Immunity PDF

Preview

Summary

Study guide for the immunity lecture....

Description

Immunity Immune System – responsible for initiating an immune response in response to an injury and/or the presence of infectious agents; removes foreign, or dead, pathogen/substances to induce healing **Elicit the removal of foreign antigens and formation of memory towards that antigen for future exposures**  Body’s defense system => responds to specific aspects of exposure to a pathogen or foreign antigen 1) Recognize the foreign material, which elicits the immune response 2) Develop a specific response toward that foreign material, and remove the foreign agent from the body 3) Store away the immune response mechanisms for future attacks by developing memory against the specific foreign agent for subsequent exposures  Components of the immune system => composed of lymphoid tissues with the presence of lymphocytes responsible for the initiation and progression of the immune response a. Lymphoid structures – lymph nodes, tonsils, spleen, thymus, and bone marrow  Lymph nodes – responsible for the production and storage of immature lymphocytes; where B and T cells are stored  Bone marrow – responsible for the production of B cells  Thymus – responsible for the maturation of T cells during early stages of development in humans b. Lymphocytes – includes T-lymphocytes, Blymphocytes, and Natural Killer cells  T-lymphocytes – mature during development in the thymus, and responsible for more cell-mediated adaptive immunity, which means they target self-cells that have been infected by the pathogen; intracellular destruction of foreign agent  B-lymphocytes – mature in the bone marrow, and responsible for humoral adaptive immunity, which means they are responsible for the production of antibodies found in the blood; extracellular destruction of foreign agent  Natural Killer – type of cytotoxic lymphocyte that are responsible for killing virally infected cells as well as responding to tumor formations within the body as part of innate immunity; only activated under the conditions of an immune response Method of action => Patrol the body looking for cells that do not express the surface protein called I MHC molecule. If the natural killer cells find a body cell that does not express this protein (except red blood cells), then it will attach itself to such cell and release chemicals that lead to cell death. c. Macrophages – responsible for phagocytosis of foreign agents to present to Helper T-cells for proliferation of B-cells and T-cells to initiate an adaptive immune response; these cells are Antigen presenting cells (APCs) because they





are specific in presenting antigens on their Class II MHC receptors to elicit an immune response “Phagocytic cells present in many tissues that function in innate immunity by destroying pathogens through phagocytosis, and act as antigenpresenting cells in acquired immunity for activation of other lymphocytes. Found within tissues throughout the body and stay within those tissues. Also induce fever in the presence of pathogens.” d. White blood cells (WBCs) – contain neutrophils, eosinophils, basophils, monocytes, and etc. for immune responses within surrounding tissues such as inflammation Neutrophils: “Most abundant type of white blood cells that are phagocytic and tend to self-destruct as they destroy pathogens, limiting their lifespan to only few days. These are found moving throughout the bloodstream, and are attracted to infected tissues, where they go and engulf pathogens, selfdestruct, and as a result form pus.” Branches of the Immune System => immune system is composed of an innate (nonspecific) immunity as well as an adaptive (specific) immunity 1. Innate (non-specific) immunity – includes both external and internal defenses; represent the first line of defense against invasion by pathogens; nonspecific mechanisms, such as fever, inflammatory response, phagocytosis, and etc., that occur in response to infiltration by a foreign agent into the body to maximize the chance of removing such agent without specificity Cells: Natural killer cells, macrophages, neutrophils, and mast cells Proteins: Complement proteins, interferons, pyrogen, histamine 2. Adaptive (specific) immunity – nonspecific immunity can elicit a more specific immune response to help remove the foreign agent even faster; this immunity recognizes the foreign substances and acts in immobilizing neutralizing, or destroying it; A vertebrate-specific defense that is mediated by B lymphocytes and T lymphocytes, and exhibits specificity, memory, and self-nonself recognition. Also activates and develops slowly after innate immunity defenses are activated Cells: B cells (Plasma and Memory) and T cells (Cytotoxic, Helper, and Memory) Proteins: Antibodies, perforin, cytokines, granzymes  Recognize specific foreign agents through antibodies that associate them to be foreign antigens  Amplifies inflammatory response and activates complement system  Immune response originating from B and T cells, which are specific immune cells with differentiated functions  Antigen-specific – antigens are responsible for triggering an immune response when they bind to specific antibodies or are phagocytized, and presented as foreign by APCs **Only antigenic (immune response) if antigen can bind to a specific receptor or an antibody to elicit an immune response; however, this immune response will be provided with memory so that subsequent future exposures to that specific antigen get a faster immune response Antigens => antigens are molecules that stimulate the production of specific antibodies and combine specifically with the antibodies produced; most antigens are foreign to the blood and to other body fluids, which is why they are best for humoral immune responses **Ability of a molecule to function as an antigen depends on its size as well as the complexity of its structure

a) Antigenic determinant sites – areas of the molecule that stimulate production of, and combine with, different antibodies; naturally occurring antigens have many antigenic determinant sites and stimulate the production of different antibodies with specificities for these sites  Actual “antigenic” portions of an antigen are these determinant sites since they are the ones responsible for binding to the antibodies and generating an immune response  Each antigen is specific because of the multiple different antigenic determinant sites, which results in multiple immune responses  Antibodies A, B, and C are different in terms of their antigens; specific to certain antigenic determinant site **For every 1 B-cell, there is 1 antigen being produced towards only 1

antibody** b) Classes of Antibodies – five different classes of antibodies are produced and found within the blood of humans; each of these classes has their own specific responsibilities and reason for initiating an immune response  IgG – approximately 80% of the plasma Ig; long-lived Ig that is the most abundant and diverse antibody; primarily crosses the placenta to protect the fetus/newborn before birth and confers passive immunity to the child **Production of IgG is stimulated in the presence of immunization  IgM – approximately 5-10% of the plasma Ig; first antibody produced in primary immune response (1st exposure to the foreign agent), fixes complement best, clumps bacteria best, and is present of B-cell membrane where it binds antigen  IgA – approximately 10-15% of the plasma Ig; predominant in external secretions such as breast milk, saliva, tears, mucous, and etc.; ability to transfer immunity to other individuals  IgE – very low concentrations in the plasma; stimulate mast cells during allergic reactions to release histamine, which is why they are responsible for allergic reactions; also protect from parasites **Hypersensitivities  IgD – approximately 0.2% of the plasma Ig; present on B-cell membranes, however, their exact function is still unclear

c) Mechanisms of Antibody Action – mechanism that antibodies follow to help stop/limit the spread of the foreign agent within the body; involves neutralization, agglutination, precipitation, opsonization, and complement  Neutralization – antibodies block off all dangerous parts of the pathogen so that it cannot infiltrate another cell to replicate itself; defends a cell from an antigen or infectious body by inhibiting any effect it has biologically  Agglutination – clumping of cells such as bacteria or RBCs in the presence of an antibody; antibodies bind to the multiple particles and joins them, creating a large complex of pathogens that cannot function like a single pathogen could  Precipitation – antibodies bind to a soluble-antigen to decrease its solubility and try to precipitate it out of the fluid as a large insoluble antigen-antibody complex; this renders the antigen inactive  Opsonization – process by which antibodies mark a pathogen for ingestion and destruction through phagocytosis; antibodies binding to the antigen attracts macrophages to the area for phagocytosis of the antigenantibody complex  Complement – “fix and activate” mechanism involving seven different types of proteins found low in blood plasma that are activated and produced during an immune response; binding of antibodies to antigens on the surface of a pathogen activates the complement system to come around and punch holes within the cell to cause lysis of that cell **Antibodies do not render antigens useless; although they might render the antigen to be inactivated, an immune response will still take place until that antigen is destroyed**

d) Basic Antibody Structure – consist of four interconnected polypeptide chains that determine the size and shape of the antibody, which is crucial to its function Each antibody contains: 1. Two identical antigen-binding sites => each site composed of 1 part heavy polypeptide chain and 1 one part light polypeptide chain joined together by disulfide bonds 2. Two long, heavy chains (known as “H chains”), two short, light chains (known as “L chains”), and a single stem region Stem region – important for classifying the antibody; antibodies from the same class exhibit the same stem region, only thing that changes are the binding sites; composed of the two heavy chains  Contains a “complement-binding site” which triggers blood complementary system to bind and cause cell lysis in that particular pathogen  Contains a “macrophage-binding site” which stimulates phagocytosis upon binding to the site

Adaptive (specific) immunity => nonspecific immunity can elicit a more specific immune response to help remove the foreign agent even faster, and this specific immunity is more precise towards the antigenic agent in both intracellular and extracellular environments; this immunity recognizes the foreign substances and acts in immobilizing neutralizing, or destroying it Types of Specific Immunity: (a)Humoral immunity – antibody-mediated immunity in extracellular locations such as the “extracellular fluids” of the body that are directed more towards inactivation or “fixed and activation” mechanisms of antibodies  Refers to the production of soluble antibodies that circulate in the blood plasma, however, these antibodies cannot cross the cell membrane and only elicit immune responses on the exterior of tissues  Involve B-lymphocytes, which are responsible for the production of antibodies  B-lymphocytes, upon stimulation, become “antibody-secreting plasma cells” (b)Cellular immunity – cell-mediated immunity in intracellular issues such as destroying self-cells that have been replicating viruses  Mediated by T-lymphocytes, which are “non-antibody-producing cells”  Involves recognition of foreign cells and destroying them Ex: virally infected cells or cancer cells Humoral Immune Response => B-lymphocytes secrete antibodies that bind to specific antigens and elicit a cascade of reactions that occur as an immune response to the formation of an antigen-antibody complex  Exposure of a B-lymphocytes to the appropriate antigen activates the B cell and causes it to enter a the division center of lymphoid organs where it undergoes many cell divisions  Mediated by B-lymphocytes => antigen-producing cells that produce specific Ig on B-cell membrane that bind to antigens to activate B-cell (1 antigen per B-cell) **Upon stimulation of B-cells, our body divides the B-cells into memory B-cells and plasma cells (a) Memory B-cells – long-lived B-lymphocytes produced during B-cell proliferation of primary immune response that form a memory against the antigen during the and are stored within the lymph nodes in their inactivate form until any further subsequent exposures take place to the same antigen; important for active immunity of secondary immune response (b) Plasma cells - B-lymphocytes responsible for the production of antibodies that are specific to the antigen being recognized (1 specific antibody per 1 plasma cell)

 B-cells are activated by Interleukin-4 (IL-4) => produced and released by activated Helper T-cells for differentiation of B-cells into either memory B-cells and plasma cells

*from TH cell Method of action => “B cell receptors bind to the antigen triggering a humoral (fight takes place outside cells) immune response, where that particular B cell undergoes clonal selection and transformation. Some B cells become effector cells known as plasma cells, which secrete antibodies that can harm the pathogen with this particular antigen, and memory B cells, which store this response and its weapons for later use (secondary immune response).” Cell-Mediated Immune Response => T-lymphocytes are responsible for killing cells that have been infected and are producing pathogenic antigens intracellularly; activated only by antigens presented to them on the surface of particular antigen-presenting cells; involves CD4, CD8, and CD25 lymphocytes **Antibodies are useless against intracellular antigens and this is why our body required a cell-mediated method of obtaining immunity**  Two major populations of T-cells that mediate cellular immunity: (a)Helper T-cells (CD4) – helper T-lymphocytes are identified by the presence of a CD4 surface molecule; enhance the immune response by improving the ability of B-cells to differentiate into plasma cells and secrete specific antibodies, and enhance the ability of cytotoxic T-cells to mount a cell-mediated immune response; aid the process of both by releasing chemical regulators known as “lymphokines”; only bind to Class II MHC **The main purpose of these T cells in both humoral and cell-mediated immunity is to help activate B cells and cytotoxic T cells by secreting cytokines** (b)Cytotoxic T-cells (CD8) – cytotoxic T-lymphocytes are identified by the presence of a CD8 surface molecule; these T-cells are responsible for attacking and killing cells that harbor foreign antigens, and this is why they are predominantly known as the “killing machines” of the adaptive immune system; activated by cytokines released from helper T-cells as well as direction interaction with an antigen-presenting cell; only bind to Class I MHC **The main purpose of these T-cells is to come into actual physical contact with the victim cells and completely destroy them with particular molecules, such as perforin, and enzymes, such as granzymes**  Other population of T-cells involved in cellular immunity: (a)Regulatory T-cells (CD25) – regulatory T-lymphocytes are identified by the presence of a CD25 surface molecule; provide a “brake” on the specific immune response and inhibit the activity of CD8 T-cells and B-cells; release Interleukin-10 (IL-10) along with TGFβ (transforming growth factor beta) to promote immune suppression; however, sometimes they tend to promote the destruction of the target lymphocytes by releasing granzymes and perforins **Important since regulatory T-cells are responsible for preventing excess T and B cell activity to guard against diseases caused by the immune system, such as hypersentivities and autoimmune issues** (b)Memory T-cells – memory T-lymphocytes are long-lived T-cells produced during T-cell proliferation of primary immune response; these cells stay within the lymph nodes until activated by a subsequent exposure to the same antigen that triggered its formation **Important since memory cells are responsible for the stronger secondary immune response**

T-lymphocyte and B-lymphocyte Activation, Mechanism of Action, and Inactivation

Activation of Helper T-cells (CD4) and subsequent lymphocytes for immune response: 1. Presence of foreign antigen results in the attraction of antigen-presenting cells, which are macrophages and dendritic cells, and causes the APC to phagocytosize the antigen so that it may be presented on its surface protein Class II MHC to reveal the presence of a foreign agent within the body 2. Antigen-presenting cells activate CD4 cells (Helper T-cells) and attract them to the site for recognition of the foreign antigen and to initiate an immune response 3. Foreign agent is presented on the Class II MHC surface molecule of the APC; Helper T-cells (CD4) specifically bind to that antigen presented on that surface molecule and elicit an immune response by secreting two important cytokines (chemical messengers): (a) Interleukin-4 (IL-4) => responsible for stimulating proliferation of activated B cells, and increase their rate of division as well as informing them to differentiate into plasma and memory cells

(b) Interleukin-2 (IL-2) => responsible for stimulating proliferation of activated T-cells and also attracts CD8 cells to the location of APC to become activated for division and recognition as well as destruction of the infected cells 4. Macrophages and dendritic cells also release Interleukin-1 (IL-1) in accordance to stimulation from the activated helper T-cells; this chemical messenger acts as a positive feedback and induces increased proliferation and activation of Tlymphocytes, and particularly CD8 cells 5. Inactive CD8 cells that migrate to the location of the APC, because of the attraction caused by IL-2, now bind to the Class I MHC surface molecule present on the APC presenting the antigen; if the CD8 receptor bind to the antigen presented, then that specific CD8 cell will undergo clonal selection Clonal selection - Proliferation (mitosis) of a lymphocyte into a clone of cells in response to binding an antigen; presentation of an antigen to specific receptors results in repeated rounds of cellular division of that lymphocyte. 1. Antigen molecules bind to the antigen receptor sites on a certain lymphocyte corresponding its epitope (shape). 2. The selected lymphocyte proliferates, and forms identical clones of itself carrying the same antigen receptors for the antigen. 3. Some proliferating cells become short-lived effector cells, which are the ones that actually help in fighting the pathogen producing the antigen, or the antigen, by attacking it. Other proliferating cells become long-lived memory cells, which are the ones responsible for responding rapidly upon subsequent exposure to the same antigen. Activated CD8 cells – bind only to Class I MHC surface molecule; every cell, except RBCs, within the body have this class of surface molecule and it is known as the body’s “self-antigen” since it helps the T-cells differentiate between foreign antigen and self-antigen 6. At the same time, specific B-cell bound to the foreign antigen is also stimulated to undergo clonal selection and proliferation in the presence of IL-4; Blymphocytes differentiate into plasma cells and memory B-cells Plasma cells – responsible for producing the specific antibody against that specific antigen to which the B-cell was initiated to differentiate to; produces and releases antibodies responsible for neutralizing, opsonizing, activating complement proteins, agglutination, and precipitation of the foreign antigen/agent 7. Helper T-cells continue to secrete stimulatory cytokines for T and B-cell proliferation; however, they also secrete interferons, which are chemical mediators that help prevent the spread of the virus to tissues and cells surrounding the site of detection Interferons – polypeptides that interfered with the ability of a second, unrelated strain of virus to infect other cells in the same culture; pr...