Transcript Mechanisms of Immunity

CLS 420
Clinical Immunology &
Molecular Diagnostics
Mechanisms of Immunity
Part One
Types of Immunity
Objectives
1. Differentiate innate (natural) immunity and
acquired (adaptive) immunity.
2. Describe the significance of the following
factors included in the first line of defense:
a.
b.
c.
d.
e.
f.
Skin and mucous membranes
Age
Metabolism
Environment
Normal flora
Concomitant disease
Objectives
3.
4.
5.
Compare specific versus non-specific immunity as it
relates to:
a.
Phagocytosis
b.
Inflammation
c.
Cellular immunity
d.
Humoral immunity
e.
Memory
f.
Opsonization
Differentiate humoral and cellular immunity.
Compare active and passive immunity, including
examples of each.
Immunity
The state of protection from
infectious disease.
Immunity
• Protection against:
– Pathogens
– Toxins
– Tumors
• Recognition of foreign vs. self
• Two branches:
– Innate
– Adaptive (acquired)
Immune function is influenced by:
•
•
•
•
Age
Nutritional status
Stress
Fatigue
What happens when foreign matter
enters the body?
Innate Immunity
The First Line Of Defense
Innate Immunity
•
•
•
•
Available at birth (innate or natural).
Generalized, nonspecific reaction.
Response to invader is rapid.
No prior exposure to foreign
substance required.
• Response doesn’t change with further
exposure.
Barriers
• Skin
• Tears, saliva,
secretions
• Mucus
• Cough Reflex
Environment
• pH
• Normal flora
• Temperature
Pathogen Recognition
• Toll-like receptors
• Complement
– Alternative Pathway
– Mannose Binding Lectin Pathway
Chemicals
• Chemicals include:
– Complement
– Histamine
– Cytokines
– Acute Phase Reactants
– Kinins
• Destroy pathogens
• Expand the immune response
• Neutralize the effects of other chemicals
Inflammation
• Capillaries dilate and blood accumulates in
the affected area.
– Redness
– Increased temperature
• Fluid accumulates in tissue (edema).
Inflammation
• Chemokines attract phagocytes into affected
area.
• Phagocytes migrate into the tissue
(extravasation) and destroy invading pathogens.
• Other chemicals are released that cause:
– Fever
– Increase WBC adhesion to vascular endothelium
– Stimulate clotting/fibrinolysis cascades
Inflammation
• Pus formation
• Macrophages clean up debris.
• Release chemicals that enhance the
inflammatory response.
• Growth factors rebuild tissue and blood
vessels.
Inflammation –
Acute
vs. Chronic
• Well defined onset and
resolution
• Mediated by
macrophages
– Fever
– Increase WBC production
– Acute phase reactants
released from liver
• Phagocytosis by
neutrophils
• Ongoing inflammatory
process
• Inability to clear pathogen
• Less defined onset &
resolution
• Macrophages and
lymphocytes involved
• Loss of tissue function
– Granuloma formation
– Scar tissue
Phagocytosis
YUM
Phagocytes
•
•
•
•
•
Dendritic cells
Neutrophils
Macrophages
Monocytes
Eosinophils
“Contact”
• Receptors on
phagocyte make
contact with foreign
material.
– May be enhanced
by opsonins
• CRP
• Complement
• Antibodies
“Ingestion/Digestion”
• Phagocyte engulfs
foreign material to
form phagosome.
• Phagosome merges
with granules in
cytoplasm.
• Granules contain
chemicals that digest
foreign material.
Chemicals
• Respiratory burst – membrane bound
oxidase converts oxygen to superoxide
anion.
• Nitric oxide synthetase- oxides arginine
releasing nitric oxide.
• Lysozyme- antimicrobial enzyme
• Defensins – cysteine rich peptides that
attack bacterial cell membranes.
Exocytosis
• Waste material is expelled from phagocyte
(exocytosis).
Cells Alive!
• Please go to
http://www.cellsalive.com/ouch1.htm
• View “Anatomy of a Splinter”.
How can long-lasting
protection be developed?
Acquired Immunity
a.k.a.
Adaptive Immunity
Characteristics
• Forms only after exposure to foreign
substance.
• Response is specific to the foreign
stimulus.
• Recognizes self vs. non-self.
• Displays memory.
• 2 forms:
– Cell mediated
– Humoral
Cell Mediated Immunity
• Controlled by T lymphocytes.
– Influence other parts of the immune system
(including the humoral response) through the
release of cytokines.
• Responsible for such processes as
delayed hypersensitivity, transplant
immunity, and tumor rejection.
Cell Mediated Process
• Foreign matter is
broken down into
small peptides.
• Peptides combine
with the Major
Histocompatibility
Complex (MCH)
molecules on the cell
membrane.
Major Histocompatibility Complex
• Found on the membrane of every
nucleated cell.
• Three classes:
– I (A, B, C loci)
– II (DR, DQ, DP loci)
– III (complement , Tumor Necrosis Factor
[TNF])
• MHC has antigen binding groove which
carries foreign peptides.
Major Histocompatibility Complex
Class II
Class I
Cell Mediated Process
• Class I MHC antigens bind peptides that
are produced within the cell
• Class II MHC molecules are found on
Antigen Presenting Cells (APC)
– Monocytes, macrophages, dendritic cells, and
B lymphocytes
• Class II molecules bind foreign peptides
that have been processed by the APC.
Recognition
• T lymphocytes
possess receptors
(TCR) that recognize
foreign antigen when
the antigen is bound
to MHC antigen.
Signaling
• TCR is coupled to CD3.
• CD3 signals the interior of the T cell that
antigen is present.
• T cell produces cytokines in response
(effector cell).
• Some T cells mature into memory T cells.
T Lymphocyte Subsets
• T helper cells (TH)
– Make up 2/3’s of the T cell population
– CD4 positive
– React with MHC class II proteins
– Assist in initiating cytotoxic response
– Stimulate humoral response
• T cytotoxic cells (TC)
– CD8 positive
– React with MHC class I proteins
Cytotoxic Response
• Tc cell recognizes foreign
peptides associated with
Class I MHC antigen.
• Cytotoxic T Lymphocyte
(CTL) binds to target cell
• Release perforin and
granzymes, leading to
apoptosis of target cell.
• Cytokines TNF and
interferon released to
prevent spread of virus.
– May injure healthy tissue.
Cells Alive!
• Please go to
http://www.cellsalive.com/ctl.htm
• View “The Cytotoxic T Lymphocyte”.
Humoral Immunity
• Major cell involved is the B lymphocyte.
– Develops into plasma cells and memory cells.
• Influenced by T helper cells.
Humoral Response
• Foreign antigen is
introduced to host.
• APCs process antigen
into peptide fragments,
then present peptide to
the TH lymphocyte.
• The TH recognizes the
foreign antigen through
its TCR and CD4.
Humoral Response
• The B cell has also
recognized the foreign
antigen via the B cell
receptor (BCR), and
processed the foreign
antigen.
• Foreign peptide is then
expressed on the surface
MHC class II molecules.
Y
Humoral Response
• TH lymphocyte recognizes that the peptide
seen by its TCR and the peptide
presented by the B cell are the same.
• TH cell releases cytokines to stimulate B
cell.
B Lymphocytes
• B cells divide into plasma
cells or memory B cells.
• Plasma cells produce and
secrete antibody.
– The antibody produced is
specific for one epitope!
• Memory cells recall
previous encounter with
foreign antigen.
– Respond quickly when
antigen is encountered again.
T Helper Lymphocytes
• Signals from the TH cell influence the class
of immunoglobulin produced by the B cell
and the ability to switch classes.
– Interleukins
– Transforming growth factor
Alternate Humoral Response
• B cells may be influenced to produce
antibody independent of T cells.
– Rapid response
– Few memory cells
– No switch to other classes of immunoglobulin
– Additional nonspecific antibody may be
produced (autoantibody)
Cells Alive!
• Please go to
http://www.cellsalive.com/antibody.htm
• View “Making Antibodies”.
Active vs. Passive Immunity
• In active immunity, the
host produces an immune
response to foreign
matter following
exposure.
• Long lasting.
• Displays memory.
• Examples include:
– Vaccinations
– Immunity following infection
• In passive immunity, the
host acquires antibody
that was produced in
another being.
• Short term protection.
• No memory.
• Examples include:
– Maternal transfer to fetus
– Immune Serum Globulin
used to treat
hypogammaglobulinemia
STRETCH
Take a break before moving on to
Part II