Chapter 22 Immune system

Diseases caused by viruses

Common cold, influenza, polio, mumps, measles, hepatitis, rubella, chickenpox, herpes, and HIV

Exposed Fc portion following antigen binding by antibody promotes

Complement fixation-Fc region of antibody binds complement proteins; complement is activated Opsonization-Fc region of antibody binds to receptors of phagocytic cells, triggering phagocytosis Activation of NK cells-Fc region of antibody binds to a NK cell, triggering release of cytotoxic chemicals

Elimination of immune complexes

Complement links immune(antigen-antibody) complexes to erythrocytes so they may be transported to the liver and spleen. RBCs are stripped of these complexes by macrophages in these organs and the rbcs continue circulating in the blood.

Tumor necrosis factor (TNF)

Cytokine that destroys tumor cells and may have other functions as well. comes from T-lymphocytes, macrophages, mast cells

Cytotoxic T Cells

(Killer, Tc, T8) display CD8 protein, recognize antigen fragments associated with MHC I molecules.

Helper T Cell

(T4, CD4) Display CD4 protein, recognize foreign fragments associated with MHC II molecules, secrete several cytokines, especially interleukin-2 that is a costimulator of helper T-cells, cytotoxic T cells, and B cells

Formation and Docking of MHC I molecules in a healthy cell

1. MHC class I molecules are synthesized by the RER, during production peptide fragments of the cell(self-antigens) bind with the MHC I molecules. 2.Transport vesicles are produced from the RER that contain MHC I molecules with bound self-antigen, they are shipped by the endomembrane system through the golgi apparatus to the plasma membrane 3.MHC I molecules with bound self antigen are displayed within the plasma membrane following fusion of the secretory vesicles with the plasma membrane.

4 steps of inflammation

1. Release of inflammatory and chemotactic factors 2. Vascular changes including vasodilation, increased capillary permeability, and display of CAMs 3. Recruitment of immune cells by Margination, Diapedeis, and Chemotaxis 4. Delivery of plasma proteins

3 major phases of an allergic reaction

1. Sensitization Phase-initial exposure to allergen, IgE antibodies bind to Fc receptors on basophils and mast cells 2. Activation Phase-reexposure to same allergen, allergen binds to the IgE antibodies 3.Effector Phase-exocytosis of contents of granules(histamine and heparin) release and formation of molecules from plasma membrane (eicosanoids) Increased inflammatory response can lead to allergic rhinitis, hives, allergic asthma, and anaphylactic shock

Formation and docking of MHC II molecules in an APC

1.MHC II molecules are synthesized by the RER of the APC. 2. MHC II are shipped by the endomembrane system through the golgi apparatus to the plasma membrane. 3.during the process of phagocytosis and destruction of an exogenous antigen, vesicles containing digested peptide fragments merge with vesicle containing MHC II, the foreign antigen binds with MHC II within the vesicle 4.MHC II molecules and foreign antigen are displayed within the plasma membrane

Helper T-lymphocyte activation for clonal selection

1st stimulation: CD4 binds with MHC class II molecule of APC; TCR interacts with antigen within MHC II molecule 2nd stimulation: Helper T-lymphocyte releases IL-2, which stimulates the helper T-lymphocyte activated helper t cell proliferates and differentitates to form a clone of activated and memory helper t cells

Cytotoxic T-lymphocyte activation for clonal selection

1st stimulation: CD8 binds with MHC I molecule of infected cell;TCR interacts with antigen within MHC I molecule. 2nd stimulation:IL-2 released from activated helper t cell stimulates the cytotoxic t-lymphocyte activated cytotoxic t cell proliferates and differentiates to form a clone of activated and memory cytotoxic t cells

B-lymphocyte activation for clonal selection

1st stimulation:Free antigen binds to BCR, B_lymphocyte engulfs and presents antigen to activated helper T-lymphocyte 2nd stimulation:IL-4 released from activated helper T-lymphocyte stimulates B-lymphocyte activated b cell proliferates and differentiates to form a clone of plasma cells and memory B-lymphocytes. plasma cells produce antibodies

2 of the major means of complement activation

Activation occurs following entry of a pathogen into the body. classical pathway-complement protein binds to an antibody that has previously attached to a foreign substance. alternative pathway-surface polysaccharides of certain bacterial and fungal cell walls bind directly with a complement protein. antibody is required only in classical pathway

Lysosyme

Antibacterial enzyme, attacks the cell wall of some bacterial (gram positive bacteria)

Cilia

Extensions of plasma membranes, sweep mucus upward so that it can be expectorated or swallowed

IgD

B-lymphocyte receptor, BCR. half life is 2.8 days. it identifies when immature B-lymphocytes may be ready for activation.

IgA

found in external secretions(skin, mucuc, saliva, tears, breastmilk, and colostrum). actions are neutralization, agglutination(great potential). half life is 5.5 days. it is associated with mucosal membranes and helps protect against local respiratory GI infections

Effector response of Helper T cells

helper t cells activate cytotoxic t cells through the release of cytokines and they also enhance formation and activity of cells of the innate immune system, including macrophages and NK cells.

Effector response of cytotoxic T-lymphocytes

if the cytotoxic t cell recognizes the foreign antigen presented by the infected cell(with MHC class I molecules), it destroys the cell by releasing granules containing the cytotoxic chemicals perforin and granzymes which induce apoptosis of abnormal cells.

Normal Flora

in skin and mucous membranes. Commensal flora, including nonpathogenic bacteria, helps prevent growth of pathogenic microbes.

Naturally acquired active immunity

infection; contact with pathogen

Benefits of Fever

inhibits reproduction of bacteria and viruses, promotes interferon activity, increases activity of adaptive immunity, and accelerates tissue repair. it has also been shown that a fever increases CAMss on the endothelium of capillaries in the lymph nodes, resulting in additional immune cells migrating out of the blood and into the lymphatic tissue.

Artificially acquired passive immunity

injection of immune serum (gamma globulin)

Clotting proteins

lead to formation of a clot that walls off microbes and prevents them from spreading into blood and other tissues. However, some bacterial species can dissolve clots

Epithelial and CT

lining of respiratory, gastrointestinal, and urogential tracts. provides a chemical, physical, and biological barrier of body structures exposed to the external environment

Variable region of antibody

located at the ends of the arms, contain the antigen-binding site, which attach to a specific antigenic determinant of an antigen.

Bacteria

microscopic, single-celled organisms 1 to 2 micrometers in size that are enclosed by a cell wall. they are prokaryotic cells. Intracellular and extracellular parasites, some produce enzymes and toxins.

Chemotaxis

migration of cells along a chemical gradient. chemicals released from damaged or dead cells diffuse outward and create a chemical gradient that attracts immune cells. recruited cells also participate in inflammatory response by releasing specific cytokines, GM-CSF-stimulate leukopoeisis. macrophages may also release pyrogens, such as interleukin-1, that induce a fever.

Acute Hypersensitivity

more commonly referred to as an allergy, it is an overreaction of the immune system to a non-infectious substance, or allergen.

Effects of Inflammation

net movement of fluid from the blood through the injured or infected area to the lymph. Increased fluid, protein, and immune cells leave the capillaries and then enter the interstitial space of the tissue, this material is known as exudate-which delivers cells and substances needed to eliminate the injurious agent and promote healing. inflammatory response typically slows down and tissue healing begins within 72 hours.

Cells of innate immunity

neutrophils and macrophages, basophils and mast cells, NK cells, and eosinophils

Neutrophils and Macrophages

neutrophils are the most prevalent leukocyte in the blood and the first to arrive during inflammatory response. Macrophages are cells that reside in tissues throughout the body, they arrive later after the inflammatory response begins and stay longer than neutrophils. neutrophils and macrophages function to engulf unwanted substances such as infectious agents and cellular debris through phagocytosis. a lysosome forms with a phagosome to create a phagolysosome which destroys the infectious agent and the residue is then exocytosed.

Multicellular Parasites

nonmicroscopic organisms that reside within a host from which they take nourishment. Eukaryotic

IgM

normally a pentamer found mostly in blood. actions are neutralization, agglutination(great potential), complement binding (great potential). Half-life is 5 days. first produced antibody, only antibody produced in fetus; component of breastmilk

Defervescence

occurs when the temperature returns to to its normal set point. this happens when the hypothalamus is no longer stimulated by pyrogens, prostaglandin release decreases, and the temperature set point reverts to its normal value. the hypothalamus stimulates the mechanisms to release heat from the body, including vasodilation of blood vessels in the skin and sweating.

Complement System

one of the most important antimicrobial groups of substances of innate immunity, composed of atleast 30 plasma proteins that make up approx. 10% of serum in blood. These proteins are collectively referred to as complement. the liver continuously synthesizes and releases inactive complement proteins into the blood, once in the blood they are activated by an enzyme cascade.

Formation of T-lymphocytes

originate in RBM, migrate to the thymus galnd and mature, in the thymus they also learn to recognize self-antigens

IgG

primary locations are body fluids including blood, lymph, CSF, serous fluid and peritoneal fluid. Actions include neutralization, agglutination, precipitation, complement activation, opsonization, natural killer cell activation. Half-life is 23 days. It is used for passive immunity, it crosses the placenta and its a component of breast milk.

Margination

process by which CAM's on leukocytes adhere to CAM's on the endothelial cells of the capillaries within the injured tissue. The result is similar to cellular "velcro". Neutrophils are generally first to arrive amd are short-lived, followed later by the longer-lived macrophages.

Diapedesis

process by which cells exit the blood by squeezing out between vessel wall cells, usually in the postcapillary venules, and then migrate to the site of infection

Epidermis:dermis

provides a physical, chemical, and biological barrier for body surface

Defecation and vomiting

removal of waste from digestive tract, eliminate microbes before they can be absorbed into the blood.

Mucus

secretion containing lysozyme, defensins, and IgA, thick secretion that helps trap microbes; contains antimicrobial substances

Saliva

secretions released into the mouth from salivary glands, contain lysozyme and IgA. helps wash away microbes, contains antimicrobial substances.

Sebaceous(oil) gland secretions

secretions that contain lactic acid and fatty acids, creates a low pH (3-5) that interferes with the growth of microbes.

Nasal secretions

secretions that contain lysozyme, defensins, and IgA, contains antimicrobial substances

Sweat gland secretions

secretions that contain lysozyme, defensins, and dermicidin, helps wash away microbes: contains antibacterial and antifungal substances

Interferons (IFN)

serves as a non-specific defense mechanism against the spread of any viral infection. A virus-infected cell helps prevent further spread of the virus by releasing IFN. after its release, IFN has 2 primary actions; IFN binds to receptors of neighboring cells, preventing them from becoming infected and triggers synthesis of enzymes that destroy viral RNA or DNA, which inhibits synthesis of viral protein. IFN stimulates NK cells to destroy virus-infected cells.

Prions

small fragments of infectious proteins that cause disease in nervous tiussue. ex; Variant Creutzfeldt-Jakob disease (bovine spongiform encephalopathy, mad cow disease)

Dermicidin

small proteins produced by the skin, antibacterial agent against both gram positive and gram negative bacteria;antifungal agent

Defensins

small proteins, create pores in the plasma membrane of microbes, compromising their integrity

Cytokines

small, soluble proteins produced by cells of both the innate and adaptive immune system to regulate and facilitate immune system activity. serve as a means of communication between the cells, control the development and behavior of efector cells of immunity, regulate the inflammatory response of the innate immunity, and in some cases, serve as weapons to destroy cells. have a short half-life

Immunoglobulin A (IgA)

specific type of antibody present in areas exposed to the environment, binds with a specific foreign substance (antigen)

Colony-stimulating factor (CSF)

stimulates leukopoiesis in bone marrow to increase synthesis of a specific type (colony) of leukocytes. comes from T-lymphocytes and monocytes. ex: G-CSF (granulocyte CSF) GM-CSF (granulocyte-macrophage CSF)

Hydrochloric acid (HCl)

strong acid produced within stomach, creates very low pH that destroys many bacteria, bacterial toxins, and other microbes that enter the stomach

Antigen

substance that binds to a component of adaptive immunity(antibody or T-lymphocyte) complete antigens possess 2 important properties: immunogenicity and reactivity

Positive selection of T-lympocytes

survival dependent upon ability to bind to MHC molecule. tested by seeing if their TCR can bind with MHC molecules on the surface of thymus epithelial cells, if not they are eliminated

Negative selection of T-lymphocytes

survival dependent upon not recognizing self-antigen. tested by thymic dendritic cells, presenting both class I and II molecules-those that bind are destroyed. only 2% of cells survive selection process in the thymus.

Eosinophils

target parasites. mechanism of destruction include degranulation and release of enzymes and other substances that are lethal to the parasite. they can also release proteins that form a transmembrane pore. also participate in the immune response associated with allergy and asthma, and engage in phagocytosis of antigen-antibody complexes.

Vibrissiae

Hairs in nasal cavity, traps microbes in the nose

Urine

urine formed in kidneys is transported out of body through urinary tract, flow of urine flushes microbes

5 major classes of immunoglobulins

IgG, IgM, IgA, IgD, IgE

All nucleated cells have these

MHC I

Protozoan Infections

Malaria, toxoplasmosis, giardiasis, amoebiasis, leishmaniasis, tichomoniasis, and african sleeping sickness

Hyaluronic acid

Mucopolysaccharide with a gel-like consistency that is located in areolar tissue of the dermis, slows migration of microbes that have penetrated the epidermis.

Binding of antigen-binding site (Fab region) of an antibody with antigen causes

Neutralization-antibody covers biologically active portion of microbe or toxin. Agglutination-Antibody cross-links cells(ex;bacteria), forming a clump Precipitation-antibody cross-links circulating particles(ex;toxins), forming an insoluble antigen-antibody complex

Viruses

Not a cell. DNA or RNA within a capsid protein. Obligate intracellular parasites; must enter cell to replicate

Defense mechanisms mediated by the complement system

Opsonization, Inflammation, Cytolysis, and Elimination of immune complexes

Multicellular parasites infections

Parasitic infection from tapeworms, lung flukes, liver flukes, blood flukes, hookworms, Trichinella, Ascaris, whipworms, and pinworms

Onset

the hypothalamus stimulates blood vessels in the dermis of the skin to vasoconstrict to decrease heat loss through the skin, and a person shivers to increase heat production through muscle contraction.

Formation and docking of MHC molecules in an unhealthy cell

Proteins of viral particles are digested by proteasomes into peptide fragments; peptide fragments are taken up into the RER. 1.as MHC I molecules are synthesized by the RER, peptide fragments of the viral particle become attached to MHC I. 2. transport vesicles are produced from the RER that contain MHC class I molecules with viral peptide fragments, they are shipped by the endomembrane system through the golgi apparatus to the plasma membrane 3. MHC I with bound foreign antigen are displayed within the plasma membrane following fusion of the secretory vesicles with the plasma membrane.

Events of Fever

Pyrogens are released and circulate in the blood, they target the hypothalamus and cause release of prostaglandin E2 which raises the temperature set point of the hypothalamus from its normal 37C. the following stages occur in response: onset, stadium, and defervescence.

Cardinal signs of Inflammation

Redness, Heat, Swelling, Pain, and Loss of function. inflammatory response typically lasts no longer than 8 to 10 days. if it last longer than 2 weeks-chronic inflammation

Stadium

the period of time where the elevated temperature is maintained, the metabolic rate increases to promote physiologic processes involved in eliminating the harmful substance, the liver and spleen bind zinc and iron to slow microbial reproduction.

Artificially acquired active immunity

vaccine; dead or attenuated pathogens

First line of defense includes

Skin, Mucous membranes, Respiratory tract, Gastrointestinal tract, urogenital tract, and secretions produced by skin, mucous membranes, and other

Exfoliation

Sloughing off of epidermal cells, removes potential pathogens from skin surface.

Diseases caused by bacteria

Streptococcal infections, staphylococcal infections, tuberculosis, syphilis, diphtheria, tetanus, lyme disease, salmonella, and anthrax

Interferon (IFN)

Two classes: IFN-alpha and IFN-beta are antiviral agents, and IFN-gamma is a pro-inflammatory agent. come from leukocytes and fibroblasts

Cytolysis

Various complement components (C5-C9_ trigger direct killing of a target by forming a protein channel in the plasma membrane of a target cell called a membrane attack complex(MAC). The mac protein channel allows an influx of fluid that causes lysis of the cell

Risks of a high fever

a fever is significant when it is above 100F. High fevers (103 in children and slightly lower in an adult) are dangerous becasue of the changes in metabolic pathways and denaturation of body proteins. Seizures may occur at sustained body temps above 102F. irreversible brain damage may occur at body temps sustained at greater than 106F, and death is likely to occur when body temp. reaches 109F.

Adaptive immunity

also known as acquired immunity, Delayed response to specific antigens to which we are exposed during our lifetime. T-lymphocytes, cell-mediated immunity. B-lymphocytes-humoral immunity, which also includes Plasma cells that synthesize and release antibodies.

Fungal Diseases

also known as mycoses, in healthy individuals in the U.S. are usually limited to superficial infections of the skin, scalp, and nails such as ringworm, diaper rash, jock itch, athletes foot. infections of mucosal linings-vaginal yeast infections or internal fungal infections-histoplasmosis, which affects respiratory system.

Innate immunity

also known as non-specific immunity, we are born with theses defenses. Immediate response to a wide array of substances. Skin and mucosal membranes-prevent entry. Nonspecific internal defenses include the following: cells such as macrophages, NK cells. Chemicals such as interferon and complement. Physiologic responses such as inflammation and fever.

Fever

an abnormal elevation of body temperature (pyrexia) of atleast 1C from the typically accepted body temp. of 37C. It results from the release of pyrogens such as IL-1, TNF-alpha, and IL-6, toxins produced by infectious agents, or in response to trauma, drug reactions, and brain tumors

immunogen

an antigen that induces an immune response and its ability to cause an immune response is termed its immunogenicity.

Inflammation

an immediate, local, nonspecific event that occurs in vascularized tissue against a great variety of injury-causing stimuli.

Antibody

an immunoglobulin protein produced against a particular antigen. antibodies do not destroy pathogens directly but facilitate the destruction by other immune cells.

Naturally acquired passive immunity

antibodies pass from mother to fetus via placenta, or to infant in her milk

APC

any immune cell that functions specifically to communicate the presence of an antigen to both helper T-lymphocytes and cytotoxic T-lymphocytes. DEndritic cells, macrophages, and B-lymphocytes function as APCs. have MHC I and MHC II

Kinins

are produced from kininogens, which are inactive plasma proteins produced by the liver and locally by numerous other cells. Kinins, including bradykinin, have similar effects to histamine-increase capillary permeability and production of CAMs. Kinins also stimulate pain receptors and are the most significant stimulus for causing the pain associated with inflammation.

5 major categories of Infectious agents

bacteria, viruses, fungi, protozoans, and muliticellular parasites

Gamma delta T cells

bind with MHC I type antigens found typically on tumor cells

Opsonization

binding of a complement to a portion of bacteria or other cell type that enhances phagocytosis, the binding protein is called an opsonin, the binding of complement makes it more likely that a substance is identified and engulfed by phagocytic cells

Coughing and sneezing

blasts of expired air, mechanical elimination of microbes or other foreign substances from the respiratory tracts

IgE

blood. produced during allergic reactions or as a result of a parasitic infection; activation of mast cells and basophils. half-life is 2 days. causes release of products from basophils and mast cells; attracts eosinophils.

Basophils and Mast cells

both are proinflammatory chemical secreting cells. substances secreted by these cells increase fluid movement from the blood to an injured tissue, also serve as chemotactic chemicals (chemicals that attract immune cells as part of the inflammatory response). they also release granules containing histamine-increases vasodilation and capillary permeability, heparin-anticoagulant, and eicosanoids-increase inflammation.

Inflammation

complement increases the inflammatory response through the activation of mast cells and basophils and by attracting neutrophils and macrophages.

Antimicrobial proteins

components of the innate immune system that function against microbes. ex; interferons and complement

Constant Region

contains the Fc region, which is the portion of the antibody that determines the biological functions of the antibody.

Interleukin(IL)

cytokine that regulates immune cells. comes from T-lymphocytes, macrophages, and other various cells. ex:IL-1 and IL-2

Natural Killer cells

destroy a wide variety of unwanted cells, including virus-infected cells, bacteria-infected cells, tumor cells, and cells of transplanted tissue. patrol the body in an effort to detect unhealthy cells-immune surveillance. they make physical contact with unhealthy cells and destroy them by releasing perforin-forms a transmembrane pore, and granzymes-enter the cell through the hole initiating apoptosis.

Fungi

eukaryotic cells that have a cell wall external to the plasma membrane. This group includes molds, yeasts, and multicellular fungi that produce spores. Proteolytic enzymes released from fungi induce inflammation that causes redness and swelling of infected area.

Protozoans

eukaryotic cells that lack a cell wall. Intracellular and extracellular parasites that interfere with normal cellular functions.

Lacrimal fluid

fluid produced by lacrimal glands; contains lysozyme and IgA. washes microbes away from surface of eyes, contains antimicrobial agents.

Cerumen

waxy secretions within external auditory meatus, waterproofs external auditory meatus, may trap microbes in external ear

Lactic acid

weak acid, produced by the vagina, creates a low pH that slows or prevents the growth of microbes