Slide Set: 8: Immune System Flashcards
1
Q
The immune system serves three major functions:
A
- It tries to recognize and remove abnormal “self” cells created when normal cell growth and development go wrong.
- It removes dead or damaged cells, as well as old red blood cells.
- It protects the body from disease-causing invaders known as pathogens.
- attempts to recognize and remove abnormal cells
2
Q
Substances that trigger the body’s immune response are called _________
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immunogens
3
Q
Immunogens that react with products of the response are known as ___________.
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antigens
4
Q
Pathologies of the immune system generally fall into one of three categories:
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incorrect responses,
overactive responses,
lack of response.
5
Q
Incorrect responses
A
Autoimmune diseases
If mechanisms for distinguishing self from non-self fail and the immune system attacks the body’s normal cells, an autoimmune disease results.
Type 1 diabetes mellitus, in which proteins made by immune cells destroy pancreatic beta cells, is an example of an autoimmune disease in humans.
6
Q
Overactive responses
A
Allergies
are conditions in which the immune system creates a response that is out of proportion to the threat posed by the antigen. In extreme cases, the systemic effects of allergic responses can be life threatening.
7
Q
Lack of immune response
A
Immunodeficiency diseases
arise when some component of the immune system fails to work properly.
Primary immunodeficiency is a family of genetically inherited disorders that range from mild to severe.
Acquired immunodeficiencies may occur as a result of infection, such as acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV). Acquired immunodeficiencies may also arise as a side effect of drug or radiation therapy, such as those used to treat cancer.
8
Q
Primary immunodeficiency
A
is a family of genetically inherited disorders that range from mild to severe.
9
Q
Acquired immunodeficiency
A
Acquired immunodeficiencies may occur as a result of infection, such as acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV). Acquired immunodeficiencies may also arise as a side effect of drug or radiation therapy, such as those used to treat cancer.
10
Q
What are the differences between bacteria and viruses?
A
- Structure
- Bacteria are cells, with a cell membrane that is usually surrounded by a cell wall. Some encapsulated bacteria also produce an additional protective outer layer known as a capsule.
- Viruses are not cells. They consist of nucleic acid (DNA or RNA) enclosed in a coat of viral proteins called a capsid. Some viruses add an envelope of phospholipid and protein made from the host’s cell membrane and incorporate viral proteins into the envelope - Living conditions and reproduction.
- Most bacteria can survive and reproduce outside a host if they have the required nutrients, temperature, pH, and so on.
- Viruses must use the intracellular machinery of a host cell to replicate. The location of pathogens in both major compartments of the body requires different defense mechanisms for each compartment. - Susceptibility to drugs
- Most bacteria can be killed by the drugs we call antibiotics. These drugs act directly on bacteria and destroy them or inhibit their growth.
- Viruses cannot be killed by antibiotics. A few viral infections can be treated with antiviral drugs, which target specific stages of viral replication.
11
Q
Viruses are not cells. They consist of nucleic acid (DNA or RNA) enclosed in a coat of viral proteins called a ____
A
capsid.
12
Q
Some encapsulated bacteria also produce an additional protective outer layer known as a ____.
A
capsule
13
Q
Viruses can be released from host cells in one of two ways:
A
(1) The virus causes the host cell to rupture, releasing virus particles into the ECF, or
(2) virus particles surround themselves with a layer of host cell membrane and then bud o from the surface of the host cell.
14
Q
The body has two lines of defense:
A
physical and chemical barriers, such as skin, mucus, and stomach acid, first try to keep pathogens out of the body’s internal environment
If this first line of defense fails, then the internal immune response takes over.
15
Q
The internal immune response has four basic steps:
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(1) detection and identification of the foreign substance,
(2) communication with other immune cells to rally an organized response,
(3) recruitment of assistance and coordination of the response among all participants, and
(4) destruction or suppression of the invader.
16
Q
The immune response is distinguished by its extensive use of chemical signaling. Detection, identification, communication, recruitment, coordination, and the attack on the invader all depend on signal molecules such as _________
A
cytokines and antibodies.
17
Q
What are cytokines?
A
Cytokines are protein messengers released by one cell that affect the growth or activity of another cell
18
Q
What are antibodies?
A
Antibodies, proteins secreted by certain immune cells, bind antigens and make them more visible to the immune system.
19
Q
The human immune response is generally divided into two categories:
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nonspecific innate immunity and speci c acquired im- munity.
20
Q
Innate immunity
A
Innate immunity is present from birth {innatus, inborn} and is the body’s nonspecific immune response to invasion.
The membrane receptors that mediate innate immunity have broad specificity and allow some immune cells to respond to molecular signals that are both unique and common to pathogenic microorganisms.
An example of a common pathogen-specific signal would be certain components of the bacterial cell wall. Because the nonspecific innate response does not target a particular pathogen, it begins within minutes to hours.
21
Q
What is inflammation?
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apparent on the skin as a red, warm, swollen area, is a hallmark reaction of cytokine-mediated innate immunity.
22
Q
Acquired immunity
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Acquired immunity (also called adaptive immunity) is directed at specific invaders and for this reason is the body’s speci c immune response. e membrane receptors that medi- ate acquired immunity are highly speci c and can distinguish between different pathogens. One characteristic of acquired immunity is that a specific immune response following rst ex- posure to a pathogen may take days. With repeated exposures, however, the immune system “remembers” prior exposure to the pathogen and reacts more rapidly.
23
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Acquired immunity can be divided into
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cell-mediated immunity and humoral immunity.
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Cell-mediated immunity
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uses contact-dependent signaling in which an immune cell binds through receptors to its target cell.
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Humoral immunity
also known as antibody-mediated immunity, uses the secreted pro- teins known as antibodies to carry out the immune response. Antibodies combine with foreign substances to make them more visible to the cells of the immune system.
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The immune system has two anatomical components:
lymphoid tissues and the cells responsible for the immune response.
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Lymphoid tissues
are found all over the body. The two primary lymphoid tissues are the thymus gland and the bone marrow, both sites where cells involved in the immune response form and mature. Some types of mature immune cells do not specialize until their first exposure to the pathogen they will fight. These mature but unspecialized immune cells are said to be naïve cells
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secondary lymphoid tissues
mature immune cells interact with pathogens and initiate a response.
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secondary tissues are divided into
encapsulated tissues and unencapsulated diffuse lymphoid tissues.
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encapsulated lymphoid tissues
The encapsulated lymphoid tissues are the spleen and the lymph nodes. Both spleen and lymph nodes have an outer wall formed from fibrous collagenous capsules.
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Spleen
The spleen contains immune cells positioned so that they monitor the blood for foreign invaders.
Phagocytic cells in the spleen also trap and remove aging red blood cells.
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The lymph nodes
The lymph nodes are part of the lymphatic circulation, which is closely associated with capillaries of the cardiovascular system.
Recall that blood pressure creates net flow of fluid out of capillaries and into the interstitial space. The filtered fluid, amounting to about 3 L>day, is picked up by lymph capillaries and passes through the encapsulated lymph nodes on its journey back to the heart.
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The unencapsulated diffuse lymphoid tissues
The unencapsulated diffuse lymphoid tissues are aggregations of immune cells that appear in other organs of the body.
They include the tonsils at the posterior nasopharynx; the gut-associated lymphoid tissue (GALT), which lies just under the epithelium of the esophagus and intestines; and clusters of lymphoid tissue associated with the skin and the respiratory, urinary, and reproductive tracts.
In each case, these tissues contain immune cells positioned to intercept invading pathogens before they get into the general circulation. Because of the large surface area of the digestive tract epithelium, some authorities consider the GALT to be the largest immune organ. Anatomically, the immune system is positioned wherever pathogens are most likely to enter the body.
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_________, are the primary cells responsible for the immune responses of the body.
The white blood cells (WBCs), or leukocytes
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Leukocytes are divided into six basic types:
(1) eosinophils,
(2) basophils in the blood and the related mast cells in the tissues,
(3) neutrophils,
(4) monocytes and their derivative macrophages,
(5) lymphocytes and their derivative plasma cells, and
(6) dendritic cells. Dendritic cells are not usually found in the blood, and therefore are often excluded from discussion of leukocytes in the blood.
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granulocytes
white blood cells whose cytoplasm contains prominent granules.
basophils
mast cells
neutrophils
eosinophils
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phagocytes
white blood cells that engulf and ingest their targets by phagocytosis
Neutrophils
Eosinophils
Monocytes
Macrophages
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cytotoxic cells
they kill the cells they attack
eosinophils
Lymphocytes
Plasma Cells
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antigen-presenting cells (APCs)
display fragments of foreign proteins on their cell surface
macrophages
monocytes
dendritic cell
lymphocytes and plasma cell
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Basophils
- rare in the circulation but are easily recognized in a stained blood smear
- large, dark blue granules in cytoplasm.
- very similar to the mast cells of tissues,
- contribute to inflammation.
- granules of these cells contain histamine, heparin (an anticoagulant that inhibits blood clotting), cytokines, and other chemicals involved in allergic and immune responses.
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Mast cells
Mast cells are concentrated in the connective tissue of skin, lungs, and the gastrointestinal tract. In these locations, mast cells are ideally situated to intercept pathogens that are inhaled or ingested or that enter through breaks in the epidermis.
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Neutrophils
- phagocytic cells that typically ingest and kill 5–20 bacteria during their short programmed life span of one or two days.
- They are the most abundant white blood cells (50–70% of the total) and are most easily identified by a segmented nucleus made up of three to five lobes connected by thin strands of nuclear material.
- are formed in the bone marrow and released into the circulation.
- Most neutrophils remain in the blood but can leave the circulation if attracted to an extravascular site of damage or infection.
- release a variety of cytokines, including fever-causing pyrogens and chemical mediators of the inflammatory response.
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Basophils contain _____
histamine, heparin (an anticoagulant that inhibits blood clotting), cytokines, and other chemicals involved in allergic and immune responses.
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Eosinophils
- These immune cells are associated with allergic reactions and parasitic diseases.
- Most functioning eosinophils are found in the digestive tract, lungs, urinary and genital epithelia, and connective tissue of the skin. These locations reflect their role in defense against parasitic invaders.
- Eosinophils are known to attach to large antibody-coated parasites, and to release substances from their granules that damage or kill the parasites.
- cytotoxic cells
- participate in allergic reactions, where they contribute to inflammation and tissue damage by releasing toxic enzymes, oxidative substances, and a protein called eosinophil-derived neurotoxin.
45
Monocytes and Macrophages
- Monocytes are the precursor cells of tissue macrophages.
- larger and more effective than neutrophils
- remove larger particles, such as old red blood cells and dead neutrophils.
- play a very important role in the development of acquired immunity because they are antigen-presenting cells.
- After a macrophage ingests and digests molecular or cellular antigens, it can insert fragments of processed antigen into its membrane so that the antigen fragment becomes as part of surface protein complexes.
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Lymphocytes
- key cells that mediate the acquired immune response of the body.
- Most lymphocytes are found in lymphoid tissues, where they are especially likely to encounter invaders.
- B lymphocytes and their derivatives are responsible for antibody production and antigen presentation.
- T lymphocytes and natural killer cells (NK cells) play important roles in defense against intracellular pathogens, such as viruses.
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Dendritic Cells
- are antigen-presenting cells characterized by long, thin processes that resemble neuronal dendrites.
- Dendritic cells are found in the skin (where they are called Langerhans cells) and in various organs.
- When dendritic cells recognize and capture antigens, they migrate to secondary lymphoid tissues, such as lymph nodes, where they present the antigens to lymphocytes.
- Antigen binding activates the lymphocytes.
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Primary function of basophils
Release chemicals that mediate inflammation and allergic responses
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Primary function of neutrophils
Ingest and destroy invaders
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Primary function of Eosinophils
Destroy invaders, particularly antibody-coated parasites
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Primary function of Monocytes/Macrophages
Ingest and destroy invaders.
| Antigen presentation
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Primary function of Lymphocytes
Specific responses to invaders, including antibody production
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Primary function of dendritic cells
Recognize pathogens and activate other immune cells by antigen presentation
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True/False
Innate immunity either clears the infection or contains it until the acquired immune response is activated.
True
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lysozyme
- respiratory tract secretions contain lysozyme,
- attacks cell wall components of unencapsulated bacteria and breaks them down.
- it cannot digest the capsules of encapsulated bacteria.
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Pathogens that get past the physical barriers of skin and mucus are dealt with first by the ______
innate immune response.
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A key element of the innate immune response is ______
the ability of certain leukocytes to recognize molecules that are unique to microorganisms (pathogen-associated molecular patterns, or PAMPs) and initiate an appropriate response.
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How do Pathogen-associated molecular patterns, or PAMPs activate the non-specific immune response? What is the initial response?
bind to leukocyte pattern recognition receptors (PRRs) that activate the nonspecific immune response.
The initial response of these immune cells to invaders is to kill them or ingest them.
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Patrolling and stationary phagocytes are attracted to areas of invasion by chemical signals known as ______.
chemotaxins
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What are chemotaxins?
Chemotaxins include bacterial toxins or cell wall components that act as PAMPs.
Products of tissue injury, such as fibrin and collagen fragments, may also indicate a location that needs defending.
Once on site, activated leukocytes fighting the invaders secrete their own chemotaxic cytokines to bring additional leukocytes to the infection site.
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______ and _______ are the primary phagocytic cells responsible for defense.
Tissue macrophages
| neutrophils
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How do macrophages activated to secrete inflammatory cytokines?
In macrophages, pattern recognition receptors known as Toll-like receptors (TLRs) activate the cell to secrete inflammatory cytokines
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Phagocytes ingest ______
unencapsulated bacteria, cell fragments, carbon, and asbestos particles, among other materials.
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The ingested particle ends up in a cytoplasmic vesicle called a _______
phagosome
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Certain bacteria have evolved a polysaccharide capsule that masks their surface markers from the host immune system. These encapsulated bacteria are not as quickly recognized by phagocytes and consequently are more pathogenic because they can grow unchecked until the immune system finally recognizes them and makes antibodies against them. Once that happens, the bacteria are “tagged” with a coat of antibodies so that phagocytes recognize them as something to be ingested, The antibodies that tag encapsulated bacteria, along with additional plasma proteins, are known collectively as ________
opsonins
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natural killer cells, or NK cells— participates in _______ response against ______
the innate response against viral infections
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True/False
NK cells act more rapidly than other lymphocytes, responding within hours of a primary viral infection.
True
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Inflammation has three important roles in fighting infection in damaged tissue:
(1) attracting immune cells and chemical mediators to the site,
(2) producing a physical barrier to retard the spread of infection, and
(3) promoting tissue repair once the infection is under control (a non-immunological function).
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The inflammatory response is created when
activated tissue macrophages release cytokines
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Acute-Phase Proteins
the body responds by increasing the concentration of various plasma proteins. Some of these proteins, produced mostly by the liver, are given the general name of acute-phase proteins.
They include molecules that act as opsonins by coating pathogens; antiprotease molecules that help prevent tissue damage; and C-reactive protein (CRP).
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Histamine
Histamine is found primarily in the granules of mast cells and basophils, and it is the active molecule that helps initiate the inflammatory response when mast cells degranulate. Histamine’s actions bring more leukocytes to the injury site to kill bacteria and remove cellular debris.
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How do histamines act in the body and what do they cause?
Histamine opens pores in capillaries, allowing plasma pro- teins to escape into the interstitial space. This process causes local edema, or swelling. In addition, histamine dilates blood vessels (vasodilation), increasing blood flow to the area. The result of histamine release is a hot, red, swollen area around a wound or infection site
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Mast cell degranulation is triggered by
different cytokines in the immune response. Because mast cells are concentrated under mucous membranes that line the airways and digestive tract, the inhalation or ingestion of certain antigens can trigger histamine release. The resultant edema in the nasal passages leads to one annoying symptom of seasonal pollen allergies: the stuffy nose. Fortunately, pharmacologists have developed a variety of drugs called antihistamines, which block the action of histamine at its receptor.
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Interleukins
are cytokines initially thought to mediate communication among the body’s different types of leukocytes. Scientists have since discovered that many different tissues in the body respond to interleukins.
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Interleukin-1 (IL-1) is secreted by ___
activated macrophages and other immune cells.
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Interleukin-1 (IL-1)'s main role is to ___
mediate the in ammatory response, but it also has widespread systemic effects on immune function and metabolism.
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IL-1 modulates the immune response by
1 Altering blood vessel endothelium to ease passage of white blood cells and proteins during the in ammatory response.
2 Stimulating production of acute-phase proteins by the liver.
3 Inducing fever by acting on the hypothalamic thermostat. IL-1 is a known pyrogen.
4 Stimulating cytokine and endocrine secretion by a variety of other cells.
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Bradykinin
Kinins are a group of inactive plasma proteins that participate in a cascade similar to the coagulation cascade.
The end product of the kinin cascade is bradykinin, a molecule that has the same vasodilator effects as histamine.
Bradykinin also stimulates pain receptors, creating the tenderness associated with inflammation. Pain draws the brain’s attention to the injury.
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Complement Proteins
Complement is a collective term for a group of more than 25 plasma proteins and cell membrane proteins.
The complement proteins are secreted in inactive forms that are activated as the cascade proceeds.
Intermediates of the complement cascade act as opsonins, chemical attractants for leukocytes, and agents that cause mast cell degranulation.
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The complement cascade terminates with the formation of _______,
membrane attack complex
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membrane attack complex
a group of lipid-soluble proteins that insert themselves into the cell membranes of pathogens and virus-infected cells and form giant pores. These pores allow water and ions to enter the pathogen cells. As a result, the cells swell and lyse.
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Acquired immune responses are ______responses in which the body recognizes a particular foreign substance and selectively reacts to it.
antigen-specific
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Acquired immunity is mediated primarily by ____
lymphocytes.
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There are three main types of lymphocytes:
B lymphocytes, T lymphocytes, and natural killer (NK) cells.
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Activated ________ develop into plasma cells, which secrete antibodies.
B lymphocytes
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Activated _____ develop either into cells that attack and destroy virus-infected cells or into cells that regulate other immune cells
T lymphocytes
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True/False
All lymphocytes secrete cytokines that act on immune cells, on non-immune cells, and, sometimes, on pathogens.
True
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Acquired immunity can be subdivided into
active immunity and passive immunity.
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Active immunity occurs when ___
the body is exposed to a pathogen and produces its own antibodies.
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Active immunity can occur _______, when a pathogen invades the body, or ______, as when we are given vaccinations containing dead or disabled pathogens.
naturally
| artificially
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Passive immunity occurs when _______
we acquire antibodies made by another organism
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Lymphocytes that all bind a particular antigen are called a ______
clone
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At birth, each clone of lymphocytes is represented by only a few cells, called ______
naïve lymphocytes.
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Effector cells
carry out the immediate response and then die within a few days.
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Memory cells
are long lived and continue reproduc- ing themselves. Second and subsequent exposures to the antigen activate the memory cells and cause rapid clonal expansion, creating a quicker and stronger secondary response to the antigen.
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_________ develop in the bone marrow.
B lymphocytes (also called B cells)
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Antibodies are also called ______, and this alternative name describes what the molecules are: globular proteins that participate in the humoral immune response.
immunoglobulins
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What happens when a clone of B lymphocytes responds to antigen exposure?
When a clone of B lymphocytes responds to antigen exposure, some of the effector cells differentiate into plasma cells.
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Plasma cells do not have antibody proteins bound in their membranes. Instead, they ___________
synthesize and secrete additional antibody molecules at incredible rates
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antibodies or immunoglobulins (Ig) are divided into five general classes:
IgG, IgA, IgE, IgM, and IgD
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Antibodies are collectively referred to as _____
gamma globulins.
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IgGs
make up 75% of plasma antibody in adults because they are produced in secondary immune responses.
Some maternal IgGs cross the placental membrane and give infants immunity in the first few months of life.
Some IgGs activate complement.
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IgA
antibodies are found in external secretions, such as saliva, tears, intestinal and bronchial mucus, and breast milk, where they bind to pathogens and flag them for phagocytosis if they reach the internal environment.
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IgEs
target gut parasites and are associated with allergic responses. When mast cell receptors bind with IgEs and antigen, the mast cells degranulate and release chemical mediators, such as histamine.
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IgM
antibodies are associated with primary immune responses and with the antibodies that react to blood group antigens. IgMs strongly activate complement.
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IgD
antibody proteins appear on the surface of B lymphocytes along with IgM, but the physiological role of IgDs is unclear.
107
Antibody Proteins shape
The basic antibody molecule has four polypeptide chains linked into a Y shape. The two sides of the Y are identical, with one light chain attached to one heavy chain. The two arms, or Fab regions, form antigen- binding sites that confer the antibody’s specificity
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The stem of the Y-shaped antibody molecule is known as the _____. This region determines the Ig class to which the antibody belongs.
Fc region
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Two classes of immunoglobulins are secreted as polymers: ___ is made up of five Y-shaped antibody molecules, and ___ has from one to four antibody molecules.
IgM
| IgA
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Antibody functions
These antibodies are most effective against extracellular pathogens (such as bacteria), some parasites, antigenic macromolecules, and viruses that have not yet invaded their host cells
111
To facilitate phagocytosis, antibodies:
1- Act as opsonins
Soluble antibodies coat antigens to facilitate recognition and phagocytosis by immune cells.
2- Make antigens clump
Antibody-caused clumping of antigens enhances recognition of the antigen for phagocytosis.
3- Activates cytotoxic cell responses
4- Inactivating bacterial toxins
5- Activating complement
6- Activating mast cells
7- Activate B lymphocytes.
The surface of every B lymphocyte is covered with as many as 100,000 antibody molecules whose Fc ends are inserted into the lymphocyte membrane. This arrangement leaves the Fab regions of the membrane-bound antibodies available to bind to free-floating extracellular antigens, such as viruses or bacterial toxins, or to bits of antigen on the surface of antigen-presenting cells. Once antigen is bound, the activated B cells then di erentiate into plasma cells and se- crete more antibodies. Some B cells differentiate into memory cells to await a subsequent invasion.
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If the immune cell that binds the antibody is an eosinophil or NK cell, Fc binding:
3- Cytotoxic cells release chemicals that destroy the antibody-bound antigen
This nonspecific response of cytotoxic cells to antibody binding is called antibody-dependent cell-mediated cytotoxicity.
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Antibodies also enhance inflammation by:
4- Inactivating bacterial toxins
Antibodies bind to and inactivate some toxins produced by bacteria. One example where antibodies neutralize a bacterial toxin is infection by Corynebacterium diphtheria. C. diphtheria is the bacterium that causes diphtheria, an upper respiratory infection. In this disease, the bacterial toxin kills host cells, leaving ulcers that have a characteristic grayish membrane. Natural immunity to the disease occurs when the host produces antibodies that disable the toxin. To develop a vaccine for diphtheria, researchers created an inactivated toxin prepa- ration that did not harm living cells. When administered to a person, the vaccine triggers antibody production without causing any symptoms of the disease. As a result, diphtheria has been almost eliminated in countries with good immunization programs.
5- Activating complement
Antigen-bound antibodies use the Fc end of the antibody molecule to activate complement.
6- Activating mast cells
Mast cells have IgE antibodies attached to their surface. When antigens or complement proteins bind to IgE, the mast cells degranulate, releasing chemicals that mediate the inflammatory response.
114
T lymphocytes carry out ______
cell-mediated immunity
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In cell-mediated immunity, cytotoxic T cells bind to cells that display foreign antigen fragments as part of a major _________ on their surface.
histocompatibility complex (MHC)
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True/False
T cells can bind to any cell
False
T cell receptors can bind only to MHC-antigen complexes on the surface of an antigen-presenting cell. That means that T cells cannot bind to free-floating antigens as B cells do.
117
What is MHC?
The major histocompatibility complexes are a family of membrane protein complexes encoded by a specific set of genes. (These proteins were named when they were discovered to play a role in rejecting foreign tissue following organ or tissue transplants.)
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There are two types of MHC molecules.
```
MHC class I molecules
MHC class II molecules
```
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MHC class I molecules
Are found on all nucleated human cells.
When viruses and bacteria invade the cell, they are digested into peptide fragments and loaded onto MHC-I “platforms.” If a cytotoxic T cell (TC cell) encounters a host cell with foreign antigen fragment on its MHC-I, the TC cell recognizes the target as either a virus-infected cell or as a tumor cell and kills it to prevent it from reproducing
120
MHC class II molecules
are found primarily on the antigen-presenting cells (APCs): macrophages, B lymphocytes, and dendritic cells. When an immune cell engulfs and digests an antigen, the fragments are returned to the immune cell membrane combined with MHC-II proteins. If a helper T cell (TH cell) encounters an APC with a foreign antigen fragment on its MHC-II, the TH cell responds by secreting cytokines that enhance the immune response.
121
Cytotoxic T Cells
Cytotoxic T (TC) cells attack and destroy cells that display MHC-I-antigen complexes. Although this may seem to be an extreme response, it prevents the reproduction of intracellular invaders such as viruses, some parasites, and some bacteria when the cells infected by these pathogens are targeted for destruction.
122
How do cytotoxic T cells kill their targets?
They do so in two ways. First they can release a cytotoxic pore-forming molecule called perforin along with granzymes, enzymes related to the digestive enzymes trypsin and chymotrypsin. When granzymes enter the target cell through perforin channels, they activate an enzyme cascade that induces the cell to commit sui- cide (apoptosis). Second, cytotoxic T cells instruct target cells to undergo apoptosis by activating Fas, a “death receptor” protein on the target cell membrane that is linked to the enzyme cascade.
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Helper T (TH) cells
Helper T (TH) cells do not directly attack pathogens and infected cells, but they play an essential role in the immune response by secreting cytokines that activate other immune cells.
124
The cytokines secreted by TH cells include
(1) interferon-gamma (IFN-g), which activates macrophages;
(2) interleukins that activate antibody production and cytotoxic T lymphocytes;
(3) colony-stimulating factors, which enhance leukocyte production; and
(4) interleukins that support the actions of mast cells and eosinophils. Helper T cells also bind to B cells and promote their di erentiation into plasma cells and memory B cells. HIV, the virus that causes AIDS, preferentially infects and destroys TH cells, leaving the host unable to respond to pathogens that otherwise could be easily suppressed.
125
There is a general pattern in immune system responses to infections and antigenic challenge
–Innate responses act quickly
–Acquired responses take longer, but are stronger
–Cytokines from both innate and acquired immune events serve to coordinate the reinforce the two sets of response
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Immune responses to extracellular bacteria
1. Activity of complement system: activated by components of bacterial cell wall
2. Activity of phagocytes: if uncapsulated, macrophages can begin to ingest bacteria immediately; presence of capsule disguises bacteria from macrophage receptor
3. Role of acquired immune response (lymphocytes)
4. Initiation of repair; recruitment of platelets and proteins of coagulation cascade; once bacteria are removed , repaired by growth factors and cytokines
127
Immune responses to viruses
1. Antibodies act as opsonins; coating viral particles to make them better targets for APCs such as macrophages
2. Macrophages that ingest viruses insert fragments of viral antigen into MHC-II molecules on membrane; macrophages secrete cytokine (interferon production)
3. Helper T cells bind to viral antigen on MHC-II molecules; activated Th cells then secrete cytokines to stimulate B lymphocytes and cytotoxic T cells
4. Previous exposure to the virus can create memory B lymphocytes with viral antibody on their surface; activates more memory cells and promotes development of plasma cellsantibody production
5. Tc cells use viral antigen –MHC-I receptors with antigen, they secrete the contents of their granules onto cell surface. Perforin molecules insert pores into host cell membrane allowing granzymes to enter; cell undergoes apoptosis
128
Hypersensitivity
Any immune response against a foreign antigen exaggerated beyond the normal
129
Four types of hypersensitivity
–Type I (immediate)
–Type II (cytotoxic)
–Type III (immune complex-mediated)
–Type IV (delayed or cell-mediated)
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Type I (Immediate) Hypersensitivity
–Localized or systemic reaction that results from the release of inflammatory molecules in response to an antigen
–Develops within seconds or minutes following exposure to an antigen
–Commonly called allergies
–The antigens that stimulate it are called allergen
131
Type I (Immediate) Hypersensitivity reactions occur via a two-step process
* Sensitization upon initial exposure to an allergen
| * Degranulation of sensitized cell
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Roles of degranulating cells in an allergic reactions
•Mast cells
–Distributed throughout the body in connective tissue
–Have granules that contain inflammatory chemicals»
- Degranulation releases histamine, kinins, proteases, leukotrienes, and prostaglandin
•Basophils
–Least numerous leukocyte in the blood
–Have granules that contain inflammatory chemicals
–Degranulate like mast cells when allergens are encountered
•Eosinophils
–Eosinophilia is the accumulation of eosinophils in blood
–Mast cell degranulation can trigger the release of eosinophils from the bone marrow
–Eosinophils in the bloodstream can degranulate
»Release large amounts of leukotrienes
»Increases severity of a hypersensitivity response
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Clinical signs of localized allergic reactions
•Usually mild and localized
•Site of reaction depends on portal of entry
•Inhaled allergens may cause hay fever
•Small inhaled allergens may reach lungs and cause asthma
•Some allergens may cause inflammation of the skin called hives, or urticaria
•Many mast cells may degranulateat once
–Release large amounts of histamine and inflammatory mediators
•Acute anaphylaxisor anaphylactic shock can result
•Clinical signs are those of suffocation
•Must be treated promptly with epinephrine
•Common causes include bee stings and certain foods
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Diagnosis of type I hypersensitivity
* Based on detection of high levels of allergen-specific immunoglobulin E (IgE)
* Test referred to as ImmunoCAPSpecific IgEblood test, CAP RAST, or Pharmacia CAP
* Can also diagnose using skin tests
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Prevention of type I hypersensitivity
• Identification and avoidance of allergens
•Food allergens identified using an elimination diet
•Immunotherapy(“allergy shots”) can help prevent allergic reactions
–Administration of a series of injections of dilute allergen
–Must be repeated every two to three years
–Not effective in treating asthma
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Treatment of type I hypersensitivity
•Administer drugs that counteract inflammatory mediators
–Antihistamines neutralize histamine
•Treat asthma with a glucocorticoid and a bronchodilator
•Epinephrine neutralizes many mechanisms of anaphylaxis
–Relaxes smooth muscle
–Reduces vascular permeability
–Used in emergency treatment of severe asthma and anaphylactic shock
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Type II (Cytotoxic) Hypersensitivity
–The Rh system and hemolytic disease of the newborn
•Rh antigen–Common to red blood cells of humans and rhesus monkeys
•About 85% of humans are Rh positive (Rh+)
•If Rh-negative (Rh−) woman is carrying an Rh+ fetus, antibody immune response may be initiated against the fetal cells
•In subsequent pregnancy, the fetus may be at risk for hemolytic disease
•Administration of anti-Rh immunoglobulin, called RhoGAM, has reduced cases of hemolytic disease of the newborn
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Type III (Immune Complex–Mediated) Hypersensitivity
– Caused by formation of immune complexes
•Triggers release of inflammatory chemicals
–Can cause localized reactions•Hypersensitivity pneumonitis
•Glomerulonephritis
–Can cause systemic reactions
•Systemic lupus erythematosus (SLE)
•Rheumatoid arthritis (RA)
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Rheumatoid arthritis (RA)
•Immune complexes deposited in the joint
–Results in release of inflammatory chemicals
–The joints begin to break down and become distorted
»Damage is progressively more severe
* Trigger not well understood
* Treated with anti-inflammatory drug
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Innate immunity vs Acquired immunity
Innate
- non specific - responds to range of signals
- immediate response
Acquired/Adaptive Immunity
- specific - attacks a specific pathogen or antigen
- slower but stronger
- memory allows for fast responses upon re-exposure
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3 types of lymphoid tissue
primary
encapsulated
diffuse
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Primary lymphoid tissues are
bone marrow and thymus
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Encapsulated lymophoid tissues are
lymph nodules and spleen
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Diffuse lymphoid tissues are
lymphoid nodules
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What does the thymus gland produce?
- T lymphocytes
| - Peptides
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What are the peptides that thymus produces?
thymosin
thymopoeitin
thymulin
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What kind of tissues are lymph nodules?
loose connective tissue densely packed with lymphocytes
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Are lymph nodules surrounded by capsule
no they are not surrounded by fibrous capsule
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where are the dividing lymphocytes located in an lymph nodule?
germinal center which is located beneath lining of organs that have direct contact with the outside world
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Give examples of lymph nodules
pharyngeal tonsils
lingual tonsils
palatine tonsils
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How does viral invasion occur?
1. innovation of the host cell
2. synthesis of new viral nucleic acids and proteins
3. self-assembly of new viral macromolecules into new virus particles
4. virus particles released from the host cell
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Which cells are granulocytes
eosinophils
basophils and mast cells
neutrophils
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Which cells are agranulocytes
macrophages and monocytes
lymphocytes
dendritic cells
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What is the function of NK cells
- induce apoptosis in infected cells
- attack some tumour cells
- secrete signals called interferon
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What are the interferon released from NK cells and what are their functions?
- a and B interferon: prevent viral replication
| - gamma interferon: activates macrophages and other immune cells
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What are the beneficial roles of inflammation?
- attract immune cells and chemical mediators to sites of infection
- create physical barriers to prevent infections from spreading
- promote tissue repair
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What are the steps of inflammatory response?
- chemical signals called cytokines are released upon tissue damage or infection
- acute-phase proteins help prevent tissue damage
- cytokines stimulate histamine release from mast cells
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What are the 2 local changes that occur due to histamine release?
1. vasodilation-->leads to heat and redness
2. nearby capillaries become more permeable
a. WBC's and plasma proteins move into tissue
b. Edema results from osmotic effect of plasma
proteins
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Cytokines are released by _____ to _____
tissue macrophages
| stimulate inflammation
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How do cytokines attract other immune cells
by increasing tissue permeability and cause fever
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Steps in an Immune Response by Lymphocytes
* Antigen stimulates a specific lymphocyte clone of cells that have surface receptors for the antigen
* Clonal expansionoccurs as the cells multiple rapidly in response to antigenic stimulation
* Some new cells become one of three types of effector cells (plasma cells, helper T cells, cytotoxic T cells)
* Other cells become memory cells, which create a stronger and more rapid response to future antigen exposure (memory T helper, memory T cytotoxic, memory B cells)
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What is a clone
group of lymphocytes that are specific to one antigen
