Chapter 8, Immune System

Compare and contrast B and T cells:

-Both B and T cells develop in the bone marrow. -B cells mature in Bone marrow, but are activated by spleen or lymph nodes. T-cells mature in thymus. -B-cells major function is to produce antibodies -T-cell's major function is to coordinate immune system and directly kill infected cells -B and T-cells are specific/adaptive immunity -B-cells are part of humoral system while T-cells are part of cell-mediated immunity

Antigen

A substance (usually pathogenic protein) that can be targeted by an antibody. Innate immunse system and adaptive immune system may produce antigens whereas only the adaptive immune system produces antibodies.

Natural Killer (NK) Cells

A type of nonspecific lymphocyte that are able to detect the down-regulation of MHC and induce apoptosis in these virally infected cells. Cancer cells may also downregulate MHC production, so NK cells also offer protection from the growth of cancer as well.

Hypersensitivity Reactions

Allergies and autoimmunity towards non-dangerous antigens.

Immunoglobulins

Antibodies can carry out many different jobs in the body. They attract leukocytes to phagocytize those antigens immediately. They cause pathogens to clump together or agglutinate, making insoluble complexes than can be phagocytized. They can block the ability of a pathogen to invade tissues, neutralizing it.

Types of Pathogens

Bacteria, Viruses, Fungi, Parasites, and Prions.

Cytotoxic T Cells (CD8)

Capable of directly killing virally infected cells by injecting toxic chemicals that promote apoptosis into the infected cell. They respond to antigens present on MHCI molecules. Most effective against viral infections.

Negative Selection

Causing apoptosis in cells that are self-reactive.

Nonspecific/ innate Immune Response

Cells can carry these out without learning.

MHC Molecules

Class 1: Displayed by all nucleated cells in the body, it can be presented on the surface of the cell. It is called the endogenous pathway because it binds antigens from inside the cell, triggers to be killed by T-cells to prevent infection. Class 2: Displayed by antigen presenting cells like macrophages, they pick up pathogens from the environment, process them, and then present them on MHC-II. This is an exogenous pathway because the antigens originated outside the cell

Innate/nonspecific Immunity

Composed of defenses that are always active against infection, but lack the ability to target specific pathogens.

Helper T Cells (CD4)

Coordinate the immune response by secreting chemicals known as lymphokines. They can recruit other immune cells and increasing their activity. The loss occurs in HIV infection, prevents the immune system from mounting an adequate response to infection. In AIDS, even weak pathogens can cause devastating consequences as opportunistic infections. They respond to MHCII.

Adaptive/specific Immunity

Defenses that target a specific pathogen. It leads to immunological memory for quicker attack upon reinfection.

Hypermutation

Each B cell tries to find the best match for its antigen-binding region.

Supressor (Regulatory) T Cells

Express CD4 but can be differentiated form helper T cells because they also express a protein called Foxp3. They tone down the immune response once infection has been adequately contained. These cells also turn off self-reactive lymphocytes to prevent autoimmune disease: self-tolerance.

Granulocytes vs aganulocytes

Granulocytes contain granules: neutrophils, eosinophils, and basophils Agranulocytes: lymphocytes and monocytes

Secondary Response

If the same microbe is encountered again, the memory cells jump into action and produce the antibodies specific to that pathogen. This helps with vaccinations.

Specific/Adaptive Immunity

Immune cells learn to recognize and respond to certain antigens. The specific immune system is further divided into the cell-mediated and the humoral immune system

Active Immunity

Immune system is stimulated to produce antibodies against a specific pathogen. This generates antibodies via B cells upon infection. Vaccines produce artificial exposure.

interferon

Interferons (IFNs) are a group of signaling proteins[1] made and released by host cells in response to the presence of pathogens, such as viruses, bacteria, parasites, or tumor cells. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses. IFNs belong to the large class of proteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens.[2] Interferons are named for their ability to "interfere" with viral replication[2] by protecting cells from virus infections. IFNs also have various other functions: they activate immune cells, such as natural killer cells and macrophages; they increase host defenses by up-regulating antigen presentation by virtue of increasing the expression of major histocompatibility complex (MHC) antigens. Certain symptoms of infections, such as fever, muscle pain and "flu-like symptoms", are also caused by the production of IFNs and other cytokines.

Spleen

Location of blood storage and activation of B cells, which turn into plasma cells to produce antibodies as part of the adaptive immune system.

Bacterial Extracellular Pathogen Infections

Macrophages, MHCII presentation, cytokines attract more cells, mast cells. Travels to lymph node where it is presented to B cells, they proliferate and travel through the bloodstream to the affected tissue. Dendritic cells are also presenting the antigen to T-cells, activating a T-cell response with CD4 T cells.

T-Cells

Main agents of cell-mediated immunity, they coordinate the immune system and kill virally infected cells

Thymosin

Maturation of T-cells, peptide hormone secreted by thymic cells.

Positive Selection

Maturing only cells that can respond to the presentation of antigen on MHC.

Granulocytes (3 types)

Neutrophils: Phagocytic, follow bacteria via chemotaxis, they can detect bacteria one they have been opsonized (tagged with antibody from B-cell). They create pus. Eosinophils: Involved in allergic reactions and invasive parasitic infections, they release histamine, an inflammatory mediator. Causing vasodilation and increased leakiness of blood vessels, allowing additional immune cells to move out of blood stream and into tissues. Basophils: Involved in allergic responses, least popular leukocyte in the bloodstream under normal conditions. Mast cells have smaller granules and exist in tissues, mucosa, and epithelium. Like basophils. They also release a lot of histamine in response to allergens, leading to inflammatory responses.

Lymphatic Structure

One-way vessel that becomes larger as they move toward the center of the body, they carry lymph and join to comprise a large thoracic duct in the posterior chest, which then delivers the fluid into the left subclavian vein. Lymph nodes are small, bean-shaped structures that provide a space for cells of the immune system to be exposed to possible pathogens.

Clonal Selection

Only B cells that bind to the antigen with high affinity will survive.

Constant Region

Part of the antibody that binds to natural killer cells, macrophages, monocytes, and eosinophils have receptors.

Monocytes

Phagocytic cells in the bloodstream, agranulocytes. They become macrophages in tissues (microglia, langerhans (skin), and osteoclasts).

Glucocorticoids

Potent immunosuppressive cure for autoimmune diseases.

Hematopoietic Stem Cells

Produce granulocytes and agranulocytes. precursur cell for all other blood cells including RBCs and WBCs

Bone Marrow

Produces all leukocytes that participate in the immune system.

Humoral Immunity

Production of antibodies that are specific to the antigens. B-cells are lymphocytes that produce antibodies, they mature in the bone marrow and are activated in the spleen and lymph nodes.

Self-Antigens

Proteins and carbs present on the surface of every cell of the body. They signal to immune cells that the cell is not threatening and should not be attacked. If it fails then autoimmunity is a problem.

Lymph Nodes

Provide a place for immune cells to communicate and mount an attack, B-cells are activated here.

Thymus

Site of maturation of the adaptive immune cells called T-cells.

Noncellular Nonspecific Defenses

Skin: Physical barrier, contains the antimicrobial enzyme defensin. Respiratory Tract: Mucous membrane with cilia that help to push up matter for expelling or swallowing. Eye and Oral Cavity: Produce antibacterial enzyme, lysozyme which is secreted in tears and saliva. Gastrointestinal Tract: Stomach secretes acid and has a lot of nonpathogenic bacteria. Complement Interferons

Complement system

The complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system,[1] which is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by the adaptive immune system. The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver, and normally circulating as inactive precursors (pro-proteins). When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end-result of this activation cascade is massive amplification of the response and activation of the cell-killing membrane attack complex. Can be activated by either a classical pathway (requires binding of an antibody to a pathogen) or an alternative pathway (does not require antibodies) Functions: Opsonization - enhancing phagocytosis of antigens Chemotaxis - attracting macrophages and neutrophils Cell Lysis - rupturing membranes of foreign cells Agglutination - clustering and binding of pathogens together (sticking)

Pattern Recognition Receptors

They recognize the category of the invader for production of appropriate cytokines to recruit the right type of immune cells. TOll like receptors

Memory T Cells

They wait until the next exposure to the same antigen.

Primary Response

They will proliferate and produce either plasma cells or memory B cells. This happens 7 to 10 days.

Naive B-Cells

Those that have not yet been exposed to an antigen, they wait in the lymph nodes for their particular antigen to come along.

Gut-Associated Lymphoid Tissue (GALT)

Tonsils, adenoids, Peyer's patches, and appendix are other immunite tissues

Passive Immunity

Transfer of antibodies to an individual. No plasma cells are transferred.

Structure of Antibody

Two identical heavy chains and two light chains. They have an antigen binding region at the Y and the variable region at the bottom.

Macrophages

Type of agranulocyte that resides within the tissue. They derive from monocytes and can become a resident population within a tissue. They become activated and they phagocytize the invader through endocytosis, it digests the invader using enzymes, and it presents pieces to other cells using a protein called major histocompatibility complex (MHC). MHC binds to a pathogenic peptide (antigen) and carries it to the cell surface, where it can be recognized by cells of the adaptive immune system. They also release cytokines to stimulate inflammation.

Viral Intracellular Pathogen Infections

Virally infected cell will begin to produce interferons, these reduce the permeability of nearby cells, reduce the rate of transcription and translation in these cells, and cause systemic symptoms. They present intracellular proteins on their surface in conjunction with MHCI in a virally infected cell. CD8 will recognize the MHCI and antigen complex as foreign and will inject toxins into the cell to promote apoptosis.

Humoral Immunity

When B cells leave bone marrow, they are mature but naive (not yet exposed to antigen). Because these antibodies dissolve and act in blood, they are called humoral immunity (driven by B-cells and antibodies)

Degranulation

When an antigen binds to antibodies on the surface of a mast cell, exocytosis of granule contents, releasing histamine and causing an inflammatory allergic reaction.

Lymphocytes

agranulocytes, responsible for antibody production, immune system modulation, and targeted killing of infected cells.

Cell Mediated Immunity

an immune response that does not involve antibodies, but rather involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. Historically, the immune system was separated into two branches: humoral immunity, for which the protective function of immunization could be found in the humor (cell-free bodily fluid or serum) and cellular immunity, for which the protective function of immunization was associated with cells. CD4 cells or helper T cells provide protection against different pathogens. Cytotoxic T cells cause death by apoptosis without using cytokines, therefore in cell mediated immunity, cytokines are not always present. The innate immune system and the adaptive immune system each comprise both humoral and cell-mediated components. Cellular immunity protects the body by: -activating antigen-specific cytotoxic T-lymphocytes that are able to induce apoptosis in body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens; activating macrophages and natural killer cells, enabling them to destroy pathogens; and stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses.

types of antigen-presenting cells

macrophages, dendritic cells, B-cells, activated epithelial cells