Exam 2

Oral Tolerance

Can be induced by feeding antigens. Mechanism is not fully understood.

Professional Antigen Presenting Cell (3)

Cells responsible for class II presentation of antigen. This class includes the phagocytes, with the exception of neutrophils. Includes: 1. Macrophages 2. Dendritic cells 3. B cells

CD

Cluster of differentiation. Name for receptors found on lymphocytes. Interacts with the MHC molecule, not the antigen. Gives MHC specificity.

T Cell Receptor Beta Chain

Composed of a variable and constant region. Variable region is rearranged in the thymus and matches D-J and then V.The beta chain has a repeat of the J and D regions that does not impact function.

T Cell Receptor Alpha Chain

Composed of a variable and constant region. Variable region is rearranged in the thymus and matches V-J and then D.

MHC Class I

Constitutively expressed on the surface of all cells. Single chain non-covalently associated with beta 2-microglobulin. Presents endogenous antigens (from inside the cell's cytoplasm) to cytotoxic T cells (CD8+). Important for virus-infected and tumor cells. Binding pocket holds 8-12 amino acids.

Subunit Vaccine (4)

Contains some part or product of a micro-organism that can produce an immune response. Disadvantage is that immunity is only stimulated against a single protein, whcih may not impart full protection. Includes: 1. Recombinant 2. Toxoid 3. Conjugated 4. Acellular

Chemokines

Cytokines that cause chemotaxis. Four broad classes of chemokines: 1. CL# 2. CCL# 3. CX3CL# 4. CXCL# Where C = cysteine, X = amino acid, L = ligand. They bind four categories of receptors expressed on the surface of leukocytes. The categories correspond to chemokine classes, with R (receptor) replacing L.

CD8+ T Cell

Cytotoxic T cell, kills target cells infected with viruses or displaying neoplastic antigens bound to Class I MHC molecules. Cytolytic mechanism involves rapid release of granules containing cytotoxins. This is cell specific and does not damage neighboring cells. These include: 1. Perforin 2. Granzymes 3. Lymphotoxin

Perforin

Cytotoxin produced by CD8+ T cells. Polymerizes on cell membrane to form a pore.

Granzymes

Cytotoxins produced by CD8+ cells. Serin proteases which cleave proteins on target cell membrane.

DAMPs

Damage-associated molecular patterns, found on host cells and trigger inflammation.

Leukocyte Adhesion Deficiency 1

Defect of neutrophil adhesion caused by LFA-1 and Mac-1 subunit defects. Occurs in humans, cattle, dogs.

Chediak-Higashi Syndrome

Defect of neutrophil chemotaxis/phagocytosis caused by microtubule defect which leads to impaired locomotion and lysosomal degranulation. Occurs in humans and cattle.

Chronic Granulomatous Disease

Defect of neutrophil microbicidal activity cuased by deficiency of NADPH oxidase that generates superoxide, therefore no oxygen-dependent killing of bacteria can occur.

Passive Immunization (2)

Defined as the protection of one individual via transfer of antibodies (or B or T cells) from another individual. Is usually short lived and can induce hypersensitivity reactions or transfer other infectious agents. Two types: 1. Natural 2. Artificial

Follicular Dendritic Cell

Dendritic cell found in B cell areas.

Interdigitating Dendritic Cell

Dendritic cell found in T cell areas.

Macrophages

Derived from myeloid progenitor cells in the bone marrow and peripheral tissues. Are highly phagocytic and present processed antigens to CD4+ T cells. They also regulate immunocytes, mediate pathogen killing, stimulate tissue repair and respond quickly to changes in microenvironment. Highly polymorphic based on tissue site.

CD4+ Treg Cell

Differentiates from naiive helper T cells in response to TGF-beta, acts on T cells and macrophages. They are created from self-reactive CD4+ T cells in the thymus by TSLP stimulated dendritic cells, and function in muting the response to self-antigen. Produce autoinflammatory cytokines IL-10 and TGF-beta that inhibit other T cells. Also inhibit APC activation, bind cytokines needed for survival, and may kill autoreactive T cells directly.

Chemotaxis

Directed leukocyte migration within tissues.

Localized Effects of Inflammation

Due to inflammatory factors released at the site of the injury. These factors increase vasodilation and permeability and increase leukocyte recruitment and activation.

Systemic Effects of Inflammation

Due to inflammatory factors released into the circulation. May include fever, increased blood pressure, loss of appetite, leukocytosis, and acute-phase proteins.

Increased Vascular Permeability

Endothelial cells contract permitting the passage of protein rich fluid. Vascular effect of inflammation. Triggered by: 1. Histamine 2. Serotonin 3. C3a 4. C5a 5. Bradykinin 6. Leukotrienes 7. Platelet-activating Factor 8. Substance P

IDO

Enzyme that depletes tryptophan in the fetus to starve autoreactive T cells and trigger antigen tolerance.

MHC Class II

Expressed predominantly on immunocytes, consists of two polymorphic chains (alpha and beta) that fold together to form a binding pocket for processed antigens. Presents exogenous antigens (from outside of the cell) to helper T cells (CD4+) to induce immune response, including antibody production, macrophage activation, and cytokine cascades. Important for exogenous threats such as bacteria, fungi, and parasites. Binding pocket fits 13-20 amino acids.

Transudate

Fluid escaping the blood vessels during vasodilation. Is extravascular fluid with low levels of protein.

FAST

Focused Assessment Sonographic Technique - refers to ultrasound of four key points on the thorax and abdomen.

Memory B Cells

Formed in the germinal center during a primary immune response and serve to generate an accelerated antibody response upon re-exposure. The antibodies produced will be affinity-matured IgG, IgA, and IgE.

CD3

Found on all T cells in association with the receptor. CD3 is a multi-subunit complex which is not antigen specific nor variable but which serves to transmit intracellular signals if the T cell receptor is engaged.

Immuno-globulin Superfamily

Found on endothelium, leukocytes, and APCs. Plays various roles in cell adhesion and acts as a ligand for integrins. Functions in firm adhesion and transmigration of the lymphocyte through HEVs. ICAM-1 is important in neutrophil migration, binds Mac-1.

Proteosomes (2)

Function to degrade large endogenous antigen molecules for presentation. Two proteosomes are found in the cell: 1. 20 S Proteosome 2. Immunoproteosome

Phagolysosomes

Function to degrade large exogenous antigen molecules for presentation. Contain proteolytic enzymes including cathpsins and endopeptides.

T Cell Receptor

Has an alpha and beta chain for antigen recognition. The chains have constant, hinge, and variable regions, and are associated with CD3 and either CD4 or CD8. Diversity is generated by a mechanism which uses somatic recombination of germline DNA. Receptors are expressed only on the cell surface and are not secreted. Each T cell expresses 10-30 K receptors of identical specificity!

Effector Lymphocytes

Have been stimulated by antigen and migrate to sites of inflammation.

Naive Lymphocytes

Have not encountered antigen. These continuously recirculate through secondary lymphoid organs.

CD4+ T Cell (4)

Helper T cell, inflammatory T cells that activate macrophages, B cells, or neutrophils by interaction with Class II MHC molecules. Co-stimulation during antigen presentation is required for activation. CD28 on the T cell binds B7 on the APC, and IL-1 induces expression of IL-2, triggering proliferation and differentiation into one of three subpopulations. No somatic hypermutation occurs. Subpopulations include: 1. CD4+Th1 2. CD4+Th2 3. CD4+Th17 4. CD4+ Regulatory T cells

MHC Heritability

Heritability is classical Mendelian, and MHC molecules may be polymorphic and/or polygenic. Wide variety of epitopes can be presented because the MHC genes have several loci on each gene, resulting in a multitude of alleles. Alleles from different loci and different genes can be expressed by the same cell type. The high number of alleles assures that most individuals are heterozygous at each MHC loci, increasing variability in offspring. Limited MHC diversity is indicative of genetic bottleneck.

Thrombocytopenia

High levels of thrombocytes in the blood, these are clotting factors. Can be caused by severe inflammation.

Abdominal Blood Glucose

If blood glucose of blood extracted from the abdomen has a difference greater than 20 (usually lower) from the blood glucose of circulating blood, this is a sign of sepsis.

ISCOMs

Immune stimulatory complexes, a type of adjuvant. Consists of a matrix of Quil A containing viral proteins. Delivers antigen to cytosol and allows induction of cytotoxic T cells.

Promiscuous

In reference to MHC, the system will bind a range of similar epitopes. The binding pocket is much more flexible than the Ab or T cell pocket, allowing more of a range of binding.

Lipid Mediators of Inflammation (2)

Includes prostaglandins and leukotrienes produced by leukocytes. Attract more leukocytes and induce various vascular effects. Steroids shut down the entire lipid mediator process of inflammation, NSAIDs shut down the prostaglandin branch.

Vasodilation (3)

Increased net blood flow resulting in heat, redness, and edema. Vascular effect of inflammation. Triggered by: 1. Prostaglandins 2. Nitric acid 3. Histamine

Chronic Inflammation

Inflammation caused by persistent stimulus. Has a prolonged duration and results in lymphocyte and macrophage accumulation. May result in scarring.

Inflammatory Factors (4)

Inflammatory factors include: 1. Coagulation and complement cascade factors 2. Lipid mediators 3. Amines and peptides 4. Cytokines

Acute Inflammation

Is initiated by warning signals from pathogens (PAMPs) and damaged cells (DAMPs). Begins within seconds to minutes following temporary tissue injury, causes redness, heat, swelling, pain, and sometimes loss of function, due to vascular effects. Benefits include dilution of toxins, isolation of invading pathogens, and initiation of repair. Pathophysiological effects include extensive tissue damage. Characterized by short duration, exudate, and neutrophil accumulation.

Post-Capillary Venule

Location where lymphocytes leave the blood, also called high endothelial venule.

MHC Class III

Loose term for all other genes in the MHC region besides Class I and II. Encodes cytokines, heat shock proteins, antigen processing and transport proteins, and complement proteins. Also encodes olfactory receptors.

TSLP

Lymphopoeitin, a cytokine that stimulates dendritic cells to save self-reactive cells and convert them to Treg cells.

LT-alpha

Lymphotoxin alpha, cytotoxin produced by CD8+ cells. Induces cell death via apoptosis.

Monocyte

Macrophage found in the blood.

Cytokine Inflammatory Factors (3)

Mainly produced by leukocytes. IL-1beta, IL-6, and TNF-alpha are important proinflammatory cytokines.

Tolerance to Fetal Antigens

Maintained by antigens hiding in the placenta, blockage of maternal antibodies from reaching the fetus, or the presence of Tregs. Also express an enzyme that depletes tryptophan from the site to starve autoreactive T cells. Fetus expresses a complement inhibitor, Crry.

Leukocyte Recruiting Inflammatory Factors (8)

May activate or recruit leukocytes. Includes: 1. TNF alpha 2. IL-1 3. Chemokines 4. C3a 5. C5a 6. Leukotriene B4 7. Thrombin 8. Fibrin-split Products

Neutrophil

Most numerous leukocyte in the blood and at sites of acute inflammation. A shot lived cell with a lifespan of 2 days. Large reserves are stored in bone marrow. Are professional phagocytes that can kill by oxygen-independent and oxygen-dependent methods.

Diapedesis

Movement of lymphocyte between endothelial cells lining post-capillary venule.

MALT

Mucossal-associated lymphoid tissue. For example, Peyer's patch and inflamed gut.

Needleless Vaccination

Needleless injections provide intradermal dispersal of vaccine. This injection style decreases disease risk, better disburses antigen, and eliminates sharps waste, though it is more expensive. Can be used for any type of vaccination.

NETs

Neutrophil extracellular traps. Are networks of extracellular fibers, primarily composed of chromatin (the neutrophil's DNA) and released granule proteins. Their excretion by neutrophils causes the death of the cell. Provide a high local concentration of antimicrobial components that trap and/or kill extracellular microbes independent of phagocytic uptake.

Imprecise Joining

Occurs during genetic rearrangement of variable region. By arbitrarily splicing nucleic acids together within the region, different reading frames are generated leading to different amino acid structure at the antigen binding pocket. This process occurs at all V-D-J junctions during recombination.

Organization

Occurs when tissue regeneration is unable to take place after inflammation, also called scarring. If connective tissue framework and/or parenchymal cells are excessively destroyed then the inflammatory lesion is essentially bonded together by fibroblast cells and collagen.

Immune-Privileged Tissues

Operationally defined as organs that experience extended survival when transplanted to conventional sites on a mismatched recipient. These tissues are resistant to immune clearance.

Immune-Privileged Sites

Operationally defined as sites where foreign tissue grafts survive for long periods of time. These sites inhibit immune response. They lack naiive lymphocytes, their extracellular fluid does not mix into lymphatic system, and they have high expresison of immunosuppressive cytokines and surface ligands. Includes the brain, eye, testis, uterus.

Natural Passive Immunity

Passed from mother to fetus/neonate through placenta or colostrum.

CD4+ Th Cell Differentiation

Pathogen can influence which Th cell population differentiates by influencing the cytokines produced during the initial interaction.

PAMPs

Pathogen-associated molecular patterns, found on pathogens and trigger inflammation.

Sepsis

Pathogens in the blood. Characterized as SIRS in combination with severe bacterial, viral, or protozoal infection.

Histamine

Peptide produced by leukocytes and platelets, derived from the amino acid histidine.

Serotonin

Peptide produced by platelets, derived from tryptophan and stored inside platelet granules.

Neuropeptides

Peptide products from nerve cells that function directly and indirectly in inflammation, for example substance P.

Anergy

Peripheral tolerance mechanism in which a lack of co-stimulation doe not allow the cell to be activated. Without co-stimulation the T-cell enters a long-lasting unresponsive state called anergy. These cells usually recognize a soluble self molecule and the process occurs in secondary lympoid tissue. B cells may also be rendered anergici if they do not receive enough positive signalling, including T cell help.

DNA Vaccines

Plasmids carry the genetic information for the antigen. Injection of plasmids into muscle cells results in temporary production of the encoded protein, MHC class I presentation, and cell-mediated immunity.

Hemostasis

Process of stopping blood leakage from a damaged blood vessel, which involves vasoconstriction and clot formation. Vascular effect of inflammation.

FasL

Produced by immune privileged tissues to kill autoreactive T cells via apoptosis.

Acute Phase Proteins

Produced by the liver, present in the blood at low levels. The liver is activated by inflammation and the production of acute phase proteins is drastically increased during systemic inflammatory response. Make good diagnostic markers.

IL-17

Proinflammatory cytokine produced by Th17 cells.

Integrin

Protein found on leukocytes and APCs. Binds to self-adhesion molecules and extracellular matrix, promoting a strong adhesion. Functions in firm adhesion and transmigration of the lymphocyte through HEVs. Mac-1 is important in neutrophil migration, binds ICAM-1.

Selectin

Protein found on leukocytes and endothelial cells. Binds carbohydrate-decorated proteins and initiates leukocyte-leukocyte and leukocyte-endothelium interactions. Functions in capture and rolling of lymphocyte travel through HEV. P-selectin is important in neutrophil adhesion, binds PSGL-1.

Hemorrhagic Exudate

Protein rich extravascular fluid that contains blood.

Serous Exudate

Protein rich extravascular fluid that is watery and does not contain cells.

Fibrinous Exudate

Protein rich extravascular fluid that ocntains high concentrations of fibrinogen and fibrin, resulting in a sticky meshwork.

Exudate (4)

Protein rich extravascular fluid. Composition may be: 1. Serous 2. Purulent 3. Hemorrhagic 4. Fibrinous

Immunization

Providing the body with specific defenses against an antigen.

Lymphoid Compartments (3)

Refers to secondary lymphoid organs at portals of antigen entry. Includes: 1. MALT 2. SALT 3. Spleen

Severe Sepsis

Refers to sepsis in combination with organ dysfunction. >1 organ system and high lactate.

Septic Shock

Refers to severe sepsis plus persistently low blood pressure that is refractory to fluids etc.

Memory T Cells

Refers to the large number of T cells responsive to an antigen after immune response. This occurs for both CD4+ and CD8+ T cells. Allows the adaptive immune response to start again very quickly without full stimulation. Some rapidly produce cytokines and enter inflamed tissue, other express CCR7 and migrate quickly to lymph nodes.

Helper T Cell Activation

Requires three signals: 1. The naive T cell is activated by the binding of the TCR and CD4+ to the MHC class II molecule of the APC. 2. Binding of a costimulatory receptor on the APC to the CD28 receptor of the T cell. Without costimulation adaptive immunity is not initiated! 3. Inflammatory cytokines deliver a third signal that determines the kind of activated T helper cell generated.

Resolution (2)

Resolution of inflammation, refers to tissue regeneration. This requires: 1. An intact connective tissue framework 2. Parenchymal cells must be labile (epithelial) or at least stable (hepatocyte) but not permanent (cardiac muscle)

Immune Privilege (4)

Restriction of immune response or the activation of immune cells. Typically, antigens from these sites are immunogens, but are protected by: 1. Tight blood barriers that exclude inflammatory/cytolytic cells 2. Expression of ligands that block Tc cell function or induce apoptosis 3. Reduced expression of class I MHC molecules 4. Increased expression of anti-inflammatory cytokines and immunosuppressive factors.

Lactate

Result of anaerobic effort of the tissues. High lactate (>2.0) indicates perfusion problems.

Homing

Selective migration of effector lymphocytes. Is dependent on where they initially encountered antigen. The expression of specific homing receptors is coupled to the location of activation. Homing can be used to enhance immunity by delivering vaccines at infection sites. It can also be applied to block lymphocyte accumulation at sites of chronic inflammation.

Polygenic

Several genes exist for a given MHC class.

Primary Lymphoid Organ

Site of T and B cell development, includes bone marrow, thymus, and bursa.

Secondary Lymphoid Organ

Site of T and B cell maturation in the presence of antigen. Includes peripheral lymph nodes, Peyer's patch.

SALT

Skin-associated lymphoid tissue. Refers to peripheral lymph nodes and inflamed skin.

Nitric Oxide

Soluble gas derived from amino acid arginine, produced by endothelial cells and leukocytes.

Marker Vaccines

Sometimes called DIVAs - differentiate infected from vaccinated animals. Useful in eradication purposes when using serology - can tell infected from vaccinated animals via ELISA. These vaccines typically elicit identical immunity as a live vaccine, but have an additional protein not found on the pathogen OR are missing a protein not essential to pathogen growth but is recognized by immune system.

Dendritic Cell

Specialized mononuclear cells found primarily in lymphoid tissues. Found in very low numbers in skin, spleen, and blood. Have long cytoplasmic processes which trap antigen and interact with T cells. They also efficiently take up immune complexes and shed immune complex bodies in exosomes for uptake and processing by B cells. Upon taking up antigen, these cells migrate to draining lymph nodes, become less phagocytic and increase expression of MHC class II molecules for interaction with T lymphocytes. Most potent activators of naive CD4+ T cells. Some dendritic cells can also activate CD8+ T cells via cross-presentation.

Calnexin

Stabilizing protein that helps attach the unbound MHC Class I molecule to the ER. Releases the molecule once a peptide binds.

Adjuvants (3)

Substances that enhance the immunogenicity of an antigen. Most proteins are poorly immunogenic by themselves as they are degraded quickly. Generally work in three ways: 1. Convert soluble protein to particulate material 2. Stimulate cytokine production by APC 3. Depot effect to maintain Ag half life

SIRS

Systemic inflammatory response syndrome. Caused by excessive acute inflammation, characterized by abnormal body temperature, heart rate, respiratory rate or blood gas, and white blood cell count. May occur in response to microbial invasion, trauma, or neoplasia.

Peripheral Tolerance (6)

T and B cells that bind self antigens are inhibited from effector function via inactivation of their clones by Treg cells. May occur by: 1. Anergy 2. Sequestering of self-antigen 3. Expression of FasL 4. Anti-inflammatory cytokine production by Treg cells 5. Expression of little classical MHC class I 6. Expression of non-classical MHC class I to inhibit NK cells

Central Tolerance

T and B cells that bind self antigens undergo apoptosis or receptor editing. This occurs in the thymus or bone marrow.

Production of T Cell Receptor

TCR has an alpha and beta chain, each of which has a variable and constant region. The variable region is made up of V, J, and D segments. Multiple rearrangements may occur within the thymus. Only TCR from one chromosome is expressed, the other undergoes allelic exclusion. Once rearrangement is successful, no further somatic rearrangement occurs, to prevent autoimmune reactions.

Rescue Pathway

The T cell receptor gene rearrangement can occur several times if one rearrangement is nonfunctional, but the intervening DNA is lost each time.

Tolerance (5)

The absence of OR failure to mount an immune response to antigens. Involves regulation of both T cells and B cells. Contributing mechanisms: 1. Deletion of self-reactive clones 2. Requirement for two signals to activate T cells 3. Treg cells that block activation of autoreactive T and B cells 4. Immune "privileged" sites and tissues 5. Sequestration of self antigens from the immune system

MHC Hypermutation Sites

The majority of variation in MHCs are in the binding pockets. This maintains structural stability while allowing them to bind a wide variety of epitopes.

Antigen Segregation

Tolerance mechanism in which a physical barrier to self-antigen access by the lymphoid system is present. Occurs in peripheral organs.

Clonal Exhaustion

Tolerance mechanism in which apoptosis occurs post-activation adue to high levels of antigens. Occurs in secondary lymphoid tissue and sites of inflammation.

Regulatory Cells

Tolerance mechanism in which self-reactive cells are suppressed by cytokins and intercellular signals. Occurs in secondary lymphoid tissue and sites of inflammation.

Cytokine Deviation

Tolerance mechanism in which self-reactive cells differentiate to Th2 cells, limiting cytokine secretion. Occurs in secondary lymphoid tissue and sites of inflammation.

CD4+Th1

Type 1 T helper cell. Has CD4 receptor and activates macrophages via interaction with MHC class II complexes. Secretes cytokines which augment non-specific immune response and inhibit Th2 differentiation. Also provides assistance to B cells for antibody production, and induces apoptosis, T cell production, and bone marrow differentiation to myeloid lineage. IL-12 and IFN-gamma favor production.

CD4+Th17

Type 17 helper T cell, secretes high levels of I-17 which activates neutrophils. IL-23, IL-6, and TGF-beta favor production.

CD4+Th2

Type 2 helper T cell, activates and differentiates B cells via MHC class II complexes, especially assists in transtion from IgM to IgE. Secretes factors driving B cell growth, regulating isotype switching, and inhibiting Th1 differentiation. IL-4 favors production.

Conjugate Vaccines

Type of subunit vaccine in which an antigen that is not very immunogenic is attached to something that is (hapten-carrier effect). Common for making vaccines against bacteria with capsules (polysaccharides).

Recombinant Vector Vaccine

Type of subunit vaccine in which the gene for an antigen is inserted into a harmless vector. The vector is a live organism that does not cause disease. It produces the protein, thus vaccinating the recipient.

Oxygen-Dependent Killing (4)

Used by neutrophils, relies on reactive oxygen species. May generate: 1. Superoxide 2. Hydrogen peroxide 3. Hydroxyl radicals 4. Hypochlorus acid

Whole-Agent Vaccine

Vaccine containing the whole agent. May be: 1. Killed/Inactivated 2. Attenuated live strain

Autogenous Vaccine

Vaccine made from microorganisms specific to a farm, usually by a licensed facility. Takes ~6 weeks for bacteria, ~12 weeks for viruses. Important heard health tool, used when new disease agents emerge or when antigenic variation occurs outside the spectrum of commercially available vaccines.

Increased Endothelial Cell Adhesiveness

Vascular effect of inflammation. Causes endothelial cells to become more adhesive, increasing leukocyte attachment and migration.

Vascular Effects of Inflammation

Vascular effects include: 1. Hemostasis 2. Vasodilation 3. Increased vascular permeability 4. Increased endothelial cell adhesiveness

Killed/Inactivated Vaccine (2) (3)

Whole agent vaccine with the organism inactivated or killed. Antigenic integrity must be maintained! Therefore must be chemically inactivated and not heat treated. Pros include: 1. More stable storage 2. Unlikely to cause disease in the immunosuppressed Cons include: 1. Induce antibodies only, difficult to induce CTL response 2. Require large amounts of antigen because organism doesn't multiply 3. Protection is shorter term, boosters and adjuvant required. Low induction of memory B and IgA.

Live Vaccine (3) (2)

Whole-agent live vaccine. Most induce Th1 and Th2 responses, viral vaccines also induce strong CTL responses. Usually contain attenuated organism. Pros include: 1. CTL response 2. Smaller amount of antigen 3. Longer term protection Cons include: 1. Less stable storage 2. May cause disease in the immunocompromised

Lymphocyte Trafficking

1. Blood vessels deliver and afferent lymphatics deliver lymphocytes to secondary lymphoid organs 2. Lymphocytes leave secondary lymphoid organs by efferent lymphatics 3. Lymphocytes are returned to the blood via the thoracic duct 4. Lymphocytes reenter the blood and are delivered to peripheral tissues

Defects in Neutrophil Function (3)

1. Defects of adhesion 2. Defects of chemotaxis/phagocytosis 3. Defects of microbicidal activity

T Cell Maturation (6)

1. Differentiates in bone marrow 2. Moves to thymus 3. Rearrangement of T cell receptor genes. Unsuccessful cells die. 4. Educated by antigen presenting cells having class I and class II MHC receptors. Self-reactive cells die. 5. Cell stops expressing either CD8 or CD4. 6. Exits the thymus via the blood.

Pyrogenic Inflammatory Factors (4)

1. IL-1 2. TNF-alpha 3. IL-6 4. Prostaglandins

B Cell Antigen Presentation (5)

1. Ig on surface of B cells bind epitopes on native antigen 2. Ig "caps" and the antigen is internalized 3. The antigen is processes similarly to macrophages 4. Peptide-MHC class II complex is exported to cell surface 5. Ligand interaction with CD4+ T cells

Exogenous Antigen Presentation (8)

1. Non-specific binding of antigen 2. Antigen is phagocytosed 3. A phagosome forms 4. Phagosome pH decreases to activate proteases and begin degradation 5. Lysosomes containing MHC class II molecule fuse with endosome and continue degradation 6. Association of processed antigen with MHC class II 7. Phagolysosome fuses with plasma membrane 8. Ligand interaction with CD4+ T cells

Requirements for Antigen Processing and Presentation (4)

1. Phagocytic Cells 2. Means for degrading larger antigen molecules 3. Molecules to present peptide fragments on cell surface 4. Receptors to distinguish foreign epitopes

Pain-Inducing Inflammatory Factors

1. Prostaglandins 2. Bradykinin

Endogenous Antigen Presentation (6)

1. Proteins are non-specifically degraded in proteosome 2. Peptides are transported from cytosol to ER 3. Peptides associate with MHC class I-calnexin molecule. MHC class I molecules do not leave the ER unless they bind peptides! 4. Peptide-MHC I molecule are exported to Golgi 5. Peptide-MHC I molecule are expressed on cell surface 6. Ligand interaction with CD8+ cells

T-Cell Activation (5)

1. T cells enter lymphoid tissue via HEV 2. Attracted to antigen presenting cells via chemokines 3. Receives multiple signals from the APC and becomes activated 4. T cell proliferates and polarizes 5. Enters circulation via thoracic duct 6. Traffic to extralymphoid rogans

Canine Criteria for SIRS (4)

1. Temp <99 or <102.5 2. HR >140 3. Resp >40 4. WBC >19,000 or <6,000 Must meet 2 of the 4 criteria to qualify as SIRS.

MHC Restriction

A given T cell receptor will only recognize antigen presented by a particular (self) MHC molecule. That is, T cells educated in one MHC allele/epitope will not interact with antigen presenting cells unless it expresses that allele bearing the same epitope.

Polymorphic

A large number of alleles exist for a given gene.

Inflammation

A physiological process involving various systems, such as immune system, circulatory system, and nervous system. Severe inflammation can result in decreased platelets and blood albumin, and increased prothrombin.

Apoptosis

A programmed cell death involving cleavage of genomic DNA.

Toxoid Vaccines

A type of subunit vaccine in which the toxin produced by a pathogen is targeted. Can be made by treating toxins with chemical inactivators such as formalin, or by heat to denature it.

MHC

Abbreviation for major histocompatibility complex. A system of gene products used for specifically recongizing and eliminating foreign antigens. These antigens can be from within host cells or from extracellular sources. Both self and non-self antigens are constitutively processed and presented to T cells. This system is polygenic, polymorphic, and promiscuous. Different MHC types present antigen to different T cell types. Three classes: 1. Class I 2. Class II

Imprinting

Activation of naive lymphocytes by antigen-presenting cells.

Freund's Adjuvant

Adjuvant containing oil-in-water emulsion which causes delayed release of antigen and enhanced uptake by macrophages. May be: 1. Incomplete (no additions) 2. Complete (plus dead mycobacteria) 3. with MDP (plus mycobacterial MDP) Complete and with MDP also induce co-stimulators in macrophages.

Subcutaneous Ephysema

Air under the skin, feels crunchy/crackly.

Vaccination

Also called active immunization. Deliberately giving an antigen so as to elicit an immune response. Uses the individual's immune system to generate protection. Provides prolonged protection and boosting can be done.

Cross-Presentation

Also called retrotranslocation. Class I presentation of exogenous antigens to CD8+ T cells by dendritic cells. Processed antigens are dumped into cytoplasm and thus able to be presented via MHC class I.

Purulent Exudate

Also called suppurative exudate. Protein rich extravascular fluid that is thick and contains white blood cells, bacteria, and cellular debris.

Alum

Aluminum hydroxide gel, used as an adjuvant. Causes delayed release of antigen and enhanced macrophage uptake. Addition of bordatella pertussis also induces co-stimulators.

Attenuation

An attenuated organism is selected because it has limited virulence and will cause infection, but not disease. Attenuation is achieved by growing an organism in vitro until it loses virulence. rDNA can be used to directly remove or mutate virulence genes such that virulence is directly attenuated.

Ideal Vaccine (3)

An ideal vaccine will: 1. Induce immunity in most individuals 2. Give long-lived immunity to all strains and variants 3. Not be toxic or induce illness at any level For veterinarians, we also must factor in cost and stability.

Toxoid

An inactivated toxin.

Artificial Passive Immunity

Antibodies from one individual are given to another.

T Cell

Antigen specific lymphocytes that recognize foreign antigens only in the context of MHC of the same haplotype. Produced by bone marrow and educated in thymus. Each T cell has a single specificity for a single epitope determined by the T cell receptor. Immunity involves the destruction of infected cells by Tc, of intracellular pathogens by Th1 activated macrophages and Th17 activated neutrophils, and the maturation and activation of B cells by Th2 cells.

Iccosomes

Antigen-containing exosome that is shed by dendritic cells. Can be taken up by B cells upon recognition by surface IgM.

Adhesion Receptors

Are expressed by lymphocytes and endothelial cells that line post-capillary venules. Regulate recirculation and homing of lymphocytes. These receptors capture the lymphocyte, roll and adhere to it, and allow it to move between endothelial cells via diapedesis. Naive lymphocytes change the types of adhesion and chemokine receptors that they express upon imprinting.

Coagulation and Complement Cascade Inflammatory Factors (5)

Are inactive proteins circulating in the blood that become activated by proteases during inflammation. Includes bradykinin, thrombin, fibrin-split-products, and C3a and C5a of the complement cascade.

Amine and Peptide Inflammatory Factors

Are mainly produced by leukocytes and other cells that induce vasodilation and vascular permeability. Includes histamine, serotonin, nitric oxide, and neuropeptides.

Beta 2-Microglobulin

Assists in assembly of MHC I molecules.

Vaccine

Biological preparation that establishes or improves the immune response to a specific antigen. Three types: 1. Subunit 2. Whole-agent 3. DNA