Chapter 17 Micro
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Who is the father of the theory of immunity?
- Edward Jenner- First Vaccine
- Robert Koch- Germ Theory of Disease
- Elie Metchnikoff- Phagocytosis (founded the first theory of immunity)
- Emil Von Behring- Diphtheria Antitoxin
- Paul Ehrlich- Theory of Immunity
- Louis Pasteur in his development of vaccination and his proposed germ theory of
- diseases exploited acquired immunity. Robert Koch’s proofs that microorganisms
- were confirmed as the caused infectious disease.
What is immunology? What is an antigen? What is an antibody?
Immunology: The study of the immune system.
- Antigen: A molecule, usually a protein or
- large polysaccharides that stimulates an adaptive immune response. Antigenic
- compounds are often components of invading microbes.
Antibody: A globulin protein molecule secreted by B cells (plasma cells) that can bind to antigens.
What are the 2 arms of the adaptive immune
system and what cell type is important for each?
- Humoral immunity: Immunity brought about by antibodies. The process that leads to
- the production of antibodies starts when B cells are exposed to free, or extracellular antigens. Primary cell type:
- B cells.
- Cell-mediated immunity: Immunity that responds to intracellular antigens, such as a virus within an infected cell. Primary cell
- type: T cells.
Where do B cells develop? Where do T cells develop?
B lymphocytes (B cells) are developed in the bone narrow and T lymphocytes (T cells) derive from the thymus.
What do antibodies bind to?
- Antibodies bind to the epitope (antigenic
- determinant) of an antigen.
What is a hapten and why does it need a carrier? What is an example we discussed in lecture?
Haptens are antigens that are composed of low molecular-weight compounds and are attached to a carrier molecule. They are too small to stimulate antibody formation by itself, but when the hapten is combined with a larger carrier molecule, usually a serum protein, the hapten and its carrier together form a conjugate that can stimulate an immune response.
- Penicillin. When penicillin combines with host proteins, the resulting combined
- molecule initiates an immune response.
Know antibody structure:
a. How many polypeptide chains does a antibody have? How many binding sites? What is the part of the antigen that binds tothe antibody called?
An antibody is composed of four polypeptide chains two identical light chains and two identical heavy chains (light and heavy refer to the relative molecular weights) that are linked by disulfide bridges (S-S). The two sections located at the end of the Y’s arms are called variable (V) regions. An epitope is the binding site of an antigen where an antibody binds to.
Know antibody structure:
b. What makes each antibody from different B
The amino acid sequences of the variable regions(V), which form the two antigen-binding sites, differ from molecule to molecule.
What is passive immunity and how can you get it?(see slide “Specific Host Defenses”, 2nd to last)
Passive immunity: The short-term immunity that results from the introduction of antibodies from another person or animal.
Naturally acquired: Antibodies pass from mother to fetus via placenta or to infant via the mother’s milk.
Artificially acquired: Preformed antibodies in immune serum are introduced by infection.
What antibody is most common in serum? Why is that (think about its function)?
- IgG accounts for about 80% of all antibodies in serum. IgG antibodies cross the walls of blood vessels and enter tissue fluids. They protect against circulating bacteria and viruses, neutralize bacterial toxins, trigger the complement system, and when bound to
- antigens, enhance the effectiveness of phagocytic cells. IgG antibodies protect fetus and newborn, and tend to last longer than other antibodies
What antibody is least common in serum? Where is it if it is not in the serum?
IgE antibodies constitute only .0002% of the total serum antibodies. IgE molecules bind by their Fc (stem) regions to receptors on mast cells and basophils, specialized cells that participate in allergic reactions.
Know the antibody isotypes:
a. What is an isotype?
b. What is their form? (monomer, dimer, pentamer)
Isotype: the genetic variation or differences in the constant region of the heavy and light chains.
- IgG, IgD, IgE are monomers
- IgM is a pentamer
- IgA is a dimer with a secretory component
Know the antibody isotypes:
a. What is their primary function? (neutralizing in blood, neutralizing in mucosa,phagocytosis/complement activation, development, parasitic infections/allergies)
- IgG: Neutralizes toxins and viruses;
- enhances phagocytosis; protects fetus and newborn.
IgM: First antibodies produced in response to initial infection; effective against microorganisms and agglutinating antigens.
- IgA: Localized protection on mucosal
IgD: Serum function not known; Presence on B cells functions in initiation of immune response.
IgE: Allergic reactions; possibly lysis of parasitic worms.
Know the antibody isotypes:
a. Where are they found or what cells use them?
IgG: Blood, lymph, and intestine
IgM: Blood, lymph, B cell surface (as monomer)
- IgA: Secretions (tears, saliva, mucus,
- intestine, milk), blood, lymph.
IgD: B cell surface, blood, lymph
IgE: Bound to mast and basophil cells throughout body, and blood.
1. How does clonal expansion and clonal
selection improve immune responses (think memory and competitive selection pressure)?
An activated B cell proliferates into large clone of cells. Some of which will differentiate into antibody-producing plasma cells. Others of the activated B cell become long-lived memory cells that are responsible for the enhanced secondary response to an antigen. This phenomenon is called clonal selection.
How can antibodies from each B cell have a unique receptor (i.e. how does that happen)?
When a B cell is activated by its first encounter with an antigen that binds to its receptor, the cell proliferates and differentiates to generate a population of antibody-secreting plasma B cells and memory B cells.
What 5 things can antibodies do?
There are 5 types of antibodies: IgG, IgM, IgA, IgD, IgE. The antibodies of the IgG class enhance phagocytosis, neutralize toxins and viruses, and also protect fetuses and newborns. The antibodies of the IgM class are especially effective against microorganisms and agglutinating antigens. They are also the first antibodies produced in response to initial infection. The antibodies of the IgA class act as localized protection on mucosal surfaces. The antibodies of the IgD class have a presence on B cell functions in initiation of immune response. Their serum function is not known. The antibodies of the IgE class are allergic reactions and are possibly lysis of parasitic worms.
What is antibody –dependent cell mediated
cytotoxicity and what does it kill?
This function resembles opsonization in that the target organism becomes coated with antibodies. However, the destruction of the target cell is by immune system cells that remain external to the target cell. If an organism, such as a parasitic worm, is too large for ingestion and destruction by phagocytosis, it can be attacked by immune system cells that remain external to it. The garget cell is first coated with antibodies. The cells of the immune system, such as eosinophils, macrophages, and NK cells, bind to the Fc regions of the attached antibodies. Finally, the target cell is then lysed by substances secreted by the cells of the immune system.
What negative effect can antibodies have on the host (i.e. “gazuntight”)?
IgE antibodies can cause an allergic response. When an antigen such as pollen cross-links with the IgE antibodies attached to a mast cell or basophil, that cell releases histamine and other chemical mediators.
What selection processes help your T cells develop? Why do they have to be selected?
T cells go through thymic selection. This weeds out T cells that will not specifically recognize self-molecules of MHC. This is important in preventing the body from attacking its own tissues.
What are the basic T cell forms and what do they do?
The basic T cell forms are T helper cells and T cytotoxic cells. Helper T cells control the immune response through the use of chemical messenger molecules called cytokines. Cytotoxic T cells (CTL) can kill intracellularly infected cells.
What is an antigen presenting cell (a.k.a. APC)? How do the help activate T cells and the immune response?
The recognition of antigens by a T cell requires that they be first processed by specialized antigen presenting cells. After processing, an antigenic fragment is presented on the APC surface together with a molecule of MHC. Fig 17.10: An APC encounters and ingests a microorganism. The antigen is enzymatically processed into short peptides, which combine with MHC class II molecules and are displayed on the surface of the APC. A receptor (TCR) on the surface of the CD4+ T helper cell (TH cell) binds to the MHC- antigen complex. If this includes a Toll-like receptor, the APC is stimulated to secrete a costimulatory molecule. These two signals activate the TH cell, which produces cytokines. The cytokines cause the TH cell (which recognizes a dendritic cell that is producing costimulatory molecules) to become activated. They proliferate and develop its effector system.
What does an activated B cell become? Which T cell type activates it and what does the B cell become?
Activated B cells become antibody-producing plasma cells. Immunoglobin receptors on B cell surface recognize and attach to the antigen, which is then internalized and processed. Within the B cell a fragment of the antigen combines with MHC class II. MHC class II antigens fragment complex is displayed on B cell surface. Receptor on the T helper cell (TH) recognizes complex of MHC class II and antigen fragment and is activated- producing cytokines, which activate the B cell. The TH cell has been previously activated by an antigen displayed on dendritic cell. B cell is activated by cytokines and begins clonal expansion. Some of the progeny become antibody-producing plasma cells.
What is cell mediated immunity? What is cytotoxic killing and which T cell type does it?
T helper cells cooperate with B cells in the production of antibodies as a part of humoral immunity and cellular immunity. Cytotoxic killing is the killing of a virus infected target cell by the cytotoxic T lymphocyte (T cytotoxic cell or CD8+ T cells). A normal cell will not trigger a response by a cytotoxic T lymphocyte, but a virus-infected cell or a cancer cell produces abnormal endogenous antigens. The abnormal antigen is presented on the cell surface in associated with MHC class I molecules. CD8+ T cells with receptors for the antigen are transformed into cytotoxic T lymphocytes (CTL). The CTL induces destruction of the virus infected cell by apoptosis.
What is a cytokine?
A small protein released from human cells that regulates the immune response; directly or indirectly may induce fever, pain, or T cell proliferation.
What is the difference between a primary and secondary immune response? Why does the difference occur?
The exposed person’s serum contains no detectable antibodies for 4-7 days. The IgM appears first in response to the initial exposure. IgG follows and provides longer term immunity. The second exposure to the same antigen stimulated the memory cells (formed from the initial exposure) to rapidly produce a large amount of antibody. The antibodies produced in response to this second exposure are mostly IgG.
How do vaccines prepare your body for a future infection by a specific pathogen?
Vaccines are introduced into the body as antigens that contain killed or inactivated living microorganisms or inactivated bacterial toxins. Immunity can be acquired this way because the body has been exposed to the foreign substance. The body produces antibodies and specialized lymphocytes to prepare the body for future infections. Vaccines are designed to stimulate an artificial adaptive immune response without the risk of infection. Vaccines are weakened, genetically modified, or simply antigenic parts of an organisms that will cause limited damage to the host.
What is the difference between an innate immune response and an adaptive immune response? (think memory and changes to antibody isotypes)
Innate immune responses involve the natural transfer of antibodies from mother to her infant. Antibodies in a pregnant woman cross the placenta to her fetus called the transplacental transfer. The antibodies can also be passed through mother’s milk. During active transfer, antigens enter the body naturally and the body induces antibodies and specialized lymphocytes. Adaptive immune responses are antigens introduced to the body through vaccines and can also be introduced by injections of preformed antibodies in immune serum.
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