Download Adaptive Immune System Chapter 16

Adaptive Immune System
Chapter 16
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 an antigen
• 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
5 attributes of the adaptive immune system
1.
2.
3.
4.
5.
Specificity
– Any adaptive response acts against only 1 particular molecule shape
(antigen) and not others
Inducibility
– Cells of adaptive immunity are activated in response to the specific
antigen
Clonality
– Once induced cells proliferate to form many generations of identical
cells
Unresponsive to self
– Adaptive immune cells don’t act on normal body cells
Memory
– Adaptive cells form memory which accounts for a fast secondary
response
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
Antigens
• Antigen: a substance that causes the body to
stimulate an adaptive immune response
• 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
• Extracellular
Exogenous
antigens
– Toxins and other secretions
– Components of cell walls, membranes, flagella
• Endogenous
• Intracellular
– 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)
• Autoantigens
– Self antigens
– Derived from normal cell processes
Endogenous
antigens
Intracellular
virus
Virally
infected
cell
Autoantigens
(normal cell antigens)
Normal
(uninfected)
cell
Major Histocompatibility Complex (MHC)
– MHC proteins hold and position antigens for
presentation
– Two classes of MHC proteins
– MHC class I- Found on every nucleated cell except RBCs
– MHC class II- Found only on B cells and antigen presenting
cells (APC) (macrophages and dendritic cells)
Major Histocompatibility Complex
(MHC)
• Antigens bind to MHC molecules
Antigen-binding grooves
Cytoplasmic
membrane
Class I MHC
on every
nucleated
cell
Class II MHC
on B cell or other
antigen-presenting
cell (APC)
Adaptive immune cells
• 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
B Cells
• Found primarily in the spleen and lymph
nodes
– Small percentage of B cells circulate in the
blood
• Respond to extracellular antigens
(exogenous antigens)
• Major function
– differentiation into plasma cells for the
eventual secretion of antibodies
– development of memory B cells (involved in a
secondary response toward the same
antigen)
B Cells
• B cells have 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 B cells each with a unique BCR in a
human
Figure 16.4 B cell receptor (BCR)
Antigen
Antigenbinding
sites
Variable
region
Cytoplasmic
membrane of
B lymphocyte
B cell receptor
(BCR)
Cytoplasm
Antibodies
• Globular proteins called immunoglobulin's
• Secreted by plasma cells
• Antibodies interact with antigens
Antibodies interacting with Antigen
Antibody A
antigenic determinants on
antigen
Antigens:
components
of cell wall
Binding sites
Bacterial cell
Antibody B
Antibodies
• Classes of antibodies
– IgM–first antibody produced
– IgG–most common (80% of serum antibodies) and
longest-lasting antibody
– IgA– associated with body secretions, provides nursing newborns
some protection against foreign antigens, newborn receives
antibodies against antigens that have infected their mothers
– IgE–involved in response to parasitic infections and
allergies
– IgD–exact function is not known
Outcomes of Antigen–Antibody
Binding
•
•
•
•
Agglutination
Opsonization
Activation of complement
Antibody-dependent cell-mediated
cytotoxicity (ADCC)
• Neutralization
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
T Cells
• Have T cell receptors (TCRs) on their
cytoplasmic membrane
• TCRs do not recognize antigens directly
• TCRs only bind antigen associated with a MHC protein
• Have either CD 4 or CD 8 protein
– T Helper lymphocyte
• Helps regulate the activities of B cells and
cytotoxic T cells
– T helper cells require antigen-presenting cells
(APCs) with MHC class II
• CD 4
T Cells
• Cytotoxic T lymphocytes (Tc or CTL)
• Have TCRs and CD8 which recognize Endogenous
antigen packaged with MHC class I protein on
virally or intracellular pathogen infected cells.
• Must be activated
• Produce perforins and granzyme
– Directly kills infected cells
• Tc cells require antigen-presenting cells with
MHC class I
2 types of adaptive immune responses
• Two types of adaptive immune responses
1. Humoral immune responses- extracellular
• Antibody immunity
– 2 types
1. T-dependent
2. T-independent
2. Cell-mediated immune responses- intracellular
pathogens (viruses replicating inside a cell)
• No antibodies are involved
Humoral Response
• Components involved in Humoral immunity:
– Extra cellular antigen
– B cells
• BCRs
– T helper cells (T-dependent humoral immunity
only)
• CD4 – helps Th cell to recognize MHC II
– MHC class II proteins
– Exogenous antigen processing
– Cytokines (chemical signalling)
Antigen presenting cells (APC)
– Use Exogenous antigen processing
– Phagocytosis and Digestion antigen
– Display antigen fragments on APC surface with
MHC
1.Macrophages
2.Dendritic cells- “scouts” very 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
3.B cells
A dendritic cell.
Antigen Processing
– 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
• CD4 protein on T helper recognizes MHC class II
• T helpers become activated when antigen is
presented on a MHC II and matches its TCR
Humoral Immune Response
• Two types
– T-independent humoral immunity
– T-dependent humoral immunity
T-independent humoral immunity
• Does not need assistance from helper T cells
• When a molecule with multiple repeating
antigen (such as a polysaccharide) cross-links
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
T-dependent humoral immunity
The process
• T-dependent
– Requires T helper cells
– Antigen is presented with MHC II to TH cell
– TH cell produces cytokines that activate the B cell
– Once B cell is activated the B cell undergoes clonal
expansion
– B cells differentiate into:
• Antibody-producing plasma cells
• Memory cells
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
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
Figure 16.19 The production of primary and secondary humoral immune responses--overview
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
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
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
Types of Acquired Immunity
• Specific immunity acquired during an
individual’s life
– Naturally acquired
• Response against antigens encountered in daily 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-
– Artificially acquired
• Active-Response to antigens introduced via a vaccine
• Passive- administration of antisera or antitoxins