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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.
• 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
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 responseStages 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– Redness– Heat– Swelling– Pain– Impairment of function
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
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.
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
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
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, antigen-
presenting 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
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