Study Unit 3 Flashcards
Antigen
-Any molecule that can trigger an adaptive immune response against itself or the cell bearing it
- any molecule that the host does not recognise as self
- either proteins or very large polysaccharides
3 stages of the adaptive immune response
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The encounter and recognition of an antigen by lymphocytes
- all lymphocytes carry plasma membrane receptors for a specific antigen
- if the lymphocyte encounters this antigen, it binds to it, called recognition
- each lymphocyte is specific for just one antigen -
Lymphocyte activation
- lymphocyte activates and undergoes multiple rounds of cell division, clonal expansion
- after activation, some lymphocytes will function as effector lymphocytes to carry out the attack
- others will serve as memory cells posed to recognise the antigen if ever it returns -
The attack launched by the activated lymphocytes and their secretions
- Activated B cells differentiate into plasma cells that secrete antibodies into the blood
- antibodies opsonize pathogens or foreign substances and target them for attack by immune cells such as macrophages
- cytotoxic T cells directly attack and kill the cells bearing the antigen
- once the attack is complete, majority of the B cells, plasma cells and T cells die by apoptosis
- this is a homeostatic response that prevents the immune response from becoming excessive and continuing after the infection has been eliminated
Primary lymphoid organs
- Bone marrow and thymus
- supply the body with mature but naive lymphocytes: lymphocytes that have not yet been activated by a specific antigen
- lymphocytes do not undergo activation in the primary lymphoid organs
Secondary lymphoid organ: thymus
- upper part of the chest
- large at birth and continues to grow until puberty, whereafter it gradually atrophies and gets replaced with fatty tissue
- consists of immature lymphocytes that develop into mature T cells
Lymphocyte clone
All the progeny cells derived by cell division from a single lymphocyte
Secondary lymphoid organ: Lymph nodes
- the fluid flowing in the lymphatic vessels is called lymph, which is interstitial fluid that has entered the lymphatic capillaries and is routed to the large lymphatic vessels that drain into systemic vessels
- during this trip, lymph flows through lymph nodes scattered along the vessels
- each node is a honeycomb of lymph-filled cavities or sinuses and large clusters of lymphocytes
- also contain many macrophages and dendritic cells
Secondary lymphoid organ: spleen
- largest secondary organ
- left part of abdominal cavity between the diaphragm and stomach
- blood passes through the vascular meshwork of the spleen’s interior, where large collections of lymphocytes, macrophages and dendritic cells are found
- the macrophages of the spleen, in addition to interacting with the lymphocytes, also phagocytose aging or dead erythrocytes
Secondary lymphoid organs: Tonsils and adenoids
- small, rounded lymphatic organs in the pharynx
- filled with lymphocytes, macrophages and dendritic cells
- their lymphocytes respond to microbes that arrive by way of ingested food as well as inspired air
Function of B cells in Adaptive Immune Response
- differentiate into plasma cells that secrete antibodies
- these proteins then travel all over the body to reach antigens identical to those that stimulated their release
- In the body fluid outside of the cell (extracellular and interstitial), antibodies combine with antigens and guide an attack that eliminates the antigens or the cells bearing them
- This antibody-mediates response is also called the humoral responses
- wide variety of targets and is the major defense against bacteria, viruses and other pathogens in the extracellular fluid and against toxic molecules (toxins)
Functions of T cells in Adaptive Immune Response
- called cell-mediated responses
Cytotoxic T cells
- upon activation, they travel to the location of the target, bind to them via the antigen and directly kill the targets via secreted chemicals
- directed against the body’s own cells that have become cancerous or infected with viruses (or certain bacteria and parasites, that like viruses, take up residence in host cells)
Helper T cells
- assist in the activation and function of B cells, macrophages, cytotoxic T cells
- they combine to an antigen and undergo activation
- once activated, they migrate to the site of B-cell activation
- B cells that have bound to an antigen present it to the helper cells
- helper T cells make direct contact with the B cell, and communication given by surface receptors induces the activation of B cells
- With cytotoxic T cells, activated helper T cells help other cells, like dendritic cells, to activate cytotoxic T cells
- B cells and Cytotoxic T cells cannot function adequately unless they are stimulated by cytokines from helper T cells
- some cytokines secreted by helper T cells can act as inflammation mediators
Regulatory T cells
- suppress the ability of certain B and cytotoxic T cells to attack a person’s own proteins (autoimmune diseases)
- the suppression of regulatory T cells has been proven a possible means of increasing cytotoxic T-cell activity in patients with cancer
B-Cell Receptors
- the plasma cells derived from a particular B cell can secrete only one particular antibody
- each B cell always displays copies of the particular antibody on its plasma membrane that the cell progeny can produce
- this surface protein (glycoprotein) serves as a receptor for the specific antigen to bind on
- B-cell receptors and plasma cell antibodies constitute part of the superfamily proteins, immunoglobulins
- each immunoglobulin is composed of four interlinked polypeptide chains
- two long chains are called heavy chains, and the two short chains are called light chains
- five major classes of immunoglobulins determined by amino acid sequence (A, D, E, G and M)
- the lower half of the two heavy chains, the Fc portion, plus an additional portion of the heavy chains and part of the light chains are identical for all immunoglobulins of a single class
- this portion is important for the interaction of the molecule with phagocytes and the compliment system
- the upper part of each heavy chain and its associated light chain form an antigen-binding site
- B-cell receptors can bind antigen whether the antigen is a molecule dissolved in the extracellular fluid or is present on the surface of a foreign cell, such as a microbe, floating free in fluids
- the particular immunoglobulin that any B cell displays as a receptor on its plasma membrane is determined during the cell’s maturation in the bone marrow
T-cell receptors
- belong to the immunoglobulin superfamily
- two-chained proteins that have variable regions that differ from one T-cell clone to another
- receptors remain embedded in the T-cell membrane and are not secreted as antibodies
- maturation occurs in the thymus
- T-cell receptors cannot combine with antigen unless the antigen is first complexed with certain of the body’s own plasma membrane proteins
- membrane protein that needs to be complexed is found on chromosome 6, the major histocompatibility complex (MHC)
- no two persons other than identical twins have the same sets of MHC, and no two individuals have the same MHC proteins on the plasma membranes of their cells
- are cellular genetic markers of biological self
- Class I MHC proteins are found on the surface of virtually all cells of the body except erythrocytes
- Class II MHC proteins are found on the surfaces of macrophages, B cells and dendritic cells
- Cytotoxic T cells require antigen to be associated with class I MHC proteins
- helper T cells require class II MHC proteins
Antigen presentation to Helper T cells
- Only B cells, macrophages and dendritic cells can act as antigen-presenting cells (APC’s)
- after a microbe or noncellular antigen has been phagocytosed or broken down into fragments by the APC, the resulting fragments then bind (with endosomes) to class II MHC proteins synthesised by the cell
- the entire complex is then transported to the cell surface, where it is displayed in the plasma membrane
- it is not the intact antigen but rather the polypeptide fragments, called antigenic determinants or epitopes of the antigen that are complexed to the MHC proteins and presented to the helper T cells
- in addition, interactions need to occur between other (nonantigenic) pairs of proteins on the surfaces of the helper T cell and the APC
- these provide a necessary costimulus for helper T cell activation
- ultimately large amounts of the cytokines interleukin 1 and tumor necrosis factor-alpha are released by the APC to activate the T helper cell
- the activated helper T cell itself now secretes various cytokines that have both autocrine effects on the helper T cell and paracrine effects on the adjacent B cells and any nearby cytotoxic T cells and NK cells
Antigen presentation to Cytotoxic T cells
- antigens that complex with class I MHC proteins arise within body cells
- they are endogenous antigens, synthesised by the body’s own cells
- in both virus-infected cells and cancerous cells, some of the endogenously produced antigenic proteins are hydrolyzed by cytosolic enzymes (in proteasomes) into polypeptide fragments, which are transported into the endoplasmic reticulum
- there, they are complexed with the host cell’s class I MHC proteins and reach the plasma membrane surface by exocytosis
- from here, cytotoxic T cells specific for the complex can bind
NK cells in the Adaptive Immune Response
- major targets are virus-infected cells and cancer cells
- attack and kill these targets directly after binding to them
- not antigen-specific
- have neither T-cell receptors nor the immunoglobulin receptors of B cells
- MHC proteins are not involved in the activation of NK cells
- their participation in an immune response is greatly enhanced by certain antibodies or by cytokines secreted by helper T cells activated during adaptive immune responses
