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83 Cards in this Set
- Front
- Back
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Immunity:
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Immunity: the protection from infectious disease
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Central lymphoid organs:
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- Bone marrow
- Thymus |
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Peripheral lymphoid organs:
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- Lymph nodes
- Spleen - Tonsils - Appendix - Peyer patches - Mucosa-associated lymphoid tissues in respiratory, GI and reproductive systems |
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Bone marrow
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Bone marrow provides signals for the
development of lymphocyte progenitors from the hematopoietic stem cells and for differentiation of B cells |
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T cell progenitors
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T cell progenitors migrate from the bone
marrow to thymus where the process of maturation occurs T cells must be able to recognise foreign antigens in order to be released. |
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B cell
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B cell maturation occurs in the bone
marrow B cells must have immunoglobulin signaling molecules and cell markers that distinguish them from non-self in order to be released. |
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Lymphocyte
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white blood cell
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Thymus Gland
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• Located in the upper portion of the
mediastinum • Essential for the proper development of the immune system • Assists with the development of antibodies • Active in the unborn fetus and throughout childhood until adolescence, when it begins to shrink in size |
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Peripheral Lymphoid Organs
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• Concentrates antigens
• Aids in processing antigens • Promotes cellular interactions needed for development of adaptive immune responses |
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Lymphatic System
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• Collects excess tissue fluid throughout the body and returns it
to the circulatory system, purifying it as it passes through the system. • Assists the circulatory system in transporting substances throughout the body. • Serves against the invasion of pathogens. • Lymph vessels around the small intestines pick up absorbed fats for transport. • Produces lymphocytes, monocytes and plasma cells Fluids move from the lymphatic system to the circulatory system. It purifies the liquid before it gets to the circulatory system. It cleans out the bacteria and pathogens that are present in the bodily fluids. |
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Lymph Nodes
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• Small, encapsulated, lymphoid
organ - Remove foreign material from lymph before it enters the bloodstream - Produces antibodies • Manufactures lymphocytes • T lymphocytes proliferate on antigenic stimulation and migrate to the follicles, where B lymphocytes are found Produce antibodies, T cells proliferate = purpose of lymph nodes Para cortex = t cells Know the cortex, where you will find the B cells T lymphocytes are typically found in the paracortex of the node B lymphocytes are typically found in the follicles and germinal centres located on the outer cortex. *Activated follicles become germinal centres for T and B cells, macrophages, dendritic cells, etc. B cells mature into plasma cells in the medulla - here they release antibodies into the blood system |
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Axillary
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Armpits
Become enlarged during infections of arms and breasts; cancer cells from breastsmay be present |
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Cervical
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Neck
Drains parts of head and neck; may be enlarged during upper respiratory infections In the neck, is where you feel the first signs of sickness - lymph nodes are located there |
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Inguinal
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Groin
Drains area of the legs and lower pelvis |
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Mediastinal
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Chest
Assists in draining infection from within the chest cavity |
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Spleen
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• Located in the left upper quadrant
of the abdomen • Consists of lymphatic tissue that is highly infiltrated with blood vessels • Filters antigens from the blood • Red pulp: supplied with arteries, where aging and injured red blood cells are removed • White pulp: contains concentrated areas of B and T lymphocytes, macrophages, dendritic cells • Produces new RBCs in the unborn fetus |
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Spleen essential?
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NO
• Phagocytic macrophages line the blood sinuses in the spleen to remove pathogens. Liver cells are regenerative • Because the blood is moving through the organ slowly, the macrophages have time to identify pathogens and worn out RBCs. • The spleen is not an essential organ for life and can be removed due to injury or disease. |
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Tonsils
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• Collections of lymphatic tissue located on each side
of the throat or pharynx. • 3 sets of tonsils: palatine, pharyngeal (adenoids) and lingual. • Contain a large number of leukocytes and act as filters to protect the body. • Not required for life and can be removed if they become a continuous site of infection. MALT: mucosa-associated lymphoid tissues = clusters typically found in tonsils, appendix, etc. Large numbers of plasma cells and provide immunity at the mucosal layers (protects vulnerable internal organs). Anything ingested = tonsils are the first point of contact |
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Innate Immunity
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• First line of defense
• Early, rapid (minutes to hours) response • Always present • Attacks non-self microbes • Does not distinguish between different microbes • Components: – Skin – Mucousmembrane – Phagocytic leukocytes (neutrophils, macrophages) – Lymphocytes (natural killer cells) – Plasma membrane proteins The cells of the innate immunity express pattern recognition receptors (PRRs) that bind with broad patterns shared by microbes. Effector response: inflammatory response, complement system, NK cells, phagocytosis by neutrophils and monocytes/macrophages. |
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Innate Immunity Mechanisms
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• Mechanisms include:
– Epithelial barriers (physical and chemical barrier from pathogens) – Phagocytic cells – Plasma proteins – Cell messenger molecules The innate immune system can distinguish self from non-self and can recognise structures shared by classes of microorganisms |
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Adaptive Immunity
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• Second line of defense
• Responds less rapidly, but more effectively • Attacks specific microbes (antigens) • Develops after exposure to the specific antigen • Provides lifelong immunity after exposure to diseaseproducing microbes or environmental agents Antigens elicit an adaptive immune response Antigens can also be nonmicrobial agents such as plant pollens, poison ivy resin, insect venom, and transplanted organs |
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Adaptive Immunity Mechanisms:
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• Mechanisms include:
– Humoral immunity (antibody proteins in the blood that attack the specific antigen) -B lymphocytes – Cell-mediated immunity (phagocytic cells that attack the specific antigen) – T lymphocytes |
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"Humoral" derivation of the name:
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fluid
Humoral = antibodies = B lymphocytes |
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B lymphocyte:
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Destroy extracellular microbes and toxins, present in the blood and mucous.
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T lymphocyte:
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Destroy intracellular microbes, like viruses
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A vaccination is an example of adaptive
immunity. |
True
In adaptive/acquired immunity, specific antigens are attacked, and immunity develops after exposure to the specific antigen. When you get a vaccine, you are getting a live, weakened, or dead microbe (a specific antigen). Your body develops antibodies to attack that antigen after you are exposed. |
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Immune Cells - Regulatory
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• Regulatory cells control the immune response
– T helper cells – T suppressor cells – Antigen presenting cells |
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Immune Cells - Effector
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• Effector cells then carry out the attack on the antigen
– T cytotoxic (or T killer) cells – B cells (produce antibodies) – Leukocytes |
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Immune Cells - Phagocytic leukocytes
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• Phagocytic leukocytes
- Macrophages - Granulocytes - Neutrophils - Eosinophils - Basophils - Dendritic cells - Natural killer cells |
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Dendritic cells and macrophages function as?
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Dendritic cells and macrophages function as antigen- presenting cells for adaptive immunity
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Innate immunity involves what kind of cells?
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Innate immunity = phagocytic white blood cells or leukocytes (neutrophils and macrophages) + NK cells
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Lymphocytes
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Lymphocytes
• Produce specific receptors for antigen (adaptive immunity) • B lymphocytes – Produce antibodies (humoral immunity) • T lymphocytes – Cell-mediated immunity |
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Macrophages
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- Mature form of monocytes
- Found in most tissues and organs - Engulf and kill invading organisms - Dispose of pathogens and infected cells - Generates digestive enzymes, hydrogen peroxide and NO that kill the pathogen - Function as antigen-presenting cells - Helps induce inflammation - Clears dead cells and debris (scavenger cells) - Myeloid Lineage - Induce inflammation and secrete signaling proteins that activate other immune cells |
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Which cells are the first to respond in response to a immune attack?
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Neutrophils are the first to respond to an immune system attack, then the macrophages.
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What are all the myeloid lineage Cells?
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Macrophages
Granulocytes Dendritic Cells |
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What are granulocytes and the two types of them:
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Granulocytes
- Short-lived, produced in increased numbers during immune (WBC) response - Types: - Neutrophils - Early responding phagocytic cell - Engulf and kill invading organisms - Eosinophils, Basophils - Involved in allergic reactions - Important defense against parasites ? Myeloid lineage |
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Which cell type is the most numerous and important?
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Neutrophils
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Dendritic Cells
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Dendritic Cells (WBC)
- Found under epithelial tissue and most organs - Captures foreign agents and transports them to lymphoid organs - Antigen-presenting cells: activate adaptive immune response by processing and presenting molecules of foreign antigens to the lymphocytes - Function as intermediary between innate and adaptive immunity Myeloid lineage |
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Natural Killer Cells
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Lymphoid Lineage
Natural Killer Cells • Part of the innate immune system • Recognize and kill tumour cells, abnormal cells, and cells infected with intracellular pathogens i.e. viruses, bacteria • Programmed to kill foreign cells by forming holes in the cell membrane These cells are very direct Does not respond to specific antigens therefore is apart of the innate immune system. Intracellular pathogen oriented |
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How do Natural Killer Cells work?
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Because the two ligands match up with both the activating and inhibitory receptor there is NO RESPONSE. The inhibitory receptor is activated
If there is a ligand for the activating receptor that matches with the NK cell ligand, the NK cell will kill that cell. This is because there is no inhibitory ligand match in order to deactivate the NK cell. MHC-1 allows inhibatory signals to be transferred by normal cells when a NK cell attaches on. (MHC -1 self recognition molecules). Without the MHC-1 complex the cell is targeted as an abnormal infected cell and labelled for destruction. |
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What is an antigen-presenting cell and what are some examples?
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Ex. Macrophages and Dendritic Cells
• Eat the invading antigen • Break it down into pieces called epitopes • Put epitopes on the cell surface, attached to major histocompatibility complex (MHC) II proteins Virus is broken down into tiny pieces: epitopes Displays these epitopes on the cell surface. These pieces are attached to the MHC proteins. This is why it is called an antigen presenting cell. The next step is the T helper cells dock the antigen presenting cell, only if the receptor matches up with the variable component of the antigen. smaller substances + "haptens" = molecules that can function like antigens |
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Antigens Attached to MHC Proteins
Can Be “Seen” by Immune Cells |
• Immune cells have
receptors that attach to MHC proteins and “see” the antigen • They also have antigen receptors • Only those T cells whose antigen receptors “fit” the antigen being displayed will respond to it |
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Complement Proteins: General
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• Major effector mechanisms of humoral and innate
immunity • Highly toxic proteins (C1 – C9) • Circulate in the plasma in an inactive form • When an antibody attaches to an antigen, the resulting immune complex can activate the complement system • Complement proteins destroy the antigen Proteins are present in the blood as functionally inactive precursors. C3 is essential for amplification |
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Complement Proteins: Actions
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• 3 pathways for recognizing microbes and
activating the complement system • Actions: – Trigger inflammation – Attract macrophages to the area – Coats foreign intruders so macrophages are more likely to engulf foreign intruders – Kill foreign intruders 3 pathways: 1) Initiation/Activation 2) Amplification of inflammation 3) Membrane attack response. Opsonization: the coating of particles/microbes which then activates phagocytosis after attachment to a complementary receptor on the phagocyte. An example of this is IgG and IgM antibodies which act as opsonins and bind to macrophage and neutrophil receptors. Regulators of the innate immune system: opsonins, cytokines, proteins of the complement system. |
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Where Do Lymphocytes
Come From? |
• Stem cells in the bone marrow or fetal liver
• B cells mature in the bone marrow • T cells mature in the thymus • Lymphocytes move to the lymph nodes to wait for an antigen-presenting cell to activate them • Each lymphocyte targets a specific antigen, approx. 1012 lymphocytes in the body • Acquire a memory response after stimulated by an antigen • Memory T and B lymphocytes remain in the body for a long time and respond more rapidly on repeat exposure than naïve cells |
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T Lymphocytes Differentiate in the Thymus --> where do they go next?
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Mature cells migrate to peripheral lymphoid
tissues,multiply and differentiate into memory T cells and mature T cell populations when encountering antigens High levels of mature T and B lymphocytes are found in the lymph nodes, spleen, skin, and mucosal tissues --> respond to an antigen. T lymphocytes only recognise peptides when they are displayed on antigen-presenting cells bound to membrane proteins encoded in the MHC molecule. B lymphocytes and the antibodies they produce are free to attach antigens anywhere/any form (proteins, lipids, etc.) |
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What is CD?
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CD = clusters of differentiation. They are involved in a variety of lymphocyte functions, incl promotion of cell-to-cell adhesion and transduction of signals that lead to lymphocyte activation.
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What are the two T cell types?
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• T helper cells (CD4+)
(mature T cell) – CD4 receptors attach toMHC II proteins – Start an immune response • T cytotoxic cells (CD8+) (mature T cell) – CD8 receptors attach to MHC I proteins – Kill infected cells |
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Pathway for Adaptive Immune Response: *Draw it out
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1. T cells are
activated by antigen > proliferates and differentiates into T helper or cytotoxic T cells 2. CD4+ T helper cells trigger B cells to proliferate and differentiate into a clone of plasma cells that produce antibodies 3. Antigen binds to B cell > lymphocytes proliferate and differentiate into plasma cells that produce antibodies that are a secreted form of B-cell receptor and have identical antigen specificity 4. Cytotoxic T cells kill cells infected with viruses/other pathogens Cytokines help T helper cells to mature into B cells and then further into a plasma cell |
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MHC I and II:
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MHC I and MHC II Proteins Both Display Antigens
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MHC I proteins:
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MHC I proteins:
• Display antigens made inside an infected cell • Tell cytotoxic T cells to kill the infected cell before it can infect other cells |
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MHC II proteins:
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MHC II proteins:
• Display antigens eaten by a phagocytic cell (dendritic, macrophage or B lymphocyte cell) • Tell T helper cells to start an immune response against the antigen |
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What are some phagocytic cell examples:
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(dendritic, macrophage or B lymphocyte cell)
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Helper T Cells
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• Master regulator for the immune system
• Activation depends on the recognition of antigen and class II MHC molecules • Secrete cytokines that influence the function of many cells of the immune system • Cytokines activate and regular B cells, cytotoxic T cells, NK cells, macrophages etc. (Table 15-1). Assistive role in the immune system - cytokines Helper T cells activate the cytokines which then activate the cytotoxic T cell (CD8+) CD8+ binds to the antigen bound to the MHC-1 |
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Two Kinds of T Helper Cells (CD4+):
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TH1 cells and TH2 cells
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TH1 cells (T Helper Cell - CD4+)
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• TH1 cells
– Stimulate the T cytotoxic cells and other phagocytic cells to attack the antigen – Produce cytokines, chemokines and surfacemolecules that kill chronically infectedmacrophages – Stimulate the production of new macrophages in bone marrow – Recruit new macrophages to infected sites – Secrete IFN-? – potent macrophage activator and stimulates B cells to produce IgG antibodies -->complement activated |
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TH2 cells (T Helper Cell - CD8+)
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• TH2 cells
– Stimulate the B cells to create antibodies against the antigen - IgE antibodies + development of allergies |
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IFN-gamma:
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IFN-gamma: Cytokines
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Chemokines:
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Chemokines: cytokines that stimulate the migration
and activation of immune and inflammatory cells. |
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T Helper Cells Release Cytokines - what are the three chemicals released?
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• Cytokines are chemicals that control the immune response
– Inflammatory mediators: cause fever; attract WBCs to the infection – Growth factors: cause WBCs to divide and mature – Cell communication molecules: used to control activity of other WBCs |
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Cytokines
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Cytokines are produced by innate and adaptive immunity
Cytokines are redundant and pleiotropic (1 cytokine can act on different cell types). The same cytokines may be produced by several different cell types. Cytokines can influence the production of other cytokines. Cytokines can act locally (most) or systemically. • Low grade inflammation and activation of the innate immune system play a key role in the pathogenesis of a number of disorders i.e. atherosclerosis, CAD, bronchial asthma, T2DM, rheumatoid arthritis, multiple sclerosis, lupus. Elevated levels of certain cytokines has been shown to increase the chances/are linked to specific diseases Decreased concentration of certain inflammatory markers which is decreasing their risk towards certain diseases |
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Where do cytokines bind and how lone are they able to survive?
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Cell to cell interfaces, bind to specific receptors
on the membrane surface of target cells. Short half-life = prevents excessive immune responses They are not stored or preformed, created on a transcription need basis |
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What are colony stimulating factors?
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Colony - Stimulating Factors: cytokines that stimulate bone marrow pluripotent stem and progenitor or precursor cells to produce large numbers of platelets, erythrocytes, lymphocytes, neutrophils, monocytes, eosinophils, basophils, and dendritic cells.
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Cytotoxic Cells
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• Activated CD8+ lymphocytes become
cytotoxic T cells after recognition of class IMHC antigen complexes on target cell surfaces • Kill by injecting preformed cytotoxic proteins onto target cells - triggers apoptosis or programmed cell death • Most direct immune response • Produce and release cytokines • Antigens derived from the virus multiply inside the infected cell and are displayed on the target cell’s surface – recognized by antigen receptors on the cytotoxic T cell Cell mediated immunity |
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All but which of the following is true about CD8 receptors?
a. They can be found on cytotoxic T cells. b. They attach to MHC I proteins. c. They signal the start of the immune response. d. They differentiate in the thymus. |
c. They signal the start of the immune response.
CD8 receptors do all of those things, but they don’t kick off the immune response (the helper T cell does that). CD8 receptors are found on cytotoxic T cells; as the name implies, they kill the infected cell. CD4+ starts off the immune response |
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B Lymphocytes
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• Like T cells, B cells have
antigen receptors • They can only be activated to attack the antigen if a T helper cell shows it to them • Transformed into antibody secreting plasma cells or into memory B cells • Antibodies released into blood and lymph where they bind and remove their unique antigen When B cell links to the helper t cell it leads to proliferation, creating hundreds of new cells. Some become plasma cells (production of antibodies) and some become B cells (memory cells). |
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Can B cells function without T cells?
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NO - B cells need the T cells, they cannot function without them. The helper T cell is important for both lines, the T cell (cytotoxic) and B cell lines.
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Activated B Cells Divide into 2 Kinds Of Cells:
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• Memory B cells: remain in the body
– In the future, they will fight off the antigen without a T helper cell telling them to do so • Plasma cells: create antibodies, special proteins designed to attach to that antigen and destroy it The stages of B-cell development are characterized be a specific pattern of Ig gene expression + cell surface phenotypic markers Plasma antibodies: released in to the blood and lymph Memory B cells: released into the peripheral tissues Antibodies can also function as membrane bound antigen receptors for B cells |
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Which immune cell creates antibodies in
response to antigens? a. Cytotoxic T lymphocytes b. Helper T lymphocytes c. Cytokines d. B lymphocytes |
d. B Lymphocytes
Remember that antibodies are created in response to antigens. B lymphocytes have antigen receptors and are activated to attack a specific antigen if a T helper cell directs them to do so. |
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What are Antibodies or Immunoglobulins?
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• Proteins of B lymphocytes
• Antigen receptors for B cells or effector molecules of humoral response Each antibody will have a variable region, not every antibody is the same. There are categories of antibodies as well The Fc (bottom) portion of the antibody determines the biologic properties that are characteristic of a particular class. Each class can interact with certain effector cells. • Each B cell clone produces antibodies with one specific antigen-binding variable region • During the immune response, class switching can occur (i.e. IgM to IgG), causing the B cell clone to produce one of the different immunoglobulin types Variable component that can be different between antibodies that can be switched between the classes. Classes are based on the variable section. (5 types+, these are the main ones) |
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IgG:
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• IgG: circulates in body fluids, attacking antigens
• Can transfer immunity from the mother to the fetus IgG makes up 75% of the total classes. |
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IgM:
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• IgM: circulates in body fluids; has five units to pull antigens together
into clumps IgM is the first circulating immunoglobulin to appear in response to an antigen and is the first antibody type made by a newborn. |
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IgA:
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• IgA: found in secretions on mucus membranes; prevents antigens from
entering the body IgA is also passed through to the baby through breast milk - the first batch of milk, called colostrum. Very rich in antibodies |
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IgD:
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• IgD: found on the surface of B cells; acts as an antigen receptor
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IgE:
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• IgE: found on mast cells in tissues; starts an inflammation
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Humoral Immunity: Adaptive Immune System
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• Eliminates extracellular microbes and
microbial toxins • Depends on differentiation of B lymphocytes into plasma cells (provide and secrete antibodies) Humoral - fluids immune system response |
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Humoral Immunity: Primary and Secondary Immune Response Steps
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1. Themacrophage must eat the antigen, then
present it to T helper cells 2. T helper cells must activate B cells 3. B cells produce antibodies 4. Plasma antibody levels rise • can take 2–3 weeks Vaccination produces a primary immune response Antigen enters the body, there is a delay in the system 1-2 weeks before the antigen is recognized in the system. Primary response = triggering of proliferation of b cells and production of antibodies from plasma cells Secondary response = larger response during the second exposure TH1 and TH2 are both T helper cells which are CD4+ cells |
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Humoral Immunity: Secondary Phases
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• B memory cells respond to the antigen
immediately • Plasma antibody levels rise within days • Booster shots cause a secondary immune response so antibody levels will be high before the disease is encountered |
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Active Immunity
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Active immunity:
- Depends on a response to the antigen by the person’s immune system - Requires days/weeks after an exposure before the immune response is developed to contribute to destruction of the pathogen (quicker on later exposure because of memory B and T lymphocytes) |
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Immunization:
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Immunization: process of acquiring the ability to respond to an antigen after
its administration by vaccine Artificially acquired active immunity |
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Passive immunity:
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Passive immunity:
- Immunity transferred from another source i.e. IgG crosses the placenta, breast milk, hyperimmune serum - Produces only short-term protection that lasts weeks to months |
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Transfer of Immunity
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There is a high maternal conc when the baby is in the womb - passive immunity. Everything is received from the mother
Once the fetus is born, the conc of maternal contribution decreases over time. The newborn now starts to develop immunity by itself. Conc from mom decreases but not completely because of the contribution from breast milk High conc after birth: breast milk and left over from being in the womb |
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If the following statement true or false:
Active immunity is achieved much quicker than passive immunity. |
False
In active immunity, an individual is exposed to an antigen, the immune response begins, and antibodies are formed in 7–10 days. In passive immunity, antibodies are created outside the host and injected, giving the individual immunity immediately. |
