Unit 5/6 Final Exam

State how long it takes for immediate innate immunity to become activated and what it involves

0-4 hours after exposure Involves action of soluble pre-formed antimicrobial molecules that circulate in the blood, are found in extracellular tissue fluids, and are secreted by epithelial cells Antimicrobial enzymes and peptides Complement system proteins

Immediate innate immunity

0-4 hours after exposure; consists of soluble, pre-formed antimicrobial molecules that circulate in blood, found in tissues, and secreted by epithelial cells (enzymes and peptides, complement proteins, anatomical barriers to infection)

3 characteristics an antigen must have to be immunogenic.

1 high molecular weight, 2 exhibit chemical complexity, and 3 exhibit foreignness (recognized as non-self by the body)

State three different ways by which cell-mediated immunity protects the body

1. Activating CTL's that are able to destroy body cells by displaying epitopes of a foreign antigen on their surface. 2. Activating macrophages/NK cells to destroy intracellular pathogens 3. Stimulating cells to secrete cytokines to influence the function of other cells involved in adaptive and innate immune responses.

The resistance to the spread of a contagious disease within a population that results if a sufficiently high proportion of individuals are immune to the disease, especially through vaccination.

(T cells) Mediated by activation of macrophages and NK cells, the production of antigen-specific cytotoxic T-lymphocytes, and the release of cytokines in response to an antigen. Most effective in destroying virus-infected cells, intracellular bacteria, and cancers. It also plays a major role in delayed transplant rejection. Directed primarily towards microbes that survive in phagocytes and microbes that infect non-phagocytic cells

2 different ways viruses may resist neutralizing antibodies

1. Antigenic shift is caused by a human influenza virus acquiring a new genome segment from an influenza virus capable of infecting other animals such as a ducks or swine. This new genome segment causes a major change in the hemagglutinin antigen. Antibodies made against the original human influenza virus can no longer bind to the new strain of virus or stick the virus to phagocytes. 2. Likewise HIV, because of its high rate of mutation and its intracellular recombination with other strains of HIV, as mentioned earlier in this unit, produces altered gp120 to which antibodies made against the earlier strains of HIV can no longer bind.

T-lymphocytes (T-cells)

-cell-mediated immunity (production of cytotoxic T-lymphocytes, CTLs); regulate the adaptive immune responses; 60-80% of lymphocytes are T-lymphocytes

State which classes (isotypes) of human antibodies possess the following characteristics: Binds to components of mucous by its Fc portion

IgA

State which classes (isotypes) of human antibodies possess the following characteristics: Is a dimer

IgA (has 4 epitope-binding sites & secretory component to protect itself from digestive enzymes in secretions)

State which classes (isotypes) of human antibodies possess the following characteristics: Activates the classical complement pathway by its Fc portion

IgG

State which classes (isotypes) of human antibodies possess the following characteristics: Binds to NK cells by its Fc portion

IgG

State which classes (isotypes) of human antibodies possess the following characteristics: Crosses the placenta

IgG

State which classes (isotypes) of human antibodies possess the following characteristics: Binds to macrophages and neutrophils by uts Fc portion

IgG and IgA

State which classes (isotypes) of human antibodies possess the following characteristics: The first antibody produced during an adaptive immune response

IgM

State which classes (isotypes) of human antibodies possess the following characteristics: Is a pentamer

IgM (has 10 epitope-binding sites)

State which classes (isotypes) of human antibodies possess the following characteristics: Functions as a B-cell receptor -

IgM and IgD

c. the type of effector cells into which activated T8-lymphocytes differentiate

In order to become CTLs, naive T8-lymphocytes must become activated by cytokines produced by antigen-presenting dendritic cells. This interaction between dendritic cells and naive T8-lymphocytes occurs primarily in the lymph nodes, the lymph nodules, and the spleen.

Oxygen-independent system: Bactericidal permeability inducing protein (BPI)

used by neutrophils to kill certain bacteria by damaging their membranes

the acute phase response

Inflammatory cytokines such as TNF-alpha, IL-1, and IL-6 stimulate hepatocytes (liver cells) to synthesize and secrete acute phase proteins Acute phase proteins function as soluble pattern-recognition receptors

describe the healing stage of inflammation

Interferon-gamma (IF-y) binds to macrophages to produce fibroblast growth factor and angiogenic factors for tissue remodeling Endothelial cells form a fine network of new capillaries into injured area to supply blood, oxygen, and nutrients to inflamed tissue Fibroblasts deposit protein collagen in the injured area and form connective scar tissue to close the open area, known as fibrosis or scarring

Describe how type I interferons are able to block viral replication within an infected host cell

Interferons induce uninfected cells to produce an enzyme capable of degrading viral mRNA Enzymes remain inactive until cell becomes infected with a virus Enzymes are activated and begin to degrade viral mRNA and block translation in the host cell This blocks viral protein synthesis and kills the infected cell Cause infected cells to produce enzymes that interfere with transcription of viral RNA or DNA

describe how intraepithelial T-lymphocytes and B-1 cells play a role in innate immunity

Intraepithelial T-lymphocytes and B-1 lymphocytesare associated with the epidermis and the mucosal epithelium. These cells recognize microbes common to the epidermis and mucous membranes and start immediate adaptive immune responses against these commonly encountered microbes.

State 3 different functions of macrophages in body defense

Kill microbes; infected cells, and tumor cells by phagocytosis Process antigens so they can be recognized by effector T-lymphocytes during adaptive immune responses Secrete lipid mediators of inflammation such as leukotrienes, prostaglandins, and platelet-activating factor (PAF) Secrete cytokines that play a role in a variety of roles in non-specific defense

Describe how an overactive TLR-4 receptor can increase the risk of SIRS in a person if Gram-negative bacteria enter the bloodstream

LPS (found on Gram-negative bacterial wall) binds to CD14 (receptor molecule), which is found on surface of macrophages and binds to TLR-4 If TLR-4 receptor is overactive, there will be an excessive amount of cytokine production Cytokines bind to receptors on target cells which stimulate the production of inflammatory mediators such as prostaglandins and leukotrienes, as well as activating both complement pathways and the coagulation pathway Excessive production of clotting factors may lead to ARDS and DIC while overproduction of prostaglandins, leukotrienes, and complement proteins can damage vascular endothelium, resulting in shock and MSOF

Name at least 5 PAMPs associated with bacteria

LPS from the gram-negative cell wall Peptidoglycan and lipoteichoic acids from the gram-positive cell wall The sugar mannose bacterial and viral unmethylated CpG DNA bacterial flagellin the amino acid N-formylmethionine found in bacterial proteins

In artificially acquired immunity, active immunization is preferred over passive immunization. Explain why.

Long-lived and proactive in fighting off deadly diseases.

Cytokines`

Low molecular weight, soluble proteins that are produce in response to an antigen and function as chemical messengers for regulating the innate and adaptive immune systems Three functional categories: Regulate innate immune responses Regulate adaptive immune responses Stimulate hematopoiesis

steps in phagocytosis: Destruction

Lysosomes (sacs produced by the Golgi apparatus) contain various digestive enzymes, microbicidal chemicals, and toxic oxygen radicals Lysosomes travel along microtubules within the phagocyte and fuse with the phagosomes containing microbes

State which type of T-lymphocyte recognizes epitopes from protein antigens on MHC-I molecules

MHC-I molecule with bound peptide on the surface of antigen-presenting dendritic cells - recognized by TCR/CD8 on the surface of a naive T8-lymphocyte to initiate cell-mediated immunity. MHC-I moleculewith bound peptide on the surface of infected cells and tumor cells - recognized by TCR/CD8 on the surface of a CTL to initiate destruction of the cell containing the endogenous antigen

State which type recognizes epitopes from protein antigens on MHC-II molecules.

MHC-II molecules - recognized by a naive T8-lymphocyte having a complementary shaped T-cell receptor (TCR) and CD8 molecule.

Name the cells in the tissue whose primary function is to present antigen to effector T-lymphocytes

Macrophages

State what type of monocytes differentiate into when they enter tissue

Macrophages (located throughout the body) Dendritic cells (located throughout the epithelium of the skin, respiratory tract, and GI tract as well as lymphoid tissues and organ parenchyma)

Name 2 endocytic PRRs

Mannose receptors → bind to microbial carbohydrates rich in mannose, fructose, and N-acetylglucosamine (NAG); may be important in removing lysosomal hydrolases produced in increased amounts during inflammation Dectin-1 → recognizes beta-glucans commonly found in fungal cell walls Scavenger receptors → found on the surface of phagocytic cells and bind to bacterial cell wall components Opsonin receptors → produced as part of the body's immune defenses that bind microbes to phagocytes Acute phase proteins (located in plasma) Complement pathway proteins (specifically C3b and C4b) Surfactant proteins in alveoli of lungs antibodies, IgG N-formyl Met receptors → receptors on neutrophils and macrophages that promotes motility and chemotaxis of phagocytes to promote phagocytosis

Describe the mechanism for Type IV (delayed) hypersensitivity and give 2 examples Delayed hypersensitivity is cell-mediated rather than antibody-mediated.

Mechanism: - T8-lymphocytesbecome sensitized to an antigen and differentiate into cytotoxic T-lymphocytes or, - CTLs while effector T4-lymphocytesbecome sensitized to an antigen and produce cytokines - CTLs, cytokines, eosinophils, and/or macrophages then cause harm rather than benefit Examples: The cell or tissue damage done during diseases like tuberculosis, leprosy, smallpox, measles, herpes infections, candidiasis, and histoplasmosis; The skin test reactions seen for tuberculosis and other infections; Contact dermatitis like poison ivy; Type-1 insulin-dependent diabetes where CTLs destroy insulin-producing cells

Describe the mechanism for Type III (immune complex-mediated) hypersensitivity and give 2 examples

Mechanism: Soluble antigen-antibody (IgG or IgM) complexes form in large amounts and overwhelm the body. They lodge in the capillaries and become trapped on the surrounding basement membrane. The complexes then activate the classical pathway. Examples: Massive Inflammation Influx of neutrophils MAC lysis

Describe the mechanism for Type V (Stimulatory) hypersensitivity and give an example

Mechanism: During type V hypersensitivity (stimulatory hypersensitivity) antibodies are made against a particular hormone receptor on a hormone-producing cell. This leads to the overstimulation of those hormone-producing cells. Example: Graves' disease - antibodies are made against thyroid-stimulating hormone receptors of thyroid cells. The binding of the antibodies to the TSH receptors results in constant stimulation of the thyroid leading to hyperthyroidism.

Describe the mechanism for Type I (IgE-mediated) hypersensitivity and give 3 examples. State how they are treated symptomatically.

Mechanism: IgE is made in response to an allergen. The Fc portionof IgE binds to the surface of mast cells and basophils. When the allergencross-links the Fab portions of the mast cell-bound IgE, this triggers histaminerelease by the mast cell (degranulation), and the synthesis of other inflammatory mediators. Examples: - Early phase allergic reactions - Late phase allergic reactions Treated symptomatically with such agents as: Epinephrine, Histamine H1-receptor antagonists, Beta2- agonists, etc.

Inflammation

vasodilation results in increased capillary permeability, enabling phagocytic WBCs such as neutrophils, monocytes, and eosinophils to enter the tissue around the injured site

Interferons

Modulate the activity of virtually every component of the immune system Induce uninfected cells to produce enzymes capable of degrading mRNA

State what is meant by pathogen-associated molecular patterns (PAMPs), and the role PAMPs play in inducing innate immunity

Molecules shared by groups of related microbes that are essential for the survival of those organisms and are not found associated with mammalian cells.

Briefly describe how monoclonal antibodies against the Fc portion of IgE may someday be used to prevent Type I allergies.

Monoclonal antibodies have been made against the Fc portion of human IgE. This, in turn, blocks the attachment of the IgE to the Fc receptors on mast cells and basophils and the subsequent release of histamine by those cells upon exposure to allergen

steps in phagocytosis: Chemotaxis

Movement of phagocytes toward an increasing concentration of some attractant such as bacterial factors, complement proteins, chemokines, fibrin split products, kinins, and phospholipid released by injured host cells

MALT (mucosa-associated lymphoid tissue)

Mucosal surfaces within the body, the most common sites of microbial invasion, are protected by the mucosal immune system consisting of the an extensive diffuse system of small concentrations of lymphoid tissue found in various sites of the body such as the gastrointestinal tract, thyroid, breast, lung, salivary glands, eye, and skin. MALT is populated by loose clusters of T-lymphocytes, B-lymphocytes, plasma cells, activated TH cells, and macrophages.

describe how NK cells recognize and kill infected cells and tumor cells that suppress MHC-I production

NK cells are also able to kill cells lacking MHC-I moleculestext annotation indicator on their surface. NK cells use a dual receptor system in determining whether to kill or not kill human cells. When cells are either under stress, are turning into tumors, or are infected, various stress-induced molecules such as MHC class I polypeptide-related sequence A (MICA) and MHC class I polypeptide-related sequence B (MICB) are produced and are put on the surface of that cell. Viruses, stress, and malignant transformation, however, can often interfere with the ability of the infected cell or tumor cell to express MHC-I molecules. Without the signal from the killer-inhibitory receptor, the kill signal from the killer-activating signal is not overridden and the NK cell kills the cell to which it has bound

Discuss how antibodies protect the body by way of ADCC by NK cells.

NK cellshave receptors on their surface for the Fc portionof certain subclasses of IgG. When IgG is made against epitopeson "foreign" virus-infected cells and cancer cells, the Fab portionsof the antibodies react with the "foreign" cell. The NK cells then bind to the Fc portion of the antibody. The NK cell then releases pore-forming proteins called perforins, proteolytic enzymes called granzymes, and chemokines. Granzymes pass through the pores and activate the enzymes that lead to apoptosisof the infected cell. As a result, the cell breaks into fragments that are subsequently removed by phagocytes. Perforins can also sometimes result in cell lysis.

Name 2 signaling PRRs found in the host cell cytoplasm

NOD-2 → recognizes muramyl dipeptide from bacterial peptidoglycan RIG-1 → recognizes viral RNA

State the role of T4-effector cells in the proliferation and differentiation of activated B-lymphocytes.

Naive B-lymphocytes become activated, proliferate, and differentiate into plasma cells in the germinal centers of lymphoid follicles while naive T-lymphocytes become activated, proliferate and differentiate into T-effector lymphocytes in the T-cell area.

Conventional immunodeficiency

Occurring as the result of a rare recessive genetic defect in the immune responses that involves the development of B/T lymphocytes that results in infections during infancy. Depending on the disorder, the lymphocytes in question were either completely absent, present in very low levels, or present but not functioning normally.

Define secondary immunodeficiency and list 4 possible contributing factors.

One is born with normal immune responses but some secondary factor or occurrence causes a decrease in immune responses 4 contributing factors: Malnutrition HIV virus Irradiation (exposure to x-rays and gamma rays) Cytotoxic drugs used in cancer therapy

major difference between the effect of the cytokines produced in response to PAMPs that bind to cell surface signaling and endosomal PRRs

PRRs found within cellular phagolysosomes (endosomes) typically detect nucleic acid PAMPs released during the phagocytic destruction of viruses and stimulate the production of antiviral cytokines called type-1 interferons (block viral replication within infected host cells as well as inflammatory cytokines)

beneficial effects of inflammation that are associated with plasma leakage and with diapedesis

Plasma flows out of the blood into the tissue which allows clotting factors, antibodies, complement proteins, nutrients, lysozymes, human defensins, and transferrin into the tissues Leukocytes enter tissue via diapedesis which increases phagocytosis, vasodilation, and allows more cytotoxic T-lymphocytes, effector T4-lymphocytes, and NK cells to ener infected tissue

what is meant by the phrase "Cytokines are pleiotropic, redundant, and multifunctional."

Pleiotropic → a particular cytokine can act on a number of different types of cells rather than a single cell type Redundant → different cytokines can carry out the same funcion Multifunctional → same cytokine is able to regulate a number of different functions

steps in phagocytosis: Ingestion

Polymerization and then depolymerization of actin filaments send pseudopods out to engulf the microbe and place it in an endocytic vessel called a phagosome Electron pump brings protons (H+) into the phagosome to lower the pH (more acidic) so when a lysosome fuses with phagosome, the pH is correct for the acid hydrolases to effectively break down cellular proteins Acidification also releases defensins, cathelicidin, and bacterial permeability inducing protein (BPI), peptides and enzymes that can kill microbes

State 2 functions of platelets

Promote clotting by sticking together after becoming activated Form platelet plugs to close up damaged capillaries Secrete cytokines and chemokines to promote inflammation

TFH cells:

Promote humoral immunityby stimulating antibody production and antibody isotypeswitching by B-lymphocytes.

TH17 cells:

Promote inflammatory response to stimulate a strong neutrophilresponse and promote the integrity of the skin and mucous membranes.

Describe how the ability of bacteria to sense their own population density, communicate with each other by way of secreted factors (cell-to-cell signaling), and behave as a population rather than as individual bacteria most likely plays an important role in pathogenicity for many bacteria

Quorum sensing - harmful exotoxins and enzymes act as a population making it harder for the immune system to effectively neutralize these harmful agents with antibodies.

Describe the overall function of antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B-lymphocytes in terms of the following: a. how they "process" exogenous antigens

Receptor-mediated phagocytosis and Macropinocytosis (a process where large volumes of surrounding fluid containing microbes are engulfed).

Describe what causes most of the tissue destruction seen during microbial infections

Released lysosomal contents → if the infection site contains a large number of microorganisms and high levels of inflammatory cytokines and chemokines are being produced, the phagocyte will empty the contents of its lysosomes extracellularly via degranulation

steps in phagocytosis: Activation

Resting phagocytes are activated by bacterial products, complement proteins, inflammatory cytokines, and prostaglandins Circulating phagocytes produce surface glycoprotein receptors that increase their ability to adhere to the inner surface of capillary walls, enabling them to squeeze out of the capillaries and travel to site of infection

Describe how desensitization (allergy) shots work to lessen the severity of Type I hypersensitivities.

Severity may be reduced by desensitization shots (allergy shots). It is thought that when very dilute allergen is given by injection, it stimulates the production of IgG and IgA. IgG and IgA then act as blocking antibodies to bind and neutralize much of the allergen in secretions before it can bind to the deeper cell-bound IgE on the mast cells in the connective tissue. The shots also appear to suppress production of IgE by inducing tolerance and/or by activating T8-suppressor cells.

4 processes that make up the inflammatory mechanism

Smooth muscles around large blood vessels contract to slow the flow of blood through capillary beds to allow more opportunity for leukocytes to adhere to walls of the capillary and squeeze out Endothelial cells of smaller blood vessels contract, increasing space between cells and resulting in increased capillary permeability (vasodilation) Selectins reversibly bind to glycoprotein receptors on the inner wall of the venule which allows leukocytes to roll along the inner wall. Adhesion molecules are activated on endothelial cells of the capillaries. Integrins attach to the adhesion molecules, allowing the leukocytes to flatten and squeeze through the spaces between the endothelial cells (diapedesis) Activation of the coagulation pathway causes fibrin clots to physically trap the infectious microbes and prevent their entry into the bloodstream

Describe one way Gram-negative bacteria may resist cytolysis

Some Gram-negative bacteria attach sialic acid to the LPS O antigen and this prevents the formation of the complement enzyme C3 convertase that is needed for the eventual formation of all the beneficial complement proteins such as C3b, C5a, and MAC.

Define antibody (also known as immunoglobulins)

Specific proteins produced by B-lymphocytes/plasma cells in response to a specific antigen and are capable of reacting with that antigen.

describe two specific examples of how an improper functioning PRR can lead to an increased risk of a specific infection or disease

Systemic Lupus Erythematosis (SLE) - people have a mutation in a gene that signals B-lymphocytes to undergo apoptosis, and as a result, these B-cells are able to bind and engulf the body's own DNA and RNA and place them in an endosome of phagolysosome where DNA is recognized by TLR-9 and RNA by TLR-7. These B-lymphocytes make antibodies against the body's own DNA and RNA Mutations in loss-of-function in the gene coding for NOD-2 that prevents NOD-2 from recognizing muramyl dipeptide - this makes a person more susceptible to Crohn's disease (inflammatory disease of large intestines)

Describe the overall function of T4-lymphocytes and their activation in terms of the following: b. What they recognize on antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B-lymphocytes

T-cell receptors in cooperation with CD4 molecules have a shape capable of recognizing peptides from exogenous antigens bound to MHC-II molecules on the surface of APCs such as dendritic cells, macrophages, and B-lymphocytes

The secondary anamnestic response peaks in only 1 - 3 days. This memory response applies to

T-dependent antigens.

a. combinatorial diversity

T-lymphocytes are able to cut out and splice together different combinations of genes along their chromosomes. Through random gene translocation, any combination of the multiple forms of each gene can join together.

State the role of T4-effector cells in activating macrophages.

T4-effector cells activate macrophages to to engulf exogenous antigens and place them in a phagosome. After lysosomes fuse with the phagosome, protein antigens are degraded by proteases into a series of peptides. These peptides eventually bind to grooves in MHC-II molecules and are transported to the surface of the APC. T4-lymphocytes are then able to recognize peptide/MHC-II complexes by means of their T-cell receptors (TCRs) and CD4 molecules.

Describe the overall function of T8-lymphocytes and their activation in terms of the following: a. the role of their TCRs and CD8 molecules

T8-lymphocytes are T-lymphocytes displaying a surface molecule called CD8. T8-lymphocytes also have T-cell receptors (TCRs) on their surface similar to those on T4-lymphocytes. The TCR on T8-lymphocytes, in cooperation with CD8, bind peptides from endogenous antigensbound to MHC-I molecules.

Name 2 signaling PRRs found on host cell surfaces

TLR-2 → recognizes peptidoglycan, lipoproteins, lipoteichoic acid, and porins TLR-4 → recognizes lipopolysaccharide (LPS) from Gram-negative cell wall, fungal mannans, viral envelope proteins, parasitic phospholipids, and heat-shock proteins TLR-5 → recognizes bacterial flagellin

Name 2 signaling PRRs found in the endosomes of phagocytic cells

TLR-3 → recognizes viral double-stranded DNA TLR-8 → recognizes viral single-stranded RNA TLR-9 → recognizes viral and bacterial unmethylated CpG sequences

compare active immunization with passive immunization in terms of tetanus prophylaxis.

Tetanus toxoid, diphtheria toxoid (active immunization) Tetanus Immune Globulin (passive immunization) See Chart: http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit6/humoral/activepassive/artificial/u3fg27.html

Discuss how antibodies protect the body by way of MAC cytolysis.

The Fab portionof IgG or IgM reacts with the epitopes on the membrane and the Fc portion of the antibody then activates the classical complement pathway. C5b6789n (MAC) then puts holes in the membrane.

d. what CTLs recognize on infected cells and tumor cells

The MHC-I molecules with bound peptide on the surface of the APCs are recognized by naive T8-lymphocytes possessing TCRs and CD8 molecules with a complementary shape. This recognition of the peptide epitope by the TCR serves as a first signal for activating the naive T8-lymphocyte for cell-mediated immunity function.

Describe the overall function of antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B-lymphocytes in terms of the following: c. the types of MHC molecule to which they attach peptides

The MHC-II molecules bind peptide epitopesfrom exogenous antigensand place them on the surface of the dendritic cell. Here the MHC-II/peptide complexes can be recognized by complementary shaped T-cell receptors (TCRs) and CD4 moleculeson naive T4-lymphocytes. MHC-I molecule with bound peptide on the surface of antigen-presenting dendritic cells can be recognized by a complementary-shaped TCR/CD8 on the surface of a naive T8-lymphocyte to initiate cell-mediated immunity

Describe the overall function of T4-lymphocytes and their activation in terms of the following: a. Their role of TCRs and CD4 molecules

The TCR recognizes the peptide while the CD4 molecule recognizes the MHC-II molecule.

When a person has hay fever, common symptoms include runny eyes, runny nose, swollen sinuses, and difficulty in breathing. In terms of humoral immunity, discuss the mechanism behind these symptoms. Also state the reason for giving antihistamines

The allergen is usually picked up by the blood and the reactions occur throughout the body. Antihistamines block the binding of histamine to histamine H1-receptors on target cells, eg, loratadine, fexofenadine, cetirizine.

b. how they are activated by antigen-presenting dendritic cells

The are activated by dendritic cells, they proliferate and differentiate into T8-effector lymphocytescalled cytotoxic T-lymphocytes (CTLs) that bind to and kill infected cells and tumor cells.

Discuss how antibodies protect the body by way of preventing bacterial adherence to host cells.

The binding of the Fab portionof the antibody to the adhesive tip of the pili, the cell wall adhesins, or the capsular molecules prevents the bacteria from adhering to and colonizing host cells. IgG - blocks adherence of bacteria in tissues IgA - blocks adherence of bacteria at mucosal surfaces within the body.

Describe how CTLs can react with and destroy virus-infected cells, cells containing intracellular bacteria, and cancer cells without harming normal cells.

The body marks infected cells and tumor cells for destruction by placing peptide epitopes from these endogenous antigens on their surface by way of MHC-I molecules. Cytotoxic T-lymphocytes (CTLs) are then able to recognize peptide/MHC-I complexes by means of their T-cell receptors (TCRs) and CD8 molecules and kill the cells to which they bind.

describe how the body recognizes an antigen as foreign.

The body recognizes an antigen as foreign when epitopes of that antigen bind to B-lymphocytes and T-lymphocytes by means of epitope-specific receptor molecules having a shape complementary to that of the epitope

The lymphoid System

The body uses the this system to enable lymphocytes to encounter antigens and it is here that adaptive immune responses are initiated.

Describe how bacterial antagonism by normal microbiota acts as a nonspecific body defense mechanism and name 2 opportunistic microbes that may cause superinfection upon destruction of the normal microbiota

The body's normal microbiota inhibit the growth or colonization of opportunistic pathogens and pathogens. Approximately 100 trillion bacteria and other microorganisms reside in or on the human body. The normal body microbiota keeps potentially harmful opportunistic pathogensin check and inhibits pathogens by: 1. Producing metabolic products (fatty acids, bacteriocins, etc.) that inhibit the growth of many pathogens; 2. Adhering to target host cells so as to cover them and preventing pathogens from colonizing; 3. Depleting nutrients essential for the growth of pathogens; and 4. stimulating the immune system. Destruction of normal bacterial microbiota by the use of broad spectrum antibiotics may result in superinfections or overgrowth by antibiotic-resistant opportunistic microbiota such as Candida and Clostridium difficile

Primary lymphoid organs

The bone marrow and the thymus B-lymphocytestext annotation indicator mature in the bone marrow while T-lymphocytestext annotation indicator migrate to the thymus and mature there.

Primary lymphoid organs

The bone marrow and the thymus constitute the primary lymphoid organs. Both B-lymphocytes and T-lymphocytes are produced from stem cells in the bone marrow. B-lymphocytes mature in the bone marrow while T-lymphocytes migrate to the thymus and mature there. After maturation, both naive B-lymphocytes and naive T-lymphocytes circulate between the blood and the secondary lymphoid organs.

Define and give at least one example of artificially acquired passive immunity.

The injection of antibody-containing serum, or immune globulin (IG) from another person/animal Example: Using of pooled adult human IG to prevent Hepatitis A and measles.

describe how the lectin pathway is activated

The lectinpathway is activated by the interaction of microbial carbohydrates with mannose-binding lectin (MBL) or ficolins found in the plasma and tissue fluids. (Lectins are carbohydrate-binding proteins.)

Give an example of naturally acquired active immunity.

The natural exposure to an infectious agent or other antigen by the body. The body responds by making its own antibodies.

Describe herd immunity and how it can protect selective populations of people

The resistance to the spread of a contagious disease within a population that results if a sufficiently high proportion of individuals are immune to the disease, especially through vaccination.

c. the type of MHC molecule to which they attach peptides

These peptides eventually bind to grooves in MHC-II molecules and are transported to the surface of the B-lymphocyte. Effector T4-lymphocytes are then able to recognize peptide/MHC-II complexes by means of their T-cell receptors (TCRs) and CD4 molecules.

State how iNKT cells recognize glycolipids in order to become activated

They have T-cell receptors (TCRs) on their surface for glycolipid antigen recognition TCRs recognize exogenous glycolipid antigens as well as self-glycolipid antigens presented by MHC-1 like molecules on antigen presenting dendritic cells Can also be activated by IL-12 produced by dendritic cells that have themselves become activated by PAMPs by binding to the PRRs of the dendritic cell

steps in phagocytosis: Attachment (both enhanced and unenhanced)

Unenhanced attachment - recognition of PAMPs by endocytic PRRs (such as scavenger receptors and mannose receptors on the surface of the phagocytes) Enhanced attachment (opsonization) - attachment of microbes to phagocytes by way of antibody molecules, the complement proteins C3b and C4b, and acute phase proteins such as mannose-binding lectin (MBL) and C-reactive protein (CRP); much more specific and efficient than unenhanced attachment

Define DAMPs and give two examples

Unique molecules displayed on stressed, injured, infected, or transformed human cells also be recognized as a part of innate immunity. Examples: Altered membrane phospholipids Heat shock proteins

two factors that can result in a nucleated human cell not producing MHC-I molecules

Viruses Malignant transformation

Describe the overall function of antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B-lymphocytes in terms of the following: b. how they "process" endogenous antigens

Viruses and bacteria are degraded into peptides by proteasomes.

Describe how NK cells are able to recognize and kill infected cells and cancer cells lacking MHC-I molecules

When cells are either under stress, are turning into tumors, or are infected, various stress-induced molecules are produced and are put on the surface of that cell Viruses and malignant transformation can sometimes interfere with the ability of the infected cell or tumor cell to express MHC-I molecules Without signal from the killer-inhibitory receptor, the kill signal from the killer-activating signal is not overridden, and the NK cell releases pore-forming proteins called perforins, proteolytic enzymes called granzymes, and chemokines Granzymes pass through pores and lead to apoptosis of infected cell

Chemokines

a group of cytokines that enable the migration of leukocytes from the blood to the tissues at the site of inflammation Increase affinity of integrins on leukocytes for ligands on vascular wall during diapedesis Regulate movement of B-lymphocytes, T-lymphocytes, and dendritic cells through lymph nodes and spleen

Hapten

a small molecule that by itself is not immunogenic but can act as an antigen when it binds to a larger protein molecule. (Ex: poison ivy)

State specifically how MAC cytolysis protects against the following:

a. Gram-negative bacteria - MAC can put holes in the outer membrane/cytoplasmic membrane of the Gram-negative cell wall causing lysis b. human cells recognized as nonself - MAC causes direct cell lysis c. enveloped viruses - MAC can damage the viral envelope

Epitope

actual portions or fragments of an antigen that react with receptors on B-lymphocytes and T-lymphocytes, as well as with free antibody molecules

Spleen

also contains many reticular fibers that support fixed macrophages and dendritic cells; blood carries microorganisms to the spleen where they are filtered out and phagocytosed by the fixed macrophages and dendritic cells and presented to B and T-lymphocytes to initiate adaptive immune responses

Oxygen-independent system: Defensins

alter cytoplasmic membranes

Immunogen

an antigen that is recognized by the body as nonself and stimulates an adaptive immune response

A left shift (elevated bands)

an increase in band forms typically occurring during acute infection

Passive immunity

antibodies from another person/animal enter the body. Since the body is not making its own antibodies or producing its own memory cells, the immunity is short lived.

Opsonization with IgG, C3b, C4b

antibodies of the isotype IgG, IgA, or IgM being made against a surface antigen of the organism or cell to be phagocytosed. The Fab portions of the antibody react with epitopes of the antigen. The Fc portionof IgG (but not IgM) can then bind to receptors on neutrophils and macrophages thus sticking the antigen to the phagocyte. The Fc portion of secretory IgA can also bind to macrophages and neutrophils for opsonization.

Innate immunity

antigen-nonspecific, occurs within several hours after exposure to any microbe; immunity at birth and is initial response by the body to eliminate microbes and prevent infection

Adaptive immunity

antigen-specific defense mechanisms that take several days to become protective and are designed to react with and remove a specific antigen; develops throughout one's life; takes several days for cells to proliferate and produce antibodies; Two major branches include humoral immunity (antibodies) and cell mediated immunity

exogenous antigen

antigens that enter from outside the body, such as bacteria, fungi, protozoa, and free viruses. They enter macrophages, dendritic cells, and B-lymphocytes through phagocytosis or pinocytosis.

autoantigen

any of an organism's own antigens (self-antigens) that stimulate an autoimmune reaction (immunity acting upon oneself).

dendritic cells enter lymphs vessels and...

are carried to regional lymph nodes. Here the microbes and other antigens in the lymph encounter changing populations of B-lymphocytes, are filtered out and phagocytosed by the fixed macrophages and dendritic cells, and are presented to changing populations of T-lymphocytes. Approximately 25 billion different lymphocytes migrate through each lymph node every day.

Oxygen-independent system: Cathelicidins

are directly toxic to a variety of microorganisms

C3b

attaches antigens to phagocytes for opsonization (enhanced attachment)

Immediate Innate Immunity:

begins 0 - 4 hours after exposure to an infectious agent and involves the action of soluble preformed antimicrobial molecules These include: antimicrobial enzymes and peptides; complement system proteins; and anatomical barriers to infection, mechanical removal of microbes, and bacterial antagonism by normal body microbiota.

State how long it takes for early induced innate immunity to become activated and what it involves

begins 4 - 96 hours after exposure to an infectious agent and involves the recruitment of defense cells as a result of PAMPSbinding to PRRs. These recruited defense cells include: phagocytic cells: leukocytes such as neutrophils, eosinophils, and monocytes; tissue phagocytic cells in the tissue such as macrophages; cells that release inflammatory mediators: inflammatory cells in the tissue such as macrophages and mast cells; leukocytes such as basophils and eosinophils; and natural killer cells (NK cells).

C3d

binds to CR2 receptors on B-lymphocytes which serves as a second signal for the activation of B-lymphocytes whose B-cell receptors have just interacted with their corresponding antigen

C4b

binds to adjacent proteins and carbohydrates on the surface of the antigen

functions of the following acute phase proteins: mannose-binding lectin (MBL)

binds to mannose-rich glycans and functions as an opsonin activating the lectin pathway

functions of the following acute phase proteins: C-reactive protein (CRP)

binds to teichoic acids and LPS of bacterial and fungal cell walls and functions as an opsonin, sticking the microorganism to phagocytes and activates the classical complement pathway

Oxygen-independent system: Lysozymes

break down peptidoglycan

Invarient NK T cells (iNKT)

bridge gap between innate and adaptive immunity; have TCRs for glycolipid antigen recognition and produce cytokines once activated; also play a regulatory role in development of autoimmune diseases and transplantation tolerance

C3a

can promote inflammatory responses that enable body defense cells and defense chemicals to leave the blood and enter the tissues

Lymph Vessels

carry these antigens, now in the lymph, to regional lymph nodes. In addition, immature dendritic cells located under the surface epithelium of the skin and the surface epithelium of the mucous membranes of the respiratory tract, genitourinary tract, and the gastrointestinal tract capture antigens through pinocytosis and phagocytosis

Briefly describe the process involved in the development of antibiotic-associated colitis

common in older adults. C. difficile survives the exposure to the antibiotic by sporulation. After the antibiotic is no longer in the body, the endospores germinate and C. difficile overgrows the intestinal tract and secretes toxin A and toxin B that have a cytotoxic effecton the epithelial cells of the colon.

Monocytes (2-8%)

compact nucleus and no visible granules Functions: Phagocytes Differentiate into macrophages and dendritic cells which leave the blood and enter tissues; important in phagocytosis and serve as antigen-presenting cells (APCs) in adaptive immune response; produce variety of cytokines Long-lived and CAN multiply

Skin

consisting of the epidermisand the dermis is dry, acidic, and has a temperature lower than 37 degrees Celsius (body temperature). These conditions are not favorable to bacterial growth. Resident normal microbiota of the skin also inhibits potentially harmful microbes. In addition, the dead, keratinized cells that make up the surface of the skin are continuously being sloughed off so that microbes that do colonize these cells are constantly being removed.

Lymph nodes

contain many reticular fibers that support fixed macrophages and dendritic cells as well as ever changing populations of circulating B-lymphocytes and T-lymphocytes.

Spleen

contains many reticular fibers that support fixed macrophages and dendritic cells as well as ever changing populations of circulating B-lymphocytes and T-lymphocytes. When microorganisms and other antigens enter the blood, they are transported by the blood vessels to the _________.

Lymph nodes

contains reticular fibers that support macrophages and dendritic cells that filter out and phagocytize organisms

Oxygen-dependent system: Oxidase (enzyme located in phagocyte cytoplasmic membrane)

converts oxygen into superoxide anion which can combine with water to form hydrogen peroxide and hydroxyl radicals Oxidase also acts as a proton pump to lower the pH within the phagosome

CD4 TH2 cells

coordinate immunity against helminths and microbes that colonize mucous membranes.

CD4 TH1 cells

coordinate immunity against intracellular bacteria and promote opsonization.

Describe the mechanism behind fever induction and indicate its possible benefits.

cytokines stimulate anterior hypothalamus to produce prostaglandin E2, which leads to an increase in bodily heat production and increased vasoconstriction (decrease of heat from skin and increase in body temperature Benefits: Increases environment temperature above optimum growth for many microorganisms Production of heat shock protein which results in production of inflammation-promoting cytokines Elevates temperature of the body increasing rate of enzyme reactions and speeding up metabolism within the body

Oxygen-independent system: Cathepsin G

damages microbial membranes

Antigen-Presenting Cells (APCs) include:

dendritic cells, macrophages, and B-lymphocytes. APCs express both MHC-Iand MHC-IImolecules and serve two major functions during adaptive immunity: 1. The capture and process antigens for presentation to T-lymphocytes 2. they produce signals required for the proliferation and differentiation of lymphocytes

Oxygen-independent system: Lactoferrin

deprices bacteria of needed iron

Unlike adaptive immunity, innate immunity does not recognize every possible antigen. Instead, it is designed to

designed to recognize molecules shared by groups of related microbes that are essential for the survival of those organisms and are not found associated with mammalian cells. These unique microbial molecules are called pathogen-associated molecular patterns.

Leukocyte differential count

determines the number of each type of leukocyte calculated as a percentage out of total number of leukocytes

Complete Blood Count (CBC)

determines the total number of leukocytes and erythrocytes per mI of blood

Name at least 2 PAMPs associated with viruses

double-stranded and single-stranded RNA from viruses

cytotoxic T-lymphocytes (CTLs)

effectordefense cells derived from naiveT8-lymphocytes.

MHC-I molecules

enable the body to recognize infected cells and tumor cells and destroy them with cytotoxic T-lymphocytesor CTLs.

Lysozyme

enzyme that breaks down peptidoglycan in bacterial cell walls (specifically bonds between NAG and NAM)

Phospholipase A2

enzyme that penetrates bacterial cell wall and hydrolyzes the phospholipids in the bacterial cytoplasmic membrane

Hyperpyrexia

fever with an extreme elevation of body temperature greater than or equal to 41.5C (106.7F)

Lactotransferrin and transferrin

found in body secretions, plasma, and tissue fluid; trap iron for use by human cells while preventing its use by microorganisms

Endocytic PRRs

found on the surface of phagocytes and promote the attachment of microorganisms to phagocytes leading to engulfment and destruction

Natural Killer (NK) cells

function to kill infected cells and tumor cells; able to kill cells to which antibodies have attached through antibody-dependent cellular cytotoxicity (ADCC); also kill human cells lacking MHC-I molecules

cytokines that are most important in stimulating acute inflammation Interleukin-1 (IL-1)

functions similarly to TNF-a and works synergistically with TNF to enhance inflammation. Functions: Promote inflammation Activate coagulation pathway Stimulate liver to produce acute phase proteins Catabolism of muscle and fat Inducing fever and sleep Stimulate synthesis of collagen and collagenase for scar tissue formation Stimulate synthesis of adhesion factors on endothelial cells and leukocytes for diapedesis Activate macrophages

State which classes (isotypes) of human antibodies possess the following characteristics: Are monomers

gG and IgD (both have 2 epitope-binding sites)

Pattern-recognition receptors (PRRs)

glycoprotein molecules on or in host cells that are able to recognize or bind to pathogen-associated molecular patterns in order to induce innate immunity; produce immediate response against microorganisms

Basophils (0-1%)

granules stain dark purple with methylene blue dye (basic); have a lobed nucleus Functions: Release histamine, leukotrienes, and prostaglandins which are all chemicals that promote inflammation by causing vasodilation, increasing capillary permeability, and increasing mucus production; produce heparin, platelet-activating factor (PAF), and IL-4 Life span is a few hours to a few days

Eosinophils (1-4%)

granules stain red with eosin (acidic dye) nucleus is lobed Functions: Granules contain destructive enzymes for killing infectious organisms Capable of phagocytosis but primarily release their contents into the surrounding environment to kill microbes extracellularly Substances released defend primarily against fungi, protozoa, and parasitic worms (helminths) -- pathogens that are too big to be consumed by phagocytosis Secrete leukotrienes and prostaglandins which are chemicals that promote inflammation by causing vasodilation and increasing capillary permeability; also secrete cytokines Life span is 8-12 days

C5b6789n (MAC)

helps to destroy Gram-negative bacteria as well as human cells displaying foreign antigens (virus infected cells, tumor cells, etc.) by causing their lysis; can also damage the envelope of enveloped viruses

Oxygen-dependent system: In neutrophils

hydrogen peroxide binds with chloride to form hypochlorous acid and singlet oxygen Neutrophils release oxidizing agents for the purpose of killing microbes extracellularly

State the primary function of mast cells in body defense

immunological first responder and carry out many of the same inflammatory- mediating functions as basophils granules contain histamine, eosinophil chemotactic factor, neutrophil chemotactic factor, platelet activating factor (PAF), and cytokines promote inflammation by causing vasodilation, increasing capillary permeability and increasing mucus production

Pyroptosis

inflammatory response-induced cell suicide as a result of PAMPs in the cytosol binding to cytoplasmic PRRs; leads to the release of PAMPs and inflammatory cytokines from the lysed cell

Oxygen-independent system: Collagenase

inhibits antimicrobial activity by breaking down proteins, RNA, phosphate compounds, lipids, and carbohydrates

Oxygen-independent system: Elastase

kills many types of bacteria

T-independent (TI) antigens

large carbohydrate and lipid molecules with multiple, repeating subunits. B-lymphocytes mount an antibody response to T-independent antigens without the requirement of interaction with effector T4-lymphocytes, but the resulting antibody molecules are generally of the IgM isotype only and do not give rise to a memory response.

An elevated White blood cell count

leukocytosis is seen in inflammation, leukemia, and parasitic infections

Mucous membranes

line body cavities that open to the exterior. The mucus is a physical barrier that traps microbes. Mucus also contains lysozyme to degrade bacterial peptidoglycan, an antibody called secretory IgAthat prevents microbes from attaching to mucosal cells and traps them in the mucous, lactoferrinto bind iron and keep it from from being used by microbes, and lactoperoxidaseto generate toxic superoxide radicals that kill microbes.

Secondary lymphoid organs

lymph nodes and the spleen, as well as less organized accumulations of lymphoid organs scattered strategically throughout the body. Adaptive immune responses require antigen-presenting cellstext annotation indicator, such as macrophages and dendritic cells, and ever changing populations of B-lymphocytes and T- lymphocytes annotation indicator. These cells gather to detect and present antigens in secondary lymphoid organs. The secondary lymphoid organs include highly organized lymphoid organs such as lymph nodes and the spleen

B-lymphocytes (B-cells)

mediate humoral immunity (antibodies) and have B-cell receptors on their surface for antigen recognition; 10-20% of lymphocytes are B-lymphocytes; most differentiate into antibody secreting plasma cells

To become activated, naive T4-lymphocytes...

migrate through lymph nodes where the TCRs on the T4-lymphocyte are able to sample large numbers of MHC-II/peptide complexes on the antigen-presenting dendritic cells for ones that "fit", thus enabling activation of that naïve T4-lymphocyte.

Danger-associated molecular patterns (DAMPS)

molecules displayed on stressed, injured, infected, or transformed human cells that can also be recognized as a part of innate immunity (ex: altered membrane phospholipids and heat shock proteins)

Danger recognition receptors (DRRs)

molecules in host cells that are able to recognize or bind to DAMPs in order to induce innate immunity; triggers the activation of inflammasomes, release of inflammatory cytokines, and pyroptosis

Pattern recognition receptors (PRRs)

molecules on/in host cells that are able to recognize or bind to PAMPs in order to induce innate immunity

Pathogen-associated molecular patterns (PAMPs)

molecules that are unique to microorganisms that are not associated with human cells. They include LPS, peptidoglycan, lipoteichoic acids, mannose, flagellin, pilin, bacterial DNA, and viral double-stranded RNA

Neutrophils (54-75%)

most abundant leukocyte; have a neutral color (granules do not stain well) and nucleus has multiple lobes Functions: important phagocytes granules contain various agents for killing microbes release enzyme Kallikrein that catalyzes the generation of bradykinins which promotes inflammation and cause vasodilation they produce enzymes that catalyze the synthesis of prostaglandins; certain prostaglandins promote inflammation by causing vasodilation and increasing capillary permeability short-lived and do not multiply; undergo apoptosis, produced in bone marrow

C5a

most potent complement protein triggering inflammation, becomes part of the Membrane Attack Complex (MAC)

Inflammasome

multiprotein complex that forms in macrophages as a result of PAMPs and DAMPs binding to their respective PRRs and DRRs that leads to an inflammatory response and the production of inflammatory cytokines

Oxygen-dependent system: In macrophages

nitric oxide combines with hydrogen peroxide to form peroxynitrite radicals

Signaling pattern recognition receptors (TLRs)

once they bind to PAMPs, they promote synthesis and secretion of cytokines, chemokines, and interferons that are crucial to innate immunity (and adaptive immunity)

Lymph nodules

phagocytize organisms through fixed macrophages and dendritic cells and present them to B-lymphocytes and T-lymphocytes to initiate adaptive immune responses

cytokines that are most important in stimulating acute inflammation Tumor necrosis factor-alpha (TNF-a)

principle cytokine that mediates acute inflammation; in excessive amounts, it also is the principle cause of systemic complications, such as the shock cascade. Functions: Acting on endothelial cells to stimulate inflammation and coagulation pathway Stimulate endothelial cells to produce selectins and ligands during diapedesis Stimulate endothelial cells and macrophages to produce chemokines Chemotaxis and recruitment of leukocytes Stimulate macrophages to secrete interleukin-1 for redundancy Activate neutrophils and promote extracellular killing Stimulate the liver to produce acute phase proteins (in plasma) Acting on muscles and fat to stimulate catabolism for energy conversion

Autophagy:

process that engulfs intracellular microbes and delivers them to lysosomes for degradation causes a phagophore to begin to form around the microbe and the surrounding cytosol, eventually forming an autophagosome A lysosome fuses with the autophagosome to form an autolysosome, and the microbe is destroyed

Oxygen-dependent system: killing systems of neutrophils and macrophages

production of reactive species (ROS)

CD4 TH17 cells

promote a local inflammatory response to stimulate a strong neutrophil response and promote the integrity of the skin and mucous membranes.

TFH cells

promote humoral immunity by stimulating antibody production and antibody isotype switching by B-lymphocytes.

endogenous antigen

proteins found within the cytosolof human cells

Cathelicidins

proteins produced by skin and mucosal epithelial cells that are toxic to a variety of microorganisms and can also bind to and neutralize LPS from Gram-negative walls to reduce inflammation

Oxygen-dependent system: Oxidizing free radicals are called

reactive oxygen species

The primary role of T4-lymphocytes is to

regulate the body's immune responses. Once naive T4-lymphocytes are activated by dendritic cells, they proliferate and differentiate into T4-effector lymphocytesthat regulate the immune responses by way of the cytokinesthey produce.

Name 4 categories of conventional immunodeficiencies and give an example of each

1. B-lymphocyte Disorders (decreased humoral immunity) 2. Hypogammaglobulinemia/Isotype Defects (decreased antibody production) 3. T-lymphocyte Disorders (little to no cell-mediated immunity) 4. Combined B- and T-lymphocyte Disorders (affects both humoral and cell-mediated immunity)

describe 2 different ways bacteria may resist antibodies that block bacterial adherence to host cells

1. Bacteria can produce immunoglobulin proteaseswhich can degrade the protective IgA found in mucus. 2. Bacteria can evade antibodies is by changing the adhesive tips of their pili as seen with Neisseria gonorrhoeae. Bacteria can also vary other surface proteins so that antibodies already made will no longer "fit."

List 3 different forms of antigen that may be used for artificially acquired active immunity and state 2 common examples of each.

1. Fragments of microorganisms (meningococcal meningitis: contains capsular polysaccharide from 4 strains of Neisseria Meningitidis / PVC 23 containing capsular material from the 23 most serious strains of S. pneumoniae in adults) 2. Killed or inactive microbes (Rabies vaccines containing killed rabies viruses / hepatitis A vaccine containing inactivated hepatitis A virus) 3. Vaccines produced by recombinant DNA technology (Cervarix and Gardasil, vaccines against HPV types 16 and 18 and types 6, 11 / RVS, an oral vaccine against human rotavirus gastroenteritis.

Describe two different ways antibodies defend the body by promoting an inflammatory response and state the importance of inflammation.

1. IgG and IgM can activate the classical complement pathway The complement pathway is activated when a complement protein complex called C1 interacts with the Fc portion of the antibody molecule isotypes IgG or IgM after they have bound to their specific antigen via their Fab portion. The C1q is the portion of the C1 complex that binds to the antibodies or the microbe. The binding of C1q activates the C1r portion of C1 which, in turn, activates C1s. This activation gives C1s enzymatic activity to cleave complement protein C4 into C4a and C4b and C2 into C2a and C2b and begin the classical complement pathway. 2. IgA - Activates the lectin/alternative complement pathway and C5a, C3a, and C4a trigger inflammation. IgE - Binds to mast cells and basophils and trigger release of inflammatory cytokines (The Fc portion of IgE can bind to receptors on mast cells and basophils. Cross linking of the cell-bound IgE by antigen triggers the release of vasodilators)

Mannose-binding lectin (MBL)

1. MBL is a soluble pattern-recognition receptor (PRR) that binds to various microbial carbohydrates such as those rich in mannose or fucose, and to N-acetylglucosamine (NAG). 2. Both mannose-binding lectin (MBL) and ficolin form complexes with MBL-associated serine proteases called MASP1 and MASP2, which are equivalent to C1r and C1s of the classical pathway. a. The binding of the MBL (or the ficolin) to the microbial carbohydrate activates the associated MASP2 giving it the enzymatic activity to split C4 into C4a and C4b

State which body cells display MHC-I surface molecules

1. MHC-I molecules present epitopesto T8-lymphocytes. - Cytokines such as interferon-alpha, interferon-beta, interferon-gamma, tumor necrosis factor increase the expression of MHC-I molecules

two examples of naturally acquired passive immunity and state why this is important to newborns and infants.

1. The placental transfer of IgG from mother to fetus during pregnancy. These antibodies generally last 4 to 6 months following birth. The immune responses reach full strength at about age 5. 2. The IgA and IgG found in human colostrum and milk of babies who are nursed. Breast-fed infants have a lower incidence of gastrointestinal infections, ear infections, atopic dermatitis, respiratory infections, urinary tract infections, meningitis, type 2 diabetes, and sudden infant death syndrome.

Importance of Inflammation: The beneficial results of the activated complement proteins include:

1. Triggering inflammation: C5a>C3a>C4a. 2. Chemotactically attracting phagocytes to the infection site: C5a; 3. Promoting the attachment of antigens to phagocytes via enhanced attachment or opsonization: C3b>C4b 4. Causing the lysis of Gram-negative bacteria, viral envelopes, and human cells displaying foreign epitopes

List 3 groups of noninfectious materials that may act as an antigen.

1. allergens, including dust, pollen, hair, foods, dander, bee venom, drugs, and other agents causing allergic reactions; 2. Foreign tissues and cells from transplants and transfusions; and 3. The body's own cells that the body fails to recognize as "normal self," such as cancer cells, infected cells, and autoantigensinvolved in autoimmune diseases.

Defensins

short cationic peptides, 30-40 amino acids long, that disrupt the cytoplasmic membrane of a variety of microorganisms causing leakage of cellular needs; also activates cells for inflammatory response

which cells normally display MHC-II surface molecules.

2. MHC-II molecules presents epitopes to T4-lymphocytes. - interferon-gamma is the main cytokine to increase the expression of MHC-II molecules

describe how NK cells bind to and kill infected cells and tumor cells through ADCC.

2. NK cells play a role in adaptive immune responses by way of antibody-dependent cellular cytotoxicity or ADCC where they bind to and kill cells to which antibody molecules have bound. 3. During ADCC, the Fab portion of the antibody binds to epitopes on the "foreign" cell. The NK cell then binds to the Fc portion of the antibody and the NK cell is then able to contact and kill the cell by inducing a programmed cell suicide called apoptosis.

Early induced innate immunity

4-96 hours after exposure; involves recruitment of defense cells as a result of PAMPs binding to PRRs Phagocytic cells → leukocytes such as neutrophils, eosinophils, monocytes, macrophages Cells that release inflammatory mediators → mast cells, basophils, eosinophils Natural killer cells

State what happens when either phagocytes are overwhelmed with microbes, or they adhere to cells too large to be phagocytosed

A phagocyte will empty the contents of its lysosomes extracellularly if the cell to which the phagocyte adheres is too large to be engulfed

In terms of humoral immunity, state what is meant by anamnestic response and discuss its role in immune defense.

A rapid heightened response against an antigen upon re exposure as a result of circulating B-memory cells, T4-memory cells, and T-8 memory cells. More exposure results in: - rapid production of antibodies - produced in greater amounts and for a longer period of time

adjuvant

A substance that enhances the body's immune response to an antigen.

Define gene translocation and relate it to each T-lymphocyte being able to produce T-cell receptor with a unique shape.

A unique system of gene-splicing evolved from B and T lymphocytes involving the movement and joining of genes from different locations along chromosomes to produce a new functional coding unit.

Secondary lymphoid organs

Adaptive immune responses require antigen-presenting cells, such as macrophages and dendritic cells, and ever changing populations of B-lymphocytes and T- lymphocytes. These cells gather to detect and present antigens in secondary lymphoid organs. lymph nodes and the spleen

Describe the overall function of antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B-lymphocytes in terms of the following: d. the role of proteasomes in the binding of peptides from endogenous antigens by MHC-I molecules.

After being broken down into peptides by proteasomes, peptideepitopes attach to a groove of MHC-I molecules that are then transported to the surface of that cell where they can be recognized by a TCR and a CD8 molecule on the surface of either a naive T8-lymphocyte or cytotoxic T-lymphocyte.

d. the role of lysosomes in binding of peptides from exogenous antigens by MHC-II molecules

After lysosomes fuse with the phagosome (phagolysosome), protein antigens are degraded by proteases into a series of peptides.

Discuss the how antibodies protect the body by agglutinating microorganisms.

Agglutination (the clumping of particles) is mainly a function of antibodies with multiple reactive Fab sitessuch as IgM and IgA. The Fab portion of the antibodies links microorganisms together (causes them to agglutinate) so they can be phagocytosed more effectively.

Innate Immunity:

An antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to almost any microbe. This is the immunity one is born with and is the initial response by the body to eliminate microbes and prevent infection.

f. the types of cells into which activated B-lymphocytes differentiate

An effector T4-lymphocyte, such as a TFH cell, use its TCRs and CD4 molecules to bind to a complementary shaped MHC-II molecules with attached peptide epitope on an activated B-lymphocyte. This interaction triggers the T4-lymphocyte to produce cytokines that enable the activated B-lymphocyte to proliferate, differentiate into antibody-secreting plasma cells, and switch classes of the antibodies being made.

Extra Credit Material: primary immunodeficiency.

An immunodeficiency that one is born with

describe 2 different ways bacteria may resist opsonization

An outer membrane molecule of Neisseria gonorrhoeae called Protein II and the M-protein of Streptococcus pyogenes allow these bacteria to be more resistant to phagocytic engulfment. S. pneumonia activates the classical complement pathway, but resists C3b opsonization, and complement causes further inflammation in the lungs. Some bacteria are able to coat themselves with host proteins such as fibronectin, lactoferrin, or transferrin. This prevents antibody molecules from binding to epitopes on the bacterial surface

T-cell receptors

Analogous to the B-cell receptor, but are composed of just two glycoprotein chains, each having a variable domain and a constant domain. TCR of most T4-lymphocytesand T8-lymphocytescan only recognize peptide epitopes from protein antigens presented by the body's own cells by way of special molecules called MHCmolecules The terminal portion of the variable domains provides specificity for binding peptides of protein antigens after the protein has been unfolded, broken into peptides, and bound to a MHC molecule.

Discuss how antibodies protect the body by immobilizing bacteria and protozoans.

Antibodies are made against the flagella of motile bacteria or the flagella or cilia of motile protozoans. The Fab portions of the antibodies bind to epitopes on these locomotor organelles and arrest the organism's movement blocking its ability to spread via taxis and motility.

Discuss how antibodies defend the body by way of neutralizing viruses.

Antibodies are made against viral capsids or envelope glycoproteins where the Fab portion binds to and covers the viral attachment molecules. This prevents viral adsorption to host cells. Neutralizing antibodies are especially important in preventing viral reinfection. IgG neutralizes viruses in tissues while IgA neutralizes viruses at mucosal surfaces within the body.

e. the type of cell to which they present peptides

Antigen-presenting dendritic cells

Describe the overall function of antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B-lymphocytes in terms of the following: e. the role of lysosomes in the binding of peptides from exogenous antigens by MHC-II Molecules.

Antigen-presenting dendritic cells produce both MHC-I and MHC-II molecules. These APCs can phagocytose infected cells and tumor cells, place them in phagosomes, and degrade them with lysosomes.

State the role of lysosomes in binding of peptides from exogenous antigens by MHC-II molecules

Antigen-presenting dendritic cells produce both MHC-I and MHC-II molecules. These APCs can phagocytose infected cells and tumor cells, place them in phagosomes, and degrade them with lysosomes.

Adaptive Immunity:

Antigen-specific defense mechanisms that take several days to become protective and are designed to react with and remove a specific antigen. This is the immunity one develops throughout life. antigen-presenting cells (APCs) such as macrophagesand dendritic cells; the activation and proliferation of antigen-specific B-lymphocytes; the activation and proliferation of antigen-specific T-lymphocytes; and the production of antibody molecules, cytotoxic T-lymphocytes (CTLs), activated macrophages, and cytokines.

Antigen

substance that reacts with antibody molecules and antigen receptors on lymphocytes

State what antigens are composed of chemically.

Antigens are large molecular weight proteins (including conjugated proteins such as glycoproteins, lipoproteins, and nucleoproteins) and polysaccharides (including lipopolysaccharides)

Active immunity

Antigens enter the body and the body responds by making its own antibodies and B-memory cells, making the immunity long lived.

Define endogenous antigen and state which class of MHC molecule primarily binds each.

Antigens found within cytosol of cells. MHC-I molecules bind peptide epitopes, typically 8-11 amino acids long, typically from endogenous antigens

Define exogenous antigen and state which class of MHC molecule primarily binds each.

Antigens that enter from outside the body and are located outside host cells. some antigen-presenting dendritic cells can cross-present epitopes of exogenous antigensto MHC-I molecules for eventual presentation to naive T8-lymphocytes.

Bony encasements

such as the skull and the thoracic cage, protect vital organs from injury and entry of microbes.

B-cell receptors

Are antibody molecules made by the cell and anchored to the outer surface of its cytoplasmic membrane. Antibodies are "Y" shaped macromolecules composed of four glycoprotein chains connected by disulfide (S-S) bonds and noncovalent bonds. The Fab portion of the antibody has specificity for binding an epitope of an antigen. The Fc portion directs the biological activity of the antibody. B-cell receptors can bind directly to epitopes on peptide, protein, polysaccharide, nucleic acid, and lipid antigens.

In terms of cell-mediated immunity, state what is meant by anamnestic response and discuss its role in immune defense.

As a result of T-lymphocytes recognizing epitopes of protein antigens during cell-mediated immunity, numerous circulating T8-memory cellsand T4-memory cellsdevelop which possess anamnestic responseor memory >> A rapid, heightened secondary response upon re-exposure of an antigen.

can be activated by both T-dependent antigens and T-independent antigens.

B-Lymphocytes

In order for naive B-lymphocytes to proliferate, differentiate, and mount an antibody response against T-dependent antigens (most proteins)

B-lymphocytes must interact with effector T4-lymphocytes called TFH cells.

Induced innate immunity:

Begins 4 - 96 hours after exposure to an infectious agent and involves the recruitment of defense cells as a result of pathogen-associated molecular patterns or PAMPS binding to pattern-recognition receptors or PRRs. These recruited defense cells include: phagocytic cells: leukocytes such as neutrophils, eosinophils, and monocytes; tissue phagocytic cells in the tissue such as macrophages; cells that release inflammatory mediators: inflammatory cells in the tissue such as macrophages and mast cells; leukocytes such as basophils and eosinophils; and natural killer cells (NK cells).

describe the problems that arise from chronic inflammation

Build up of reactive oxygen species destroys surrounding tissue and is replaced with scar tissue SIRS, including hypotension, tissue destruction and wasting, ARDS, DIC, hypovolemia, MSOF, and even death Heart disease, Alzheimer's, diabetes, cancer

Define and give at least one example of artificially acquired active immunity.

By giving a safe form of the antigen artificially, the body will produce its own antibodies and develop long-lived memory cells. Example: Influenza vaccines

After activation of naive T-4 lymphocytes....

the dendritic cell produces cytokines that contribute to proliferation of the T4-lymphocytes and their differentiation into effector T4-lymphocytes, the cells the body uses to regulate both humoral immunity and cell-mediated immunity through the cytokines they produce.

describe how the classical complement pathway is activated

C1 is activated by interacting with Fc portion of antibody molecules after they are bound to an antigen via Fab portion C1 complex consists of C1q, C1r, C1s C1q activates C1r, which activates C1s to cleave C4 into C4a and C4b and C2 into C2a and C2b C4b and C2a combine to form C4b2a (C3 convertase) which cleaves hundreds of molecules of C3 into C3a and C3b C3b binds to C3 convertase to form C5 convertase that cleaves C5 into C5a and C5b

describe how the alternative complement pathway is activated

C3b binds to the cell wall and other surface components of microbes/IgG antibodies. protein Factor B then combines with the cell-bound C3b to form C3bB. Factor D then splits the bound Factor B into Bb and Ba, forming C3bBb. A serum protein called properdin then binds to the Bb to form C3bBbP that functions as a C3 convertase ---> enzymatically splits hundreds of molecules of C3 into C3a and C3b. The alternative complement pathway is now activated.

T4-lymphocytes

CD4 molecules and T-cell receptors (TCRs) on their surfaces; function to regulate adaptive immunity through cytokine production

T8-lymphocytes

CD8 molecules and TCRs on surface, differentiate into cytotoxic T-lymphocytes (CTLs)

State the mechanism by which cytotoxic T-lymphocytes kill the cells to which they bind.

CTLs are able to kill virus infected cells by inducing a programmed cell death known as apoptosis. When the TCRand CD8of the CTL binds to the MHC-I/epitopeon the surface of the virus-infected cell or tumor cell, this sends a signal through a CD3 molecule which triggers the release of the cytotoxic perforins/granzymes/granulysin granules from the CTL: Perforins - polymerize and form pores in the membrane of the infected cell, increasing the permeability of the infected cell, contributing to cell death. Granzymes - activate the caspase enzymes that lead to apoptosis of the infected cell. Caspases - proteases that destroy the protein structural scaffolding of the cell - the cytoskeleton - and nucleases that degrade both the target cell's nucleoprotein and any microbial DNA within the cell Macrophages - removes membrane-bound apoptotic fragments of the infected cell after it is destroyed

from what cells cytotoxic T-lymphocytes are derived

CTLs are defense cells derived from naive T8-lymphocytes

Novel immunodeficiency

Common less severe immunodeficiencies that involve the decreased ability to combat just one type of infection.

State the primary function of dendritic cells in body defense

the primary function of dendritic cells is to capture and present protein antigens to naive T-lymphocytes they engulf and degrade w/ their lysosomes peptides from microbes bind to MHC-II molecules and then are put on the surface of the dendritic cell TCR, CD4 molecules on naive T4-lymphocytes recognize

TH2 cells:

Coordinate immunity against helminths and microbes that colonize mucous membranes.

Compare TH1, TH2, TH17, Treg, and TFH lymphocytes in terms of their primary function(s) in immunity TH1 Cells

Coordinate immunity against intracellular bacteria and promote opsonization.

State what DTaP stands for and what specifically is being injected with the DTaP vaccine.

DTaP is a vaccine for children to make them immune against three deadly diseases caused by bacteria: diphtheria, tetanus and whooping cough. The diphtheria and tetanus components of a toxoid antigen are injected.

4 ways the body deprives microorganisms of iron

Decreased intestinal absorption of iron from diet Decrease of iron in plasma and increase in storage of iron as ferritin Increase in synthesis of human iron-binding proteins, making it unavailable to microbes Decreased ability of bacteria to synthesize their own iron chelators via fever

e. how CTLs kill infected cells and tumor cells

Dendritic cell produces cytokines such as interleukin-6 (IL-6), IL-4, IL-12, and T-cell growth factor-beta (TGF-β) that contribute to proliferation of the T8-lymphocytes and their differentiation into effector T8-lymphocytes (CTLs) that are able to bind to and kill infected cells and tumor cells displaying the same peptide/MHC-I complex on their surface.

Name the primary type of cell that functions as an antigen-presenting cell to naive T4-lymphocytes and naive T8-lymphocytes.

Dendritic cells - Both T4 and T8 Antigen-presenting cells - T8 Infected cells and tumor cells - T8

Describe the overall function of antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B-lymphocytes in terms of the following: f. the types of cells to which they present peptides

Dendritic cells, infected cells, tumor cells, antigen-presenting cells

b. junctional diversity

During gene translocation, specialized enzymes in the T-lymphocyte cause splicing inaccuracies wherein additional nucleotides are added or deleted at the various gene junctions. This change in the nucleotide base sequence generates even greater diversity in Fabshape. Each T-lymphocyte becomes genetically programmed to produce a T-cell receptor (TCR) having a unique shape to fit a specific epitope. The T-cell receptors involved in adaptive immunity consist of an alpha (α) and a beta (β) chain. The variable domains of the α and β chains (red) provide specificity for binding a peptide bound to a MHC molecule. The terminus of the constant domains (purple) anchors the receptor to the cytoplasmic membrane of the T-lymphocyte. (S-S = disulfide bond).

State the overall function of T8-lymphocytes in adaptive immunity

During its development, each T8-lymphocyte becomes genetically programmed, by gene-splicing reactions similar to those in B-lymphocytes and T4-lymphocytes, to produce a TCR with a unique shape capable of binding epitope/MHC-I complex with a corresponding shape.

State the role of proteasomes in binding of peptides from endogenous antigens by MHC-I molecules.

During the replication, viral, bacterial, or tumor proteins are degraded into a variety of peptide epitopes by organelles proteasomes (Use ATP to digest proteins into peptides). Endogenous antigens pass through proteasomes where they are degraded into a series of peptides.The peptides then bind to the grooves of newly synthesized MHC-I molecules.

Describe the overall function of B-lymphocytes and their activation by T-dependent antigens in terms of the following: a. the antigen receptor on their surface

Each B-lymphocyte becomes genetically programmed, through a process called gene translocation, to make a unique B-cell receptor. Molecules of that B-cell receptor are placed on its surface where it can react with epitopes of an antigen.

describe the process of diapedesis, indicated the role of P-selectins, integrins, and adhesion molecules

Early in inflammation, injury or infection triggers the release of leukotrienes, prostaglandins, and histamine which cause vasodilation and contraction of endothelial cells Binding of histamine triggers upregulation of P-selectin molecules and platelet activating factor (PAF) on endothelial cells of the venule Binding of PAF upregulates surface expression of LFA-1 on leukocyte and this binds firmly to intercellular adhesion molecule (ICAM-1) on endothelial cells Leukocytes flatten out, squeeze between endothelial cells, and move along basement membrane as they are attracted to chemotactic agents generated by cells at the site of the injury

Briefly describe why there is a heightened secondary response during anamnestic response

Effector memory T-cells (TEM cells) circulate in the blood whereas tissue resident memory T-cells (TRM cells) are found within the epithelium of the skin and mucous membranes. A subsequent exposure to that same antigen results in: A more rapid and longer production of cytotoxic T-lymphocytes (CTLs) A more rapid and longer production of T4-effector lymphocytes Triggering of nonspecific innate immune responses.

b. how they "process" exogenous antigens

Epitopes of exogenous antigens, such as viruses, bind to a complementary shaped B-cell receptor on a B-lymphocyte. The antigen is engulfed and placed in a phagosome.

describe two ways certain viruses may evade cell-mediated immunity

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) inhibit proteasomal activity so that viral proteins are not degraded into viral peptides Herpes simplex viruses (HSV) can block the TAP transportof peptides into the endoplasmic reticulum Adenoviruses and Epstein-Barr Viruses (EBV) code for proteins that blocks apoptosis

Describe the overall function of T4-lymphocytes and their activation in terms of the following: c. The role of antigen-presenting dendritic cells in the activation of naive T4-lymphocytes

Exogenous antigens enter antigen-presenting dendritic cells through phagocytosis. The microbes are engulfed and placed in a phagosome, then are degraded by lysosomes into peptides. The peptides bind to MHC-II molecules and transported to the surface of an APC. T4-lymphocytes are then able to recognize peptide/MHC-II complexes by means of their T-cell receptors (TCRs) and CD4 molecules.

Like IgG, C3b, and to a lesser extent C4b, can function as opsonins, that is..

they can attach antigens to phagocytes. One portion of the C3b binds to proteins and polysaccharides on microbial surfaces; another portion attaches to CR1 receptors on phagocytes, B-lymphocytes, and dendritic cells for enhanced phagocytosis

Discuss how antibodies protect the body by way of neutralizing exotoxins.

For an exotoxin to cause harm it must first bind to receptors on a susceptible host cell. Antitoxin antibodies are made against microbial exotoxins. The Fab portionbinds to the exotoxin molecules before they can interact with host target cells and thus neutralizes the toxin. IgG neutralizes toxins in tissues while IgA neutralizes toxins at mucosal surfaces within the body.

Lymphocytes (25-40%)

Functions: Mediate the adaptive immune responses Only small portion are found in the blood; majority are found in lymphoid tissue Circulate back and forth between the blood and the lymphoid system of the body Life span of days to years 3 major populations

The primary role of T8-lymphocytes is to

to kill infected cells and tumor cells by inducing apoptosis of those cells. Once naive T8-lymphocytes are activated by dendritic cells, they proliferate and differentiate into T8-effector lymphocytescalled cytotoxic T-lymphocytes (CTLs)that bind to and kill infected cells and tumor cells.

In terms of infectious disease, state what humoral immunity is most effective against

Humoral immunity is most effective against microbes or their toxins located in the extracellular spaces of the body.

Anatomical barriers

tough, intact barriers that prevent the entry and colonization of many microbes. Examples include the skin, the mucous membranes, and bony encasements.