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PBD Exam 1 Fall 2011 Liu-Katovich
PBD FALL 2011 EXAM 1
129
Pharmacology
Professional
09/14/2011

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Term
Name the two types of Immunity
Definition
Innate and Adaptive
Term
List the characteristics of Innate Immunity
Definition
Fast(min/hours)
1st defense
Limited in diversity of infections
general/vague recognition
same response to repeat infections
Defense
-Barriers(skin,mucous
-phagocytes
-fever
-inflammation
Cells
-phagocytes(macrophages/neutrophils)
-Dendritic cells
-Natural Killer Cells
Molecules
-cytokines
-complement proteins
Term
List the Characteristics of Adaptive Immunity
Definition
Slower(days/weeks)
2nd defense
Large diversity of infections
Specific recognition
More rapid/efficent response to repeat infections.(immunologic memory)
Defense
-cell killing
-tagging of antigen by antibodies for removal
Cells
-T and B lymphocytes
Molecules
-Antibodies
-Cytokines
Term
List the 4 exterior component of Innate Immunity
Definition
1.Physical Barriers(Skin, mucous,hair,cilia)
2. Chemical effectors(stomach acid)
3. Micro-ecology (normal flora)
4. Secretions (sebaceous/lysozymes)
Term
Name the 3 ecological coexistence relationships
Definition
1. Commensalism: One party benefits with no harm or benefit to the other party.
2. Mutualism: Both parties benefit.
3. Parasitism: One party benefits while bringing harm to the other party.
Term
What is the consequence of overuse of anti-biotics?
Definition
-reduce normal flora
-creates super bugs (resistant to antibiotics)
Term
In what secretions can you find lysozymes?
Definition
Saliva
sweat
milk
mucous
tears
Term
Lysozymes are more effective against gram + or gram - bacteria?
Definition
Gram +
-smaller cell wall
-no LPS
- peptidoglycan easier accessibility to cleave
Term
List the 3 key cell types of Innate Immunity
Definition
I. Neutrophils
II. Macrophage/ dendritic cells
III. Natural Killer (NK) cells
Term
Leukocytes can be broken down into classes, name them.
Definition
Granulocytes and agranulocytes
Term
List the cells that fall under granulocytes(PMNs: Polymorphonuclear leukocytes)
Definition
Neutrophils (50-60% in blood)
Basophils (<1%)
Eosinophils (1-3%)
Mast Cells
Term
List the cells that make up agranulocytes(contains granules negative in classic staining)
Definition
Lymphocytes (T, B, NK) (30%)
Monocytes (2-10%) /Macrophages
Term
Which granulocyte(PMN) is the first line of defense against: bacteria, fungi, cellular debris, foreign substances
Definition
Neutrophils
Term
Which granulocyte (PMN) has nuclei divided into 3-5 lobes
Definition
neutrophils
Term
What are the 3 types of granules found in neutrophils?
Definition
1. specific
2. azurophilic
3. tertiary
Term
Which granulocyte (PMN) is involved with allergic reactions and parasitic infections?
Definition
Eosinophils
Term
Which granulocyte (PMN) is involved mainly with inflammation response and stains blue with basic dye?
Definition
Basophil
Term
What are the relative percentages of each granulocyte (PMN)in blood?
Definition
Neutrophils- 65%
Eosinophils- 1-3%
Basophils- .3-.5%
Term
What is the process of recruitment of immune factors in response to agents released by bacteria or bacteria activated tissue macrophages, epithelial cells and endothelial cells to migrate to the site of infection
Definition
Chemotaxis
Term
What is a popular chemoattractant for neutrophils?
Definition
Chemokine IL-8 (interluekin -8)
Term
What receptors on neutrophil surfaces interacts with cytokine IL-8?
Definition
CXCL cytokine receptor
Term
What is the process neutrophils utilize to migrate from the blood stream into tissue across the endothelium called?
Definition
Diapedesis
Term
Describe the process of neutrophil diapedesis
Definition
Change to expression of surface receptors -> Adhere to endothelium -> “Rolling” -> Spreading -> Extravasation -> reach site of infection
Term
What is the name of the receptors constitutively expressed on their cell surface to recognize pathogens-associated molecular patterns (PAMPs)?
Definition
pattern recognition receptors (PRRs)
Term
Neutrophils (and other immune cells) have pattern recognition receptors (PRRs) to recognize _________.
Definition
pathogens-associated molecular patterns (PAMPs)
Term
How many genes to PRRs contain for recognizing major microbes?
Definition
~1000
Term
What are the two major types of PRRs?
Definition
A. Toll-like receptors (TLRs): originally identified in fruit fly protectign it from lethal fungal infections.
B. Mannan-binding lectin (MBL): recognizing bacterial poly mannose that is not present on human cells.
Term
Describe the process of TLR4(a TLR that uses a bacteria's LPS as a ligand) and neutrophil activation,
Definition
Bacteria's LPS binds with LPS binding protein of the neutrophil--> This complex binds with non-transmembrane protein CD14--> This bound CD14 and TLR4 "sandwich" MD2 to form complex--> This activates MAPK which performs kinase activity--> activation of effector factors
Term
What are the main functions of the complement system?
Definition
A. Lyse microbes/transformed cells through MAC
B. Stimulate and generate inflammatory and chemoattractant factors
C. Opsonization(targeting/flagging) to facilitate phagocytosis
Term
What are the 3 activation pathways for the complement system?
Definition
A. Lectin pathway: Mannan-binding lectin (MBL)-mediated.
B. Alternative pathway: C3 and factor B-mediated
C. Classic Pathway
Term
What are the key parts of the activated complement system?
Definition
C3b
C5a
C5-9
Term
Describe the function of C3b of the activated complement system
Definition
a major opsonin to tag microbes to facilitate phagocytosis.
Term
Describe the function of C5a of the activated complement system
Definition
a potent chemoattractant to recruit neutrophils
Term
Describe the function of C5 thru C9 of the activated complement system
Definition
They are components of MAC (membrane attack complex) causing cell lysis.
Term
What is the role of CR3(complement receptor 3) in the activated complement system?
Definition
complement receptor 3, or CD11b/CD18, binds to C3b that is bound to the tagged microbe for phagocytosis.
Term
Generation of superoxide anions through activation of NADPH oxidase to damage infected cells or bacteria is called?
Definition
Respiratory burst
Term
Describe characteristics of Chronic Granulomatous Disease
Definition
-Mostly X-linked recessive(65%)
-Repeated infections on skin and internal organs
-50% live past 20
-Mutations in gp91 PHOX gene for x-linked recessive
-Autosomal mutations are p47,p22,p67 PHOX genes
*Low to no NADPH oxidase mediated production of reactive oxygen species(ROS) in neutrophils
-No Respiratory burst!
Term
What is the treatment of Ganulomatous Disease?
Definition
Antibiotics
INFgamma
Bone Marrow Transplant
granulocyte infusion
Term
Describe the roles of Macrophages
Definition
-Defend host tissues against infection
-responsible for removal of damaged/dying cells
-prevent reactive inflammatory response
Term
Where do mature macrophages clear hematopoietic cells, release cytokines to stimulate maturation of hematopoietic cells and recycle nutrients such as iron
Definition
Bone Marrow
Term
Spleen red pulp ________ clear senescent RBCs and neutrophils.
Definition
Macrophages
Term
What are the two types of macrophages?
Definition
1. resident
2. monocyte derived
Term
Microglia, originating from monocytes during early development, are important why?
Definition
- remove unwanted neurons during brain remodeling
- After birth, microglia develop into CNS immune cells functioning as both resident macrophages and neutrophils
Term
What is the lifespan of Monocytes?
Definition
1-3 days (4x of granulocytes)
Term
Resident macrophages become activated by PRRs as a result of?
Definition
-response to inflammation
-tissue injury
-cell debris
-presence of foreign substances
Term
True or False: The adhesion, spreading, and extravastion process of monocyte recruitment is similar to neutrophil infiltration to the site of infections
Definition
TRUE
Term
True or False: The flow of monocytes to tissue is bidirectional as compared to neutrophils which is unidirectional.
Definition
FALSE
Both are unidirectional
Term
What are the 3 main functions of Macrophages in Innate Immunity?
Definition
1. Phagocytosis
2. Cytotoxicity
3. Cytokine production
Term
How do macrophage phagocytosis differ from neutrophil phagocytosis?
Definition
All is the same, TLRs and MBL, but they use a more complex receptor to identify apoptotic cells. Apoptotic cells flip phosphotidylserine (PS) from the inner membrane to the outer. Macrophages use TIM4 on their membrane to recognize PS.
Term
How do macrophage phagocytosis differ from neutrophil phagocytosis?
Definition
All is the same, TLRs and MBL, but they use a more complex receptor to identify apoptotic cells. Apoptotic cells flip phosphotidylserine (PS) from the inner membrane to the outer. Macrophages use TIM4 on their membrane to recognize PS.
Term
Describe the cytotoxicity function of macrophages.
Definition
After ingestion, phagosome fuses with a lysosome and the microbe is killed within ROS, RNS, and lysosomal enzymes.
Term
Describe the cytokine production function of macrophages.
Definition
They produce proinfammatory cytokines (IL-1 and TNF) as well as chemokine IL-8 to attract neutrophils to the site of infection.
Term
Neutrophils: express ____ level NADPH oxidase, very ______ level or no iNOS
Definition
High
Low
Term
Macrophages:____ levels of NADPH oxidase and ____ level of iNOS after stimulation.
Definition
Lower
High
Term
True or False: iNOS, which is not present in resting immune cells, rapidly upregulates (in hours in macrophages) upon stimulation producing nitric oxide.
Definition
TRUE
Term
True or False:Peroxynitrite (ONOO-) is much more reactive (toxic) than either superoxide or nitric oxide alone.
Definition
TRUE
Term
What percentage of blood lymphocytes are Natural Killer Cells?
Definition
5-15%
Term
What is the life span of NK Cells?
Definition
days to a few weeks
Term
What do the granules of NK cells contain?
Definition
perforin and granzymes
Term
What are the main targets of NK Cells?
Definition
virus-infected cells and malignant cells (tumors)
Term
What duo receptor system controls activity of the NK Cells?
Definition
KAR(s): Killing Activating Receptor(s)
KIRs: Killing Inhibiting Receptors
Term
Which MHC class associated with NK Cells?
Definition
MHC I
Term
What is the function of perforin?
Definition
19-24 perforin proteins assemble into a pore on the surface membrane, leading into the target cell lumen. Large enough to allow granzymes to pass through.
Term
What is a granzyme?
Definition
cysteine protease
Term
Describe the function of granzymes
Definition
1. Cleaves pro-caspase-3 into a caspase-3 dimer. That degrades nuclear lamins and inactivates DNA damage repair PARP.
2. Cleaves Bid, which releases cytochrome c into cytsol. That activates caspase 9 which in turn activates caspase-3 mediated cell death.
Term
True or False: MIC is used for self recognition.
Definition
FALSE
HLA is used for self recognition. MIC is used for antigen presentation.
Term
What receptors are recognized by NK Cells that are expressed on a good/healthy cell
Definition
HLA-E and HLA-A/B/C
Term
What receptors are recognized by NK Cells that are expressed on a infected/transformed cell
Definition
MIC-A/B
Term
In recognizing a healthy cell by the NK cell, what does HLA-E bind to and what does HLA-A/B/C bind to?
Definition
HLA-E binds to CD158 and HLA-A/B/C binds and dimerizes CD94 and CD159
Term
CD158, CD159, and CD94 are considered _______.
Definition
KIRs - Killing Inhibiting Receptors
Term
Which two units are activated by CD158, CD159, and CD94 to produce phosphatase activity, or dephosphorylation?
Definition
ITIM and SHP-1
Term
True or False: Through dephosphorylation, the NK cell is inhibited from destroying the healthy cell.
Definition
TRUE
Term
On an infected/transformed cell, this receptor is either not present or very lowly expressed for recognition by the NK cell.
Definition
HLA-E or HLA-A/B/C
Term
True or False: MIC-A/B is lowly expressed on infected/transformed cells
Definition
FALSE
MIC-A/B is highly expressed in infected cells
Term
MIC-A/B recognizes what membrane protein on the NK Cell at the beginning of the NK cell activation pathway?
Definition
CD314
Term
CD314 and DAP10 activate this kinase to achieve phosphorylation, thus activating the NK cell.
Definition
P13
Term
What kind of receptor would CD314 be considered?
Definition
KAR
Killing Activating Receptor
Term
List the Characteristics of Adaptive Immunity
Definition
Slower(days/weeks)
2nd defense
Large diversity of infections
Specific recognition
More rapid/efficent response to repeat infections.(immunologic memory)
Defense
-cell killing
-tagging of antigen by antibodies for removal
Cells
-T and B lymphocytes
Molecules
-Antibodies
-Cytokines
Term
What are the 3 cell types involved in Adaptive immunity ?
Definition
1. Antigen presentation
-macrophage and dendritic cells
2. Antigen recognition
- T-lymphocytes
3. Antibody production
- B-lymphocytes
Term
Where can dendritic cells (immature form) be found?
Definition
present in various tissues where antigen entry is anticipated: skin, lymph nodes, and blood, lining of airway and intestine, and interstitial spaces of most organs
Term
What are skin dendritic cells called?
Definition
Langerhans cells
Term
How do dendritic cells interact with phagocytizing pathogens?
Definition
Through PRRs like TLRs
Term
Once the dendritic cell is activated, where does it go?
Definition
Activated dendritic cells mature, then migrate to the lymph node
Term
How long do activated dedritic cells?
Definition
For a few days or weeks
Term
True or false: Their origin is not completely clear although most they are from monocyte lineage.
Definition
True
Term
What percentage of WBCs are T and B cells?
Definition
~30%
Term
Where does lymphocyte stem cells orginate from?
Definition
Bone marrow pluripotent stem cells
Term
Where do lymphocyte stem cells differentiate into B-cells?
Definition
Bone Marrow
Term
Where do lymphocyte stem cells differentiate into T-cells?
Definition
Thymus
Term
Where do mature T and B cells populate?
Definition
Lymphoid and related tissues
-lymph nodes
-spleen
-mucosal tissues
-lymph
-blood
Term
A part of a substance from a non-self or transformed self macro (cellular) structure, usually in nature of complex structures such as proteins, polysaccharide, or glycolipids; able to stimulate immune cells.
Definition
Antigen
Term
A antigenic determinant structure in antigen with the correct structure and size that that can fit into the binding motif of the recognition site on an immune cell.
Definition
Epitope
Term
What is the length of a typical epitope?
Definition
6 or more amino acids or monosaccharides
Term
What are the two antigen presentations methods?
Definition
1.Cytosolic/endogenous pathway
-intracellular antigen
2. Endocytic/exogenous pathway
-extracellular pathway
Term
Cytosolic/endogenous pathway
uses what MHC complex?
Definition
MHC-I
Term
Endocytic/exogenous pathway uses what MHC complex?
Definition
MHC-II
Term
Describe the Cytosolic/endogenous pathway
Definition
Virus or Intracellular bacteria-->tagged with ubiquitin-->degraded into peptides in protesome-->Transported into the ER by TAP proteins-->Peptides are loaded on MHC-I-->Taken to Golgi A.-->undergoes post-translational modfications(matures)-->travels to membrane to be presented on cell surface
Term
Describe the Endocytic/exogenous pathway
Definition
Extracellular antigen-->taken up by endocytosis and phagocytosis into vesicles-->proteases break it down into peptides-->MHC-II matures in ER and Golgi A. then leaves-->MHC-II binds to peptides-->goes to surface and presents.
Term
What kind of cells are MHC-I found on?
Definition
All cells, except RBCs
Term
What kind of cells are MHC-II found on?
Definition
Only APCs (macrophage, dendritic cells and B cells)
Term
Describe the structure of MHC-I
Definition
Made of 2 peptides alpha and Beta2-microglobulin. The alpha chain is polymorphic. A1-A2-A3-B2m
Term
Describe the structure of MHC-II
Definition
Made of 2 homologous peptides, a1a2 b1b2
Term
Describe MHC-II loading
Definition
MHC-II are prevented from binding peptides in the ER by the invariant chain(CD74)-->MHC-II alpha and beta chains assemble with the invariant chain(CD74) in the ER-->Leaves ER and enters phagolysosome-->invariant chain(CD74) is cleaved by cathepsin S, leaving a small peptide, CLIP--> HLA-DM catalyzes the release of CLIP-->peptide replaces CLIP-->sent to plasma membrane
Term
What is the understood equivalent of MHC (Major Histocompatibility Complex)?
Definition
HLA (Human Leukocyte Antigen) = MHC (Major Histocompatibility Complex)
Term
What makes up Classical MHC-I?
Definition
HLA-A, HLA-B, HLA-C (antigen presentation, all cells)
Term
What makes up non-Classical MHC-I?
Definition
HLA-E, HLA-G, HLA-F, MICA, MICB, HFE
Term
What makes up Classical MHC-II?
Definition
HLA-DP, HLA-DQ, HLA-DR (antigen presentation, APCs)
Term
What makes up non-Classical MHC-II?
Definition
HLA-DM, HLA-DN, HLA-DO, TAP, TAPBP
Term
What makes up MHC-III?
Definition
Members of the complement system, e.g., C2, C4A and cytokine TNF
Term
Which human chromosome can you find the genes for the majority of the MHC complexes?
Definition
Chromosome 6
Term
True or False: The classical MHC-I (a- chain) and MHC-II molecules are most polymorphic proteins known
Definition
TRUE
Term
What determines the polymorphism of MHC-I and II?
Definition
Polymorphism is centered on the antigen binding grooves
Term
MHC-I associated peptides arerecognized by ______ T-cells (CD_)
Definition
cytotoxic T cells (CD 8+)
Term
MHC-II associated peptides are recognized by _____ T cells (CD_)
Definition
helper T cells (CD 4+)
Term
What type of receptor forms a complex with CD3 and CD247 (Zeta chain) for signaling transduction?
Definition
T-Cell Receptors: TCRs
Term
Describe the Cytotoxic T cell-mediated killing
Definition
A complex is formed with TCR:CD3:CD8 and MHC-I on the target cell-->recruits Tyrosine kinase-->phosphorylates tyrosine on ITAM domains of CD3 and CD247-->recruits protein kinase, ZAP-70--> phosphorylation cascade iniated-->release of perforin and granzymes to kill cell(like NK killing)
Term
Describe the Helper T Cell action with CD4 and not CD8
Definition
Same ITAM-ZAP-70 signaling pathway,but the phosphorylation cascade activates the CD4+ helper T-cell to:
- Differentiate into TH1 cells to promote cell-mediated cytotoxicity.
- Differentiate into TH2 cells to promote antibody generation.
Term
Where do immature B cells develop into mature, yet naïve, B cells
Definition
bone marrow
Term
True or False: Naïve B cells express IgD and IgM as antigen receptors
Definition
TRUE
Term
When do B cells differentiate into other cells?
Definition
They enter circulation and migrate to lymphoid tissues. Through interaction with T helper cells, B cells are activated and turn into antibody-producing plasma cells or memory cells.
Term
What is the function of antibodies?
Definition
neutralize pathogen, opsonize microbes for phagocytosis, activate complement, prevent attachment of microbes to mucosal surfaces
Term
List the components of Immunoglobulins (Ig)
Definition
Light chain and heavy chain
Variable chain and constant chain
Term
Which region determines the Ig type?
Definition
Constant region
Term
Which region is the antibody binding site?
Definition
Variable region
Term
True or False: T cells only recognize peptide type antigenic epitopes that are presented by MHC-I/II of APCs.
Definition
TRUE
Term
Which two cytokines induce "AB-class switching"?
Definition
IL-4 and IL-5 induce Ig “class switching” in antibody production.
Term
True or False: In Ig class switching, the variable region is changed, not the constant.
Definition
FALSE:
The constant region change and the variable regions remains the same.
Term
CD4 Interacts with Class 2 (4x2) = 8
CD8 interacts with class 1 (4x1) = 8
Definition
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