is stimulated to secrete a costimulatory
molecule. These two signals activate the TH cell,
which produces cytokines.
TH cell receptor
(TCR)
The cytokines cause the TH cell to
become activated.
B cell
T helper cell
Antigen
Microorganism
carrying antigens
Antigen
fragment
(short peptides)
Complex of MHC
class II molecule
and antigen
fragment
Cytokines
Costimulatory molecule,
(required to activate T cells
that have not previously
encountered antigen)
Humoral Immune Responses
• Two types
– ________________humoral immunity
– ________________humoral immunity
T-dependent humoral immunity
The process
• T-dependent
–
– Antigen is presented with __________to TH cell
– TH cell produces _________that activate the B cell
– Once B cell is activated the B cell undergoes _____
_____________________
– B cells differentiate into:
•
•
Clonal selection and differentiation of B cells.
Stem cell
Stem cells differentiate into mature B cells,
each bearing surface immunoglobulins
against a specific antigen.
Antigen
B cell III complexes with
its specific antigen and
proliferates.
B cells
I
II
III
IV
Memory cells
Some B cells proliferate into longlived memory cells, which at a
later date can be stimulated to
become antibody-producing
plasma cells. See Figure 17.17.
Other B cells
proliferate into
antibody-producing
plasma cells.
Plasma cells
Plasma cells secrete antibodies
into circulation.
Antigens in circulation now attached
to circulating antibodies
Cardiovascular system
T-dependent humoral response
worksheet
T-independent humoral immunity
•
• When a molecule with ________________
____________________________the BCRs on
a B cell
– 1. The B cell is activated
– 2. undergoes clonal expansion
– 3. the clones become plasma cells which secrete
antibodies
T-independent humoral immunity
Polysaccharide
(T-independent antigen)
Epitopes
B cell receptors
T-independent humoral response
worksheet
Humoral Immune Responses
• Memory B Cells and the Establishment of
Immunological Memory
– Produced by B cell proliferation but do not secrete
antibodies
– Have BCRs complementary to the antigenic
determinant that triggered their production
– Long-lived cells that persist in the lymphoid tissue
– Initiate antibody production if antigen is
encountered again
Outcomes of Antigen–Antibody
Binding
•
•
•
•
•
The results of antigen–antibody binding.
Agglutination
Reduces number of infectious
units to be dealt with
PROCTECTIVE
MECHANISM OF BINDING Activation of complement
ANTIBODIES
Causes inflammation and
TO ANTIGENS
cell lysis
Complement
Bacteria
Bacterium
Lysis
Antibody-dependent
cell-mediated cytotoxicity
Opsonization
Coating antigen with antibody
enhances phagocytosis
Phagocyte
Antibodies attached to target cell cause
destruction by macrophages, eosinophils,
and NK cells
Eosinophil
Epitopes
Neutralization
Blocks adhesion of
bacteria and
viruses to mucosa
Virus
Bacterium
Large target cell (parasite)
Toxin
Blocks
attachment of
toxin
Perforin and
lytic enzymes
Cell mediated response
• The Players
– Intracellular antigen (virally infected cells)
– T cytotoxic cells (Tc)
– Cytotoxic T lymphocytes (CTLs)
– CD8
– T helper cells
– APCs
• Macrophages
• Dendritic cells
– MHC class I
T Cells and Cell Mediated Immunity
• T cytotoxic cells (Tc)
–
• Have ______________which recognize Endogenous
antigen packaged with ___________protein on _____
________________________________
• Produce perforins and granzyme
– Directly kills infected cells
• Tc and CTLs require antigen-presenting cells with
MHC class I
Antigen presenting cells (APC)
• Macrophages
• Dendritic cells- “scouts” most important!
– Found under surface of skin and mucous
membranes
– After acquiring antigen they will migrate to lymph
nodes to interact with B and T cells
A dendritic cell.
Antigen Processing
• Endogenous – from pathogens living
within a cell the antigen is broken down
and packaged inside the cell with MHC I
and displayed on the cell surface
Processed antigen
presented with
MHC class I
Virus
Processed
antigen
Virus-infected cell
MHC
class I
Virus-infected cell (example
of endogenous antigen)
Virus-infected cell
Cell-Mediated Immune Responses
• See worksheet or next 3 slides explain process
Cell-Mediated Immune Responses
Steps involved in activation of CTL’s (see
worksheet)
• Antigen presentation- an APC (usually dendritic
cell) presents antigen on a MHC class I protein to
Tc cells (T cytotoxic cells)
– The one with matching TCR binds to dendritic cell
– CD8 on Tc cell recognizes MHC I
• Helper T cell stimulates Tc cell -A T helper cell
will provide a signal to the Tc to undergo
differentiation into a CTL and clonal expansion
Steps involved in activation of CTL’s
• Differentiation- the signal from the Th cell
causes the Tc cell to differentiate into a CTL
• Clonal expansion- CTLs reproduce to form
memory T cells and CTL clones
• Self-stimulation- the clonal CTLs cells no
longer need an APC or helper T cell, they will
signal themselves and leave the lymph node
ready to attack virally infected cells
Steps involved in activation of CTL’s
• Activated CTLs with their TCRs and CD8 will
recognize virally infected cells with endogenous
antigen packaged with MHC class I, since viral
antigens are presented on the cytoplasmic
membrane
• CTLs will bind to the infected cell with its TCR
and complementary MHC I/antigen complex
– Once bound the CTL kills their target
• By activating apoptotic factors
– Perforin and granzymes
Figure 16.15b A cell-mediated immune response: perforin-granzyme cytotoxic pathway
Tc cell
Perforin
Granzyme
Perforin
complex (pore)
Granzymes activate
apoptotic enzymes
Inactive
apoptotic
enzymes
Active apoptotic
enzymes induce
apoptosis
Virally infected cell
Apoptosis.
Natural Killer (NK) Cells
• Granular leukocytes destroy cells that don’t
express MHC I
• Kill virus-infected and tumor cells
• Attack parasites
Immunological Memory
• Primary response occurs after initial contact
with Ag
• Secondary (memory) response occurs after
second exposure
Figure 16.19 The production of primary and secondary humoral immune responses--overview