Immune System

Defense system

NonspecificImmunity

Specific Immunity

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

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 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

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 Subacute Subacute

Delayed Immediate cytotoxic Immune complex

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, 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