Microbiology Combined Study Guide | Test 3

Virulence factors

traits of a microbe that promote pathogenicity

"Immunoglobuins"

"Antibodies"

Phagocytes

-Phagocytes are cells that recognize pathogens and destroy them through phagocytosis. -Phagocytes degrade pathogens through phagocytosis, which involves engulfing the pathogen, killing and digesting it within a phagolysosome, and then excreting undigested matter.

Describe the 2 divisions of adaptive immunity and define their targets.

"Cell mediated immune responses" and "Antibody immune responses". -Cell mediated immune responses are controlled and carried out by t cells and often act against intracellular pathogens. -Antibody immune responses are often directed against extracellular pathogens and toxins. Both are powerful defensive reactions that have the potential to severely and fatally attack the body's own cells. B-cells carry out antibody immune responses, though T cells play roles in regulating and fulfilling such immune responses.

Pathogenesis

"Development of disease" Pathogens enter the body through portals of entry and leave through portals of exit. *Stages of Pathogenesis:* -Exposure -Adhesion -Invasion -Infection -Transmission. Protozoa adhere to target cells through complex mechanisms and can cause cellular damage through release of cytopathic substances. Some protozoa avoid the immune system through antigenic variation and production of capsules.

Compliment System

"Group of about 30 proteins in blood plasma that complement defense reactions and help attract phagocytes to foreign cells; can help promote lysis of the foreign cell" -The complement system involves numerous precursor proteins that circulate in plasma. These proteins become activated in a cascading sequence in the presence of microbes, resulting in the opsonization of pathogens, chemoattraction of leukocytes, induction of inflammation, and cytolysis through the formation of a membrane attack complex (MAC). -Set of serum proteins designated numerically according to their order of discovery -Complement activation results in lysis of the foreign cell -Indirectly trigger inflammation and fever -Complement can be activated in three ways *Three Complement Pathways* -Classical pathway -Alternative pathway -Lectin pathway

Immunoblots-western blots

"Immunoblots" Also called a "western blot" -Technique to detect antibodies against multiple antigens -Used to confirm the presence of proteins

Immunodeficiencies

"Insufficient immune response" Conditions resulting from defective immune mechanisms: *Primary immunodeficiency diseases* -Result from some genetic or developmental defect -Develop in infants and young children -Primary immunodeficiencies are caused by genetic abnormalities; secondary immunodeficiencies are acquired through disease, diet, or environmental exposures -Primary immunodeficiencies may result from flaws in phagocyte killing of innate immunity, or impairment of T cells and B cells. -Primary immunodeficiencies include chronic granulomatous disease, X-linked agammaglobulinemia, selective IgA deficiency, and severe combined immunodeficiency disease. *Acquired immunodeficiency diseases* -Develop as a direct consequence of some other recognized cause -Develop in later life -Result from a number of causes: -Secondary immunodeficiencies result from environmentally induced defects in B cells and/or T cells. -Causes for secondary immunodeficiencies include malnutrition, viral infection, diabetes, prolonged infections, and chemical or radiation exposure. -Severe stress; suppression of cell-mediated immunity results from an excess production of corticosteroids -Malnutrition and environmental factors; Inhibit production of B cells and T cells -Acquired immunodeficiency syndrome (AIDS); opportunistic infections, low CD4 cells, presence of HIV

Cytotoxic T cells

"Kill stuff" A type of lymphocyte that kills infected body cells and cancer cells. Releases Cytokines -MHC I -CD8 -Endogenous

MCH I

"Major histocompatibility complex" -Expressed on all cells except RBC -Mediates viral immunity

Helper T cells

"Mediate adaptive response" Activate macrophages, B cells and T cells. -MHC II -CD4 -Exogenous

*Essay* Define PAMPs and describe 3 specific PAMPs.

"Pathogen-associated molecular pattern" -PAMPs are conserved molecular structures produced by microorganisms and recognized as foreign by the receptors of the innate immune system. -Not shared with their host; -Shared by many related pathogens -Are relatively invariant; that is, do not evolve rapidly (in contrast, for example, to such pathogen molecules as the hemagglutinin and neuraminidase of influenza viruses). Examples: 1) *Peptidoglycan* found abundantly in the Gram-positive cell wall 2) *Flagellin* of bacteria flagella 3) *Lipopolysaccharide (LPS)* from the outer membrane of the Gram-negative cell wall

Immunodiffusion

(A type of Precipitation Reaction) An immune test in which antibodies and antigens diffuse from separate wells in agar to form a line of precipitate

Major Histocompatibility Complex and APC

*Antigen-Presenting Cells* -Group of antigens first identified in graft patients -Major histocompatibility antigens are glycoproteins found in the membranes of most cells of vertebrate animals -Hold and position antigenic determinants for presentation to T cells -Cross-presentation is a mechanism of antigen presentation and T-cell activation used by dendritic cells not directly infected by the pathogen; it involves phagocytosis of the pathogen but presentation on MHC I rather than MHC II. Antigens bind in the antigen-binding groove of MHC molecules -Antigen-presenting cells (APCs) primarily ingest pathogens by phagocytosis, destroy them in the phagolysosomes, process the protein antigens, and select the most antigenic/immunodominant epitopes with MHC II for presentation to T cells.

*Essay* Discuss 3 types of barrier defenses and provide an example of each.

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Antibodies vs. Antigens

*Antibodies* -Proteins that attach to antigens, keeping them from harming the body -Specialized proteins that aid in destroying infectious agents *Antigens* -Foreign material that invades the body -Toxin or other foreign substance that induces an immune response in the body, especially the production of antibodies.

Antigenic drift vs Antigenic shift

*Antigenic Drift* point mutations over time *Antigenic Shift* overnight; reassortment and jump Influenza viruses use both antigenic drift and antigenic shift to avoid being recognized by the immune system.

Describe the mechanisms viruses use for adhesion and antigenic variation

*Antigenic Variation* changes in surface antigens that occur in a microbial population

Vaccine Types

*Attenuated (modified live) Vaccines* -Use pathogens with reduced virulence Process of reducing virulence is called attenuation -Can result in mild infections -Active microbes stimulate a strong immune response -Can provide contact immunity -Modified microbes may retain enough residual virulence to cause disease in susceptible individuals *Inactivated (killed) Vaccines* -Safer than live vaccines -Whole agent vaccines -Deactivated but whole microbes *Subunit Vaccines* -Antigenic fragments of microbes -Often require multiple doses to achieve full immunity -Often contain adjuvants -Chemicals added to increase effective antigenicity *Toxoid Vaccines* -Chemically or thermally modified toxins used to stimulate active immunity --- -Live attenuated vaccines and inactivated vaccines contain whole pathogens that are weak, killed, or inactivated. Subunit vaccines, toxoid vaccines, and conjugate vaccines contain acellular components with antigens that stimulate an immune response.

Chemical Defenses

*Chemical and Enzymatic Mediators Found in Body Fluids* -Lysozyme (breaks the bonds of NAG/NAM) -Urine (Low pH) -Lactoferrin-sequesters iron -Cerumen (earwax) -Surfactant has antibacterial properties. *Antibacterial Peptides* AMPs found on the skin and in other areas of the body are largely produced in response to the presence of pathogens. These include dermcidin, cathelicidin, defensins, histatins, and bacteriocins. Plasma contains various proteins that serve as chemical mediators, including acute-phase proteins, complement proteins, and cytokines. -The antimicrobial peptides (AMPs) are a special class of nonspecific cell-derived mediators with broad-spectrum antimicrobial properties. -Some AMPs are produced routinely by the body, others are produced in response to the presence of an invading pathogen -A family of AMPs called defensins can be produced by epithelial cells throughout the body as well as by cellular defenses such as macrophages and neutrophils . -Defensins may be secreted or act inside host cells; they combat microorganisms by damaging their plasma membranes. -AMPs called bacteriocins are produced exogenously by certain members of the resident microbiota within the gastrointestinal tract

Explain the difference between a communicable disease and a noncommunicable disease

*Communicable Disease* A disease that can be spread from one person or species to another. *Noncommunicable Disease* A disease that is not transmitted by another person, a vector, or the environment

Compare contact, vector, and vehicle modes of transmission

*Contact Transmission* Contact transmission can be direct or indirect through physical contact with either an infected host (direct) or contact with a fomite that an infected host has made contact with previously (indirect). *Vector Transmission* Vector transmission occurs when a living organism carries an infectious agent on its body (mechanical) or as an infection host itself (biological), to a new host. *Vehicle Transmission* Vehicle transmission occurs when a substance, such as soil, water, or air, carries an infectious agent to a new host.

Explain how descriptive, analytical, and experimental epidemiological studies go about determining the cause of morbidity and mortality

*Descriptive Epidemiology* collection and analysis of data *Analytical Epidemiology* -Comparison of a diseased group and a healthy group -Analytical epidemiology studies are observational studies that are carefully designed to compare groups and uncover associations between environmental or genetic factors and disease. *Experimental Epidemiology* -Involves a hypothesis and controlled experiments -Experimental epidemiology studies generate strong evidence of causation in disease or treatment by manipulating subjects and comparing them with control subjects. *Retrospective Epidemiology* Retrospective epidemiology studies use historical data to identify associations with the disease state of present cases. Prospective epidemiology studies gather data and follow cases to find associations with future disease states.

Types of epidemiological studies

*Descriptive epidemiology* -Carefully tabulate data concerning a disease -Record location and time of the cases of disease -Collect patient information -Try to identify the index case of the disease -Usually results in developing a hypothesis of causation that could be tested by more rigorous observational and experimental studies. *Analytical Epidemiology* -Seeks to determine the probable cause, mode of transmission, and methods of prevention -Useful in situations when Koch's postulates can't be applied -Often retrospective -Investigation occurs after an outbreak has occurred *Experimental epidemiology* -Test a hypothesis concerning the cause of a disease -Apply Koch's postulates

Identify and differentiate between emerging and reemerging infectious diseases

*Emerging* Infectious diseases that are new, increasing in incidence, or showing a potential to increase in the near future Emerging diseases are those that are new to human populations or that have been increasing in the past two decades. Reemerging diseases are those that are making a resurgence in susceptible populations after previously having been controlled in some geographic areas. *Reemerging* Infectious diseases that existed in the past but for a variety of reasons are increasing in incidence or in geographic range

Patterns of Incidence (Occurrence)

*Endemic Disease* constantly present in a population *Sporadic Disease* occurs occasionally in a population *Epidemic* widespread outbreak of an infectious disease *Pandemic* an epidemic that is geographically widespread

Differentiate between endotoxins and exotoxins

*Endotoxins* released only when bacteria die and their cell walls break down *Exotoxins* toxic substances that bacteria secrete into their environment Bacterial toxins include endotoxin and exotoxins. Endotoxin is the lipid A component of the LPS of the gram-negative cell envelope. Exotoxins are proteins secreted mainly by gram-positive bacteria, but also are secreted by gram-negative bacteria.

Study of Diseases

*Etiology* Study of the cause of disease *Epidemiology* Branch of medical science concerned with the incidence, distribution, and control of diseases that affect large numbers of people. -When studying an epidemic, an epidemiologist's first task is to determinate the cause of the disease, called the etiologic agent or causative agent. -Connecting a disease to a specific pathogen can be challenging because of the extra effort typically required to demonstrate direct causation as opposed to a simple association. -We utilize the Koch postulates and Molecular Koch postulates

TCR

*T Cell Receptor* The TCR is similar in structure to immunoglobulins, but less complex. Millions of unique epitope-binding TCRs are encoded through a process of genetic rearrangement of V, D, and J gene segments.

Organ Transplantation and Rejection

*Graft Rejection* -Rejection of tissues or organs that have been transplanted -Grafts perceived as foreign by a recipient undergo rejection -Normal immune response against foreign MHC proteins present on graft cells -Likelihood of rejection depends on the degree to which the graft is foreign to the recipient -Based on the type of graft *Graft-versus-host Disease* -Donated bone marrow cells regard the patient's cells as foreign -Donor and recipient differ in MHC class I molecules --Grafted T cells attack all of the recipient's tissues -Donor and recipient differ in MHC class II molecules --Grafted T cells attack the host's antigen-presenting cells -Immunosuppressive drugs can stop graft-versus-host disease

Humoral vs. Cellular

*Humoral Immunity* Specific immunity produced by B cells that produce antibodies that circulate in body fluids *Cellular Immunity* Immune response that relies on T cells to destroy infected body cells

The Production of Hybridomas

*Hybridomas* Tumor cells created by fusing antibody-secreting plasma cells with cancerous plasma cells called myelomas (Alt definition:) cells created during the production of monoclonal antibodies by the fusion of an antibody-specific lymphocyte and a tumour cell

Compare different types of infectious diseases, including iatrogenic, nosocomial, and zoonotic diseases

*Iatrogenic Disease* A condition that is caused by a medical treatment *Nosocomial Disease* A disease acquired in a healthcare facility. *Zoonotic Disease* A disease communicable from animals to humans under natural conditions; also know as zoonosis

Classes of antibodies

*IgM* - first antibody produced (first acting) *IgG* - Most common and longest-lasting antibody *IgA* - (Secretory IgA) associated with body secretions (Typically in mucous membranes *IgE* - Associated with basophils, involved in response to parasitic infections and allergies *IgD* - Nobody knows Remember "*GAMED*"

Inflammation and fever

*Inflammation* -Nonspecific response to tissue damage from various causes -Characterized by redness, heat, swelling, and pain -Migration of phagocytes -Increased blood flow delivers leukocytes to site of infection -Attach to receptors lining vessels via margination -Squeeze between vessel's walls -Attracted to site of infection by chemotactic factors -Neutrophils arrive first, followed by monocytes -Tissue repair is the final stage of inflammation it delivers extra nutrients and oxygen to site -Some sites cannot be fully repaired and form scar tissue *Acute inflammation* -Develops quickly and is short lived -Is typically beneficial -Is important in the second line of defense -Dilation and increased permeability of the blood vessels (diapedesis) -Migration of phagocytes -Tissue repair *Chronic inflammation* -Long-lasting -Damage to tissues can cause disease

Overview of innate defenses

*Innate Immunity* -Resistance to most plant and animal pathogens -Species resistance -Due to physiological processes of humans that are incompatible with those of the pathogen -Correct chemical receptors are not present on human cells -Conditions may be incompatible with those needed for pathogen's survival -Humans do not have innate resistance to a number of pathogens Main first lines of defense: -External physical barriers to pathogens -Protective cells, bloodborne chemicals, and processes

Immunity

*Innate* An individual's genetically predetermined resistance to certain diseases. *Adaptive* Ability of the body to react to specific microbial infection. ANTIGEN SPECIFIC

*Essay* Distinguish between different major histocompatibility complexes in terms of where they are found, which cells recognize them, and what types of antigens they present.

*Major Histocompatibility Complexes* -Proteins that identify self present antigens to the attacker cells of the immune system. Very important in tissue transplantation -Family of membrane protein complexes encoded by a specific set of genes *MHC I* -Comprised of an MHC-encoded a chain and a b2-microglobulin chain -Present on all nucleated cells -Bind endogenous antigens synthesized in a cell -Present antigen to cytotoxic T cell lymphocytes -Bind CD8 adhesion molecules on cytotoxic T cells -Presence of foreign or over-abundant antigens targets cell for destruction *MHC II* -Comprised of MHC-encoded a and b chains -Present only on antigen-presenting cells such as dendritic cells, macrophages, and B cells -Binds exogenous antigens -Bind CD4 adhesion molecules on helper T cells -Presence of foreign antigens induces antibody production, and attracts immune cells to area of infection

The Role of Normal Microbiota in Innate Immunity

*Microbiota* The term for the microbes that are normally present in and on the human body; usually beneficial -The resident microbiota provide a physical defense by occupying available cellular binding sites and competing with pathogens for available nutrients. *Microbiome* All of the microorganisms that live in a particular environment, such as a human body *Microbial antagonism* -Competition between microbes -Normal microbiota compete with potential pathogens Activities of normal microbiota make it hard for pathogens to compete: -Consume nutrients -Create an environment unfavorable to other microorganisms -Help stimulate the body's second line of defense -Promote overall health by providing vitamins to host

Subtypes of Helper T Cells

*Th1 Cells* -Stimulate cytotoxic T cells and produce memory cytotoxic T cells -Stimulate macrophages and neutrophils (PMNs) for more effective intracellular killing of pathogens -Stimulate NK cells to kill more effectively *Th2 Cells* -Stimulate B cell activation and differentiation into plasma cells and memory B cells -Direct antibody class switching in B cells *Th17 Cells* -Stimulate immunity to specific infections such as chronic mucocutaneous infections *Memory Helper T Cells* -"Remember" a specific pathogen and mount a strong, rapid secondary response upon re-exposure

Diagnosis of Hypersensitivities

*Type I* -Based on detection of high levels of allergen-specific IgE -Test referred to as ImmunoCAP specific IgE blood test, CAP RAST, or Pharmacia CAP -Can also diagnose using skin tests

Causes of Autoimmune Disorders

-Occur more often in the elderly -Are more common in women than men -May result when an individual begins to make antibodies or cytotoxic T cells against normal body cell -Estrogen may stimulate destruction of tissue by cytotoxic T cells -Some maternal cells may cross the placenta, colonize the fetus, and trigger autoimmune disease later in life -Fetal cells may cross the placenta and trigger autoimmunity in the mother -Environmental factors such as viral infections -Genetic factors such as certain MHC genes -T cells may encounter self-antigens that are normally "hidden" -Microorganisms may trigger autoimmunity due to molecular mimicry -Failure of the normal control mechanisms of the immune system

Monoclonal and Polyclonal antibodies

*Monoclonal* Antibodies produced by a single clone of B lymphocytes and that are therefore identical in structure and antigen specificity. -Monoclonal antibodies provide higher specificity than polyclonal antisera because they bind to a single epitope and usually have high affinity. -Monoclonal antibodies are typically produced by culturing antibody-secreting hybridomas derived from mice. mAbs are currently used to treat cancer, but their exorbitant cost has prevented them from being used more widely to treat infectious diseases. Still, their potential for laboratory and clinical use is driving the development of new, cost-effective solutions such as plantibodies. *Polyclonal Antibodies* Antibodies produced by injecting animals with a specific antigen. A series of antibodies are produced responding to a variety of different sites on the antigen. -Injection of an antigen into an animal will result in a polyclonal antibody response in which different antibodies are produced that react with the various epitopes on the antigen. -Polyclonal antisera are useful for some types of laboratory assays, but other assays require more specificity. Diagnostic tests that use polyclonal antisera are typically only used for screening because of the possibility of false-positive and false-negative results. Passive Immunotherapy: -Administration of antiserum that contains preformed antibodies -These are called monoclonal and polyclonal antibodies -Provides immediate protection against a recent infection or ongoing disease -Antisera have several limitations --Can trigger allergic reactions called serum sickness --Antibodies of antisera are degraded relatively quickly --Individual not protected from subsequent infections -Limitations are overcome through development of hybridomas

Types of acquired immunity

*Naturally acquired* -Response against antigens encountered in daily life -Placenta -Breast Milk -Acquired through sickness *Artificially acquired* -Response to antigens introduced via a vaccine Distinguished as either active or passive *Passive* -Acquired through normal life activity -Inserting antibodies into yourself from another person -Short-term because of the lack of memory cells *Active* -Getting sick and acquiring immunity and creating long term memory cells -Vaccinating yourself to artificially stimulate response and long term memory cells -Artificial active immunity is the foundation for vaccination and vaccine development.

Pathogen Degradation

*Phagocytosis* -Cells capable of phagocytosis are called phagocytes -Phagocytosis is not completely understood Can be divided into six stages: -Chemotaxis -Adherence -Ingestion -Maturation -Killing -Elimination

Explain the difference between prevalence and incidence of disease

*Prevalence* the percentage of people within a population who have a specific illness *Incidence* the number of *new* cases of a disease in a given area or population during a given period of time

*Essay* Compare and contrast primary and opportunistic pathogens and provide an example of each.

*Primary Pathogens* -A microbe able to cause disease in an otherwise healthy individual -Primary pathogens are capable of causing pathological changes associated with disease in a healthy individual, whereas opportunistic pathogens can only cause disease when the individual is compromised by a break in protective barriers or immunosuppression. -Virus, bacteria, fungi, or any biological entity that causes a disease when it gains entry into a victims body. -The disease caused by the primary pathogen is usually one that stresses the victims immune system -The immune system is preoccupied in either fighting the microbes that have caused the primary disease or in many cases weakened to a large extent by the disease and the treatment that follows -Examples: HIV, Measles, Malaria *Opportunistic Pathogen* -Also called secondary pathogens -A secondary infection can sometimes occur after the host's defenses or normal microbiota are compromised by a primary infection or antibiotic treatment. -A microbe that causes disease only when introduced into an unusual location or into an immunocompromised host -A primary pathogen gives rise to the opportunity for other microbes that either live in the body without causing harmful effects, as their numbers are under control by a healthy immune system. OR those that are present in the external environment but which are typically easily dealt with by a healthy immune system so they grow in number and begin to cause problems of their own. -Examples include Bacteria or Fungi that live in the GI tract and are harmless under normal conditions but which can cause serious problems in a person affected by the disease

Explain the difference between protozoan parasites and helminths

*Protozoan Parasites* Unicellular, or single-cell, organisms that may be flagellates, amoebae, sporozoans, apicomplexans, or ciliates. *Helminths* multicellular parasitic organisms commonly called worms or flukes

*Essay* Please define the following and provide an example: reservoir, passive carrier, and active carrier.

*Reservior* "The habitat (living or nonliving) which an -Infectious agent lives and multiples" Animals, food, feces... etc *Passive Carrier* -Harbors and disseminates pathogens without having had the disease -Persons who mechanically transfer a pathogen without ever being infected by it -Someone who doesn't wash their nasty hands *Active Carrier* "Has readily apparent clinical case of disease" -Individuals who have been exposed to an harbor a disease-causing organism and who have done so for some time, even though they may have recovered from the disease.

Distinguish between signs and symptoms of disease

*Signs* Objective information; can be seen, measured, heard, or felt -Color, pulse, edema *Symptoms* Subjective information -Dyspnea, pain, nausea

Differentiate between species resistance and innate immunity.

*Species Resistance* Natural ability of one type of organism to resist infection by pathogens that cause disease in another type of organism *Innate Immunity* Immunity that is present before exposure and effective from birth. Responds to a broad range of pathogens.

*Essay* Please distinguish among sporadic, endemic, epidemic, and pandemic diseases, providing an example of each.

*Sporadic Disease* disease that occurs occasionally in a population -Rabies *Endemic Disease* disease constantly present in a population -Chicken Pox *Epidemic Disease* disease acquired by many hosts in a given area in a short time -(2003) Severe Acute Respiratory Syndrome (SARS) *Pandemic Disease* an epidemic disease that occurs worldwide -Spanish Influenza -HIV/AIDS -"The Black Death" Sporadic diseases only occur rarely and largely without a geographic focus. Endemic diseases occur at a constant (and often low) level within a population. Epidemic diseases and pandemic diseases occur when an outbreak occurs on a significantly larger than expected level, either locally or globally, respectively.

Hypersensitivity Treatment

-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

Allergy

-An allergy is an adaptive immune response, sometimes life-threatening, to an allergen. -Abnormal hypersensitivity acquired by exposure to an antigen

Emerging and reemerging

-Both WHO and some national public health agencies such as the CDC monitor and prepare for emerging infectious diseases. -An emerging infectious disease is either new to the human population or has shown an increase in prevalence in the previous twenty years

Cancer Immunobiology and Immunotherapy

-Cell-mediated immune responses can be directed against cancer cells, many of which do not have the normal complement of self-proteins, making them a target for elimination. -Abnormal cancer cells may also present tumor antigens. -These tumor antigens are not a part of the screening process used to eliminate lymphocytes during development; -Thus, even though they are self-antigens, they can stimulate and drive adaptive immune responses against abnormal cell -Cancer results from a loss of control of the cell cycle, resulting in uncontrolled cell proliferation and a loss of the ability to differentiate. -Adaptive and innate immune responses are engaged by tumor antigens, self-molecules only found on abnormal cells. These adaptive responses stimulate helper T cells to activate cytotoxic T cells and NK cells of innate immunity that will seek and destroy cancer cells. -New anticancer therapies are in development that will exploit natural adaptive immunity anticancer responses. These include external stimulation of cytotoxic T cells and therapeutic vaccines that assist or enhance the immune response.

The Tissues and Organs of the Lymphatic System

-Composed of lymphatic vessels and lymphatic cells, tissues, and organs, includes primary and secondary lymphoid organs -Screen the tissues of the body for foreign antigens Lymphoid organs: *Primary lymphoid organs* (Primary = Origin sites* -Red bone marrow -Thymus *Secondary lymphoid organs* (Secondary = Gathering points) -Lymph nodes -Spleen -Tonsils -Mucosa-associated lymphoid tissue (MALT)

Antigen Presenting Cells

-Dendritic cells -Macrophages -B cells Has MHC II

EIA

-Enzyme immunoassays (EIA) are used to visualize and quantify antigens. They use an antibody conjugated to an enzyme to bind the antigen, and the enzyme converts a substrate into an observable end product. The substrate may be either a chromogen or a fluorogen.

T Independent Antigens

-Have many identical, repeating epitopes Induce antibody response without assistance of helper T cells -T-independent immunity is weak, disappears quickly, and induces little memory -T-independent responses are stunted in children -Can cause childhood diseases that are rare in adults -T cell-independent activation of B cells involves cross-linkage of BCRs by repetitive nonprotein antigen epitopes. It is characterized by the production of IgM by plasma cells and does not produce memory B cells.

Nosocomial infections

-Hospital Epidemiology: Healthcare Associated (Nosocomial) Infections -Types of healthcare associated infections (HAIs): -Healthcare-associated infections (HAI), or nosocomial infections, are acquired in a clinical setting. Transmission is facilitated by medical interventions and the high concentration of susceptible, immunocompromised individuals in clinical settings. -Nosocomial diseases are contracted in hospital settings, whereas iatrogenic disease are the direct result of a medical procedure *Exogenous* Pathogen acquired from the health care environment *Endogenous* Pathogen arises from normal microbiota as a result of factors within the health care setting *Latrogenic* Results from modern medical procedures *Superinfections* Use of antimicrobial drugs reduces competition from some resident microbiota, allowing other microbes to thrive

Quarantining

-Individuals suspected or known to have been exposed to certain contagious pathogens may be quarantined, or isolated to prevent transmission of the disease to others. -Hospitals and other health-care facilities generally set up special wards to isolate patients with particularly hazardous diseases such as tuberculosis or Ebola -These wards may be equipped with special air-handling methods, and personnel may implement special protocols to limit the risk of transmission

Type IV (Delayed or Cell-Mediated) Hypersensitivity

-Inflammation occurs 12 to 24 hours after contact with certain antigens -Results from the actions of antigen, antigen-presenting cells, and T cells -Delay reflects the time it takes for macrophages and T cells to migrate to and proliferate at the site of the antigen -Type IV hypersensitivities are not mediated by antibodies, but by helper T-cell activation of macrophages, eosinophils, and cytotoxic T cells. The Tuberculin Response: -Skin exposed to tuberculosis or tuberculosis vaccine reacts to an injection of tuberculin beneath the skin -Used to diagnose contact with antigens of M. tuberculosis --No response when individual has not been infected or vaccinated --Red, hard swelling develops in individuals previously infected or immunized -Response mediated by memory T cells, causing a slowly developing inflammation --- *Allergic contact dermatitis* -Cell-mediated immune response resulting in an intensely irritating skin rash -Triggered by chemically modified skin proteins that the body regards as foreign -In severe cases, acellular, fluid-filled blisters develop -Can be caused by poison ivy, formaldehyde, cosmetics, and chemicals used to produce latex -Treated with corticosteroids *Hypersensitivity pneumonitis* -Inhalation of antigens deep in the lungs stimulates the production of antibodies -Subsequent inhalation of the same antigen stimulates the formation of immune complexes -Activates complement -Goes by many different names associated with various forms of exposure. -Associated with bird droppings is sometimes called pigeon fancier's lung or poultry worker's lung—both common in bird breeders and handlers. -Cheese handler's disease, farmer's lung, sauna takers' disease, and hot-tub lung are other names for HP associated with exposure to molds in various environments

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 allergens -Type I hypersensitivity requires sensitization of mast cells with IgE, involving an initial IgE antibody response and IgE attachment to mast cells. On second exposure to an allergen, cross-linking of IgE molecules on mast cells triggers degranulation and release of preformed and newly formed chemical mediators of inflammation. Type I hypersensitivity may be localized and relatively minor (hives and hay fever) or system-wide and dangerous (systemic anaphylaxis). The roles of degranulating cells in an allergic reaction: *Mast cells* -Distributed throughout the body in connective tissue -Have granules that contain inflammatory chemicals -Degranulation releases histamine, kinins, proteases, leukotrienes, and prostaglandins

Mechanical Defenses

-Microbes trapped in dead skin cells or mucus are removed from the body by mechanical actions such as shedding of skin cells, mucociliary sweeping, coughing, peristalsis, and flushing of bodily fluids (e.g., urination, tears) -In addition to physical barriers that keep microbes out, the body has a number of mechanical defenses that physically remove pathogens from the body, preventing them from taking up residence -Includes the shedding of skin cells, the expulsion of mucus via the mucociliary escalator, and the excretion of feces through intestinal peristalsis.

Pattern Reconigtion

-Phagocytes can also recognize molecular structures that are common to many groups of pathogenic microbes. -Recognition often takes place by the use of phagocyte receptors that bind molecules commonly found on pathogens, known as pathogen-associated molecular patterns (PAMPs). -The receptors that bind PAMPs are called pattern recognition receptors, or PRRs. Toll-like receptors (TLRs) are one type of PRR found on phagocytes. -Such structures are called pathogen-associated molecular patterns (PAMPs). Common PAMPs include the following: -peptidoglycan, found in bacterial cell walls; -flagellin, a protein found in bacterial flagella; l-ipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria; -lipopeptides, molecules expressed by most bacteria; and -nucleic acids such as viral DNA or RNA. *Toll-like receptors (TLRs)* -Integral membrane proteins produced by phagocytic cells -Bind pathogen-associated molecular patterns (PAMPs) -Initiate defensive responses: --Apoptosis --Secretion of inflammatory mediators --Stimulate adaptive immune response

T-Dependent Antigens

-Small and lack repetitive epitopes -Immune responses against them require the assistance of helper T cells -Th2 cells induce B cells that recognize the same antigen -T cell-dependent activation of B cells involves processing and presentation of protein antigens to helper T cells, activation of the B cells by cytokines secreted from activated TH2 cells, and plasma cells that produce different classes of antibodies as a result of class switching. Memory B cells are also produced. -Protein antigens are called T-dependent antigens because they can only activate B cells with the cooperation of helper T cells. Other molecule classes do not require T cell cooperation and are called T-independent antigens.

Classes of T Cells

-T cells can be categorized into three distinct classes: helper T cells, regulatory T cells, and cytotoxic T cells. -All T cells produce cluster of differentiation (CD) molecules, cell surface glycoproteins that can be used to identify and distinguish between the various types of white blood cells -CD4 and CD8 are the two most important used for differentiation of the classes. -Helper T cells and regulatory T cells are characterized by the expression of CD4 on their surface, whereas cytotoxic T cells are characterized by the expression of CD8. -Helper T cells and regulatory T cells can only be activated by APCs presenting antigens associated with MHC II. -Cytotoxic T cells recognize antigens presented in association with MHC I, either by APCs or by nucleated cells infected with an intracellular pathogens -Helper T cells serve as the central orchestrators that help activate and direct functions of humoral and cellular immunity -Cytotoxic T cells are the primary effector cells for cellular immunity -Immature T lymphocytes are produced in the red bone marrow and travel to the thymus for maturation. -Thymic selection is a three-step process of negative and positive selection that determines which T cells will mature and exit the thymus into the peripheral bloodstream. -Central tolerance involves negative selection of self-reactive T cells in the thymus, and peripheral tolerance involves anergy and regulatory T cells that prevent self-reactive immune responses and autoimmunity. -T cells can be divided into three classes—helper T cells, cytotoxic T cells, and regulatory T cells—based on their expression of CD4 or CD8, the MHC molecules with which they interact for activation, and their respective functions. -Activated helper T cells differentiate into TH1, TH2, TH17, or memory T cell subtypes. Differentiation is directed by the specific cytokines to which they are exposed. TH1, TH2, and TH17 perform different functions related to stimulation of adaptive and innate immune defenses. Memory T cells are long-lived cells that can respond quickly to secondary exposures. -Once activated, cytotoxic T cells target and kill cells infected with intracellular pathogens. Killing requires recognition of specific pathogen epitopes presented on the cell surface using MHC I molecules. Killing is mediated by perforin and granzymes that induce apoptosis. -Superantigens are bacterial or viral proteins that cause a nonspecific activation of helper T cells, leading to an excessive release of cytokines (cytokine storm) and a systemic, potentially fatal inflammatory response.

White Blood Cells (Leukocytes)

-The formed elements of the blood include red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Of these, leukocytes are primarily involved in the immune response. -All formed elements originate in the bone marrow as stem cells (HSCs) that differentiate through hematopoiesis. *Natural Killer Cell* -Natural killer (NK) cells are lymphocytes that recognize and kill abnormal or infected cells by releasing proteins that trigger apoptosis. -Recognizes abnormal cells, binds to them, and releases perforin and granzyme molecules, which induce apoptosis -Targets virus-infected cells *Macrophage* -Large agranular phagocyte that resides in tissues such as the brain and lungs --- *Granulocytes:* -Granulocytes are leukocytes characterized by a lobed nucleus and granules in the cytoplasm. These include neutrophils (PMNs), eosinophils, and basophils. -Contain large granules that stain different colors -Remember B.E.N. or the ones that end in Phil. *Basophil* -Stains with basic dye methylene blue, has large amounts of histamine in granules, and facilitates allergic responses and inflammation *Eosinophil* -Eosinophils target parasitic infections. Eosinophils and basophils are involved in allergic reactions. Both release histamine and other proinflammatory compounds from their granules upon stimulation. Mast cells function similarly to basophils but can be found in tissues outside the bloodstream. -Stains red/orange with acidic dye eosin, has histamine and major basic protein in granules, and facilitates responses to protozoa and helminths -Targets tapeworm in the intestines -Phagocytize pathogens -Capable of diapedesis *Neutrophil* -Neutrophils are the leukocytes found in the largest numbers in the bloodstream and they primarily fight bacterial infections. -Stain lilac with mix of acidic and basic dyes -Targets bacteria in a skin lesion -Phagocytize pathogens -Capable of diapedesis --- *Agranulocytes:* Cytoplasm appears uniform under a light microscope *Lymphocytes* -Most involved in adaptive immunity -Natural killer lymphocytes *Monocytes* -Monocytes are large, mononuclear leukocytes that circulate in the bloodstream. They may leave the bloodstream and take up residence in body tissues, where they differentiate and become tissue-specific macrophages and dendritic cells. -Leave the blood and mature into macrophages -Phagocytic cells that devour foreign objects --- *Mast Cells* -Mast cells appear to be derived from the same common myeloid progenitor cell as neutrophils, eosinophils, and basophils. -Functionally, mast cells are very similar to basophils -They contain many of the same components in their granules (e.g., histamine) -They also play a role in allergic responses and other inflammatory reactions.

Types of Hypersensitivities

-Type I (immediate) -Type II (cytotoxic) -Type III (immune complex-mediated) -Type IV (delayed or cell-mediated) Notice that types I-III are B-cell/antibody-mediated hypersensitivities, whereas type IV hypersensitivity is exclusively a T-cell phenomenon.

Autoimmune Disease

A disease in which the immune system attacks the organism's own cells -Autoimmune diseases result from a breakdown in immunological tolerance. The actual induction event(s) for autoimmune states are largely unknown. -Treatments for autoimmune diseases generally involve anti-inflammatory and immunosuppressive drugs. Some autoimmune diseases attack specific organs, whereas others are more systemic. -Two major categories: *Systemic autoimmune diseases* Systemic autoimmune diseases include multiple sclerosis, myasthenia gravis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. *Single-Organ autoimmune disease* Organ-specific autoimmune diseases include celiac disease, Graves disease, Hashimoto thyroiditis, type I diabetes mellitus, and Addison disease. (Can effect many different organs) -Blood cells -Endocrine organs -Nervous tissue -Connective tissue *Blood Cells* -Individuals produce antibodies against red blood cells -Causes severe anemia -Precise cause is unknown -Some cases follow viral infection or treatment with certain drugs *Endocrine* -Autoimmune responses can develop against cells in the pancreas or thyroid gland -Can cause destruction of the gland and hormone deficiencies -Type 1 diabetes mellitus -Can result from damage to the islets of Langerhans -Treatment with immunosuppressive drugs delays the onset in some individuals *Nervous Tissue* -Multiple sclerosis -Cytotoxic T cells destroy the myelin sheaths that insulate brain and spinal cord neurons -Impairs vision, speech, and neuromuscular function *Connective Tissue* -Rheumatoid arthritis --- *Systemic lupus erythematosus (SLE)* -Autoantibodies against DNA cause immune complex formation -Can cause glomerulonephritis and kidney failure -Many other autoantibodies can also occur -Against red blood cells, platelets, lymphocytes, muscle cells -Trigger unknown -Treatment with immunosuppressive drugs reduces autoantibody formation -Treatment with corticosteroids reduces inflammation

Grafts

A graft is body tissue removed and attached to a different place -Genetic differences, especially among the MHC (HLA) genes, will dictate the likelihood that rejection of the transplanted tissue will occur. -Transplant recipients usually require immunosuppressive therapy to avoid rejection, even with good genetic matching. This can create additional problems when immune responses are needed to fight off infectious agents and prevent cancer. -Graft-versus-host disease can occur in bone marrow transplants, as the mature T cells in the transplant itself recognize the recipient's tissues as foreign. -Transplantation methods and technology have improved greatly in recent decades and may move into new areas with the use of stem cell technology to avoid the need for genetic matching of MHC molecules. *Autograft* skin transplanted from one's self *Isograft* use of identical twin's tissue *Allograft* use of tissue from another person *Xenograft* tissue from another species

Inflammation

A localized physical condition in which part of the body becomes reddened, swollen, hot, and often painful, especially as a reaction to injury or infection. -Inflammation results from the collective response of chemical mediators and cellular defenses to an injury or infection. -Acute inflammation is short lived and localized to the site of injury or infection. Chronic inflammation occurs when the inflammatory response is unsuccessful, and may result in the formation of granulomas (e.g., with tuberculosis) and scarring (e.g., with hepatitis C viral infections and liver cirrhosis). -The five cardinal signs of inflammation are erythema, edema, heat, pain, and altered function. These largely result from innate responses that draw increased blood flow to the injured or infected tissue. -Fever is a system-wide sign of inflammation that raises the body temperature and stimulates the immune response. -Both inflammation and fever can be harmful if the inflammatory response is too severe.

*Essay* List and explain the application of Koch's postulates and discuss their importance.

A sequence of experimental steps for directly relating a specific microbe to a specific disease -Koch's postulates specify the procedure for confirming a particular pathogen as the etiologic agent of a particular disease. Koch's postulates have limitations in application if the microbe cannot be isolated and cultured or if there is no animal host for the microbe. In this case, molecular Koch's postulates would be utilized. -Koch's postulates are used to determine whether a particular microorganism is a pathogen. Molecular Koch's postulates are used to determine what genes contribute to a pathogen's ability to cause disease. Koch's postulates are as follows: -The bacteria must be present in every case of the disease. -The bacteria must be isolated from the host with the disease and grown in pure culture. -The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host. -The bacteria must be recoverable from the experimentally infected host. However, Koch's postulates have their limitations and so may not always be the last word. They may not hold if: -The particular bacteria (such as the one that causes leprosy) cannot be "grown in pure culture" in the laboratory. -There is no animal model of infection with that particular bacteria. A harmless bacteria may cause disease if: -It has acquired extra virulence factors making it pathogenic. -It gains access to deep tissues via trauma, surgery, an IV line, etc. -It infects an immunocompromised patient. -Not all people infected by a bacteria may develop disease-subclinical infection is usually more common than clinically obvious infection.

Transfusion reaction

A serious, and potentially fatal, complication of a blood transfusion in which a severe immune response occurs because the patient's blood and the donated blood do not match

Pyrogen

A substance, typically produced by a bacterium, that produces fever when introduced or released into the blood. Resets the temperature control of the hypothalamus

Phagocytosis.

A type of endocytosis in which a cell engulfs large particles or whole cells

Lymphocytes

A type of white blood cell that make antibodies to fight off infections -B cells -T Cells

Adaptive Immunity

Adaptive immunity is the body's ability to recognize and defend itself against distinct invaders and their products -Adaptive immunity is an acquired defense against foreign pathogens that is characterized by specificity and memory. The first exposure to an antigen stimulates a primary response, and subsequent exposures stimulate a faster and strong secondary response. -Adaptive immunity is a dual system involving humoral immunity (antibodies produced by B cells) and cellular immunity (T cells directed against intracellular pathogens). -Antigens, also called immunogens, are molecules that activate adaptive immunity. A single antigen possesses smaller epitopes, each capable of inducing a specific adaptive immune response. *Five attributes of adaptive immunity:* -Specificity -Inducibility -Clonality -Unresponsiveness to self -Memory Involves activity of lymphocytes *Two main types of lymphocytes:* -B lymphocytes (B cells) Mature in the bone marrow -T lymphocytes (T cells) Mature in the thymus *Two types of adaptive immune responses:* -Cell-mediated immune responses -Antibody immune responses (humoral)

Acute, Chronic, Latent

An acute disease is short in duration, whereas a chronic disease lasts for months or years. Latent diseases last for years, but are distinguished from chronic diseases by the lack of active replication during extended dormant periods.

Immune Complexes

An immune complex, sometimes called an antigen-antibody complex, is a molecule formed from the integral binding of an antibody to a soluble antigen. The bound antigen and antibody act as a unitary object, effectively an antigen of its own with a specific epitope. --Can damage organs. Antigen-antibody complexes can form, settle in kidneys and joints, and activate complement system leading to inflammation

Hemolytic disease of the newborn (HDN)

Condition developing in fetus when mother's blood type is Rh-negative and baby's blood is Rh-positive; antibodies in mother's blood enter fetus' bloodstream through placenta and destroy fetus' red blood cells; causes anemia, jaundice, and enlargement of spleen; treated with intrauterine blood transfusion; also called erythroblastosis fetalis

Cell Junctions

Contact points between the plasma membranes of tissue cells -Tight junctions -Desosomes -Gap junctions

Antibodies

Antibodies (also called immunoglobulins) are glycoproteins that are present in both the blood and tissue fluids. -Antibodies (immunoglobulins) are Y-shaped glycoproteins with two Fab sites for binding antigens and an Fc portion involved in complement activation and opsonization. -The basic structure of an antibody monomer consists of four protein chains held together by disulfide bonds. -The two largest chains are identical to each other and are called the heavy chains. -The two smaller chains are also identical to each other and are called the light chains. -The two 'arms' of the Y-shaped antibody molecule are known as the Fab region, for "fragment of antigen binding." -The Fab region is the variable region, which serves as the site of antigen binding. -The constant region of the antibody molecule includes the trunk of the Y and lower portion of each arm of the Y. -The trunk of the Y is also called the Fc region, for "fragment of crystallization

Five functions of Antibodies

Antigen-binding sites are complementary to epitopes Antibodies function in several ways: *Activation of complement and inflammation* The complement system *Neutralization* Antibodies cover biologically active portion of microbe or toxin *Opsonization* (To make tasty) Coating antigen with antibodies to enhance phagocytosis *Oxidation* Antiboides have catalytic properties that allow them to form reactive oxygen species that kill the bacteria they bind to *Aggluntination* Antibodies bind to multiple antigens causing them to clump together and prevent transport throughout the body *Antibody-Dependent Cellular Cytotoxicity (ADCC)* antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells

MHC I and MHC II

Antigens bind in the antigen-binding groove of MHC molecules "MHC I is for all cells, MCH II is for professionals" -Major histocompatibility complex (MHC) is a collection of genes coding for glycoprotein molecules expressed on the surface of all nucleated cells. *MHC class I* -Present on all cells except red blood cells -Recognizes endogenous antigens -MHC I molecules are expressed on all nucleated cells and are essential for presentation of normal "self" antigens. Cells that become infected by intracellular pathogens can present foreign antigens on MHC I as well, marking the infected cell for destruction. *MHC class II* -Present on antigen-presenting cells (APCs) -Include B cells, macrophages, and dendritic cells -Recognizes exogenous antigens -MHC II molecules are expressed only on the surface of antigen-presenting cells (macrophages, dendritic cells, and B cells). Antigen presentation with MHC II is essential for the activation of T cells.

Hypersensitivities

Any immune response against a foreign antigen exaggerated beyond the norm

Plasma Cells

Cells that develop from B cells and produce antibodies. -Majority of cells produced during B cell proliferation -Only secrete antibody molecules that are complementary to the specific antigen -Short-lived cells that die within a few days of activation -Their antibodies and progeny can persist

Mast Cells

Cells that release chemicals (such as histamine) that promote inflammation.

Epitopes

Certain regions of an antigen molecule that stimulate immune responses

Immunoglobulin Responses

Compared to the primary response, the secondary antibody response occurs more quickly and produces antibody levels that are higher and more sustained. The secondary response mostly involves IgG. -Secondary exposures to T-dependent antigens result in a secondary antibody response initiated by memory B cells. The secondary response develops more quickly and produces higher and more sustained levels of antibody with higher affinity for the specific antigen. Multiple Choice

Cytokines

Chemicals released by the immune system communicate with the brain. "Molecular Messengers" -Numerous chemical mediators produced endogenously and exogenously exhibit nonspecific antimicrobial functions. -Many chemical mediators are found in body fluids such as sebum, saliva, mucus, gastric and intestinal fluids, urine, tears, cerumen, and vaginal secretions. -Cytokines are proteins that facilitate various nonspecific responses by innate immune cells, including production of other chemical mediators, cell proliferation, cell death, and differentiation. -Cytokines play a key role in the inflammatory response, triggering production of inflammation-eliciting mediators such as acute-phase proteins, histamine, leukotrienes, prostaglandins, and bradykinin. -Cytokines are soluble proteins that act as communication signals between cells. -Cytokines may be released to stimulate production of chemical mediators or other cell functions, -These include cell proliferation, cell differentiation, inhibition of cell division, apoptosis, and chemotaxis -Three important classes of cytokines are the interleukins, chemokines, and interferons. -The interleukins were originally thought to be produced only by leukocytes (white blood cells) and to only stimulate leukocytes, thus the reasons for their name. -Interleukins are also produced by and stimulate a variety of cells unrelated to immune defenses. -The chemokines are chemotactic factors that recruit leukocytes to sites of infection, tissue damage, and inflammation. -Interferons are a diverse group of immune signaling molecules and are especially important in our defense against viruses. -Type I interferons (interferon-α and interferon-β) are produced and released by cells infected with virus -Cytokines stimulate the production of acute-phase proteins such as C-reactive protein and mannose-binding lectin in the liver. -These acute-phase proteins act as opsonins, activating complement cascades through the lectin pathway -Some cytokines also bind mast cells and basophils, inducing them to release histamine, a proinflammatory compound. -Histamine receptors are found on a variety of cells and mediate proinflammatory events -In addition to histamine, mast cells may release other chemical mediators, such as leukotrienes. -Prostaglandins are chemical mediators that promote the inflammatory effects of kinins and histamines. -Prostaglandins can also help to set the body temperature higher, leading to fever -Another inflammatory mediator, bradykinin, contributes to edema -Autocrine -Paracrine -Endocrine

Brief History of Immunization

Chinese noticed children who recovered from smallpox did not contract the disease again. they infected children with material from a smallpox scab to induce immunity This process was known as *Variolation* -Variolation spread to England and America but was stopped because of risk of death -Variolation against smallpox originated in the 10th century in China, but the procedure was risky because it could cause the disease it was intended to prevent. Modern vaccination was developed by Edward Jenner, who developed the practice of inoculating patients with infectious materials from cowpox lesions to prevent smallpox. -1796 - Edward Jenner discovered process of vaccination -1879 - Louis Pasteur developed a vaccine against Pasteurella multocida -Antibody transfer developed when it was discovered that vaccines protect through the action of antibodies

Opsonization

Coating antigen with antibody enhances phagocytosis and renders it less effective by surrounding its binding sites

Hemolysis

Destruction of red blood cells

Exoenzymes

Dissolve extracellular barriers and penetrate through or between cells Exoenzymes and toxins allow pathogens to invade host tissue and cause tissue damage. Exoenzymes are classified according to the macromolecule they target and exotoxins are classified based on their mechanism of action.

Public Health Organizations

Epidemiology and Public Health Agencies at the local, state, national, and global level share information concerning disease: The United States Public Health Service -National public health agency -CDC World Health Organization (WHO) -Coordinates public health efforts worldwide -The World Health Organization (WHO) is an agency of the United Nations that collects and analyzes data on disease occurrence from member nations. WHO also coordinates public health programs and responses to international health emergencies. The Centers for Disease Control and Prevention monitors notifiable diseases and publishes weekly updates in the Morbidity and Mortality Weekly Report -Public health agencies work to limit disease transmission -Enforce standards of water and food safety -Work to reduce disease vectors and reservoirs -Establish and enforce immunization schedules -Locate and treat individuals exposed to contagious pathogens -Establish isolation and quarantine measures

Epidemology

Epidemiology is the science underlying public health. The branch of medical science concerned with the incidence, distribution, and control of diseases that are prevalent among a population at a special time and are produced by some special causes not generally present in the affected locality.

ELISA

Enzyme-Linked Immunosorbent Assay (test to detect anti-HIV antibodies) -Stands for enzyme-linked immunosorbent assay -Uses an enzyme as the label --Reaction of enzyme with its substrate produces a colored product, indicating a positive test -Commonly used to detect the presence of serum antibodies -*Direct ELISA* is used to quantify an antigen in solution. The primary antibody captures the antigen, and the secondary antibody delivers an enzyme. Production of end product from the chromogenic substrate is directly proportional to the amount of captured antigen. -*Indirect ELISA* is used to detect antibodies in patient serum by attaching antigen to the well of a microtiter plate, allowing the patient (primary) antibody to bind the antigen and an enzyme-conjugated secondary antibody to detect the primary antibody. --- Advantages of the ELISA: -Can detect either antibody or antigen Sensitive -Can quantify amounts of antigen or antibody -Easy to perform and can test many samples quickly -Relatively inexpensive and easy to automate -Plates coated with antigen can be stored for later testing

Frequency of Disease

Epidemiologists track occurrence of diseases using two measures *Incidence* Number of new cases of a disease in a given area during a given period of time *Prevalence* Number of total cases of a disease in a given area during a given period of time -Occurrence also evaluated in terms of frequency and geographic distribution -They also evaluate mobidity and mortality rates

Nonspecific immunity

General defense mechanisms that provide animals with protection from infection and disease but are not targeted at a particular pathogen. -Nonspecific innate immunity provides a first line of defense against infection by nonspecifically blocking entry of microbes and targeting them for destruction or removal from the body.

Extravasation

Extravasation of white blood cells from the bloodstream into infected tissue occurs through the process of transendothelial migration.

Antigens

Foreign substances that trigger the attack of antibodies in the immune response. Properties of antigens: -Molecules that the body recognizes as foreign and worthy of attack -Recognized by three-dimensional regions called epitopes on antigens -Large foreign macromolecules make the best antigens -Include various bacterial components as well as proteins of viruses, fungi, and protozoa -Food and dust can also contain antigenic particles -An antigen's ability to stimulate an immune response depends on several factors, including its molecular class, molecular complexity, and size.

How do helminths avoid the immune system

Helminthic worms are able to avoid the immune system by coating their exteriors with glycan molecules that make them look like host cells or by suppressing the immune system.

Type III (Immune Complex-Mediated) Hypersensitivity

Immune Complex Mediated -Type III hypersensitivities result from formation and accumulation of immune complexes in tissues, stimulating damaging inflammatory responses. -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 Rheumatoid arthritis

Neutralization test

Immune test that measures the ability of antibodies to neutralize the biological activity of pathogens and toxins Viral neutralization -Cytopathic effect --Viruses introduced into appropriate cell cultures will kill the cells -Ability of virus to kill culture cells is neutralized when virus is first mixed with antibodies against it -Viral neutralization test --Mixture of virus and serum added to cell culture --Absence of cytopathic effect indicates presence of antibodies against the virus in the serum --Identifies whether individual has been exposed to a particular virus

Natural Killer Cells

Killing by natural killer lymphocytes -Natural killer cells (NK cells) are mononuclear lymphocytes use nonspecific mechanisms to recognize and destroy cells that are abnormal in some way. -Cancer cells and cells infected with viruses are two examples of cellular abnormalities that are targeted by NK cells -Secrete toxins onto surface of virally infected cells and tumors -Differentiate normal body cells because they have membrane proteins similar to the NK cells

Infections

Invasions and multiplications of microorganisms in body tissues Diseases can either be noninfectious (due to genetics and environment) or infectious (due to pathogens). Some infectious diseases are communicable (transmissible between individuals) or contagious (easily transmissible between individuals); others are noncommunicable, but may be contracted via contact with environmental reservoirs or animals (zoonoses) Infections and disease can be caused by pathogens in the environment or microbes in an individual's resident microbiota. Infections can be classified as local, focal, or systemic depending on the extent to which the pathogen spreads in the body. Viral pathogens use adhesins for initiating infections and antigenic variation to avoid immune defenses. Fungi initiate infections through the interaction of adhesins with receptors on host cells. Some fungi produce toxins and exoenzymes involved in disease production and capsules that provide protection of phagocytosis.

Absess

Localized collection of pus usually accomplished by swelling and inflammation; abscesses can occur in tissues, organs and contained spaces

Morbidity

Morbidity means being in a state of illness, whereas mortality refers to death; both morbidity rates and mortality rates are of interest to epidemiologists.

Percentage of white blood cells

Neutrophils = 60% Lymphocytes = 30% Monocytes = 8% Eosinophils = 3% Basophils = ~0% "*N*ever *L*et *M*y *E*ngine *B*low; 60, 30, 8, 3, 0".

Explain the roles of portals of entry and exit in the transmission of disease and identify specific examples of these portals

Pathogenic microbes have definite routes of entry and exit from infected hosts Mucous membranes (mucosa) that line Respiratory, Gastrointestinal, Genitourinary tracts Skin (usually damaged in some way: nicks, abrasions, punctures, insect bites, etc.)

Memory B Cells

Produced during a B cell response, but are not involved in antibody producing during the initial infection; are held in reserve for the rest of your life in case you encounter that pathogen again.

Memory B cells

Produced during a B cell response, but are not involved in antibody producing during the initial infection; are held in reserve for the rest of your life in case you encounter that pathogen again. -Produced by B cell proliferation but do not secrete antibodies -Have BCRs complementary to the epitope that triggered their production -Long-lived cells that persist in the lymphoid tissue -Initiates antibody production if antigen is encountered again

Interferons

Proteins (cytokines) secreted by T cells and other cells to aid and regulate the immune response

Cytokines

Proteins secreted by cytotoxic T cells to aid in antigen destruction

Type II (Cytotoxic) Hypersensitivity

Results when cells are destroyed by an immune response: -Often the combined activities of complement and antibodies -A component of many autoimmune diseases -Type II hypersensitivities result from antibodies binding to antigens on cells and initiating cytotoxic responses. Examples include hemolytic transfusion reaction and hemolytic disease of the newborn. Two significant examples: -Destruction of blood cells following an incompatible blood transfusion -Destruction of fetal red blood cells --- The ABO system and transfusion reactions: -Blood group antigens are surface molecules of red blood cells -Each person's red blood cells have A antigen, B antigen, both antigens, or neither antigen -Transfusion reaction can result if an individual receives different blood type -Donor's blood group antigens may stimulate the production of antibodies in the recipient that destroy the transfused cells. --- 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− woman is carrying an Rh+ fetus, 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

Serological Tests That Use Antigens and Corresponding Antibodies

Serology is the determination of the presence of specific antigens or antibodies in blood serum Serological tests are available to identify a variety of antigens and antibodies in serum Serological tests have several uses: -Monitor the spread of infection within a population -Establish diagnosis of disease

B Lymphocytes (B Cells) and Antibodies

Specificity of the B cell receptor (BCR): -Each B lymphocyte has multiple copies of the B cell receptor (BCR) -Each B cell generates a single BCR -Two variable regions of the BCR form the antigen-binding sites -Each BCR recognizes only one epitope -The entire repertoire of an individual's BCRs is capable of recognizing millions of different epitopes -B lymphocytes or B cells produce antibodies involved in humoral immunity. B cells are produced in the bone marrow, where the initial stages of maturation occur, and travel to the spleen for final steps of maturation into naïve mature B cells. -B-cell receptors (BCRs) are membrane-bound monomeric forms of IgD and IgM that bind specific antigen epitopes with their Fab antigen-binding regions. Diversity of antigen binding specificity is created by genetic rearrangement of V, D, and J segments similar to the mechanism used for TCR diversity.

Cell-Mediated Response

The branch of acquired immunity that involves the activation of cytotoxic T cells, which defend against infected cells.

The Membrane Attack Complex

The complex of terminal complement components that forms a pore in the membrane of the target cell, damaging the membrane and leading to cell lysis.

Degranulation

The emptying of granules from the interior of a mast cell into the extracellular environment.

Precipitation reaction

The formation of a solid from a solution during a chemical reaction. Precipitates are often formed when two aqueous solutions are mixed together.

Precipitation Tests

The interaction of soluble antigens with IgG or IgM antibodies (layered over each other) to form a preciptate (substance) -Among the simplest of serological tests -Antigens and antibody are mixed in the proper proportion form large complexes called precipitates -Antigen-antibody complexes are also called immune complexes -When present in the correct ratio, antibody and antigen will form a precipitin, or lattice that precipitates out of solution. -A precipitin ring test can be used to visualize lattice formation in solution. The Ouchterlony assay demonstrates lattice formation in a gel. The radial immunodiffusion assay is used to quantify antigen by measuring the size of a precipitation zone in a gel infused with antibodies.

Types of Antigens

The key difference between endogenous and exogenous antigens is that the endogenous antigen is generated within the cells while the exogenous antigen enters the body from the outside. *Exogenous Antigens* Antigens from outside the cell that have been engulfed by the cell that displays them *Endogenous Antigens* Antigens produced by microbes that multiply inside the cells of the body *Autoantigens* Antigens on the surface of normal body cells

Periods of Disease

The periods of disease include the incubation period, the prodromal period, the period of illness, the period of decline, and the period of convalescence. These periods are marked by changes in the number of infectious agents and the severity of signs and symptoms.

Physical Defenses

The physical defenses of innate immunity include physical barriers, mechanical actions that remove microbes and debris, and the microbiome, which competes with and inhibits the growth of pathogens. *Physical defenses* -The skin, mucous membranes, and endothelia throughout the body serve as physical barriers that prevent microbes from reaching potential sites of infection. Tight cell junctions in these tissues prevent microbes from passing through. -Structures, chemicals, and processes that work to prevent pathogens entering the body -Skin and mucous membranes of the respiratory, digestive, urinary, and reproductive syste -Physical barriers play an important role in preventing microbes from reaching tissues that are susceptible to infection -In addition to physical barriers that keep microbes out, the body has a number of mechanical defenses that physically remove pathogens from the body, preventing them from taking up residence -Shedding of skin cells and mucocillary sweeping *Skin* -Skin has chemicals that defend against pathogens -Antimicrobial peptides (defensins) secreted by dermal cells -Perspiration secreted by sweat glands -Salt inhibits growth of pathogens -Antimicrobial peptides called dermcidins act against many bacteria and fungi -Lysozyme destroys cell wall of bacteria *-Epidermis:* -Multiple layers of tightly packed cells -Few pathogens can penetrate these layers -Shedding of dead skin cells removes microorganisms -Epidermal dendritic cells phagocytize pathogens *-Dermis:* -Collagen fibers help skin resist abrasions that could introduce microorganisms *Mucous Membranes* -The mucous membranes lining the nose, mouth, lungs, and urinary and digestive tracts provide another nonspecific barrier against potential pathogens. -Mucous membranes consist of a layer of epithelial cells bound by tight junctions. -The epithelial cells secrete a moist, sticky substance called mucus, which covers and protects the more fragile cell layers beneath it and traps debris and particulate matter, including microbes. -Mucus secretions also contain antimicrobial peptides *Endothelia* -The epithelial cells lining the urogenital tract, blood vessels, lymphatic vessels, and certain other tissues are known as endothelia. -These tightly packed cells provide a particularly effective frontline barrier against invaders. -The endothelia of the blood-brain barrier, for example, protect the central nervous system (CNS), which consists of the brain and the spinal cord.

Clonal Deletion

The process of destroying B and T cells that react to self antigens

Hematopoiesis

The production of blood cells

Modes of disease transmission

Transmission is from a reservoir or a portal of exit to another host's portal of entry Reservoirs of human disease can include the human and animal populations, soil, water, and inanimate objects or materials. *Contact Transmission* -Direct contact transmission: Usually involves body contact between hosts. Transmission within a single individual can also occur. -Indirect contact transmission: Pathogens are spread from host to host by fomites. -Droplet transmission: Spread of pathogens in droplets of mucus by exhaling, coughing, and sneezing. *Vehicle Transmission* -Airborne transmission: When pathogens travel more than 1 meter via an aerosol. Aerosols can occur from various activities. Sneezing, coughing, air-conditioning systems, sweeping. -Waterborne transmission: Important in the spread of many gastrointestinal diseases. Fecal-oral infection. -Foodborne transmission: Spread of pathogens in and on foods. Inadequately processed, cooked, or refrigerated foods. Foods may become contaminated with feces . -Bodily fluid transmission: Bodily fluids such as blood, urine, saliva can carry pathogens. Prevent contact with conjunctiva or breaks in the skin or mucous membranes. *Vector Transmission* -Vectors: animals that transmit disease among hosts -Biological vectors: Transmit pathogens and serve as host for some stage of the pathogen's life cycle. Biting arthropods transmit many diseases to humans. -Mechanical vectors: Passively transmit pathogens present on their body to new hosts.

Virulence

Virulence, the degree to which a pathogen can cause disease, can be quantified by calculating either the ID50 or LD50 of a pathogen on a given population. "Virulence factors" contribute to a pathogen's ability to cause disease. Fungal and parasitic pathogens use pathogenic mechanisms and virulence factors that are similar to those of bacterial pathogens Bacterial pathogens may evade the host immune response by producing capsules to avoid phagocytosis, surviving the intracellular environment of phagocytes, degrading antibodies, or through antigenic variation.

*Essay* Define virulence and discuss two ways virulence of a pathogen can be quantified in the lab and what the results of each indicate.

Virulence: The degree of pathogenicity (Ability to cause disease) ****************** ****************** ****************** ****************** ****************** ****************** ****************** ****************** ******************

*Essay* Discuss inflammation in terms of cause, multiple effects, and potential benefits / drawbacks.

When inflammation occurs, chemicals from the body's white blood cells are released into the blood or affected tissues to protect your body from foreign substances. This release of chemicals increases the blood flow to the area of injury or infection, and may result in redness and warmth. *Causes* -Inflammation is caused by a number of physical reactions triggered by the immune system in response to a physical injury or an infection. *Effects* -Cells begin signalling by release chemokines to alert that a problem has occurred. -Mast cells release histamine -Vasodialation -The small branches of arteries enlarge when supplying blood to the damaged region, resulting in increased blood flow. -Capillaries become easier for fluids and proteins to infiltrate, meaning that they can move between blood and cells. -The body releases neutrophils. A neutrophil is a type of white blood cell filled with tiny sacs that contain enzymes and digest microorganisms. *Benefits* The body has more localized resources to fight off the infection using WBC's or begin healing and repair. *Draw backs* The Inflammatory Reponse: -Redness -Swelling -Heat Pain