Chapter 15

Phagocytosis

Three types of phagocytic cells: - Neutrophils are the first to arrive at an infection. - Mononuclear phagocytic cells (monocytes in the blood and macrophages and dendritic cells in the tissues) arrive later. - There are organ-specific phagocytes in the liver, spleen, lymph nodes, lungs, and brain. ---- Some of these, called fixed phagocytes, are immobile in the walls of these organs.

Local inflammation

Tissue damage that causes necrosis Immune system exposed to DAMPs - danger associated molecular patterns Stimulates innate immune responses and inflammation

Immediate Hypersensitivity

Abnormal B cell response to allergen - Effects seen seconds to minutes after exposure - Can be caused by foods, bee stings, pollen, etc. Dendritic cells stimulate TH2 helper T cells to secrete interleukin-4 and interleukin-13, which stimulate B and plasma cells to secrete IgE antibodies These antibodies do not circulate in the blood but attach to mast cells and basophils. When re-exposed to the same allergen, these antibodies bind with it and stimulate the production of histamine, leukotrienes, and prostaglandin D, producing allergy symptoms.

Delayed Hypersensitivity

Abnormal T cell response that produces symptoms 24−72 hours after exposure Symptoms are caused by secretion of lymphokines, not histamine, so taking antihistamines has little effect. Example: contact dermatitis caused by poison oak, ivy, or sumac

Allergies

Abnormal response to allergens (antigens) - Also called hypersensitivity - Two types: ----- Immediate hypersensitivity ----- Delayed hypersensitivity

Interferons

Antiviral polypeptides produced by infected cells Three types identified - Alpha and beta - inhibit viral replication and assembly - Gamma - helps fight infections and cancer New antiviral drugs are being developed using interferons.

Lymphokines

Autocrine regulators Cytokines specific to lymphocytes Called interleukins - see Table 15.7 Many stimulate B cell or cytotoxic T cell activity. Subtypes of helper T cells also produce lymphokines - TH1 - produces IL-2 and gamma interferon - activates killer T cells and stimulates NO production in macrophages - TH2 - produces IL-4, IL-5, IL-13 and others - stimulates B cells and humoral immunity, recruits eosinophils and induces IgE production - TH17 - secretes IL-17 - fights infections in skin, lungs, and mucous membranes; stimulates neutrophils

Antigens

Cell surface molecules that stimulate the production of specific antibodies and combine with those antibodies - Foreign antigens illicit an immune response. The immune system can distinguish "self" from "nonself." - Antibodies bind to their specific antigens. - Large molecules can have several antigenic determinant sites or epitopes, that stimulate the production of and binding to antibodies.

Activation of Innate Immunity

Cells distinguish "self" from "nonself" using pathogen-associated molecular patterns (PAMPs) unique to the pathogens. - Immune cells have pathogen recognition receptors, such as toll-like receptors for PAMPs on their surface. - So far, 10 distinct toll-like receptors have been identified. - These cells respond by secreting chemokines to recruit more immune cells or activate specific immune cells.

Active Immunity pt 2

Development of the secondary response provides active immunity Requires prior exposure to the antigen and then protects the body from future infections Active immunity is also used to make vaccines. These vaccines include an antigen but are not virulent (disease-causing).

Clonal Selection Theory

Explains how the secondary immune response works: - A person inherits lymphocytes specific to almost every pathogen, but there are few of each type. - When exposed to foreign antigens, immune cells respond by making many copies of themselves. - Germinal centers in secondary lymphoid organs develop to produce the clones The primary response triggers a massive production of cells that can respond to that antigen. These cells respond much quicker after exposure a second time.

Innate Immunity

Includes external and internal defenses Serves as a first line of defense against pathogens - Examples: epithelial membranes, high acidity in stomach, cells that can engulf/kill pathogens, fever

Immune Complex Diseases

Involve free antigen-antibody complexes that stimulate complement proteins and inflammation - Usually self-regulating because complexes are removed via phagocytosis - Complex formation may be prolonged or spread to other organs, leading to prolonged inflammation. May result from infections from bacteria, viruses, or parasites - Hepatitis B results in free complexes that cause damage to arteries due to inflammation. May also result from complexes formed by self antigens and autoantibodies - Rheumatoid arthritis and lupus

Killer, Helper, and Regulatory T Lymphocytes

Killer (cytotoxic) T Lymphocytes - Have surface molecules called CD8 - Destroy body cells that harbor foreign antigens ---- Usually from a pathogen (virus or fungus), but can be due to a malignancy (cancer) ---- Transplant cells - Cell-mediated destruction means the T cells must touch the target victim. ---- Secrete perforins to create large pore in cell ---- Secrete granzymes to trigger apoptosis in cell through the action of caspase enzymes

Lymphocytes & Lymphoid Organs

Lymphocytes - Derived from stem cells in the bone marrow. - These stem cells seed the thymus, spleen, and lymph nodes. ---- The thymus is the site of new T lymphocytes through late childhood. It degenerates in adulthood, and new T lymphocytes are made through mitosis in secondary lymphoid organs. ---- The bone marrow and thymus are considered primary lymphoid organs.

B Lymphocytes

Lymphocytes that come directly from bone marrow to seed other organs (not the thymus) are called B lymphocytes. They combat bacterial and some viral infections. They secrete antibodies into blood and lymph so can be far from the victim. This is called humoral immunity or antibody-mediated immunity.

T Lymphocytes

Lymphocytes that seed the thymus become T lymphocytes. These then seed the blood, lymph nodes, and spleen. T lymphocytes attack host cells that have become infected with a virus or fungus, transplanted human cells, and cancer cells. T lymphocytes do not produce antibodies. They must be in close proximity to the victim cell in order to destroy it. This is called cell-mediated immunity

Phagocytosis in Tissues

Neutrophils and monocytes squeeze through gaps in post-capillary venule walls to enter tissue in a process called extravasation, or diapedesis. Attracted to site by a process called chemotaxis by cytokines called chemokines The pathogen becomes engulfed by pseudopods. The vacuole containing the pathogen fuses with a lysosome. The pathogen is digested.

Local Inflammation Pt 2

Occurs when bacteria enter a break in the skin Initiated by nonspecific mechanisms of phagocytosis by toll-like receptors - Macrophages and mast cells release cytokines and chemokines to attract phagocytic neutrophils. - Complement proteins are activated, which also attract phagocytic cells. - More phagocytic cells arrive via extravasation from nearby venules. T lymphocytes are the last to arrive Mast cells degranulate and secrete heparin, histamine, prostaglandins, leukotrienes, cytokines, and TNF-α. - These produce warmth, swelling, and pain (classic symptoms). - They also recruit more leukocytes. Neutrophils - Kill microorganisms through phagocytosis - Release NETS (neutrophil extracellular traps) to trap pathogens - Undergo programmed cell death and spill protein-digesting enzymes into the surrounding tissues, causing pus - Release granule proteins that draw monocytes to the area Monocytes - Enlarge into macrophages - Phagocytose apoptotic neutrophils and release growth factors and other agents that will end inflammation and promote repair. As inflammation progresses, B lymphocytes produce antibodies against bacterial antigens. - Formation of antigen-antibody complexes amplifies phagocytosis by neutrophils, monocytes, and macrophages, a process called opsonization Symptoms of inflammation - Redness and warmth due to histamine stimulated vasodilation - Swelling - vasodilation - Pain - release of PGE2 - Pus - phagocytosis

Histocompatibility Antigens

On surface of all body cells (except mature RBCs); also called human leukocyte antigens (HLAs) Coded for by four genes (A, B, C, D) on chromosome 6 called major histocompatibility complex (MHC) - Many versions of each gene are possible, so most people have different combinations. - An organ transplant requires an MHC match.

Active Immunity & the Clonal Selection Theory

Primary response - After infection, it takes 5−10 days before antibodies are detected in the blood. - The person will get sick. Secondary response - Later exposure to the same infection results in maximum antibody production in less than 2 hours. - The person will likely never get sick.

Autoimmunity

Produced by failure of immune cells to recognize and tolerate "self" antigens - Autoreactive T lymphocytes and autoantibodies are produced, causing inflammation and organ damage. - Common autoimmune diseases include rheumatoid arthritis, type 1 diabetes, multiple sclerosis, Grave's disease, pernicious anemia, thyroiditis, psoriasis, and lupus

Introduction

Protect against disease-causing agents called pathogens Make up the immune system Two types: - Innate (nonspecific) immunity - inherited - Adaptive (specific) immunity - learned from exposure to specific pathogens; function of lymphocytes

Fever

Regulated by hypothalamus A chemical called an endogenous pyrogen sets the body temperature higher. - Produced as a cytokine by leukocytes - Endotoxins from some bacteria stimulate leukocytes to produce these cytokines. - Along with fever, they also induce sleepiness and a fall in plasma iron concentration (which limits bacterial activity).

Haptens

Smaller, nonantigenic molecules that can become antigens when bound to other proteins These are useful for creating antigens for research and diagnosis. Assays looking for reaction particularly agglutination.

Helper T Lymphocytes

Surface molecule is CD4 Improve ability of B lymphocytes to become plasma cells and enhance ability of cytotoxic T cells to kill targets - Secretion of lymphokines

Regulatory T Lymphocytes, T(reg)

Surface molecules CD4 and CD25 Previously called suppressor T lymphocytes Inhibit response of B lymphocytes and killer T lymphocytes Activates the FOXP3 gene that codes for a transcription factor needed for development of T(reg) lymphocytes People with genetic deficiencies in regulatory T lymphocyte production may develop autoimmune diseases and allergies.

Adaptive Immunity

The acquired ability to defend against specific pathogens after exposure to these pathogens - Mediated by antigens and antibodies