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Immunology
Cytokines, CDs etc
100
Medical
Graduate
05/13/2009

Additional Medical Flashcards

 


 

Cards

Term
IL-1
Definition

Producer - macrophage, endothelial cell, epithelial cell

 

Actions - Inflammation, fever (via prostaglandins), incr. acute phase proteins liver, increase Th1 cells

Term

IL-2

(producer cell, actions)

Definition

Producer cells - TH0, TH1, TC cells.

 

Actions - lymphocyte proliferation (T,B, NK) and NK--> cytotoxcity

Term

 

 

IL-3 multicolony CSF

Producer, Actions

Definition

Producer cells - CD4+ T cells, thymic epithelial cells;

 

Actions - synergestic action in early hematopoesis;

Term

 

IL-4

producer, actions

Definition

producer cells - TH2, mast cells

 

actions - B cell activation, IgE and IgG4 switch, decr. TH1 cells/macrophages, decr. IFN-gamma, decr. DC-IL-12, incr. mast cells, TH0-->TH2;

Term

 

IL-5

producer cell, actions

Definition

producer cells: TH2 cells, mast cells;

 

actions: incr. IgA (post switch), incr. eosinophil growth and differentiation, incr. CD25 on mem. B cells, incr. growth of activated B cells;

Term

 

IL-6

producer cells, actions

Definition

producer cells - T cells, macrophages, endothelial cells.

 

actions - incrs. T and B cell growth/differentiation, incr. plasma cell growth, acute phase protein production, fever;

Term

 

IL-10

producer cells, actions;

Definition

producer cells - many cells, T reg cells

 

actions - incrs. MHC II Class for B cells, decrs. TH1, decrs. cytokine secretion, co-stimulates mast cells, immunosuppressive, suppresses activation of macrophages;

Term

 

IL-12

producer cells, actions

Definition

producer cells - DCs, macrophages;

 

actions - incr. NK cells, TH0-->TH1;

Term

 

IL-13

producer cells, actions

Definition

producer cell - TH2 cells

 

actions - B-cell growth/differentiation, decrs. macrophage inflammatory cytokine prudction, and decrs. TH1 cells and IgE switch;

Term

IL-17

producer cells, actions

Definition

producer cell - TH17

 

actions - IL-2 like, incrs. growth of intestinal epithelium, T cells and NK cells, pre Tc --> Tc inflammation by recruiting immune cells to infected tissue, IgG3 switching, involved in TH 17 differentiation;

Term

IG-23

producer cells, actions

Definition

producer cells - DCs

 

actions - IL-2 like, incr. growth of ints. epithelium, T cells and NK cells, pre Tc --> Tc inflammation by recruiting immune cells to infected tissue, IgG3 switching, involved in TH17 differentiation;

Term

TGF B

producer cell, actions

Definition

producer cell - CD4 T cells;

 

actions - IgA switch factor, incr. B cell growth, incr. macrophage activation, incr. neutrophils, decr. T cell activation, incr. fibrosis and wound healing, incr. phagocytic activity;

Term

 

TNF alpha (cachectin)

producer cells, actions

Definition

producer cells - macrophages, NK cells, T cells;

 

actions - local inflammation, fever (toxic shock at high concentration), incr. endothelial cells;

Term

TNF-beta (lymphotoxin, LT)

producer cells, actions;

Definition

producer cells - T cells, B cells;

 

actions - Killing, incr. endothelial cells;

Term

IFN - gamma

producer cells, actions

Definition

producer cells - TH1 cells, NK cells, CD 8 cells, T reg cells;

 

actions - macrophage activation,  incr. expression of MHC and FcRs on B cells, incr. IgG1 class switching (post switch), decr. IL-4 and TH2 secretion factor for Human IgG1;

Term
cytokines definition
Definition
molecules that are released by activated cells that enhance suppress or regulate all cells of the immune system;  made by T cells macrophages, and other cells.
Term
Interferons (IFN) general
Definition

limit viral infections induce fever inflammation, and antibody production;

IFN alpha/Beta = type I

IFN gamma = type II

Term
Interleukin IL-32
Definition
produced by T cells, DCs, and monocytes macrophages, to regulate cell growth, differentiation, and apoptosis;
Term
Colony stimulating factor (CSF)
Definition
control development of stem cells into different lineages made in the bone marrow;
Term
chemokines (definition)
Definition
proinflammatory mediators; regulate chemotaxis and cell homing;
Term
perforins def
Definition
membrane pore forming proteins released by cytotoxic T cells.
Term
Toll Like Receptors (TLRs) recognize:
Definition

1. lipids and lipopeptides

2. proteins

3. Nucleic acids

4. self ligands including HSP, Fibrinogen, hyaluronan, fibronectin;

Term

Toll like receptors (TLR)

Downstream effects

Definition

1. recruitment of adaptor proteins

2. activation of signal transduction molecules

3. activation of MAP Kinases

4. nuclear translocation of NF-kappaB

Term

L Selectin (CD62L)

Vascular Addressins and Homing specif.

Definition

vascular addr. on EC of blood vessels: CD34, glyCAM-1;

 

Homing specificity:virgin lymphocytes to lymph nodes;

Term

L Selectin (CD62L)

vascular addressin: MAdCAM

Specificity?

Definition
virgin lymphocytes to peyer's patches.
Term

alpha4/beta7 integrin

vascular addressins: MAdCAM VCAM-1

homing specificity?

Definition

virgin lymphocytes to peyers patches;

memory effector cells to lamina propria of GI tract;

Term

cutaneous lymphocyte antigen (CLA)

vascular addressins: E-Selectin P-Selectin

homing specificity?

Definition
memory effector cells to skin
Term

VLA-4/LFA-1

vascular addressins: VCAM-1/ICAM-1(CD54)

homing specificity?

Definition
activated lymphoblasts and memory effector cells to sites of inflammation;
Term

Bence Jones Proteins

def.

Definition
light chain dimers in the urine of some patients with myeloma;
Term

Enzymatic cleavage of IgG

Papain

Pepsin

Definition

Papain: cleaves molecule N terminal to the disulfide bonds in the hinge = 2 Fab and 1 Fc segmen.

 

Pepsin: cleaves the molecule C terminal to the disulfide bonds in the hinge region generating an F(ab')2 molecule and Fc fragments.

Term

Ig type in Blood

Tissue Fluids

Definition

blood - IgG & IgM; low levels of IgA, IgD, IgE;

 

tissue fluids - IgG; trace IgM and IgA monomers;

Term

Ig Type in Secretions

Fetus

Definition

Secretions - IgA dimers; small amt of IgG in tears, bronchi, esophagus, gut, breast milk;

 

Fetus - Passive IgG from mom (IgG1,3,4)

Term

Ig type Beneath Epithelium

Brain

Definition

Beneath epithelium - IgE on mast cells

 

Brain - nowhere unless blood brain barrier is damaged.

Term
IgG surface of serum
Definition

long half life 3 wks (cept IgG3)

found in lymph and blood

secreted late primary early secondary

subtypes 1,4,3 cross to fetus

opsonizing antibody

mediates ADCC

neutralizes viruses and toxins

Term
IgM cell surface
Definition

monomer on B cell surface (no hinge)

5 fxn binding sites (10 possible)

first Ig to appear during ontogeny

first Ig during an immune response (pentamer)

Natural isohemagglutinin (anti-AB)

Term
IgD surface
Definition

second recptor on B cell (with M)

sensitive to proteolysis

rare but found in serum

Term
IgE surface
Definition

binds basophils mast cells, and eosinophils;

no hinge

short half life

extra H domain

Allergy and anaphylaxis

protection against worms;

Term
IgA cell surface
Definition

dimer in secretions

two subclasses

short half life

major Ig in body and external secretions

protects mucosal surfaces

Term
IG Heavy and light chain isotypes
Definition
heavy - mu, gamma, alpha, delta, epsilon;

light chain - kappa, lambda;
Term

Isotypes

def

Definition
determine the class of immunoglobulin (A,M,G,D,E) by the heavy chains (mu,gamma,delta,alpha, epsilon)
Term

allotypes

def.

Definition

allelic forms of the same protein which vary among members of the same species.

Changes in one or two AAs in constant region of heavy or light chain.

Term

Idiotypes (Ids)

definition

Definition

variable region of the heavy and light chains of the antibody.

you can generate anti-Id antibodies against the variable regions of one homogeneous (clonal) immunoglobuilin that will not react with other immunoglobulin molecules and for the B cell that made it. Anti-IDs can go into the combining site or on the periphery of the combining site.

Term

 

Components of TCR complex

Definition

TCR (does not extend into cytosol);

CD3 (gamma, delta, epsilon chains) that form 2 pairs that extend into the cytosol of the cell;

CD3 associates with TCR once it has bound its antigen;

zeta molecules exntend into the cytosol and bind the TCR

Term
heavy chain locus
Definition
chromosome 14 with V,D,J segments and 11 constant regions. Two Ch regions are pseudogenes
Term

Kappa chain locus

lambda chain locus

Definition

kappa chain locus - chromosome 2 with VJ segments and single Ck segment;

 

lambda chain locus - chromosome 22 w/ VJ segments and 4 Clambda gene segments;

Term

Antibody rearrangments

order

Definition

Ag independent only in B cells

H chain first

Lambda chains second (kappa before beta)

Term

allelic exclusion

def.

Definition

each cell selects only one parental Vh and one parental Vl (kappa/lambda)

each B cell clone has one BCR (many copies of it)

Term

 

TCR

chain combinations

Definition

alpha/beta - biclonal (two alphas) or monoclonal (alpha/beta)

 

gamma/delta - allelically excluded, always monoclonal;

Term

prozone

postzone

def.

Definition

prozone - in excess of antibody weak or no precipitation may occur;

 

postzone - if antigen is in excess, weak or no precipitation may occur;

Term

 

Direct Coombs Test

Definition

Used to detect the mother's anti-Rh IgG in the babys blood (acquired through the placenta);

agglutination of the newborn's RBC coated with the mother's anti-Rh AB by an anti-IgG Ab;

if agglutination occurs the child has hemolytic disease;

Term

 

 

Indirect Coombs Test

Definition

used to detect the prescence of anti-Rh Ab in the serum of the mother;

Rh positive RBCs are treated with the mother's serum.  If it contains anti-Rh antibody these RBCs will be coated with the mother IgG anti-Rh Ab;

Term

 

Complement Nomenclature

(exception)

Definition

When a protein is cleaved by a protease the smaller fragment is labeled 'a' and the larger one 'b' (Ex. C3 --> C3a &C3b)

 

exception: C2 --> C2a (bigger) & C2b (smaller)

Term

Complement System

Overview Fxn.

Definition
30 serum and cell surface proteins.  Provides innate and immediate protection to infections disease before immune response.  Major effector of the humoral immune system and mediator of inflammation.
Term

Complement

Specific Fxns.

Definition

A. Generation of peptides with potent biological activities.

B. Formation of macromolecular complexes with enzymatic or membrane altering properties.

C. Covalent modification of other macromolecules.

Term

Protective Effects of Complement

(4)

Definition

A. Lysis of bacteria

B. Causing inflammation (recruiting neutrophils, etc.)

C. Opsonization (marking for uptake by phagocytes)

D. Preventing immune complex damage (removal from circulation)

Term

Classical Pathway

Recognition

Definition
C1 Complex: Single C1q subunit and dimers of C1r and C1s;
Term

CP Activators

(4)

Definition

IgM, IgG (3,1,2,4), Apoptotic Cells, Oxidized LDL;

Immunoglobulins are the most important activators.  C1q binds to the Fc portion of immunoglobulins.  One IgM molecule or two IgG molecules can activate C1q;  Only aggregated (bound) immunoglobulin not soluble can activate.

Term
Attachment of C3 (CP)
Definition

C1q + Ig activates the serine protease activity in C1s which cleaves C4 and C2 into two fragments each.

Cleaved C2 has protease activity and breaks C3 into two fragments.

C2+C4 = C3 Convertase + C3b = C5 Convertase

Term
Covalent attachement of C3 and C4
Definition

C3 and C4 have a posttranslational modification an internal thiolester bond, an unstable high energy intermediate.

After cleavage of C3 or C4 by proteases the thioester gets exposed and gets attached to nearby proteins or carbohydrates (cell surfaces, bacteria, viruses, and Igs.

Term

Lectin Pathway Activators

(1)

Definition

Mannose containing microbial carbohydrates Agalactosyl IgG

Mannose binding lectin (MBL)

Term

Attachment of C3 lectin Pathway

 

Definition
Mannose Binding Lectin (MBL) associated with MASP (serine proteases) 1 &2 and are homologus to C1r C1s and cleave C2 and C4.  C3 converstase and C5 convertase formed in the same fashion.
Term
Membrane Attack complex (MAC)
Definition

A. Lytic channels form once C5 converatase cleaves C5.  C5b binds to C6 and C7;

B. C8 binds and begins membrane perturbation;

C. C9 binds and then undergoes conformational change which allows it to selfpolymerize into a pore.

D. MAC disrupts cellular homeostasis, allowing ions, water, and bacteriocidal proteins (lysozyme) across the cellular membrane.

Term

C1qR

ligand

sites of expression

biological effects

 

Definition

ligand - C1q bound to immune complexes;

sites of expression - leukocytes, endothelium, epithelium, platelets;

biological effects - phagocytosis (main), oxidative burst by PMN, ADCC, cytokine release;

Term

 

 

CR1 (CD35)

Ligand, expression, biological effects

Definition

ligand - C3b, C4b;

 

expression - RBC, PMN, monocytes, B cells, FDC, Kupffer cells, glomerular podocytes;

 

Effect - removal of IC, phagocytosis, antigen presentation;

Term

 

 

CR2 (CD21)

ligand, expression, biological effect

Definition

ligand - C3d,g;

 

expression - B cells, thymocytes, FDC;

 

Effects - B cell co activator, antigen presentation;

Term

 

CR3 (CD 11b/CD18)

ligand, expression, biological activity;

Definition

ligand - C3Bi;

expression - PMN, monocytes;

biologic activity - phagocytosis;

Term

CR4 (CD11c/CD18)

ligand, site of expression, biological function;

 

Definition

ligand - C2bi

expression - PMN, monocyte;

biological effect - phagocytosis;

 

Term

 

 

Anaphylatoxins

Definition

small amino terminal fragments of C3, C4, and C5 generated during complement activation are potent inflammatory mediators;

The polypeptides responsible for anaphylactoid shock and death.

They bind to specific cell surface receptors.  They promote inflammation/recruitment of neutrophils, monocytes to tissue injury, and promote hemostatis and cytokine production;  Can also result in tissue damage or organ failure in widespread complement activation;

Term

 

Regulation of C1s Activity

Definition
C1 esterase inhibitor (C1-INH) is a soluble serine proteinase inhibitor (serpin)
Term
Regulation of C3 Convertase by Regulators of complement activation (RCA) proteins
Definition

Main regulation at the level of C3/C5 convertases;

Factor I cleaves C3 into inactive fragments.

RCA proteins with Co-Factor activity - cleave C3/4 in presence of Factor I;

Factor H, C4bp, Membrane cofactor protein (MCP), CR1 (CD 35);

Term

 

RCA proteins with Decay acceleration activity

Definition

disrupt the non covalent association of C3 with enzymatic components of the convertases (C2a/Bb)

Factor H, C4bp, Decay accelerating factor (DAF), CR1 (CD35);

Term

 

Regulation of MAC

(3)

Definition

Vitronectin (S protein) - binds C5b-7 trimer and renders it hydrophilic, preventing membrane insertion;

Clusterin (SP-40) - prevents C5b-9 that forms in the serum from binding to cells;

CD59 - membrane protein on erythrocytes, leukocytes, and endothelial cells.  binds to C8 and prevents incorporation and polymerization of C9.

Term

 

Prothymocyte V region

Rearrangement Order

Definition

 

gamma, delta, beta, alpha

Term

 

TCR Positive Selection

Definition

Cortex of Thymus - If TCRs on a T cell recognize class I or class II with high affinity --> apoptosis.

If the TCR do not recognize Class I or II with any affinity --> die of neglect.

 

TCRs with low/medium affinity for Class I/II migrate to the medulla.

Term

 

Negative Selection

Definition
medulla of Thymus - TCRs that recognize Class I/II plus peptide with high affinity undergo apoptosis.
Term

 

Location of T cells in the periphery

(4)

Definition

a. cortex of lymph node

b. periarterial sheath of spleen

c. intranodal areas of peyer's patches (lower GI)

d. activated by heat shock proteins and mycobacteria;

Term

 

 

Ligands for B7 costimulatory molecules

expressed on APC (2)

Definition

CD28

CD152 (CTLA-4)

Term

 

 

Interacts with CD40 expressed on APC (1)

Definition

 

 

 

CD154(CD40L)

Term

 

 

Adhesion Molecules on T Cell

(2)

Definition

CD11a/CD18(LFA-1)

CD49d/CD29 (VLA-4)

Term

 

 

Homing molecule

Naive T Cell --> lymph Node via HEV

(1)

Definition
CD62L(L-selectin)
Term

 

 

Alpha Chain of the IL-2 receptor on

activated T and B cells

(1)

Definition
CD25
Term

 

 

Signals in T/APC immune response

(3)

Definition

signal 1 - recognize MHC/peptide via TCR

 

Signal 2 - engagement of costimulatory molecule w/ ligand

 

Signal 3 (pseudo)  - binding of integrin to integrin receptors strengthens the avidity of the rxn. 

Term

 

 

anergy

(def)

Definition
when the TCR-MHC peptide interaction occurs in the absence of the co-stimulatory signal the cell is anergized (tolerized) and will no longer differentiate or die.  Important in periphery where self reactive T cells reside.
Term

 

 

CD4+ Regulatory T Cells

Definition

a)  Foxp3CD4+CD25+ T cells (T reg) --> develop in the thymus, require TCR engagement but once activated suppress (via cytokines) the proliferation and activation of CD4 and CD8 T cells;

b) Tr1 -develop in periphery produce IL-10

c) Th3 - develope in periphery involved in oral tolerance produce (TGF-B and IL10);

Term

 

Biologic Fxns of Chemokines

(5)

Definition

1. leukocyte chemotaxis

2. integrin activation during leukocyte endothelial interactions

3. leukocyte degranulation and mediator release

4. angiogenesis/angiostasis

5. fibrosis and wound healing

Term

 

 

Th1 cell

dev./fxn

Definition

Th0-->Th1 via antigen & IFNgamma;

involved in cell mediated immunity & defense against intracellular pathogens;

Produce:

IL-2 (B cell incr. Ab opson. of Bact. & act. Tc); IFN-gamma (mac. incr. kill & B cell Ab ops. of bacteria);

 TNF a/b (neutro microb. killing);

Term

 

 

Th2 cell

dev. fxn. mol. produced

Definition

Th0-->Th2 via antigen, IL-4 (NK T cells);

Gen. of hum. immun., inhib inflam., Reg IgE against parasites;

Produce: IL-4,5,13;

Term

 

Th1 & Th2

common cytokines produced

(5)

Definition

 

 

 

IL-3, GMCSF, IL-10, TGF-B, IL-6;

both can become memory cells;

Term

 

 

Th17

dev./fxn./mol. prod.

Definition

Th0-->Th17 via TGF-B, IL-12, IL-6;

inflammatory resp. against extracellular pathogens;

Produce: IL-17;

Term

 

 

Treg

dev./fxn./mol. prod.

Definition

Th0-->Th17 via TGF-B;

fxn. - immunosuppresion of T cell and macrophages;

produce immunosuppresive: IL-10 & TGF-B;

Term

 

 

Dendritic Cell (DC)

cytokines produced

(5)

Definition

 

 

 

IL-12, TGF-B, IL-23, TNF-a, INF-a

Term

 

 

NK Cell

cytokine (1)

Definition

 

 

 

IFN-gamma;

Term

 

 

Macrophage

cytokines produced

(5)

Definition

 

 

IL-12, IL-1, TNF, IL-6, IL-8;

Term

 

 

Mast Cell

cytokines produced (1)

Definition

 

 

IL-4;

Term

 

 

NKT cell

cytokine produced

(1)

Definition

 

 

IL-4;

Term

 

 

 

Immunosupprs. & tissue repair by Monocytes

Definition

 

 

Early - TGF-B & IL-10 (immunosuppresion)

 

Late - TGF-B, arginase (tissue repair)

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