Lecture 8 Immunology and disease: how vertebrate immunity works.
Mechanisms of Immunity Part One Types of Immunity CLS 420 Clinical Immunology & Molecular...
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Transcript of Mechanisms of Immunity Part One Types of Immunity CLS 420 Clinical Immunology & Molecular...
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Mechanisms of Immunity
Part One
Types of Immunity
CLS 420Clinical Immunology &Molecular Diagnostics
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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. Skin and mucous membranes
b. Age
c. Metabolism
d. Environment
e. Normal flora
f. Concomitant disease
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Objectives
3. Compare specific versus non-specific immunity as it relates to:a. Phagocytosisb. Inflammationc. Cellular immunityd. Humoral immunitye. Memoryf. Opsonization
4. Differentiate humoral and cellular immunity.5. Compare active and passive immunity, including
examples of each.
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Immunity
The state of protection from infectious disease.
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Immunity
• Protection against:– Pathogens– Toxins – Tumors
• Recognition of foreign vs. self
• Two branches:– Innate– Adaptive (acquired)
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Immune function is influenced by:
• Age • Nutritional status• Stress• Fatigue
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What happens when foreign matter enters the body?
Innate ImmunityThe First Line Of Defense
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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.
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Barriers
• Skin
• Tears, saliva, secretions
• Mucus
• Cough Reflex
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Environment
• pH
• Normal flora
• Temperature
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Pathogen Recognition
• Toll-like receptors
• Complement – Alternative Pathway
– Mannose Binding Lectin Pathway
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Chemicals
• Chemicals include:– Complement– Histamine– Cytokines– Acute Phase Reactants– Kinins
• Destroy pathogens • Expand the immune response• Neutralize the effects of other chemicals
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Inflammation
• Capillaries dilate and blood accumulates in the affected area.– Redness– Increased temperature
• Fluid accumulates in tissue (edema).
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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
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Inflammation
• Pus formation
• Macrophages clean up debris.
• Release chemicals that enhance the inflammatory response.
• Growth factors rebuild tissue and blood vessels.
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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
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PhagocytosisYUM
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Phagocytes
• Dendritic cells
• Neutrophils
• Macrophages
• Monocytes
• Eosinophils
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“Contact”
• Receptors on phagocyte make contact with foreign material.– May be enhanced
by opsonins• CRP• Complement• Antibodies
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“Ingestion/Digestion”
• Phagocyte engulfs foreign material to form phagosome.
• Phagosome merges with granules in cytoplasm.
• Granules contain chemicals that digest foreign material.
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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.
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Exocytosis
• Waste material is expelled from phagocyte (exocytosis).
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Cells Alive!
• Please go to http://www.cellsalive.com/ouch1.htm
• View “Anatomy of a Splinter”.
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How can long-lasting protection be developed?
Acquired Immunity
a.k.a.
Adaptive Immunity
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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
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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.
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Cell Mediated Process
• Foreign matter is broken down into small peptides.
• Peptides combine with the Major Histocompatibility Complex (MCH) molecules on the cell membrane.
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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.
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Major Histocompatibility Complex
Class I
Class II
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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.
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Recognition
• T lymphocytes possess receptors (TCR) that recognize foreign antigen when the antigen is bound to MHC antigen.
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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.
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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
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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.
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Cells Alive!
• Please go to http://www.cellsalive.com/ctl.htm
• View “The Cytotoxic T Lymphocyte”.
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Humoral Immunity
• Major cell involved is the B lymphocyte.– Develops into plasma cells and memory cells.
• Influenced by T helper cells.
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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.
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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
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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.
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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.
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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
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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)
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Cells Alive!
• Please go to http://www.cellsalive.com/antibody.htm
• View “Making Antibodies”.
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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
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STRETCH
Take a break before moving on to Part II