Acquired Immunodeficiency Syndrome (AIDS) Infection
with the human immunodeficiency virus (HIV) and the subsequent development of AIDS has become a major source of morbidity and mortality in the United States and throughout the world. Two kinds of HIV virus have been identified to cause human disease: HIV-
Describe the effects of cortisol, epinephrine and norepinephrine (Kristin C)
Effects of Cortisol: Cortisol mobilizes substances needed for cellular metabolism and stimulates gluconeogenesis (the formation of glucose from noncarbohydrate sources, such as amino or free fatty acids in the liver). Cortisol also enhances the elevation
Describe the effects of cortisol, epinephrine and norepinephrine (Kristin C)
Effects of Epinephrine and Norepinephrine: Catecholamines (epinephrine and norepinephrine) at concentration levels reached during stress may decrease cellular immunity and increase autoimmune responses. There is also a good table of the physiologic effect
Describe the function of helper T cells (Kristin C)
Function of Helper T Cells: These cells do not directly attack invaders. They release a number of chemicals (interleukins and interferons) that activate other cells of immunity and inflammation. These cells are a part of our adaptive immunity.
Define neoplasia. (Cindy)
abnormal mass of tissue in which growth exceeds and is uncoordinated with that of the normal tissues. Do not obey the laws of normal cell growth, serve no useful purpose, do not occur in response to an appropriate stimulus, and continue to grow at the exp
What is the function of mechanical, physical and biochemical barriers?
Physical barriers offer protection from invaders; tightly associated epithelial cells of the skin and membranes in the gastrointestinal, genitourinary, and respiratory tracts.
What is the function of mechanical, physical and biochemical barriers?
When pathogens penetrate barriers, they may be removed by mechanical means - sloughed off with dead skin cells, expelled by coughing/sneezing, or flushed through urine. In upper respiratory tract, mucus and cilia aid in trapping invaders.
What is the function of mechanical, physical and biochemical barriers?
Biochemical barriers include mucus, sweat, saliva, tears, and earwax. Sebaceous glands secrete acids that kill bacteria/fungi. Normal bacterial flora contributes to innate protection as well.
What are the clinical symptoms of inflammation?
Redness, Heat, Swelling, Pain, Loss of Function
3 steps of inflammation
1. Vasodilation causes slower blood velocity and increases blood flow to area. 2. Increased vascular permeability and leakage of fluid out of vessel leads to edema and swelling. This increases blood flow and increases red blood cells at the site of injury
What are the three plasma protein systems involved in inflammation?
Complement system, Clotting (coagulation) system & the Kinin system -
Complement system
- can be activated by antigen-antibody reactions (through the classical pathway), or by other products, especially bacterial polysaccharides (through the lectin pathway or the alternative pathway), resulting in the production of biologically active fragme
Clotting (coagulation) system
- A group of plasma proteins that, when activated sequentially, form a fibrinous meshwork at an injured or inflamed site. Stops bleeding, localizes microorganisms, keeps invaders at the site of greatest inflammatory cell activity, and provides a meshwork
Kinin system -
Interacts closely with the coagulation system. Final product is the small-molecular weight molecule bradykinin, which is produced from a larger precursor molecule, kininogen. At low doses it causes dilation of blood vessels, acts with prostaglandins to in
What is the function of Granulocytes in inflammation:
- The primary circulating WBCs, which contain enzymes capable of killing microorganisms and catabolizing debris ingested during phagocytosis. These include neutrophils, eosinophils, and basophils.
What is the function of Neutrophils in inflammation:
- are the predominant phagocytes of the early inflammatory response, arriving 6 to 12 hours after the initial injury. Neutrophils are mature cells, and therefore cannot divide and are sensitive to acidic environments, so they are short-lived and turn into
What is the function of Eosinophils in inflammation:
- serve as the body's primary defense against parasites and help regulate vascular mediators released from mast cells. They help limit inflammation, and help control histamine.
What is the function of Platelets in inflammation:
- Cellular fragments formed from megakaryocytes that circulates in the blood and is important in anticoagulation, stimulation of inflammation and tissue growth, and destroying bacteria. They interact with coagulation cascade to stop bleeding and release b
What is the function of Lymphocytes in inflammation:
- A nonphagocytic leukocyte of the adaptive immune response that is immunologically competent and serves as the precursor for B and T lymphocytes.
What is the function of Natural killer cells in inflammation:
- NK cells are lymphocytes capable of killing target cells by binding specific receptors with or without the aid of antibodies and by releasing chemicals toxic to the targeted cells.
What is the function of Monocytes in inflammation:
- A phagocyte produced in bone marrow that migrates into tissues and is transformed into a macrophage. Macrophages are important in cellular initiation of the inflammatory response. They are the predominant phagocytic cell in the late inflammatory respons
What is the role of cytokines in inflammation?
Cytokines are produced by cells of the acquired immune system that mediate interactions between cells to kill bacteria; active during inflammatory response. Cytokines activate macrophages to further kill infectious microorganisms. They can be anti-inflamm
Interferons are...
a family of cytokines that protect against viral infections.
tumor necrosis factor-alpha
One of the most important cytokines. Which induces fever, causes increased synthesis of inflammation-related serum proteins by the liver, and causes muscle wasting (cachexia) and intravascular thrombosis in cases of severe infection and cancer.
Describe the steps of tissue healing. Step 1
1. Resolution (regeneration) is the return of tissue to nearly normal structure and function. Repair is healing by scar tissue formation. Both begin with the phagocytic "cleaning up" called debridement of the site of injury by removal of fibrin clots afte
Describe the steps of tissue healing. Step 2
2. Damaged tissue proceeds to resolution (restoration of the original tissue structure and function) if little tissue has been lost or injured tissue is capable of regeneration. This is called healing by primary intention.
Describe the steps of tissue healing. Step 3
3. Tissues that sustained extensive damage or those incapable of regeneration heal by the process of repair resulting in the formation of a scar. This is called healing by secondary intention.
Describe the steps of tissue healing. Step 4
4. Resolution and repair occur in two separate phases, the reconstructive phase in which the wound begins to heal and the maturation phase in which the healed wound is remodeled. The most important cells during healing are fibroblasts because they secrete
Describe the steps of tissue healing. Step 5
5. Dysfunctional would healing can occur as a result of abnormalities in either the inflammatory response or the reconstructive phages of resolution and repair. There can be insufficient repair, excessive repair, or infection.
What are the differences between natural and acquired immunity?
Natural immunity is innate resistance, and acquired immunity is gained after birth.
What are the two types of acquired immunity?
Active & Passive immunity
Active acquired immunity is produced by...
an individual after either natural exposure to an antigen or after immunization.
Passive acquired immunity does not involve...
the host's immune response at all. It occurs when preformed antibodies or T cells are transferred from a donor to the recipient. This can occur naturally, as during pregnancy or artificially, as when antibodies are injected to fight against a specific dis
Describe humoral immunity.
Humoral immunity: Antibody circulates in the blood and binds to antigens on infectious agents. This interaction can result in direct inactivation of the microorganism or activation of a variety of inflammatory mediators that will destroy the pathogen. Ant
Describe cell mediated immunity.
Cell-mediated immunity: T cells undergo differentiation during an immune response and develop into several subpopulations of effector T cells that react directly with antigen on the surface of cells or infectious agents. Some develop into T cells that can
antigen-presentation:
in order to produce a protective humoral or cellular iimmune response, the first step is antigen presentation. During this step, phagocytes (particularly macrophages) break up/process, and present antigenic fragments on the cell surface. APCs (Antigen-pre
what are the 2 types of antigens the immune system responds to?
In general, the immune system responds to 2 types of antigens: exogenous (originate from the outside of the body i.e. infectious microorganisms) and endogenous (synthesized within the body/within a cell ie. viruses). Classifications are MHC molecules. MHC
antigen processing:
refers to the process by which exogenous and endogenous antigens are broken up and linked with the appropriate MHC molecule (Class I or II)
antigen-binding:
At the tip of each arm of the Y-shaped molecule is an area called the antigen-binding, or antibody-combining, site, which is formed by a portion of the heavy and light chains. Every immunoglobulin molecule has at least two of these sites, which are identi
What are the types and roles of T lymphocytes?
3 types: Helper T cells, (Th), Killer T cells a (Tc) and Supressor T cells
3 types: Helper T cells
are required to support both humoral and cell-mediated immunity, humoral - refers to B cell activation by an antigen and formation of plasma cells to secrete specific antibiodies (Th2), cell-mediated - process in which T cytotoxic cells removed invading a
3 types: Killer T cells a (Tc)
responsible for cell-mediated destruction of tumor cells or cells with infected viruses. the CTLs must directly adhere to the target cell through antigen presented by MHC class I molecules and appropriate CD molecules
3 types: Supressor T cells
regulate the immune response.
What are the differences in primary and secondary immune response? (Sarah S)
- Primary Immune Response- The initial administration of antigen induces this response. This response is characterized by intial IgM followed by IgG against the same antigen. It usually dominated by IgM, with lesser amounts of IgG. If no further exposure
What are the differences in primary and secondary immune response? (Sarah S)
- Secondary Immune Response- Results from a second challenge by the same antigen. Has a more rapid production of a larger amount of antibody, predominately IgG. It is faster than the primary because of memory cells that do not require further differentiat
How does the immune system develop and at what point are is immune development complete. (Sarah S)
- In exposure to an infectious agent, antibodies are produced from B and T cells. The T lymphocytes attack the antigen directly. The cells develop into memory cells that "remember" the antigen and respond even faster when that antigen enters the body agai
Define allergy
Allergy: Hypersensitivity and immunologic protective reaction caused by exposure to environmental antigens. These can include medicines, natural products (e.g., pollens, bee stings), infectious agents, and any other antigen that is not naturally found in
Define autoimmunity
Autoimmunity: A condition in which the immune system considers an individual's own body tissues to be foreign antigens and initiates an immune response against the tissues; a disturbance in the immunologic tolerance of self-antigens.
Define alloimmunity.(Kaylee)
Alloimmunity: A condition in which the immune system of one individual produces an immunologic reaction against tissues of another individual. Alloimmunity can be observed during immunologic reactions against transfusions, transplanted tissue, or the fetu
What are the four types of hypersensitivity reactions? (Kaylee)
Type I: IgE -mediated Hypersensitivity Reactions, Type II: Tissue-specific Hypersensitivity Reactions, Type III: Immune Complex-mediated Hypersensitivity Reactions, Type IV: Cell-Mediated Hypersensitivity Reactions
Type I: IgE -mediated Hypersensitivity Reactions
� Is known as allergy or most allergic reactions.
Type I reactions are mediated by
� antigen-specific IgE and the products of tissue mast cells. Fc receptors on mast cells specifically bind IgE that has not previously interacted with antigen. After a large amount of IgE has bound to the mast cells, an individual is considered sensitized
Mechanisms of IgE-mediated Hypersensitivity:
o The most potent mediator of IgE-mediated hypersensitivity is histamine, which affects several key target cells. Acting through H1 receptors, histamine contracts bronchial smooth muscles (bronchial constriction), increases vascular permeability (edema),
Clinical Manifestations of a Type I reaction
o Are attributable mostly to the biologic effects of histamine. The tissues most commonly affected by type I responses contain large numbers of mast cells and are sensitive to the effects of histamine released from them. These tissues are found in the GI
GI allergy is caused primarily by
o antigens that enter through the mouth, usually foods of medicines. Symptoms include: vomiting, diarrhea, or abdominal pain. Foods most often implicated in GI allergies are milk, chocolate, fish, citrus fruits, eggs, wheat, nuts, and peanut butter.
Effects of allergens on the mucosa of the eyes, nose, and respiratory tract include
o conjunctivitis (inflammation of membranes lining the eyelids), rhinitis (inflammation of the mucous membranes of the nose), and asthma (constriction of the bronchi). Symptoms are caused by vasodilation, hypersecretion of mucus, edema, and swelling of th
Urticaria, or hives, is a skin manifestation of
o allergic reactions. Urticaria is characterized by white fluid-filled blisters (wheals) surrounded by areas of redness (flares). This wheal and flare reaction is usually accompanied by itching.
The central problem in allergic diseases of the lung is
o obstruction of the large and small airways of the lower respiratory tract by bronchospasm (constriction of smooth muscle in airway walls), edema, and thick secretions. This leads to ventilator insufficiency, wheezing, and difficult or labored breathing.
Type II: Tissue-specific Hypersensitivity Reactions
� Type II hypersensitivities are generally reactions against a specific cell or tissue. Cells express a variety of antigens on their surfaces, some of which are called tissue-specific antigens because they are expressed on the plasma membranes of only cer
� There are five general mechanisms by which type II hypersensitivity reactions can affect the cells:
o 1) The cell may be destroyed by antibody IgM or IgG and complement. o 2) The antibody may cause cell destruction through phagocytosis by macrophages. o 3) Toxic products produced by neutrophils activated by the complement damage the tissues. o 4) Antibo
Type III: Immune Complex-mediated Hypersensitivity Reactions
� Most Type III hypersensitivity diseases are caused by antigen-antibody (immune) complexes that are formed in the circulation and deposited later in vessel walls or other tissues. The primary difference between Type II and Type III mechanisms is that in
Type III reactions are not
� organ specific, and symptoms have little to do with the particular antigenic target of the antibody. The harmful effects of immune complex deposition are caused by complement activation, particularly through the generation of chemotactic factors for neu
Clinical manifestations include:
� Serum-sickness, Raynaud phenomenon, and Anthus reaction.
Type IV: Cell-Mediated Hypersensitivity Reactions
� Whereas types I, II, and III hypersensitivity reactions are mediated by antibody, type IV reactions are mediated by T lymphocytes and do not involve antibody.
Type IV mechanisms occur through either
� cytotoxic T lymphocytes (Tc cells) or cytokine-producing Th1 cells. Tc cells attack and destroy cellular targets directly. Th1 cells produce cytokines that recruit and activate phagocytic cells, especially macrophages. Destruction of the tissue is usual
� Clinical examples of Type IV Hypersensitivity Reactions
o Graft rejection, the skin test for tuberculosis, allergic reactions resulting from contact with poison ivy or metals, T cells against type II collagen contribute to the destruction of joints in rheumatoid arthritis, T cells against a thyroid cell surfac
What is the difference between immediate and delayed hypersensitivities? (Reed)
- Immediate hypersensitivities are reactions that occur within minutes to a few hours after exposure to an antigen. Anaphylaxis is the most rapid and severe immediate hypersensitivity reaction. It can either be systemic or localized. Symptoms include itch
a) example of systemic reaction:
reaction to bee sting
b) example of cutaneous(localized)
: pain, swelling, redness which occur at the site of exposure (i.e. an injection from a vaccine)
-Delayed hypersensitivities (onset)
may take several hours to appear and are at maximum severity days after reexposure to the antigen
What are the factors influencing infection by a pathogen? (Reed) -Mechanism of Action:
direct damage of cells, interference with metabolism, and causing dysfunction b/c of the accumulation of pathogenic substances and toxin production.
What are the factors influencing infection by a pathogen? (Reed) Infectivity
-: ability of pathogen to invade and multiply in the individual
What are the factors influencing infection by a pathogen? (Reed) Pathogenicity
-: ability of an agent to produce disease
What are the factors influencing infection by a pathogen? (Reed) Virulence
-: potency of a pathogen measured in terms of the number of microorganisms required to kill a host
What are the factors influencing infection by a pathogen? (Reed) Immunogenicity
-: ability of pathogens to induce an immune response
What are the factors influencing infection by a pathogen? (Reed) Toxigenicity
-: a factor important in determining a pathogen's virulence
Compare bacterial, viral, and fungal infections. (Janay)
Bacteria have developed many sophisticated mechanisms to avoid host defenses. Two of the most important are capsules and toxins
Capsules
: Encapsulated bacteria can avoid phagocytosis by neutrophils and macrophages because their capsules make it difficult for the phagocytes to adhere to and engulf the organisms. Effective phagocytosis must await opsonization of the organism by complement a
Toxins
: The two major categories are exotoxins and endotoxins. Exotoxins are proteins from gram-positive bacteria that are released during cell growth. They are frequently cytotoxic. Endotoxins are lipopolysaccharides (lipid A and lipid O) that are released fro
Septicemia
-the proliferation of bacteria in the blood.
Viruses enter host cells and cells and use the metabolic processes of host cells to
proliferate. Their replication is totally dependent on their ability to infect a permissive host cell. The replication cycle has six phases: absorption, penetration, uncoating, replication, assembly and release. The first step requires binding of the viru
Viral diseases are the most common
afflictions of humans and include a veriety of diseases ranging from the common cold to AIDS.
Cellular effects of viruses:
The cessation of DNA, RNA, and protein synthesis, Disruption of lysosomal membranes, resulting in release of "digestive" lysosomal enzymes that can kill the cell, Fusion of host cells, producing multinucleated giant cells, Alteration of the antigenic prop
Fungi have thick...
polysaccharide walls that make them relatively impervious to most antibiotics. These organisms can live anywhere in the body, although they are found most commonly on the skin. Fungi can adapt to the host environment and frequently colonize the skin. They
Fungi are capable of...
causing serious systemic infection, especially in immunocompromised individuals who have decreased phagocytic and T lymphocyte function (opportunistic infection).
Candida albicans can involv
e the mouth throat, esophagus, intestines, and bloodstream (fungemia).
Cryptococcus neoformans
. Causes serious opportunistic infection of the lung and CNS
Fungi are usually diagnosed by
staining with india ink or potassium hydroxide and by culture. Treatment for mild skin infections is usually with a topical fungicide. Serious infection requires highly toxic antifungal medications, such as amphotericin
Primary (Congenital) Immunodeficiencies
Most are a result of a single gene defect. Usually the mutation is sporadic and not inherited. Mutations occur before birth, but onset of symptoms may be early or later, depending on syndrome. The three most common are variable immune deficiency, selectiv
B lymphocyte deficiencies
Selective IgA deficiency is characterized by a lack of IgA production and results from an inability of plasma cells to class-switch to IgA. Because the secretory immune system is compromised, infections of the GI tract are most common, along with lung and
Bruton agammaglobulinemia
results from defects in the bursal-equivalent tissue necessary for B-cell development. Children with this disorder have absent or very low levels of all of the immunoglobulin types and are highly prone to all types of infection, especially those by encaps
T lymphocyte deficiencies
T lymphocyte deficiencies can affect both the humoral and the cellular immunity because they frequently result in a decrease in the important interleukins necessary for full adaptive immune responses.
DiGeorge syndrome
results from congenital absence of thymus gland or hypoplasia and diminished parathyroid gland development. T-cell number and function are severely compromised, resulting in numerous fungal infections (especially of the GI tract) and bacterial and viral p
Combined deficiencies
Severe combined immunodeficiency disease (SCID) is caused by a failure of stem cell development into mature lymphocytes. Most children with SCID have few or no T and B lymphocytes, but they do have normal numbers of neutrophils and macrophages. SCID can a
Bare lymphocyte syndrome
is characterized by a lack of ability by macrophages and lymphocytes to express MHC class I or II antigens. This particularly severe form of SCID results in disrupted intercellular communication and the inability of the immune system to effectively presen
Wiskott-Aldrich syndrome
is an X-linked recessive disorder characterized by decreased IgM antibody production. This markedly inhibits the ability of an affected individual to defend against encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae, as well
Complement deficiencie
s Deficiencies in complement most commonly result in infections by encapsulated organisms because of a lack of adequate opsonization of these organisms and therefore inadequate phagocytosis and removal of the organisms from the body. Any part of the compl
Phagocytic deficiencies
are often associated with inadequate opsonization of encapsulated bacteria as described on the previous screen. Phagocytosis can also be impaired by inadequate numbers of phagocytes, especially neutrophils. Most neutrophil deficiencies are acquired, but t
Secondary (Acquired) Immune Deficiencies
These are much more common than primary deficiencies. They are not related to genetic defects but are complications of other physiologic or pathophysiologic conditions. Conditions known to be associated with these deficiencies are listed on pg. 198