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Donati - Physiology Spring Quarter 2010
Exam 1
84
Physiology
Professional
03/19/2010

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Term
Cardinal Signs of Inflammation
Definition
Rubor - Redness
Tumor - Swelling
Calor - Heat
Dolor - Pain
Term
The release of ___ can cause all 4 cardinal signs of inflammation
Definition
HISTAMINE (released by mast cell)
Term
Vasodilation leads to ___
Definition
Increased permeability
Term
Increased permeability leads to ___
Definition
Plasma and WBCs leaking out (swelling and pain)
as well as
Increased blood flow (redness and heat)
Term
Leukocyte for acute inflammation. Also most common. 1st on the scene.
Definition
Neutrophil
Term
Least common leukocyte. Involved in allergic reaction. Becomes a mast cell in tissue.
Definition
Basophil
Term
Involved in immunity from parasites
Definition
Eosinophils
Term
Involved in chronic inflammation. Natural Killer Cells. T and B cells.
Definition
Lymphocytes
Term
Also in chronic inflammation. Largest, differentiates into macrophages in tissues.
Definition
Monocytes
Term
Four steps in leukocyte extravasation
Definition
Rolling, firm adhesion, transmigration, chemotaxis
Term
Rolling
Definition
Upregulated expression of E- and P-selectin on endothelial cells.
Sialyl-Lewis X.
L-selectin
Term
Firm adhesion
Definition
Increased avidity for ICAM-1 and VCAM-1.
This is the rate limiting step in leukocyte extravasation.
Term
Transmigration
Definition
PECAM-1 adhesion molecule that guides WBC to migrate b/w two endothelial cells.
Term
Chemotaxis
Definition
WBC moving up a chemical gradient until it reaches the site of infection.
Term
Causes rubor
Definition
Prostaglandins and histamine
Term
Causes Tumor
Definition
Histamine
Term
Causes Calor
Definition
Prostaglandins
Term
Causes pain
Definition
Prostaglandins
Term
Major cytokines in acute inflammation
Definition
IL-1 and IL-6
Term
Acute inflammation usually leads to ___
Definition
Resolution
Term
Acute inflammation rarely leads to ___
Definition
Scar formation
Term
Chronic inflammation usually leads to ___
Definition
Scar formation
Term
Chronic inflammation rarely leads to ___
Definition
Regeneration
Term
Example of serous inflammation
Definition
Skin blister, fluid edema. This is directly beneath the epidermis.
Term
Example of fibrinous inflammation
Definition
Fibrin leaks out of vessels.
Term
Example of suppurative inflammation
Definition
Pus = PMNs, edema, necrotic cell debris. Ex: Absesses
Term
Example of ulcerations
Definition
Surface of an organ shedding of necrotic tissue
Term
Resolution of Inflammation
Definition
Return to normal permeability.
Drainage of edema into lymphatic vessels.
Pinocytosis/Phagocytosis of edema fluid.
Phagocytosis of PMNs and debris by macrophages.
Term
Macrophage/Lymphocyte stimulation.
Definition
Cycle of activation.
Activated lymphocyte releases interferon gamma which activates macrophage which releases interleukin-1 and TNF which activates a lymphocyte.
Term
Maturation of lymphocytes
Definition
B lymphocytes: Stem cells --> Bone marrow --> blood --> lymph nodes, spleen, mucosal and cutaneous lymph tissue.
T lymphocytes: Stemm cells --> thymus --> blood, lymph --> Lymph nodes, spleen, mucosal and cutaneous lymph tissue.
Term
What happens in secondary lymphoid tissues?
Definition
1. Trapping and concentrating foreign substances carried in the blood and lymph.
2. Main sites of antibody production and induction of antigen-specific T cells.
Term
Why is secondary lymphoid tissues important?
Definition
This gives the antigens and lymphocytes a specific place to meet for the first time.
Term
Lymphocyte recirculation
Definition
Naive lymphocytes keep migrating from node to node looking for antigen presenting cell to present the correct antigen to it.
Effector lymphocytes: T cells migrate to the site of infection. B cells secrete antibody from lymphoid organ.
Term
Innate Immune system
Definition
Physical barrier to infection, i.e. epithelium, mucus, saliva, tears.
Phagocytic cells, i.e. macrophages and neutrophils.
Natural Killer cells (cytotoxicity).
Term
Innate immune system
Definition
Complement system (alternative and lectin pathways), membrane attack complex.
Cytokines and plasma proteins (interferons, C-reactive protein)
Fever
Term
Properties of the innate immune system
Definition
Fast (minutes)
Non-specific
Limited diversity
No memory
Primitive
Reliable (no auto-immunity)
Term
Phagocytic Cell Receptors
Definition
Phagocytic cells recognize bacteria via receptors which bind molecules that are not found on mammalian cells.
Toll-like receptors (TLR-4 binds LPS (endotoxin))
N-formyl methionine receptor
Mannose receptor - bacterial glycoproteins end in mannose residues.
Term
NK Cell cytotoxicity
Definition
NK cells recognize and target cells without MHC Class I molecules.
MCH Class I inhibits NK Cytotoxicity by binding Killer immunoglobulin-like receptors (KIRs)
MHC Class I molecules are down regulated in virally infected cells and cancer cells so NK Cells will destroy these cells.
Term
Adaptive Immune System
Definition
Slow (days)
Diverse (due to genetic recombination)
Specific
Memory
Specialized
Term
Haptens
Definition
Small immunogenic molecule that have no immune response on their own. They must bind to a large carrier molecule/protein, which will ellicit an immune response against the hapten AND the carrier combined (conjugated).
Term
Immunogens seen differently by B and T Cells
Definition
B cells recognize BENDS and bind there. T cells recognize LINEAR spitopes of the antigen. Needs expressed antigen peptied in the APCs.
Term
The complement system
Definition
Consists of several inactive zymogens in the serum. They are unstable and cleaved into smaller molecules.
"b" are larger subunits which bind to membranes as opsonins
"a" are smaller and go away as cytokines/chemokines
Term
Complement cascade functions
Definition
Opsonization (b) - Tagging particles and microorganisms for removal by immune system cells that have complement receptors, removal of immune complexes, and enhancement of B cell activation.
Basically the macrophages will phagocytose what has been tagged with opsonin.
Term
Opsonization and phagocytosis
Definition
C3 becomes C3a and C3b. C3b binds microbes and antibody/antigen complexes while C3a acts as chemoattractant.
C3b is STRONG and C4b is WEAK.
Term
"a" components of complement cascade functions
Definition
Recruitment and activation of phagocytic and inflammatory cells to the site of complement activation. Activates mast cells (to release histamine to increase permeability), releases anaphylatoxins (C5a > C3a > C4a)
Term
Complement cascade's ultimate goal is to form the ___
Definition
MAC (membrane attack complex) which results in cell lysis
Term
The complement activation pathways
Definition
There are 3 of them.
Classical (C1, C4, C2, C3 (requires Ab)). Think 1423.
Alternate - properdin pathway
Mannose Binding Lectin or Lectin pathway (uses MBL to initiate the pathway.

All 3 result in the formation of a C3 + C5 convertase. They all converge at the terminal pathway.
Term
Classical Complement pathway
Definition
C1 complex has Ab (C1q). C1r and C1s are enzymes that chop.

C1 chops C4 into C4a and C4b. C1 also chops up C2 into C2a and C2b. C3 convertase (C4b2b) chops C3 into C3a and C3b. C5 convertase (C4b2b3b) chops C5 into C5a and C5b. Once C5b is formed, the pathway feeds into the terminal pathway.
Term
The membrane attack complex consists of
Definition
C5b, 6, 7, 8, and 9. 9 is the main penetrating portion of the pore. Even if some bacteria are resistant to the MAC, we will attract macrophages with C3b.
Term
What activates the Alternative pathway?
Definition
Anything that hydrolyzes C3 will activate the alternative pathway. Ex: plasmin, cellophane, cobra venom, bacteria, aggregated IgA etc.
Term
Alternative Pathway
Definition
C3 to C3a and C3b. C3b binds bacteria. Factor D binds Factor B to make Ba and Bb. Now is C3bBb. Properdin comes to stabilize C3bBb complex. C3bBb complex is C3 convertase, which splits C3 into C3a and C3b, which adds more C3b to ultimately make the C5 convertase. C5 convertase is C3b^nBb. This C5 convertase splits C5 into C5a and C5b. Formation of C5b initiates the terminal pathway --> MAC formation.
Term
Lectin pathway
Definition
MBL binds mannose on bacteria (note this is the only difference between Lectin pathway and classical. Remember in classical the first step is C1 complex. I.e. the terminal mannose residue in lectin pathway is equivalent to the Ab in the classical pathway.
Term
Convertase review:

1. Classical C3 convertase
2. Classical C5 convertase
3. Alternative C3 convertase
4. Alternative C5 convertase
5. Lectin C3 convertase
6. lectin C5 convertase
Definition
1. C4b2b
2. C4b2b3b
3. C3bBb
4. C3b^nBb with properdin stabilizer
5. C4b2b
6. C4b2b3b
Term
Terminal Pathway
Definition
Identical formation of MAC once C5 convertase is formed in all 3 pathways.
Term
Complement pathway regulation
Definition
C3b has a short half life.
Term
Complement pathway regulation - C3b inactivators.
Definition
Factor H, DAF, and Factor I.
Break apart stable structures and enzymatically cleave C3b.
Term
Factor H polymorphism predisposes one to ___
Definition
Age related macular degeneration
Term
Complement pathway Regulation
Definition
C1 inhibitor - regulates classical pathway, and can also regulate lectin pathway by dissociating components of MBL.
C4 binding protein - breaks apart the classical and lectin C3 convertase (C4b2b).
Anaphylatoxin inactivator - Messes with the "a" cytokines/chemokines
Vitronectin (S protein) - Prevents MAC formation
Term
Cells with complement receptors:

1. CR1 - specifies C3b, C4b
2. CR2 - specifies C3b, EBV
3. CR3 - Specifies C3b
4. CR4 - Specifies C3b
5. C1q - Specifies C1q
Definition
1. On RBCs, macrophages, PMN, and B cells
2. On B cells
3. On macrophages, PMN
4. On macrophages, PMN
5. On B cells, macrophages, platelets, and endothelial cells
Term
Complement deficiencies
Deficiency of early cascade members (C1, C4, C2, and C3) will lead to a deficiency in ___
Definition
Opsonization
Term
Complement deficiencies.
Deficiency of late cascade members (C5, C6, C7, C8 and C9 will lead to a deficiency in _______
Definition
formation of MAC.
5, 6, 7, or 8 can lead to difficulty killing gram negative bacteria.
Term
Antigen Presenting Cells Capturing Antigen
Definition
APCs are dendritic cells (i.e. langerhans cells in skin). They are macrophages and B cells as well. They capture the antigen through phagocytosis or pinocytosis.
Term
Antigen presentation to T cells
Definition
MCH restricted. T cells recognize antigen fragments (peptides) bound and presented by antigen presenting molecules (MHC).
Term
T cell subsets.
1. ALL T cells have ___
2. Cytotoxic T cells have ____
3. Helper T Cells have ____ also

Helper T Cells can be either TH1 or TH2.

4. TH1 secretes ___
5. TH2 secretes ___
Definition
1. CD3
2. CD8
3. CD4
4. IFN gamma, IL-2
5. IL-4,5,6,9,10
Term
MHC Organization.
1. MHC Class I genes encode proteins which present antigen to ___
2. MHC Class II genes encode proteins which present antigens to ___
3. MHC Class III genes encode ___
Definition
1. CD8 (cytotoxic) T cells only
2. CD4 (helper) T cells only
3. complement proteins and cytokines
Term
MHC Class II Structure
Definition
Heterodimers
alpha chains
beta chains - beta 2 domain has binding site for CD4
Term
MHC Class II expression
Definition
MHC Class II is expressed on APCs (dendritic cells), macrophages, and B cells. They only present to CD4 T cells (Helper T cells).
Term
___ Cells have MHC Class I, and only ___ Cells have MHC Class II
Definition
All, Antigen Presenting Cells
Term
MHC Class I structure
Definition
1 chain
alpha chain contains antigen binding site
alpha 3 domain has binding site for CD8
Beta 2 microglobulin must be associated with alpha chain for MHC class I molecule to be expressed.
Term
MHC Class I expression
Definition
MHC Class I is expressed on ALL nucleated cells. Only present antigen to CD8 T cells (and APCs). Viruses and mutated protein are expressed via MHC I.
Term
Ig structure
Definition
2 light chains
2 heavy chains
Both contain Ig domains. Both contribute to the antigen binding site.
Term
Light chain - Classes
Definition
Kappa and lambda. Light chains on a single Ab are always identical - i.e. either 2 kappa or 2 lambda.
Term
Variable domain of Ab
Definition
Variable region at amino-terminus makes up the antigen binding site. Fab fragment contains both variable and constant domains from light and heavy chains. Fc only has constant domain from heavy chain.
Term
The primary amino acid sequence of the ________ determines the isotype of the immunoglobulin. (i.e. IgG - gamma ______
or IgA - alpha ______)
Definition
heavy chains
Term
Important features of Ig Isotypes
1. Placental passage
2. Presence in secretions
3. Activation of complement
4. Opsonization activity
5. Neutralizing activity
6. Allergic activity
7. Not in serum
Definition
1. IgG
2. IgA
3. IgG and IgM
4. IgG and IgM
5. IgG, IgA and IgM
6. IgE
7. IgD
Term
Human Immunoglobulin Loci
1. Heavy Chain
2. Light chain
Definition
1. Contains V, D, J and C.
2. Contains V, J, and C. No D region in light chain gene.
Term
CDR3 (Hyper variable region) found in this region of both the heavy and light chain
Definition
J region
Term
End product of each chain has ____ of each domain
Definition
1
Term
Light chain synthesis
Definition
Mu heavy chain polypeptide combines with kappa chain polypeptide to make IgM. IgM expressed on the surface which makes an immature B cell.
Term
Ig Class Change
Definition
Variable domain does NOT change. The only thing that changes is the constant region of the heavy chain (C region).
Term
Ig Class Change needs ______ to switch classes
Definition
CD4 T Cells
Term
Mechanisms of antibody diversity
Definition
Combinatorial diversity (Combining V, D and J)
Junctional diversity - Recombination between V D and J is not precise. Gives N-nucleotide additions )N-region diversity)
Assorted heavy and light chains
Term
T Cell Receptor
Definition
2 alpha chains
2 beta chains
1 Constant and 1 Variable in each chain.
Associated with CD3.
- 2 epsilon chains
- delta chain
- 1 gamma chain
2 zeta chains
Term
TCR Loci
Definition
Beta chain is just like the heavy chain for Ig - VDJC

Alpha chain is just like light chain of Ig - VJC (no D)
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