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Immunology Exam 1 Melissa
Immuno Flash Cards
100
Immunology
Undergraduate 4
11/01/2012

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Term
Hapten
Definition
A small molecule that reacts with a specific antibody but cannot induce the formation of antibodies unless bound to a carrier protein or other large antigenic molecule.
Term
Adjuvant
Definition
An adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect in itself.
Term
What cells are involved in eradicating the virally infected cells?
Definition
NK and Tc cells
Term
B-cell Markers
Definition
KIT (SCF) Development
IL-4 (memory) 7 (development) 10 (plasma) Receptors
VLA-4 (VCAM-1 Development)
ICAM-1 (LFA-1 for Tcell signaling)
CCR7 (CCL21 from HEV to LN)
BAFF Receptor (Bcell activating factor)
CD40R (T-cells)
CD40L (Dendritic)
Term
B-cell Receptor and co-receptor
Definition
Ig, Ig alpha, Ig beta, CD19, CR2, CD81
Term
T-cell markers
Definition
CD4 (Th)
CD8 (Tc)
CD2, 5 and 44 (Attachment and signaling)
IL-7R and Notch-1 Receptor (Signaling Thymocyte --> T-cell)
Term
TCR and Coreceptors
Definition
TCR ( Alpha/beta or gamma/delta)
2 zeta chains
2 CD3 Receptors (delta, gamma and 2 epsilon)
CD4 and 8
Term
Stem Cell Marker
Definition
CD34
Term
Costimulatory Molecules
Definition
Tcells: CD28 --> B7 (CD80)increases proliferation and CTLA --> B7 decreases
B-cells:CD40L (Dendritic) CD40R (Tcell)
*this second signal is not required for Tc Cells!
Term
Antibody Dependent Cell Mediated Cytotocxicity (ADCC)
Definition
ADCC is mediated by the NK cells

When NK cell (loaded with pre-formed cytotoxic granules) encounters the target cell coated with Abs its FcRs interact with Fc portions of the Abs
Cross-linking of the FcgammeRs leads to release of the toxins that kill the target cell
Term
Th1 Function
Definition
Cellular Funtion - macrophage activation
Term
Th2 Function
Definition
Humoral Fuction - antibody production, need for ADCC
Term
MHC class I structure
Definition
An MHC Class I molecule is composed of one membrane-bound heavy alpha chain and noncovalently bonded beta2 microglobulin

The heavy chain has three extracellular (alpha1, alpha2 & alpha3) domains

1 & 2 domains form the peptide (Ag-derived) binding site
Term
MHC class II structure
Definition
An MHC Class II molecule is composed of two membrane-bound chains: a chain and b chain. Each of them have two extracellular domains

a1 & b1 domains form the binding site fro the Ag-derived peptide
Term
MHC I isotypes
Definition
ABC EFG
Term
MHC II isotypes
Definition
DM DO DP DQ DR
Term
Soluble C3 convertase
Definition
iC3Bb
Term
Alternative C3 Convertase
Definition
C3bBb
Term
Classical C3 Convertase
Definition
C4b2a
Term
Ab predominate in the blood
Definition
IgM, IgG, and monomeric IgA
Term
Ab in fetus
Definition
IgG transported by FcR of mother
Term
Ab in fluids/secretions
Definition
Dimeric IgA
Term
Ab on skin/epithelial
Definition
IgE
Term
Immunogenicity
Definition
The ability of an antigen to elicit immune responses is called immunogenicity, which can be humoral and/or cell-mediated immune responses.
Term
How is anergy induced?
Definition
Some self-reactive T cells leak the negative selection mechanisms in the thymus & enter peripheral circulation

However, they are not going to be activated because when APCs present self-Ags, they do not express co-stimulatory molecules

Without 2nd signal T cell instead of activation becomes anergic (not responding to Ag)
Term
IL-2 function
Definition
IL-2 is secreted by T cells during their activation & is a major cytokine of the adaptive immunity

Secreted IL-2 is a ligand of IL-2R of the T cells, promoting their proliferation & differentiation

Both signals (through MHC/Ag & TCR and CD28 & B7) are required for expression of IL-2 gene
Term
Is costimulation necessary for effector functions?
Definition
Effector cells recognize Ag on the target cells & mediate their function without requirement for 2nd signal
Term
Outcomes of opsinization through antibody
Definition
The opsonization thus promotes phagocytosis of pathogens

Alternative role of opsonization is in the classical pathway of complement activation because Abs bound to the surface of the pathogen cause complement fixation
Term
TNF alpha
Definition
Induce local & systemic inflammatory reactions
Term
IL-1
Definition
Lymphocytes’
activation,
Production of IL-6
Term
Innate Immunity - viral infections
Definition
Extracellular phase
Complement system
Virolysis
Neutralization (Abs-mediated)

Intracellular phase
Type I interferon
Activation of the NK cells
Increases expression of ligands on the infected cells specific to the receptors on the NK cells

Natural killer cells
Destroy the virally infected cells
Term
Innate Immunity - Bacterial Infectin
Definition
Macrophages are the first responders:
Phagocytosis
Synthesis of cytokines

Stimulating the liver

Chemokines promoting chemotaxis of neutrophils to the center of infection

Growth Factors for bone marrow

Liver
Acute-phase proteins
Complement system
Tagging the pathogen for phagocytosis
Lysing the pathogen

Bone marrow
More macrophages and neutrophils
Term
Innate Immunity
Definition
All reactions are Ag non-specific (just against any molecular structures foreign to the human body)

Remaining major features of the innate immunity are:
No increase in response with repeated exposure to a given pathogen (no memory cells)
It is nonclonal defense mechanism
Term
MHC I
Definition
MHC Class I molecules are assembled in the ER, where they make complexes with antigenic peptides derived from the cytosol

The CD8 receptors bind to MHC I molecules to insure that Tc cells recognize a cytosol-derived Ag
Term
MHC II
Definition
MHC Class II molecules are also assembled in the ER (as MHC Class I) but they make complexes with antigenic polypeptides derived from the endocytic vesicles

The CD4 receptors bind to MHC II molecules to insure that TH cells recognize a endocytic vesicles-derived Ag
Term
Chemokines
Definition
regulate migration (trafficking) of cells (chemotaxis)

Combined with cell-adhesion molecules, the chemokines facilitate the extravasation of leukocytes and homing in the tissues in areas of the immune reaction
Term
Interferons (IFN)
Definition
Interferons were originally so named because they interfere with viral replication

There are two types of the Interferons:
Type I (IFN-α & IFN-β), Type II (IFN-gamma)

Mechanisms of action:

Activation of natural killer (NK) cells

Upregulation of the expression of MHC class I molecules (thus increasing the recognition and killing of virus-infected cells)
Term
Type I INF
Definition
can be produced by ANY infected cell
Term
Type II INF
Definition
secreted by TH, TC & NK cells
Term
TGF-β
Definition
The transforming growth factor beta

The overall function of TGF-β is to down-regulate the inflammatory response, it is a negative feedback mechanism ‘switching off’ the inflammation-related reactions of the immune system when they are no longer needed

Mechanism of action:

It suppresses proliferation & differentiation of the immunocompetent & somatic cells

It is involved in regulation of cells apoptosis

Inhibit activation of macrophages
Term
Hematopoietins
Definition
Interleukins (IL-3; IL-5; IL-7)
erythropoietin (EPO)
Granulocyte CSF (G-CSF)
macrophage CSF (M-CSF)
Granulocyte-macrophage CSF (GM-CSF)
Term
CSF's
Definition
CSFs are produced in the bone marrow in response to inflammatory cytokine IL-1

They promote maturation of the corresponding lineages of hemopoietic cells
Term
Interleukin 12 Innate immunity
Definition
Innate Immunity:
Stimulates production of tumor necrosis factor-alpha (TNF-α)

Mediates enhancement of the cytotoxic activity of NK cells
Term
Interleukin 12 Adaptive immunity
Definition
Adaptive immunity:
It stimulates the production of interferon-gamma (IFN-γ)

Mediates enhancement of the cytotoxic activity of CD8+ TC cells
A T cell stimulating factor and growth factor

It promotes differentiation of naive T cells into Th1 cells
Term
Interleukin I (IL-1)
Definition
IL-1 is secreted by monocytes & macrophages, fibroblasts, Dendritic cells and upon activation by many other types of blood cells

Its functions:

An endogenous pyrogen (induces fever)

Induces accumulation of leukocytes to the center of inflammation by regulating chemotaxis:

Promotes the expression of cell-adhesion molecules & chemokines

Activates vascular endothelium

Plays a role in regulation of the hematopoiesis
Induces secretion of IL-6
Term
Interleukin 6 (IL-6)
Definition
IL-6 is produced by both lymphoid and nonlymphoid cells (T & B cells, monocytes and macrophages, fibroblasts, hepatocytes, keratinocytes, astrocytes, endothelial cells, and various tumor cells)

Secretion of IL-6 is primarily triggered by IL-1

IL-6 is a pleiotropic cytokine, affecting:

Production of the acute phase proteins by liver

Activation of B cells

Promotes B cells differentiation into plasma cells & immunoglobulins (Ab) synthesis


Activation of T cells

Promotes production of cytokines by CD4+ cells
Term
Tumor Necrosis Factor (TNF-α)
Definition
TNF-α is secreted by monocytes, macrophages, neutrophils, NK cells and CD4+ T cells and some tumor cells
TNF-α is the major member of the TNF superfamily
The main trigger for its production are lipopolysaccharides in gram-negative bacteria
TNF-α exists in both membrane-bound and soluble forms
TNF-α functions:
Causes vasodilation and increased vasopermeability
Induces secretion of the cell-adhesion molecules & chemokines
Promotes expression of MHC class II molecules
Anti-tumor immunity
Term
The major cytokines involved in triggering innate immunity reactions are:
Definition
Interleukin-1 (IL-1)

Tumor necrosis factor-α (TNF-α)

Interleukin-6 (IL-6)
Term
TH1 cytokines
Definition
IL-2 IL-12 and INF gamma
Term
TH2 cytokines
Definition
IL-4 and IL-5
Term
Major cytokines mediating Treg cells function are
Definition
IL-10
TGF-β
Term
Polygenic
Definition
There are several genes encoding MHC proteins with different Ag-binding specificities
Term
Polymorphic
Definition
There are multiple alleles of each gene
Term
The diversity of MHC molecules is due to
Definition
Existence of the gene families, consisting of multiple genes encoding different chains of MHC molecules

Genetic polymorphism, which is presence of multiple alternative forms (alleles) of a gene
Term
Neutrophils’ Extravasation 4 steps
Definition
Step I: rolling of neutrophils along the blood vessel wall is slowing down

Step II: neutrophils hold to endothelial cells and stop rolling

Step III: diapedesis (neutrophil squeezes between neighboring endothelial cells & leave the blood vessel)

Step IV: movement into the center of the infection
Term
Fas Ligand
Definition
type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family

Its binding with its corresponding receptor induces apoptosis
Term
DISC
Definition
FasR forms the Death-Inducing Signaling Complex (DISC) upon binding with FasL
Term
PAMPS
Definition
Pathogen-Associated Molecular Patterns

highly conserved among microorganisms, BUT NOT expressed by human tissues

Molecular structure recognized by the innate immune system

A typical PAMP is bacterial DNA
Term
PRR
Definition
PAMPs are recognized by specific Pattern Recognition Receptors (PRRs)
Term
Secreted PRR
Definition
opsonins that bind to microbial walls to tag them for degradation by the complement system or by phagocytosis

Mannose-binding lectin (MBL) is secreted by liver as one of acute-phase proteins. It recognizes carbohydrates on bacteria, yeast & some parasites
Term
Endocytic PRR
Definition
are expressed on the surface of phagocytes and mediate the uptake & transport of the pathogen to lysosomes

Mannose receptors
Scavenger receptors
NOD1 & NOD2 (proteins with nucleotide-binding domain)
Term
Signaling PRR
Definition
TLR
Term
Fc(gamma)RI
Definition
expressed on monocytes, macrophages & dendritic cells

alpha and gamma chains, gamma chain mediates function

FcRI can bind to IgG in the absence of Ag *

Once IgG traps an Ag on the surface of monocytes, macrophages & dendritic cells it leads to its uptake and destruction
Term
high affinity membrane receptors for Fc portion of IgE
Definition
Mast cells and basophils
Term
In the primary follicles
Definition
unprimed B cells
Term
In the follicular centers
Definition
Activated B cells
Term
Paracortex
Definition
T cell area
T cells already differentiated in the thymus
Term
Dendritic cells
Definition
antigen presentation
iDC recognize specific chemical signatures on the pathogens through pattern recognition receptors (PRRs) such as the toll-like receptors (TLR)

In the process of phagocytizing and degrading the proteins of the pathogens and migrating to the lymph nodes they become mature Ag-presenting DCs (mDC)

Upon maturation DCs acquire CD80, CD86 and CD40 receptors (co-stimulatory molecules) important for their function in T Cell activation.

Link between adaptive and innate immunity
Term
Basophil
Definition
WBC, granulocyte, which granules are susceptible to staining by base dyes
Express receptors for IgE, IgG, complement & histamine (role in allergic reactions)
Granules of the basophils contain:
Heparin & Peroxidase
Prostaglandins & Leukotrienes (factors of anaphylaxis)
Platelet activating factor
IL-4, cytokine that stimulates the proliferation of activated B-cells
IL-5, the growth factor for eosinophils
Term
Mast Cell
Definition
are residents of the connective tissue of bone marrow origin
They secrete:
Histamine
Leukotrienes
Different enzymes
Term
First class of ab made in immune response
Definition
IgM
Term
IgG subclasses
Definition
IgG1,2,3,4
Term
Which IgG does not cross placenta easily?
Definition
IgG2
Term
IgG not a complment activator
Definition
IgG4
Term
Papain
Definition
digests into 3 segments 2 Fab and one Fc
Term
Pepsin
Definition
digests into 2 segments F(ab)2 and Fc
Term
Mercaptoethanol
Definition
2 H chains and 2 L chains
Term
Somatic recombination
Definition
process of constructing an exon which includes a single version of all variable constituents of each segment (VL & JL for light chain & VH, JH & D for heavy chain) to be transcribed into mRNA

This is the first factor contributing to the ultimate diversity of Abs.
Term
recombination signal sequences (RSSs)
Definition
The recombination of V, J & D regions of gene segments is directed by recombination signal sequences (RSSs)
Term
V(D)J recombinase
Definition
The set of enzymes that combine V, D & J segments is called V(D)J recombinase & is encoded by recombination-activation genes (RAG-1 & RAG-2)
Term
Steps in Somatic Recombination
Definition
Step 1: RAG-1 binds to one type of RSS & RAG-2 to another
Step 2: Interaction between two RAGs
Step 3: Detachment of the formed loop
Step 4: Removal of nonfunctional ‘signal joint’
Step 5: Formation of coding joint
Term
Junctional Diversity
Definition
The second factor contributing to diversity of the Abs hypervariable regions

addition of nucleotides (that were not encoded in the germline DNA) by the enzymes involved in formation of the coding joint

The added nucleotides are:

P nucleotides

N nucleotides
Term
Alternative RNA splicing
Definition
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene (pre-mRNA) are reconnected in multiple ways during RNA splicing. The resulting different mRNAs are translated into different protein isoforms.
Term
naive B cells
Definition
After maturation in the bone marrow B cells are released into peripheral blood circulation & before encounter with an Ag

Only IgM & IgD
Both these isotypes can be expressed simultaneously on the same cell (an unique feature, characteristic only for naïve B cells)
Term
Combinatorial Association
Definition
(third*) contribution to the overall diversity of Ig molecules

the association of heavy & light chains, the combinatorial (in different combinations, either , or  light chains & either one of 9 heavy chains isotypes with the same Ag specificity) association
Term
naive B cells encounter ag
Definition
triggers their proliferation (clonal expansion in the secondary lymphoid tissues, mainly in the lymph nodes) & differentiation

Ultimately these processes lead to evolvement of Plasma cells and production of Abs

As the immune response progresses, Abs with different properties are made as a result of:

Somatic hypermutation

Isotype switching
Term
Somatic Hypermutation
Definition
The point mutations (single-nucleotide substitutions) are randomly introduced at a high rate throughout the rearranged V regions (only!) of heavy chain & light chain genes
Term
Somatic hypermutation is dependent on the enzyme
Definition
activation-induced cytidine deaminase (AID)
Term
affinity maturation
Definition
After somatic hyper mutation

As the adaptive immune response proceeds, Abs of progressively higher affinity are produced
Term
Isotype Switching
Definition
Isotype switching occurs only in B cells primed with Ag (proliferating in the response to antigenic stimulus) and, as somatic hypermutation, is dependent on AID enzyme (activation-induced cytidine deaminase)

Occurs by somatic hypermutation
Term
B cell development stages
Definition
Precursors in BM > - selection> + selection > blood/lymph circulation > priming > activation > Proliferation and differentiation
Term
Stem cell to plasma cell
Definition
HSC > Lymphoid cell > Pro B > Pre B > Immature > Mature > Activated > IgM secreting > class switching >Memory and Plasma cells
Term
Pre-B-Cell Receptor
Definition
Difference is in the lack of Ig light chain, which is replaced by the surrogate light chain made up from the VpreB & 5 polypeptides

Pre-B cell receptor is not expressed on the cell membrane, it remains in the cell’s cytoplasm
Term
Allelic Exculsion
Definition
In a developing B cell, the process of Ig gene rearrangement is tightly controlled that only one heavy chain & one light chain of the same specificity are expressed
Term
Pre B cell receptor role in allelic exclusion
Definition
Once rearrangement of the first immunoglobulin locus is successful, the synthesis of  chain & assembly of the pre-B cell receptor signals:

To stop transcription of RAG genes
To degrade the existing RAG proteins
To stop further somatic rearrangement in the M heavy chain locus
Term
Affinity
Definition
the strength of the reaction between a single antigenic determinant and a single combining site on the antibody
Term
Avidity
Definition
a measure of the overall strength of binding of an antigen (by its multiple epitopes) with multivalent antibodies

It is influenced by both the valence of the antibody and the valence of the antigen and is more than the sum of the individual affinities
Term
Stromal Cells of the Bone Marrow
Definition
provide special microenvironment for B cells maturation. They make direct contact with developing B cells & produce specific growth factors, such as Stem Cell Factor (SCF), IL-7 and some others
Term
DC secrete
Definition
IL-6, IL-15, 8D6 & BAFF, which induce transformation of B cells into large centroblasts
Term
Thymus-Independent (TI-2) Ags
Definition
TI-2 Ags are composed of repetitive epitopes expressed on the surface of microorganism at so high density that they cross-link B cell receptors & co-receptors so extensively that there is no need for additional signals
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