Transcript Immune System - Dr. Annette M. Parrott

Immune System
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
– Transferrins
• 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
• Interferon Animation
Complement
Complement Cascade Animation
Phagocytosis
Phagocyte Mobilization
Fever
• Regulated my hypothalamus
• Due to pyrogens secreted my leukocytes &
macrophages
• Causes liver and spleen to sequester zinc
and iron
• Increases metabolic rate (repair)
Inflammatory response
Stages
Inflammation Animation
• Release of Chemical Alarms
• Vasodilatation & Permeability of BV
• Emigration of phagocytes: Dispose cellular debris &
pathogens
• Sets the stage for repair
• Prevent spread of damaging chemicals & pathogens
Signs of inflammation
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Redness
Heat
Swelling
Pain
Impairment of function
Comparison of Immune Cells
Adaptive 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
Antigens and antigen receptors
• Antigens can be entire microbes, parts of
microbes or chemical components of
pollen, egg white, blood cells,…….
Self antigens: MHC proteins
• 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
• 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.
Antigen receptors
• Genes determine what foreign
substance will be recognized.
• An antigen determines which T or B
cells will be activated.
• Lymphocytes make over a billion
different receptors.
• Gene segments of a few hundred bits
are reshuffled and combined--somatic
recombination.
• The newly assembled gene is expressed
as a receptor on the cell surface.
Humoral immune response
• Antigen challenge—the meeting between
a naïve immunocompetent lymphocyte
and an invading antigen.
• Occurs in lymphoid tissue such as spleen
or lymph node.
• If antigen challenge is presented to a B
cell then the humoral immune response
is provoked.
Clonal
Selection
Monoclonal Antibody
Production
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 immune
response
• Secondary
immune response
Antibody defense: PLANe
• Precipitation
• Lysis: Complement fixation and activation
• Agglutination
• Neutralization
• Enhancing phagocytosis
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.
Cell-mediated immunity: T-cells
• Activation of T cells—T cell receptors bind
to antigen presented by the antigen-MHC
complex.
• CD4 and CD8 proteins interact with antigen
and help maintain MHC-antigen coupling.
• Types of T-cells
– Helper T cells (CD4)
– Cytotoxic T cells (CD8)
– Memory T-cells
Activated T cell
• Activation leads to enlargement,
differentiation and proliferation of T
cells.
• T cells that are reproduced are clones
of originally activated T cell.
• Activation, differentiation and
proliferation occurs in secondary lymph
organs and tissue.
• Activation leads to release of
inflammatory cytokines.
Homeostatic imbalances :
Immunodeficiencies
• Abnormally behaving immune cells
• Severe combined immunodeficiency (SCID)
syndromes
– Congenital conditions
• Acquired immune deficiency syndromes
– Hodgkin’s Disease
– HIV
– AIDS
Homeostatic imbalances :
Autoimmune disease
– Tend to be more prevalent in women
• Type I diabetes—destroys pancreatic beta
cells
• Multiple sclerosis—destroys myelin
sheaths
• Myasthenia gravis—impairs communication
between nerve and muscle
• Lupus erythematosus—systemic disease of
skin, kidneys, heart, and lungs
• Rheumatoid arthritis—destruction of
joints
Organ transplants
• Autografts—grafts from the same
person to another body site
• Isografts—grafts between genetically
identical individuals
• Allografts—grafts among the same
species
• Xenografts—grafts taken from another
animal species
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
Animations
• 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
Resources
• Components of the Immune System
Animation
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.
– 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.
• 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.
5. Antibodies are proteins produced by B cells, and each antibody is specific to
a particular antigen.
6. A second exposure to an antigen results in a more rapid and enhanced
immune response.
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, antigenpresenting cells (APCs), helper T-cells and killer T-cells.
[See also 2.D.4]
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