Chapter 22: The Lymphatic System and Immunity Flashcards
define immunity.
Immunity or resistance is the ability to ward off damage or disease through our defenses.
Lymphatic and immune system:
a) Draining excess interstitial fluid
c) Transporting dietary lipids
d) Carrying out immune responses
(NOT b) Maintaining water homeostasis in the body)
compare the two basic types of immunity.
The two general types of immunity are (1) innate and (2) adaptive.
Innate (nonspecific) immunity refers to defenses that are present at birth. Innate immunity does not involve specific recognition of a microbe and acts against all microbes in the same way. Among the components of innate immunity are the first line of defense (the physical and chemical barriers of the skin and mucous membranes) and the second line of defense (antimicrobial substances, natural killer cells, phagocytes, inflammation, and fever). Innate immune responses represent immunity’s early warning system and are designed to prevent microbes from entering the body and to help eliminate those that do gain access.
Adaptive (specific) immunity refers to defenses that involve specific recognition of a microbe once it has breached the innate immunity defenses. Adaptive immunity is based on a specific response to a specific microbe; that is, it adapts or adjusts to handle a specific microbe. Adaptive immunity involves lymphocytes - MOST VARIABLE IN IMMUNE SYSTEM (a type of white
blood cell) called T lymphocytes (T cells) T Helper Cells most important cells in the immune system and B lymphocytes (B cells). The body system responsible for adaptive immunity (and some aspects of innate immunity) is the lymphatic system. This system is closely allied with the cardiovascular system, and it also functions with the digestive system in the absorption of fatty foods. In this chapter, we explore the mechanisms that provide defenses against intruders and promote the repair of damaged body tissues.
list the components of the lymphatic system.
resistance – AKA immunity – the state of being resistant to injury, particularly by poisons, foreign proteins, and invading pathogens
- pathogens – disease producing microbes
- susceptibility – vulnerability or lack of resistance
- innate (nonspecific) or innate immunity – defenses that are present at birth
- adaptive (specific) immunity – defenses that involve specific recognition of a microbe once it has breached the innate immunity defenses
lymphatic system – the body system responsible for adaptive (and some aspects of
innate) immunity
- consists of lymph, lymphatic vessels, structures and organs containing lymphatic tissue (lymphocytes within a filtering tissue), and red bone marrow
- lymph – fluid confined in lymphatic vessels and flowing through the lymphatic system until it is returned to the blood. LYMPH FROM SMALL INTESTINES APPEARS WHITE BECAUSE OF LIPIDS
- It is interstitial fluid that passes into lymphatic vessels
- Major difference between interstitial fluid and lymph is location: interstitial fluid is found between cells, lymph is located within lymphatic vessels and tissues.
- lymphatic tissue – a specialized form of reticular tissue that contains large numbers of lymphocytes.
- Lymphocytes are agranular WBCs
- Two types of lymphocytes participate in adaptive immune responses: B cells and T cells
describe the functions of the lymphatic system.
functions of the lymphatic system – 3 primary functions
- Drains excess interstitial fluid – from tissue spaces and return it to the blood. Functions closely with the CV system.
- Transports dietary lipids – lymphatic vessels transport lipids and lipidsoluble vitamins (A, D, E, K) absorbed by the GI tract
- Carries out immune responses – initiates highly specific responses directed against particular microbes or abnormal cells.
describe the organization of lymphatic vessels.
Thymus – a bilobed organ located in the superior mediastinum posterior to the sternum and between the lungs in which T cells develop immunocompetence.
- Enveloping layer of connective tissue holds the two lobes together closely
- A connective tissue capsule separates the two lobes
- Trabeculae – extensions of the connective tissue capsule
- Penetrate inward and divide each lobe into lobules
a) Macrophage – process and presentation of foreign antigens to T cells
b) Dendritic cell – processes and presents antigen to T and B cells
c) B cells – process and presents antigen to helper T cells
d) Plasma cell – produces and secretes antibodies
- High content of lymphoid tissue and rich blood supply make the thymus appear reddish in the living body
- With age, fatty infiltrations replace the lymphoid tissue and the thymus takes on a more yellowing colour.
- The thymus weighs about 70g at birth, but the functional portion can weigh as little as 3g in old age.
- Before it atrophies, it populates the secondary lymphatic organs and tissues with T cells.
- Each thymic lobule consists of a deeply staining outer cortex and a lighterstaining central medulla.
Cortex – large numbers of T cells and scattered dendritic cells, epithelial cells, macrophages
- Immature T cells migrate from red bone marrow to the cortex where they proliferate and begin to mature.
- Dendritic cells – derived from monocytes; have long branched projections, assist the maturation process
- Specialized epithelial cells in the cortex have several long processes that surround and serve as a framework for up to 50 T cells
- These epithelial cells help “educate” the pre-T cells in a process known as positive selection
- Only about 2% of developing T cells survive in the cortex. The remaining cells die via apoptosis
- Thymic macrophages help clear out the debris of dead and dying cells.
- The surviving T cells enter the medulla
Medulla
- Widely scattered, more mature T cells, epithelial cells, dendritic cells, macrophages.
-
Thymic corpuscles (AKA Hassall’s corpuscles) – epithelial cells that become arranged into concentric layers of flat cells that degenerate and become filled keratohyalin granules and keratin 1. May serve as sites of T cell death in the medulla
- function as a type of filter – as lymph enters, foreign substances are trapped by the reticular fibers within the sinuses of the node a. then macrophages phagocytize some substances, lymphocytes destroy others through immune responses.
lymph nodes – approx. 600 bean shaped nodes, scattered throughout body along the lymphatic vessels. Both superficial and deep, usually occur in groups. Large groups near mammary glands and in the axillae and groin
- capsule – dense connective tissue that covers each lymph node and extends into the node as trabeculae.
- Trabeculae – capsular extensions that divide the node into compartments, provide support, and provide a route for blood vessels into the interior of a node.
- Internal to the capsule is a supporting network of reticular fibers and fibroblasts.
- Stroma – the supporting framework of connective tissue – in a lymph node, consists of the capsule, trabeculae, reticular fibers, and fibroblasts.
- Parenchyma – functioning part of a lymph node.
- Divided into superficial cortex and a deep medulla
- The cortex consists of an outer cortex and an inner cortex
- outer cortex – contains lymphatic nodules
- lymphatic nodules (follicles) egg-shaped aggregates of B cells
- primary lymphatic nodule – lymphatic nodule that consists chiefly of B cells 1. after the B cells recognize an antigen, the primary lymphatic nodule develops into a secondary lymphatic nodule.
- secondary lymphatic nodule – form in response to an antigen and are sites of plasma cell and memory B cell formation
- most lymphatic nodules in the outer cortex are secondary lymphatic nodules.
- Center contains a light-staining cell region called a germinal center with B cells, follicular dendritic cells, and macrophages.
- When follicular dendritic cells “present” an antigen, B cells proliferate and develop into antibody producing plasma cells or develop into memory B cells
B cells (or B lymphocytes) and plasma cells
a. Antibody-producing plasma cells – circulate in the plasma
b. Memory B cells – remember an antigen, speed response in the future
inner cortex – does not contain lymphatic nodules
a. consists mainly of T cells and dendritic cells that enter a lymph node from other tissues.
b. The dendritic cells present antigens to T cells, causing their proliferation
c. The newly formed T cells migrate from the lymph node to areas of the body where there is antigenic activity
Medulla – contains B cells, antibody producing plasma cells that have migrated out of the cortex into the medulla, and macrophages embedded in a network of reticular fibers and reticular cells
afferent lymphatic vessels – entry vessels for a lymph node
a. penetrate the surface of the node at several points
b. valves point toward the node, directing lymph inward
sinuses – series of irregular channels that contain branching reticular fibers, lymphocytes, and macrophages.
- From the afferent lymphatic vessels, lymph flows into the subscapular sinus immediately below the capsule
- From here, lymph flows through the trabecular sinuses which extend through the cortex parallel to the trabeculae
- From these, lymph flows into medullary sinuses, which extend through the medulla
efferent lymphatic vessels – the exit point for lymph leaving a node
- wider and fewer in number than afferent vessels.
- Contain valves that face away from the node, direct fluid away from it.
Hilum – slight depression on one side of the lymph node from which efferent lymphatic vessels leave the lymph node and blood vessels enter and exit the node.
Filtration – lymph enters faster than it leaves a node.
- Moves slowly within the node, allowing filtration time.
- The lymph passes through multiple nodes before returning to the blood, so has multiple filtration stops to clean out debris and microbes.
- Measures about 12 cm in length.
Spleen – largest single mass of lymphatic tissue in the body
- Located in the left hypochondriac region between the stomach and diaphragm
- Superior surface is smooth and convex, conforms to the concave surface of the diaphragm
- Multiple organs make indentations in the visceral surface of the spleen
- Gastric impression - stomach
- Renal impression – left kidney
- Colic impression – left colic flexure of large intestine
- Spleen is surrounded by a capsule of dense connective tissue and is covered by a serous membrane (the visceral peritoneum)
- Trabeculae extend inward from the capsule
- Stroma of the spleen – capsule plus trabeculae, reticular fibers, fibroblasts
- Parenchyma of the spleen consists of two different types of tissues: white pulp and red pulp.
- white pulp – lymphatic tissue consisting mostly about lymphocytes and macrophages arranged around branches of the splenic artery called central arteries
- Blood flowing into the spleen through the splenic arteries enters the central arteries of the while pulp
- Within the white pulp, B cells and T cells carry out immune functions, similar to lymph nodes, while spleen macrophages destroy blood=borne pathogens by phagocytosis
- red pulp – consists of blood-filled venous sinuses and cords of splenic tissue called splenic cords – AKA Billroth’s cords.
- Splenic cords consist of RBCs, macrophages, lymphocytes, plasma cells, and granulocytes.
- Veins are closely associated with the red pulp.
- With the red pulp, spleen performs 3 functions related to blood cells:
- Removal of ruptured, worn out, or defective blood cells and platelets by macrophages
- Storage of platelets, up to one-third of the body’s supply
- Production of blood cells (hemopoiesis) during fetal life
- mucosa associated lymphatic tissue (MALT) – lymphatic nodules scattered throughout the lamina propria (connective tissue) of mucous membranes lining the GI, urinary, and reproductive tracts and respiratory airways
lymphatic nodules (follicles) – egg-shaped masses of lymphatic tissue that are not surrounded by a capsule
- tonsils – an aggregation of large lymphatic nodules embedded in the mucous membrane of the throat.
- Usually 5, form a ring at the junction of the oral cavity and oropharynx and at the junction of the nasal cavity and nasopharynx.
- Strategically placed to participate in immune responses against inhaled or ingested foreign materials.
- pharyngeal tonsil or adenoid – single tonsil embedded in the posterior wall of the nasopharynx
- palatine tonsils – lie at the posterior region of the oral cavity, one on either side a. the tonsils commonly removed in a tonsillectomy
- lingual tonsils – located at the base of the tongue a. may also require removal during a tonsillectomy.
explain the formation and flow of lymph.
formation and flow of lymph – recall 3 liters per day of interstitial fluid is not reabsorbed by the blood capillaries
- this fluid forms lymph
- the small amount of plasma proteins that do leave blood plasma cannot return to it, so they enter lymph also.
skeletal muscle pump – same “pumps” that aid venous blood return to heart.
- Milking action of skeletal muscle contraction/relaxation compresses lymphatic vessels, forces lymph toward the junction of the internal jugular and subclavian veins
respiratory pump – inhalation and exhalation affect abdominal pressure which pushes lymph toward the thoracic region.
- In both cases, valves prevent back flow
distinguish between primary and secondary lymphatic organs.
primary lymphatic organs – the sites where stem cells divide and become immunocompetent
- the primary lymphatic organs are the red bone marrow and the thymus
- pluripotent stem cells in red bone marrow give rise to mature, immunocompetent B cells and to pre-T cells.
- Pre-T cells migrate to the thymus where they mature and become immunocompetent T cells.
immunocompetent – the ability to mount an immune response
secondary lymphatic organs and tissues – the sites where most immune responses occur
- include the lymph nodes, spleen, lymphatic nodules.
describe the components of innate immunity.
nonspecific resistance: innate defenses – external physical and chemical barriers provided by the skin and mucous membranes and also various internal defenses: antimicrobial substances, natural killer cells, phagocytes, inflammation, and fever.
first line of defense: skin and mucous membranes – physical and chemical barriers
Barriers used by the innate defense include epidermis, mucus, hairs, cilia, lacrimal apparatus, saliva, urine, vaginal secretions, sebum, perspiration and gastric juices.
a. Epidermis – outer epithelial layer of the skin
- Many layers of closely packed, keratinized cells
- Formidable physical barrier
- Shedding helps remove microbes from the surface
- Usually only penetrated if broken – cuts, burns, etc.
b. mucous membranes – line body cavities
* Epithelial layer secrets mucus
c. Mucus – lubricates and moistens the cavity surface 1. Lightly viscous, traps many microbes and foreign substances.
d. hairs in nose – mucous coated 1. Trap and filter microbes
e. cilia in upper respiratory tract – in the mucous membrane
- Waving action of cilia propels inhaled dust and microbes that have been trapped in mucus toward the throat.
- Coughing and sneezing accelerate movement of mucus and its trapped junk out of the body
- Swallowing sends mucus to the stomach where gastric juice kills the bugs.
lacrimal apparatus – manufacture and drain away tears in response to irritants
- Blinking spreads tears over the surface of the eyeball
- Continuing washing action of the tears helps dilute microbes and prevent them from settling
Lysozyme – enzyme capable of breaking down the cell wall of certain bacteria
- Present in tears, saliva, perspiration, nasal secretions, and tissue fluids
Saliva – produced by the salivary glands
- Washes microbes from surfaces of teeth and from the mucous membrane of the mouth
- Flow of saliva reduces colonization of the mouth by microbes
i. flow of urine – cleanses the urethra and retards microbial colonization of the urinary system
j. vaginal secretions – move microbes out of the female body 1. Slightly acidic, discourages bacterial growth
k. defecation and vomiting – expel microbes
l. Sebum – oily substance secreted by sebaceous glands in skin
- Forms a protective film over the skin’s surface
- Unsaturated fatty acids in sebum inhibit the growth of certain pathogenic bacteria and fungi
- The acidity of the skin (pH 3-5) is due in part by the secretion of fatty acids and lactic acid
- m. Perspiration – flushes microbes from the surface of the skin
gastric juice – mixture of hydrochloric acid, enzymes, and mucus
- Strong acidity, pH 1.2-3, destroys many bacteria and most bacterial toxins
SECOND LINE OF DEFENSE: internal defenses – internal antimicrobial substances, phagocytes, natural killer cells, inflammation, fever
antimicrobial substances – 4 main types that discourage microbial growth: interferons (IFNs), complement system, iron-binding proteins, and antimicrobial proteins
a. interferons (IFNs) - proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses
- IFNs diffuse to uninfected neighboring cells, inducing synthesis of antiviral proteins that interfere with viral replication
- IFNs do not stop viruses from attaching to and penetrating host cells but they do stop replication.
- Three different types of interferons: alpha, beta, and gamma IFN
b. complement system – a group of normally inactive proteins in blood plasma and on plasma membranes
- When activiated, these proteins “complement” or enhance certain immune reactions
- The complement system causes cytolysis (bursting) of microbes, promotes phagocytosis, and contributes to inflammation
c. iron-binding proteins – inhibit the growth of certain bacteria by reducing the amount of available iron 1. Ex. Transferrin (found in blood and tissue fluids), lactoferrin (found in milk, saliva, and mucus), ferritin (found in the liver, spleen, and red bone marrow), and hemoglobin
d. antimicrobial proteins – short peptides that have a broad spectrum of antimicrobial activity
- Ex. Dermicidin (produced by sweat glands), defensins and cathelicidins (produced by neutrophils, macrophages, and epithelia), and thrombocidin (produced by platelets)
- Kill a wide range of microbes
- Attract dendritic cells and mast cells, which participate in immune responses
- Microbes exposed to AMPs do not appear to develop resistance, as often happens with antibiotics
natural killer (NK) cells - the next non specific defense when pathogens pass the skin, mucous membranes, or antimicrobial substances in blood.
- About 5-10% of lymphocytes in the blood are NK cells
- Also present in the spleen, lymph nodes, and red bone marrow
- NK cells lack the membrane molecules that identify B and T cells but have the ability to kill a wide variety of infected body cells and certain tumour cells
- NK cells attack any cells that display abnormal or unusual plasma membrane proteins
- When NK cells bind to a target cell, granules containing toxic substances from NK cells are released
- Perforin – a protein contained in some of the granules released by NK cells that inserts into the plasma membrane of the target cell, causes perforations in the membrane 1. Result: extracellular fluid flows into the cell, the cell bursts
Cytolysis – bursting of a cell by filling with ECF
Granzymes – released by other granules of NK cells
- protein-digesting enzymes that induce the target cell to undergo apoptosis
- This attack kills the infected cell but not the microbes inside but they can be destroyed by phagocytes
i. Phagocytes – specialized cells that perform phagocytosis.
* Two major types: neutrophils, macrophages
j. Neutrophils – migrate to site of infection
k. Macrophages – develop from monocytes in response to infection **NON SPECIFIC CELLULAR DISEASE RESISTANCE MECHANISM
l. wandering macrophages – migrate to the infected area
m. fixed macrophages – remain in specific tissues
* Types: histiocytes (connective tissue), stellate reticuloendothelial cells – AKA Kuppfer cells (in the liver), alveolar macrophages (lungs), microglial cells (nervous system), tissue macrophages (spleen, lymph nodes, red bone marrow)
Phagocytosis – ingestion of microbes or particles 1. 5 phases:
o. Chemotaxis – chemically stimulated movement of phagocytes to a site of damage
* Chemicals that attract phagocytes might come from microbes, WBCs, damaged tissue cells, or activated complement proteins
p. Adherence – phagocyte attaches to the microbe or particle
1. The binding of complement proteins to the invading pathogen enhances adherence
q. Ingestion – process of engulfing the microbe
- Plasma membrane of the phagocyte extends projections called pseudopods that engulf the microbe
- When pseudopods meet around the microbe, they fuse and surround the microorganism with a sac called a phagosome
r. Digestion – the phagosome enters the cytoplasm and merges with lysosomes to form a single larger structure called a phagolysosome.
- The lysosome contributes lysozyme which breaks down microbial cell walls and other digestive enzymes that degrade carbohydrates, proteins, lipids, and nucleic acids
- the phagocyte also forms lethal oxidants such as superoxide anion (O-), hypochlorite anion (OCl-), and hydrogen peroxide H2O2) in a process called an oxidative burst
s. Killing – the onslaught of lysozyme, digestive enzymes, and oxidants within a phagolysosome quickly kills many microbes.
1. Any materials that cannot be degraded further remain in structures called residual bodies
V. Inflammation – nonspecific, defensive response of the body to tissue damage
- May be caused by pathogens, abrasions, chemical irritations, distortion or disturbances of cells, and extreme temperatures
- 4 characteristics – redness, pain, heat and swelling
- Can also cause loss of function (ex. Inability to detect sensations) 1. Depending on site and extent of injury
d. 3 basic stages – vasodilation and increased permeability of blood vessels, emigration of phagocytes from the blood to interstitial fluid, tissue repair
1. vasodilation and increased blood vessel permeability – 2 immediate responses in the blood vessels in a region of tissue injury
Increased permeability – substances normally retained in blood are permitted to pass from the blood vessels
- Permits defensive proteins such as antibodies and clotting factors to enter the injured area from the blood
Vasodilation allows more blood to flow through the damaged area
- Helps remove microbial toxins and dead cells
Produce 3 of the signs and symptoms of inflammation: heat, redness, swelling 1. Pain results from injury to neurons and from toxic chemicals released by microbes and also increased pressure from edema
Substances that contribute to vasodilation and permeability:
Histamine – released by mast cells in connective tissue and basophils and platelets in blood.
a. Also released by neutrophils and macrophages attracted to the site of injury
b. Causes vasodilation and increased permeability of blood vessels
Kinins – polypeptides formed in blood from inactive precursors called kininogens
- Induce vasodilation and increased permeability
- Serve as chemotactic agents for phagocytes
- Ex. Bradykinin
- Affect some nerve endings, causing much of the pain associated with inflammation
Prostaglandins – especially those of the E series are released by damaged cells
- Intensify the effects of histamine and kinins
- May also stimulate the emigration of phagocytes through capillary walls
- Intensify and prolong the pain associated with inflammation
Leukotrienes – produced by basophils and mast cells.
- Cause increased permeability
- Also function in adherence of phagocytes to pathogens and as chemotactic agents that attract phagocytes
Complement – different components of the complement system stimulate histamine release, attract neutrophils by chemotaxis, and promote phagocytosis a. Some components of complement can also destroy bacteria
Increased permeability of capillaries allows leakage of clotting factors into tissues
- Clotting sequence is set in motion, fibrinogen is ultimately converted to an insoluble, thick mesh of fibrin threads that localizes and traps invading microbes and blocks their spread.
Emigration – the sticking to and squeezing through blood vessels by cells
- The larger amount of blood accumulating causes neutrophils to stick to the endothelium
- The neutrophils squeeze through the wall of the blood vessel to reach the damaged area
- This process depends on chemotaxis
Leukocytosis – an increase in WBCs in the blood
- Steady stream of neutrophils is supplied by increased production in red bone marrow
Neutrophils – predominate in early infection
- die off quickly
- Monocytes follow neutrophils into the infected area and transform into wandering macrophages
- The macrophages engulf damaged tissue, microbes, and worn-out neutrophils
Pus – collection of dead cells and fluid
- Occurs in most inflammatory responses
- Usually continues until the infection subsides
- Sometimes pus reaches the surface of the body or drains into an internal cavity and is dispersed
- Other times, the pus remains after the infection is terminated and gradually is destroyed and absorbed over a period of days.
Fever – abnormally high body temp that occurs because the hypothalamic thermostat is reset
- Commonly occurs during infection and inflammation
- Many bacterial toxins elevate body temp 1. Sometimes by triggering release of cytokines such as interleukin-1 from macrophages
- Elevated body temp intensifies the effects of interferons, inhibits the growth of some microbes, and speeds up body reactions that aid repair
describe how T cells and B cells arise and function in adaptive immunity.
Define adaptive immunity, and describe how T cells and B cells arise.
specific resistance: immunity – the ability of the body to defend itself against specific invading agents such as bacteria, toxins, viruses, and foreign tissues
I. antigens (Ags) - substances that are recognized as foreign and provoke immune responses
- Meaning antbody generators
II. maturation of T cells and B cells – both develop in primary lymphatic organs (red bone marrow and the thymus) from pluripotent stem cells that originate in the red bone marrow. Hormone produced in Thymus produces hormone for maturation.
- B cells complete their development in the red bone marrow 1. Continues throughout life
- T cells develop from pre-T cells that migrate from red bone marrow into the thymus 1. Most T cells arise before puberty, but they continue to mature and leave the thymus throughout life.
- B and T cells named for where they mature
- B cells – bursa equivalent AKA red bone marrow
- T cells – thymus
- d. Before leaving the maturation location, both B cells and T cells develop immunocompetence
III. Immunocompetence – the ability to carry out adaptive immune responses
- B cells and T cells begin to make several distinctive proteins that are inserted into their plasma membranes
- Some of these proteins function as antigen receptors
- Helper T cells AKA CD4 T cells 1. In addition to antigen receptors, their plasma membranes include a protein called CD4
IV. antigen receptor – molecules capable of recognizing specific antigens
V. helper T cells and cytotoxic T cells – two major types of mature T cells that exit the thymus
- Cytotoxic T cells AKA CD8 T cells 1. Their plasma membranes contain a protein called CD8
- Both have very different functions
explain the relationship between an antigen and an antibody.
types of adaptive immunity – two types, both triggered by antigens
I. cell mediated immunity – cytotoxic T cells directly attack invading antigens
- Particularly effective against intracellular pathogens (may be viruses, bacteria, or fungi inside cells), some cancer cells, and foreign tissue transplants
- Always involves cells attacking cells
II. antibody mediated immunity – B cells transform into plasma cells which synthesize and secrete antibodies (Abs) AKA immunoglobulins
- Works mainly against extracellular pathogens, including viruses, bacteria, and fungi that are in body fluids outside cells
- AKA humoral immunity
III. Often both types work together
- When an antigen enters the body, only a small group of lymphocytes have the correct antigen receptors to respond to that antigen
- The antigen spreads in body cells and tissues
- The antigen present in cells provokes cell mediated response and antigen present in ECF provokes antibody-mediated response.
antibodies (Abs) or immunoglobulins (Igs) - specific proteins synthesized and secreted by B cells that have transformed into plasma cells
- A given antibody can bind to and inactivate a specific antigen
Helper T cells aid the immune responses of both cell-mediated and antibody-mediated immunity
D. Humors – body fluids I. Ex. Blood and lymph
E. humoral immunity – AKA antibody-mediated immunity
I. Because it involves antibodies that bind to antigens in body humors (fluids)
F. principle of clonal selection – the process by which a lymphocyte proliferates and differentiates in response to a specific antigen
- The result of clonal selection is formation of a population of identical cells (clones) that can recognize the same antigen as the original lymphocyte.
- Before exposure to a given antigen, only a few lymphocytes can recognize it, but after clonal selection, thousands can respond to that antigen
- Clonal selection occurs in secondary lymphatic organs and tissues a. Swollen lymph nodes are often clonal selection occurring
- Two major types of cells develop in the clone: effector cells and memory cells
- Effector cell – carry out immune responses that ultimately result in destruction or inactivation of the antigen
- Include active helper T cells, active cytotoxic T cells, and plasma cells
- Most effector cells eventually die after the immune response has completed
- Memory cell – do not actively participate in the initial immune response to the antigen
- If the same antigen enters the body in the future, the 1000’s of memory cells of a lymphocyte close are available to initiate a faster reaction than the first time.
- Memory cells respond to the antigen by proliferating and differentiating into more effector cells and more memory cells 1. Include memory helper T cells, memory cytotoxic T cells, memory B cells
- Most memory cells do not die at the end of the immune response, they last up to decades.
compare the functions of cell-mediated immunity and antibody-mediated immunity.
antigens (Ags) - two important characteristics – immunogenicity and reactivity
Immunogenicity – the ability to provoke an immune response by stimulating the production of specific antibodies, the proliferation of specific T cells, or both
Reactivity – the ability of the antigen to react specifically with the antibodies or cells it provoked
complete antigens – substances with both immunogenicity and reactivity
Antigens = substances that have reactivity (in scientist language)
- The term antigen implies both immunogenicity and reactivity, and the word is used that way in this course
E. Ex. Of antigens – entire microbes or parts of microbes, chemical components of bacterial
structures such as flagella, capsules, and cell walls, and bacterial toxins
F. Epitopes – small parts of a large antigen molecule that act as the triggers for immune responses
- AKA antigenic determinants
- Most antigens have many epitopes, each of which induces production of a specific antibody or activates a specific T cell.
G. Hapten - a smaller substance that has reactivity but lacks immunogenicity
- Can stimulate an immune response only if attached to a larger carrier molecule
- Ex. Lipid toxin in poison ivy: triggers immune response combining with a body protein
- Ex. Some drugs ex. Penicillin
- Hapten-stimulated immune responses are responsible for some allergic reactions to drugs and other substances in the environment
H. Genetic recombination – process by which shuffling and rearranging of a few hundred versions of several small gene segments are put together in different combinations as the lymphocytes are developing from stem cells in red bone marrow and the thymus I. Similar to shuffling a deck of 52 cards and dealing 3 cards. Same 52 cards, but many many combinations of 3 cards possible.
- major histocompatibility complex (MHC) antigens - “self-antigens”
- AKA human leukocyte antigens (HLA) because first identified on WBCs
- Surface proteins on WBCs and other nucleated cells (not RBCs) that are unique for each person (except identical twins)
- Used to type tissues and help prevent rejection of transplanted tissues
- 1000’s-100,000’s MHC molecules mark the surface of each body cell except RBCs
- Normal function is to help T cells recognize that an antigen is foreign, not self
- Responsible for transplant rejections, and the foreign tissue does not have the same MHC antigens
- Two types of major histocompatibility complex antigens: class I and class II
- Class I MHC molecules are built into the plasma membrane of all body cells except RBCs
- Class II MHC molecules appear on the surface of antigen-presenting cells
pathways of antigen processing - two ways, depending on whether the antigen is located inside or outside body cells
- Exogenous antigens are outside body cells
- Endogenous antigens are inside body cells
- T cells only recognize fragments of antigenic proteins that are processed and presented in a certain way
B cells can recognize and bind to antigens in lymph, interstitial fluid, and blood plasma
antigen presenting cells (APCs) - special class of migratory cells that processes and presents antigens to T cells during an immune response
- APCs include macrophages, B cells, and dendritic cells, which are present in the skin, mucous membranes, and lymph nodes
- APCs process and present exogenous antigens. After processing and presenting an antigen, APCs migrate from tissues via lymphatic vessels to lymph nodes
Exogenous antigens – foreign antigens present outside body cells
I. Steps in processing and presenting an exogenous antigen by an APC:
- Ingestion of the antigen – by phagocytosis or endocytosis
- Digestion of the antigen into peptide fragments – Within the phagosome or endosome, protein digesting enzymes split large antigens into short peptide fragments
- Synthesis of MHC II molecules – At the same time, the APC synthesizes MHC-II molecules at the ER
- Packaging of MHC-II molecules – once synthesized, the MHC II molecules are packaged into vesicles
- Fusion of vesicles – the vesicles containing the antigen peptide fragments and MHC II molecules merge and fuse
- Binding of peptide fragments to MHC II molecules – after fusion, the antigen peptide fragments bind to MHC II molecules
- Insertion of antigen-MHC-II complexes into the plasma membrane – the combined vesicle undergoes exocytosis and the antigen-MHC-II complexes are inserted into the plasma membrane
II. After processing the antigen, the APC migrates to lymphatic tissue to present the
antigen to T cells
Endogenous antigens - foreign antigens present inside cells
I. Steps to process and present an endogenous antigen:
- Digestion of the antigen into peptide fragments – within the infected cell, protein digesting enzymes split the endogenous antigen into short peptide fragments
- Synthesis of MHC I molecules – at the same time, the infected cell synthesizes MHC-I molecules at the ER
- Binding of peptide fragments to MHC-I molecules – the antigen peptide fragments enter the ER and then bind to MHC I molecules
- Packaging of antigen-MHC-I molecules – from the ER, antigen-MHC-I molecules are packaged into vesicles
- Insertion of antigen-MHC-I complexes into the plasma membrane – the vesicles that contain antigen-MHC-I complexes undergo exocytosis and the complexes are inserted into the plasma membrane
II. The display of an endogenous antigen bound to an MHC-I molecule signals that a cell has been infected and needs help
III. Most body cells can process and present endogenous antigens.
Cytokines – small protein hormones that stimulate or inhibit many normal cell functions, such as cell growth and differentiation.
- Secreted by lymphocytes, APCs, fibroblasts, endothelial cells, monocytes, hepatocytes, kidney cells
- Some cytokines stimulate proliferation of progenitor blood cells in red bone marrow
- Others regulate activities of cells involved in innate defenses or adaptive immune responses.
distinguish between the action of natural killer cells and cytotoxic T cells.
types of T cells
helper T cells or CD4 T cells – Most T cells that display CD4 develop into Helper T cells
- Inactive helper T cells recognize exogenous antigen fragments associated with MHC II molecules at the surface of an APC.
- With the aid of the CD4 protein, the helper T cell and APC interact with each other (antigenic recognition), costimulation occurs, and the helper T cell becomes activated.
- Once activated the helper T cells undergoes clonal selection and forms clones of helper T cells that consist of active helper T cells and memory T cells
active helper T cells
- Within hours after costimulation, active helper T cells start secreting a variety of cytokines, including Interleukin 2
Interleukin 2 – needed for virtually all immune responses and the prime trigger of T cell proliferation
- can act as a costimulator for resting helper T cells or cytotoxic T cells
- Enhances the activation and proliferation of T cells, B cells, and natural killer cells
- Beneficial positive feedback system:
- Helper T cell secretes IL-2
- IL-2 binds to the receptors on the plasma membrane of the cell that secreted it – autocrine
- Stimulates cell division
- More helper T cells secrete more IL-2 which causes more cell division
- Paracrine – acts on neighboring helper T cells, cytotoxic T cells, or B cells 1. If any of those neighboring cells are already bound to the same antigen, IL-2 serves as a costimulator
memory helper T cells – not active cells
- Can quickly proliferate and differentiate into more active helper T cells and more memory helper T cells if the same antigen enters the body again in the future.
cytotoxic T cells or CD8 T cells - Most T cells that display CD8 develop into cytotoxic T cells
- Recognize foreign antigens combined with MHC-I molecules on the surface of body cells infected by microbes, some tumor cells, and cells of a tissue transplant.
- Recognition requires the TCR and CD8 protein to maintain the coupling with MHC-I.
- To become activated, cytotoxic T cells require costimulation by IL-2 or other cytokines produced by active helper T cells that have already become bound to copies of the same antigen
- Maximal activation of cytotoxic T cells requires presentation of antigen associated with both MHC-I and MHC-II molecules
- Once activated, the cytotoxic T cell undergoes clonal selection, resulting in clones of active cytotoxic T cells and memory cytotoxic T cells
- Instead, they can quickly proliferate and differentiate into more active and memory cytotoxic T cells if the same antigen enters the body again. I. elimination of invaders
active cytotoxic T cells – attack other body cells that have been infected with the antigen
memory cytotoxic T cells – do not attack infected body cells
- Cytotoxic T cells are the soldiers that march to do battle with foreign invaders in cell-mediated immune responses.
- They leave secondary lymphatic organs and tissues and migrate to seek out and
- destroy infected target cells, cancer cells, and transplanted cells.
- Cytotoxic T cells recognize and attach to target cells, then deliver a “lethal hit” that kills the target cells.
- Cytotoxic T cells kill infected body cells like natural killer cells, but only target body cells with one particular type of microbe (natural killer cells do not differentiate between one infection or another)
- Two principal mechanisms for killing infected target cells:
- Recognize and bind to infected target cells with microbial antigens displayed on their surface
- Release granzymes
- Once the infected cell is destroyed, the released microbes are killed by phagocytes
Granzymes - protein-digesting enzymes that trigger apoptosis
- Bind to infected body cells and release two proteins from granules: perforin and granulysin
- May also secrete lymphotoxin (T cell toxin that fragments DNA) and gamma-interferon and macrophage migration inhibition factor
- Once the target cell is destroyed, the cytotoxic T cell and seek out and destroy another target cell.
- These enzymes cause the target cell’s DNA to fragment, and the cell dies
Perforin - protein that inserts into the plasma membrane of the target cell and creates channels in the membrane, resulting in ECF flowing into the cell and the cell bursting (cytolysis)
Granulysin - enters through the perforin channels and destroys microbes by creating holes in their plasma membranes
Lymphotoxin - toxic molecule released by cytotoxic T cells that destroys target cells by activating enzymes in the target cell
Gamma-interferon – attracts and activates phagocytic cells
Macrophage migration inhibition factor – prevents migration of phagocytes from the
infection site
define immunological surveillance.
immunological surveillance - immune response carried out by cytotoxic T cells, macrophages, and natural killer cells
- The immune system recognizes a tumor antigen as non-self and destroys any cancer cells carrying that antigen.
- Most effective in eliminating tumor cells due to cancer-causing viruses
- For this reason, transplant recipients taking immunosuppressive drugs to prevent transplant rejection have an increased incidence of virusassociated cancers.
tumor antigens - molecules that are rarely, if ever, displayed on the surface of a normal cell.
- When a normal cell transforms into a cancerous cell, it often displays tumor antigens.
distinguish between a primary response and a secondary response to infection.
primary response - peaks 10-17 days after an initial contact with an antigen, no antibodies are present for several days. Then a slow rise in the antibody titer, first IgM and then IgG, followed by a gradual decline in antibody titer. I. Memory cells remain for decades.
secondary response - accelerated, more intense response to the same antigen that occurs after a new encounter with the same antigen.
- Results in rapid proliferation of memory cells
- The antibody titer is far greater than during a primary response and consists mainly of IgG antibodies.
- Antibodies produced during a secondary response have an even higher affinity for the antigen than those produced during a primary response.
Recovery from an infection without antimicrobial drugs is usually because of the primary response. In a secondary response, you may recover before even knowing you are sick.
describe how self-recognition and self-tolerance develop.
self recognition and self tolerance - to function properly, a person’s T cells must have two traits, self recognition and self tolerance
I. Self-recognition – must be able to recognize your own MHC proteins
II. Self-tolerance – must lack reactivity to peptide fragments from your own proteins
- B cells also display self-tolerance
- Loss of self-tolerance leads to development of autoimmune diseases.
Positive selection – the process by which pre-T cells in the thymus develop the capability for self-recognition
- Some pre-T cells express T cell receptors (TCRs) that interact with self-MHC proteins on epithelial cells in the thymic cortex
- Because of this interaction, the T cells can recognize the MHC part of an antigen- MHC complex a. These T cells survive
- Other immature T cells that fail to interact with thymic epithelial cells are not capable of recognizing self-MHC proteins. a. These cells undergo apoptosis
Negative selection – the process by which development of self-tolerance occurs I. By a weeding-out process in which T cells interact with dendritic cells located at the junction of the cortex and medulla in the thymus
- T cells with receptors that recognize self-peptide fragments or other self-antigens are eliminated or inactivated.
- The T cells selected to survive do not respond to self-antigens, the fragments of molecules that are normally present in the body.
- Negative selection occurs via both deletion and anergy
- Deletion – self-reactive T cells undergo apoptosis and die
- Anergy – T cells remain alive but are unresponsive to antigenic stimulation. an inactive, self responsive cell
Only 1-5% of the immature T cells in the thymus receive proper signals to survive during both positive and negative selection and emerge as mature, immunocompetent T cells.
B cells also develop tolerance through deletion and anergy
- While developing in the bone marrow, those cells exhibiting antigen receptors that recognize common self-antigens are deleted.
- Once B cells are released into the blood, anergy appears to be the main mechanism for preventing responses to self-proteins
- When B cells encounter an antigen not associated with an antigenpresenting cell, the necessary costimulation signal is often missing
- In this case, the B cell is likely to become anergic (inactivated) rather than activated.
