Transcript Immune System - Dr. Annette M. Parrott

Immune System
A Dr.
Production
Nonspecific
Immunity
Specific
Immunity
Defense
system
First line of defense: Surface membrane
barriers
• Skin and mucous membrane
– Layered epidermis and shedding of epithelial
cells
– Sebum inhibits growth of bacteria and fungi
– Mucous traps microbes, dust and pollutants.
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Lacrimal apparatus
Saliva
Vaginal secretions
Flow of urine
Defecation and vomiting
Gastric juices destroy bacteria and
their toxins
Other 1st Line Defenses
Oral Cavity
Antimicrobial enzymes in saliva
(e.g. lysozyme and
lactoperoxidase) inhibit
microbes, Resident flora
Skin
pH (3-5), sebum
Respiratory
Cavity
Hairs, cilia, mucociliary escalator,
Sticky mucus (lysozyme) traps
dust and microbes.
GI Tract
low pH and digestive enzymes,
flushing action
Eyes
Tears, (lysozyme). flushing action
Vagina
pH, flushing action, resident flora
Second line of defense:
chemical and cellular defenses
• Antimicrobial proteins
– Interferon
– Complement
• Natural killer cells
• Phagocytes
– Neutrophils
– Dendritic cells
– Macrophages
• Wandering
• Fixed
– Eosinophils
Interferons
• Produced by
lymphocytes,
macrophages and
fibroblasts.
• Interfere with
translation of viral
proteins
• Degrade viral RNA
• Activate macrophages
and NK cells
• = cytokine
• Interferon Animation
Complement-
plasma membrane protein control to
destroy invading cells
Uses + feedback
Complement Cascade Animation
Phagocytosis, 2
Phagocytes - cells which "eat"
foreign material to destroy them
Phagocytes are formed from stem
cells in bone marrow (stem cells are
undifferentiated WBC's)
Found in invertebrates
•Neutrophil - phagocytize
bacteria
•Eosinophils - secrete enzymes
to kill parasitic worms among
other pathogens
Macrophage - "big
eaters" phagocytize
just about anything
Phagocyte Mobilization
Wound Site Response
Major Histocompatibility Complex
• Normally your immune
cells do not attack your
own body tissues, which
all carry the same pattern
of self-markers
• This set of unique
markers on human cells is
called the major
histocompatibility
complex (MHC). There are
two classes:
– MHC Class I proteins,
are on all cells and
activate cytotoxic T cells
– MHC Class II proteins,
are only on certain
specialized cells and
activate helper T cells
Natural Killer Cells
• Unique to vertebrates
• NK cells patrol the body,
attaching to infecting cells
presenting MHC I antigens
but can recognize stressed
cells & work in the absence
of antibodies and MHC
• release small granules of pp
(perforin & granzyme =
cytokines) that cause
apoptosis in target cell
– Cell Formation
– NK Cell Interacting with a
Virus-Infected Cell
Fever & Inflammatory response
Inflammation Animation & Stages
• Unique to vertebrates
• Release of Chemical Alarms (histamines and cytokines) by
Mast Cells
• Vasodilation & Permeability of BV
• Migration of phagocytes: Dispose cellular debris &
pathogens
• Prevent spread of damaging chemicals & pathogens
– Signs of inflammation: Redness, Heat, Swelling, Pain, Impairment of
function
Fever
• Regulated by hypothalamus, due to pyrogens secreted by
leukocytes & macrophages
• Causes liver and spleen to sequester zinc and iron
• Increases metabolic rate (repair)
Adaptive (specific) Resistance
• Specificity—recognition of particular antigens
• Memory—remembers previously encountered antigens
• Systemic—immunity is not restricted to the initial infection
site
• Immune responses
– Antibody-mediated or humoral immune responses (late
1800s)
– Cell-mediated immune responses (mid 1900s)
T Lymphocytes
•CD4 T cell also known as a
T Helper (Th)
cell
•CD8 T cell also known as a
Cytotoxic T
(Tc) cell
Mechanisms of Cytotoxic T cells (TC) Action
• Bind to the target cell and
release perforin into its
membrane
• Secreting lymphotoxin, which
fragments the target cell’s
DNA
• Releasing tumor necrosis
factor (TNF), which triggers
apoptosis
• Secreting gamma interferon,
which stimulates
phagocytosis by macrophages
• Similar to NKs, but need
APCs or antigens to activate
them
Mechanisms of T Helper (TH) Action
• Once primed by APC presentation of antigen, they:
– Chemically or directly stimulate proliferation of other T cells
– Stimulate B cells that have already become bound to antigen
• Without TH, there is no immune response
• TH cells interact with B cells that have antigen fragments on
their surfaces bound to MHC II receptors and to divide more
rapidly and begin antibody formation
• Cytokines released by TH amplify nonspecific defenses
Humoral (antibody-mediated) immune system
Cellular (cell-mediated) immune system
Control of freely circulating pathogens
Control of intracellular pathogens
Intracellular antigens are
expressed on the surface of an
APC, a cell infected by a virus, a
bacterium, or a parasite.
Extracellular antigens
A B cell binds to the
antigen for which it is
specific. A T-dependent B
cell requires cooperation
with a T helper (TH) cell.
T cell
Cytokines activate T
helper (TH) cell.
Cytokines activate
macrophage.
Cytokines
Cytokines
B cell
The B cell, often with
stimulation by cytokines
from a TH cell, differentiates
into a plasma cell. Some B
cells become memory cells.
Cytokines from the TH
cell transform B cells
into antibody-producing
plasma cells.
Plasma cells
proliferate and
produce antibodies
against the antigen.
Activation of
macrophage
(enhanced
phagocytic activity).
TH cell
Cytotoxic T
lymphocyte
Plasma cell
A T cell binds to
MHC–antigen
complexes on the
surface of the
infected cell,
activating the T cell
(with its cytokine
receptors).
Memory cell
Some T and B cells differentiate
into memory cells that respond
rapidly to any secondary
encounter with an antigen.
Lysed target cell
The CD8+T cell
becomes a cytotoxic
T lymphocyte (CTL)
able to induce
apoptosis of the
target cell.
Antigens and antigen receptors
• Antigens can be entire microbes, parts of microbes or chemical
components of pollen, egg white, blood cells
• Plasma cells secrete specific antibody at the rate of 2000 molecules per
second
• Complement fixation is the main mechanism used against cellular
antigens
• Antibodies bound to cells change shape and expose complement binding
sites
• T Cell Dependent Antigens
MHC proteins & APCs
• Antigens on our own cells
are self-antigens
• MHC proteins are
glycoproteins that mark
the cell as self.
– Class I MHC proteins are
on all body cells. Receptors
on TC
– Class II MHC proteins are
only on certain cells that
act in the immune
response. Receptors on TH
– Antigen Processing
Immunocompetence
• Immature Lymphocytes
= in bone marrow
• T and B cells that have
not been exposed to an
antigen are naïve.
• Binding with an antigen
completes
differentiation into
functional B and T
cells.
• B cells mature in the
bone marrow.
• T cells mature in the
thymus.
Clonal
Selection
Monoclonal Antibody
Production
Mechanisms of Antibody Action
Antibodies
“immunoglobulins”
Immunoglobulin classes
• IgD is attached to B-cell plasma
membrane
• IgM is released during primary
response. Indicates current
infection.
• IgG is the most aboundant. Can
cross placenta & blood vessel
walls.
• IgA found in body secretions
prevents attachment to body
surfaces.
• IgE causes release of histamine
(allergies) by attaching to mast
cells & basophils.
Immunological memory
Primary vs Secondary Immune Response
Active Humoral Immunity
•B cells encounter antigens
and produce antibodies
against them
Passive Humoral Immunity
•B cells not challenged by
antigen
•No immunological
memory
•Protection ends when
antibodies naturally
degrade in the body
dendritic cells, macrophages
Cell-mediated immunity
• Antibodies can only inactivate an antigen and
NOT destroy it.
• Antibodies prepare an organism for destruction
by innate defenses.
• T cells can only recognize and respond to
processed fragments of protein.
• T cells are suited for cell to cell interaction and
target body cells infected by virus, bacteria and
abnormal or cancerous body cells or cells that
are transplanted or infused.
• Cells & Organs of the Immune System. Review & Quiz
Autoimmunity and Allergy
• Autoimmunity diseases
are produced by failure
of the immune system to
recognize and tolerate
self-antigens, and can
result from a variety of
mechanisms.
• Allergies can be divided
into immediate
hypersensitivity and
delayed hypersensitivity,
both of which can cause
the release of histamine.
• In extreme cases, the
widespread release of
histamine can lead to
anaphylactic shock.
Hypersensitivities
Hypersensitivity Reactions in the Skin
Hypersensitivities
Acute
Immediate
Subacute
cytotoxic
Subacute
Immune complex
Delayed
Type I Hypersensitivity
Type I Hypersensitivity
Animation
Type II Hypersensitivity
Type III
Hypersensitivity
Type III
Hypersensitivity
Essential knowledge 2.D.4: Plants and animals have a variety of
chemical defenses against infections that affect dynamic
homeostasis.
b. Mammals use specific immune responses triggered by
natural or artificial agents that disrupt dynamic
homeostasis.
1. The mammalian immune system includes two types of specific
responses: cell mediated and humoral.
2. In the cell-mediated response, cytotoxic T cells, a type of
lymphocytic white blood cell, “target” intracellular pathogens when
antigens are displayed on the outside of the cells.
3. In the humoral response, B cells, a type of lymphocytic white blood
cell, produce antibodies against specific antigens.
4. Antigens are recognized by antibodies to the antigen. Antigens &
Epitopes, Antigen Processing
5. Antibodies are proteins produced by B cells, and each antibody is
specific to a particular antigen. ABO Type II Sensitivity
6. A second exposure to an antigen results in a more rapid and
enhanced immune response.
Essential knowledge 2.E.1: Timing and coordination of
specific events are necessary for the normal
development of an organism, and these events are
regulated by a variety of mechanisms.
• Programmed cell death (apoptosis) plays
a role in the normal development and
differentiation.
– Immune function
LO 2.29 The student can create representations and models to
describe immune responses.
LO 2.30 The student can create representations or models to
describe nonspecific immune defenses in plants and animals.
Essential knowledge 2.D.4: Plants and animals have a
variety of chemical defenses against infections
that affect dynamic homeostasis.
a. Plants, invertebrates and vertebrates have
multiple, nonspecific immune responses.
– Invertebrate immune systems have nonspecific response
mechanisms, but they lack pathogen-specific defense
responses. (phagocytes present in all animals, sponges can
attack tissues from other sponges)
– Plant defenses against pathogens include molecular
recognition systems with systemic responses; infection
triggers chemical responses that destroy infected and
adjacent cells, thus localizing the effects.
– Vertebrate immune systems have nonspecific and
nonheritable defense mechanisms against pathogens.
Plant defenses against pathogens include molecular recognition
systems with systemic responses; infection triggers chemical
responses that destroy infected and adjacent cells, thus localizing
the effects.
PR pathogenesis related proteins
Essential knowledge 3.D.2: Cells communicate with
each other through direct contact with other cells
or from a distance via chemical signaling.
• a. Cells communicate by cell-to-cell contact.
– Immune cells interact by cell-cell contact, and killer Tcells. Interaction of Antigen Presenting Cells and Thelper Cells
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Essential knowledge 3.D.4: Changes in signal
transduction pathways can alter cellular response.
• a. Conditions where signal transduction is blocked
or defective can be deleterious, preventative or
prophylactic.
– Diabetes, heart disease, neurological disease, autoimmune
disease, cancer, cholera
Epidermis:
A Complex Plant Tissue
- Covers and protects plant surfaces
-Secretes a waxy, waterproof
cuticle
-In plants with secondary growth,
periderm replaces epidermis
-protection, increase absorption
area in roots, reduces H2O loss in
stem & leaves,
-Regulates gas exchange in leaves
Signaling between Plants and Pathogens
Xenohormesis: Sensing the
Chemical Cues of Other Species
Many plant molecules interact
with and modulate key
regulators of mammalian
physiology in ways that are
beneficial to health, but why?
We propose that heterotrophs
(animals and fungi) are able to
sense chemical cues
synthesized by plants and
other autotrophs in response
to stress. These cues provide
advance warning about
deteriorating environmental
conditions, allowing the
heterotrophs to prepare for
adversity while conditions are
still favorable.
Antigen Shifting
• A pathogen may
escape recognition
by the immune
system if it
changes its surface
antigens. Such
antigen shifting is
an example of
evolution by natural
selection.
Immune-enhancing role of vitamin C and zinc and effect on
clinical conditions. Wintergerst ES, Maggini S, Hornig DH. Ann
Nutr Metab. 2006;50(2):85-94. Epub 2005 Dec 21.
• Vitamin C concentrations in the plasma and leukocytes rapidly decline
during infections and stress. Supplementation of vitamin C was found
to improve components of the human immune system such as
antimicrobial and natural killer cell activities, lymphocyte proliferation,
chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to
maintaining the redox integrity of cells and thereby protects them
against reactive oxygen species generated during the respiratory burst
and in the inflammatory response. Likewise, zinc undernutrition or
deficiency was shown to impair cellular mediators of innate immunity
such as phagocytosis, natural killer cell activity, and the generation of
oxidative burst. Therefore, both nutrients play important roles in
immune function and the modulation of host resistance to infectious
agents, reducing the risk, severity, and duration of infectious diseases.
Resources
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Components of the Immune System Animation
The Body: The Immune System
Chapter 17 - Adaptive Immunity: Specific Defenses of the Host
Flash animation of a NK cell interacting with a normal body cell.
Flash animation of a NK cell interacting with a virus-infected cell or
tumor cell not expressing MHC-I molecules.
Flash animation of apoptosis by NK cells.
HIV Replication
A&P Chapter 22: Lymphatic System and Immunity
Blood & Body Defenses Notes
Defense Mechanisms and the Immune System
Introducing the Bloody Characters of Specific Immunity
Adaptive Immunity in Prokaryotes
Games Parasites Play
Immune System notes
Innate Immune System Unit 4