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243 Cards in this Set

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What are the three major functions of innate immunity?
Initiate rapid response at entry site.

Limit the spread of infection.

Initiate adaptive immune response at secondary lymphoid site
Approximately how many epitopes can the immune system recognize?
10^7
What is the time frame for innate immunity?
0-4 hours
What is the time frame for an early induced response?
4-96 hours
The time frame for a full blown adaptive immune response is...
>96 hours
Inflamation is characterized by..
Redness
Heat
Swelling
Pain
Inflamation is caused by...
Effectors of innate immunity
When does wound healing occur relative to inflamation?
The final phase of the inflmmatory response.
List 14 effectors of innate immunity.
Skin
Mucous
Surfactants
Lysozyme
Phospholipases
Histidine rich peptides
Alpha and beta defensins
Complement
Interferons
Cytokines
Acute phase reactants
Phagocytes
NK cells
B1 cells
What are the four key steps in the innate immune response against bacterial pathogens?
Complement activation

Induction of cytokine synthesis by resident macrophages, endothelium and epithelium.

Neutrophil and macrophage recruitment.

Dendritic cell maturation.
Why aren’t host cells as susceptible to C3b as microbial pathogens?
Factor H has an affinity for sialic acid which is more heavily expressed on host cells.
Factor H scrapes C3b off host cells by displacing factor B.
C3b that is scraped off is quickly degraded by factor I proteolysis.

Host cells also express decay accelerating factor which competes with factor B for C3b binding so less complexes are formed on the cell surface.
How does a factor I deficiency present?
High susceptibility to pyogenic infection early life.

Low circulating C3 levels.
What are the functions of C3b?
Opsonin (iC3b)
Part of C3 convertase
Part of C5 convertase
What are the effects of C3a after it is cleaved from C3?
Anaphylotoxin-activates mast cells, increases vascular permeability and contracts smooth muscle.
Which complement component is the most potent anaphylatoxin as well as a chemoatractant of neutrophils?
C5a
What is chronic granulomatous disease (CGD)?
Inability to mount a respiratory burst in phagocytes because of bad coding for radical making machinery.

X-linked and autosomal forms.

Cannot reduce nitro blue tetrazolium (NBT) with respiratory burst stimulus.
TLR 1,2 and 6 are involved in the recognition of...
Gram positive bacteria
TLR 3 recognizes...
Double stranded RNA
TLR 4 recognizes...
LPS, pili, RSV F protein
TLR 5 recognizes...
Gram negative flagellin
TLR9 recognizes...
Unmethylated CpG DNA
Activation of a toll like receptor on a dendritic cell causes it to...
make cytokines
mature
migrate to secondary lymphoid site.
In order for LPS to activate TLR4, it is also necessary to have normal...
Lipopolysacharide binding protein (LBP)
CD14 coreceptor
MyD88 and IRAK transduction proteins
The three most important cytokines are...
IL-1, IL-6 and TNF-a
Cytokines increase the adhesive properties of circulating immune cells whereas chemokines...
Attract them to the site of infection.
When cytokines reach the liver they cause...
Production of acute phase reactants such as C-reactive protein, mannose binding lectin, surfactants and complement components.
The main source of complement protein is...
The liver.
CRP and MBL made in the liver cause....
Activation of the classical complement pathway.
Fever is primarily important because...
Immune cells function better with a low grade fever.
Fever is induced in the hypothalamus by....
IL-1, IL-6 and TNF-a
Fatigue and mild anorexia during infection are effects of...
IL-1, IL-6 and TNF-a on the brain.
Unlike bacterial infections, viral infections cause the release of...
IFN-a and IFN-b (type 1 interferon alpha and beta)
Type 1 interferons in the innate immune response to viral infections protect neighbouring cells and induce....
maturation of dendritic cells
activation of NK cells
What substances can cause dendritic cell maturation?
TLR agonists
Cytokines
Type 1 interferons
Summarize the steps of the innate immune response against bacteria.
Activation of the complement system
Signaling via TLRs
Production of pro-inflammatory cytokines
Recruitment of neutrophils and macrophages
Maturation of dendritic cells and migration to secondary lymphoid site
Summarize the steps of the innate immune response against viruses.
Signaling via TLRs

Production of pro-inflammatory cytokines

Production of type I interferons

Maturation and migration of dendritic cells to secondary lymphoid site.

Migration of dendritic cells to secondary lymphoid site
SIRS is defined by two or more of which criteria?
Temperature >38C or Tachycardia (>90)
Hyperventilation (>20)
PaCO2 <32 mm Hg)
WBC count >12,000 or <4000/mm3, or >10%immature (band) forms
Sepsis is SIRS but by definition also includes...
infection
Severe sepsis is defined as...
Sepsis (SIRS) with organ dysfunction, hypoperfusion or hypotension.
Septic shock is defined as..
Septic hypotension despite adequate fluid resuscitation.
Mortality rate in septic shock is approximately...
Close to 50%
About 20% for severe sepsis
Risk factors for sepsis include...
AIDS
Immunosuppressive agents
Malnutrition
Malignancy
Diabetes
The shock or loss of volume in septic shock is attributable to..
Complement components C3a and C5a which increase vasular permeability.
DIC is attributable to...
Increase in adhesion expression due to Il-1, IL-6 and TNF-a
Septic shock is managed by..
fluid resuscitation
antibiotics
vasopressors
activated protein C to reduce clot formation (only in high risk adults)
Candidate genes that could be associated with sepsis risk or mortality include....
TNFa and TNFb
IL-1 receptor antagonist
IL-6
IL-10
TLR4 (G-) and TLR2 (G+)
CD14
The CD3 marker is found on...
All T lymphocytes
The CD19 marker is found on..
All B lymphocytes
B1 cells make predominantly which types of antibodies?
IgM
Absence of IgG predisposes to pyogenic infections because...
IgG is a highly effective opsonin against bacteria that express a capsule like Strep pneumo, S. pyogenes, and Staph aureus.
How many classes of immunoglobulins are there?
5
(ADEGM)
Which immunoglobulin is an opsonin?
IgG
Which immunoglobulin causes sensitization of mast cells and therefore allergic responses?
IgE
Which immunoglobulin can cross the placenta?
IgG
Which Immunoglobulins are active at mucosal surfaces?
IgA and IgG
Which immunoglobulins cause activation of the classical complement system?
IgM and IgG
Which immunoglobulins neutralize toxins and prevent the adherence of pathogens?
IgM, IgA and IgG
The M in IgM is derived from...
The greek letter variant of the heavy chain. Mu.
Antisotypic antibodies bind to..
Constant regions of heavy chains.
They are used in assays to tell how much is circulating of each immunoglobulin.
Each immunoglobulin interacts with how many antigens?
2
Papain will cleave an immunoglobulin at...
The disulfide bond.
Releases two FAB (fraction antigen binding) and one FC (fraction crystalizeable)
Cleavage with pepsin will yield..
1 FAB'2 which is the top part of the immunoglobulin Y unseperated.
How many hypervariable (CDR) regions are there in each heavy and light chain?
3
Antigen specificity is determined by these regions.
The maximum number of CDR's in each FAB region of an immunoglobulin is..
6
Antigen affinity increases as more of these participate in antigen binding up to a maximum of 6 on each FAB region.
What are the two types of epitope recognition an immunoglobulin can preform?
Linear (based on a sequence)
Conformational (based on the structure of the whole protein)
The uniqueness of the immunoglobulin (idiotype) can be exploited by...
Making antibodies against the antibodies as in the treatment of B cell tumors like multiple myeloma.
Anti-idiotypic antibodies recognize...
Antigen binding sites and are very specific.
Anti-isotypic antibodies recognize..
Constant regions of heavy and light chains.
They are less specific than anti-idiotypic antibodies which recognize variable regions.
In what conformation does IgM typically exist?
A pentamer.
Five molecules of IgM that can bind 10 epitopes.
To activate the classical complement system we need either...
one IgM or two IgG
In the classical complement system the C1qrs complex activated by IgM or IgG acts on the substrates....
C2 and C4
The products from the cleavage of C2 and C4 in the classical complement system go on to make....
a C3 convertase
What are the four mechanisms that underly antibody diversity?
MULTIPLE GERMLINE GENE SEGMENTS.
JUNCTIONAL DIVERSITY.
COMBINATORIAL DIVERSITY.
SOMATIC HYPERMUTATION.
Variable regions of heavy immunoglobulin chains are made by...
D-J rearrangement (DNA)
V-DJ rearrangement (DNA)
Primary RNA coding
Splicing
Protein synthesis

Gene rearrangments mediated by RAG-1 and RAG-2 components of VDJ recombinase.
Variable regions of light immunoglobulin chains are made by...
V-J rearrangement (DNA)
Primary RNA coding
Splicing
Protein synthesis

Gene rearrangments mediated by RAG-1 and RAG-2 components of VDJ recombinase.
Is antibody diversity generated by the existence of multiple germ-line gene segments driven by antigen?
No
Junctional diversity in immunoglobulins is generated by....
Random pieces of nucleic acids that are added to terminal ends of V,D or J segments every time rearrangement occurs.
Frame shifts are common.
Combinatorial diversity in immunoglobulins results from the fact that...
any heavy chain can pair with any light chain.
Somatic hypermutation is a source of diversity for immunoglobulins because...
Immune cells divide very rapidly.
Those that mutate in a way that increases their antigen affinity are selected for. (affinity maturation)
When does somatic hypermutation occur?
When B cells are triggered to divide and replicate their DNA during the initiation of the adaptive immune response.
Where does somatic hypermutation take place?
In secondary lymphoid sites.

All other sources of diversity occur in bone marrow because they happen in B-cell precursors.
In a PRIMARY immune response , the main circulating antibodies are....
IgM
In a SECONDARY immune response, the main circulating antibodies are...
Immunoglobulins other than IgM which are made by memory B cells.
Memory cells do NOT make..
IgM
The isotype (constant region) can change throughout an infection but the....will not.
Idiotype
The mechanism by which immunoglobulin class switching occurs is...
Looping out and switching of constant region coding segment at the level of B-cell DNA.
Class switching is induced by and dependant upon...
T-Cells.

They promote gene transcription and unzip the DNA so RAG-1 and RAG-2 recombinase can get in and preform the switch.
What are two examples of diseases in which class switching does not occur?
Activation-induced cytidine deaminase deficiency (Hyper IgM-2 syndrome)

Defects in uracil DNA glycosylase
Is the production of IgD from IgM dependent on class-switching?
No. This is the only change that is not dependant on class switching at the DNA level. It occurs by mRNA splicing.
ELISA stands for...
Enzyme-linked Immunosorbent Assay.
How is a radioimmunoassay different from ELISA?
It is a competition assay.
When making monoclonal antibodies, the spleen cells from the immunized mouse are fused with...
Myeloma cells lacking in HGPRT. (Hypoxanthine guanosine phosphoribosyl transferase)
The immunized mouse spleen cells fused with HGPRT deficient myeloma cells in monoclonal antibody manufacture are treated with...
hypoxanthine, aminopterin, and thymidine (HAT trick) that prevents growth of unfused tumor cells.
Do T cells undergo affinity maturation?
No. This is why they depend on HLA's high diversity to present antigen.
What are the polypeptide subunits of a T cell receptor (TCR)?
Alpha and Beta subunits. Each contains a variable and constant region.
What are the main differences between TCR's and BCR's.
BCR recognizes substrate and/or its tertiary structure. TCR recognises only peptide-HLA molecule complex.

BCR has 2 recognition sites, TCR has 1 site.

BCR can be secreted, TCR is always surface bound.

TCR molecules do not undergo affinity maturation

Overall TCR have weaker interactions with antigen
By what three mechanisms is TCR diversity generated?
Multiple germline genes
Combinatorial diversity
Junctional diversity
At the DNA level, how are the alpha and beta sunbunits of TCR's made from multiple germ lines?
Alpha-V/J rearrangement
Beta- V/D/J rearrangement
What secondary surface protein complex is responsible for signal transduction between the TCR and the inside of the cell?
CD3+
What are the two major flavors of T-Cells?
CD4+ (TH1 and TH2)
CD8+ (Cytotoxic T-cells)
CD4+ T-cells recognize complexes of antigenic peptides with...
HLA (MHC) class 2
Only called HLA in humans.
CD8+ T-cells recognize complexes of antigenic peptides with...
HLA (MHC) class 1
Only called HLA in humans.
HLA class 1 is found on the surface of....
Every nucleated cell in the body.
Important for flagging intracellular pathogens.
HLA class 2 is expressed on the surface of....
Professional antigen presenting cells such as dendritic cells, B-cells and macrophages.

Epithelial cells in the thymus involved in immune selection.

For unclear reasons in activated human T-cells.
HLA surface proteins are upregulated in the presence of...
Cytokines
HLA expression is polygenic, polymorphic and codominantly expressed. What are the involved genes?
HLA Class I:
HLA-A, HLA-B and HLA-C

HLA class II:
HLA-DPab, HLA-DQab, HLA-DRab
The only HLA gene that does not have many alleles and is thus not polymorpic is...
HLA-DRab
What determines the nature and specificity of peptide binding to HLA?
The length of the peptide.
The sequence.
What sort of peptides does HLA class I like to bind?
8-10 amino acid sequences with specific anchor residues.
What sort of peptides does HLA class II like to bind?
13+ amino acid sequences with specific anchor residues.
In order to activate a T-Cell. The TCR must see...
Both the right epitope and the right HLA complexed together.
Allograft rejection results from...
Recognition of non-self HLA (allogeneic HLA) molecules by "alloreactive" T-cells. The body then treats the graft as antigen.
Superantigens are peptides that can...
Bind and crosslink both the TCR and the HLA molecule independent of the TCR specificity.

Eg. Staphylococcal enterotoxins (SEs) which cause food poisoning and TSST-1 which causes toxic shock syndrome.
How is class 1 HLA made in the ER transported to the cell surface and bound to the conserved beta 2 microglobulin?
Calnexin
After HLA class 1 binds to the beta 2 microglobulin and calnexin is rereleased what chaperones are used to bring the empty (HLA class 1 without a peptide) towards the TAP site where it can bind peptides?
Calreticulin and ERP 57
Tapesin binds it to TAP
What is the role of TAP in the proccessing of intracellular pathogens?(endogenous pathway)
To transport peptide fragments generated in the cytoplasm through the ER to the peptide binding cleft of HLA class 1.
What is the consequence of a TAP mutation?
Nor surface expression of HLA class 1.
They are unstable without the peptide.
How are the peptide that are transported by TAP and ultimately bound to HLA class 1 generated in the cytoplasm?
The proteosome
How does Cytomegalovirus infection affect HLA class 1?
Induces retrograde transport and degradation of empty HLA class I by the proteosome.
How do Herpes viruses affect HLA class 1 ?
They block TAP
How does Adenovirus infection affect HLA class 1?
Keeps the HLA class 1-peptide complex in the ER so there is no surface presentation.
If you do not have an intracellular infection what do HLA class 1 molecules present at the cell surface?
Peptides derived from self proteins.
In the exogenous pathway peptides that bind for presentation HLA class 2 are generated in ....
Endocytic vesicles. (relatively neutral pH)
NOT in the ER like the peptides for HLA class 1
During the transport of HLA class 2 from the ER to the endocytic vesicle where it will bind peptide from the extracellular pathogen, the binding cleft is plugged by...
A molecule called the invariant chain.
The invariant chain is cleaved...
In the endocytic vesicle when it begins to acidify.
It leaves behind a small portion known as the CLIP peptide.
CLIP peptides in the binding site of HLA class 2 are substituted for extracellular pathogen peptide by...
HLA-DM
How does HLA class 2 presentation direct the T-cell response?
Activation of CD4+ T cells which help B cell activation and antibody production.

Critical for fighting extracellular pathogens.
How does HLA class I presentation direct the T-cell response?
Activation of CD8+ T cells that kill infected cells and secrete anti-viral cytokine.
Naive T-cells routinely come into contact with professional antigen presenting cells and "scan" for peptide-HLA complexes through the interaction of...
ICAM-1 on the dendritic cell, B-cell or macrophage
and
LFA-1 on the T-cell
For a T-cell to become activated by a profesional antigen presenting cell (APC) it has to stay in contact with it for approximately...
24 hours.
Affinity and valency (stickiness) increases between LFA-1 and ICAM-1 occurs that facilitates this.
For a t-cell to be activated what are the three signals that are necessary?
Interaction of TCR with peptide-HLA complex on APC (activation)

CD28 on T cell binds CD80 and CD86 on APC
(Survival and proliferation)

Cytokines secreted by activated APC
(differentiation)
What are the key characteristics of immature dendritic cells?
-tissue resident, quiescent
-highly endocytic
-low level expression of
costimulatory molecules
and HLA
-poor stimulators of T cells
What are the key charcteristics of activated dendritic cells?
-Homes to lymph node
-Endocytosis shut down
-High level expression of
costimulatory molecules and HLA
-Highly stimulatory for T cells
CD80 and CD86 are expressed by...
Professional APC's
What happens If a T cell interacts with an antigen presenting cell lacking CD80/86?
It becomes anergic.
This is a safety mechanism to prevent autoreactive cells.
What cytokines act on CD8+ t-cells during their activation by APC's?
IL-12 or Type I IFN
What cytokines act on CD4+ t-cells during their activation by APC's?
Th1: IL-12 and IFNγ
Th2: IL-4
How can CD4+ T-cells help in the activation of CD8+ T-cells?
Provision of IL-2
Maturation of APC (Through CD40-CD40 ligand interaction)
CD40 ligand is expressed only on...
Activated CD4+ T-cells
B-Cell precursor cells are made in and negatively selected against those that bind self antigen in...
The bone marrow
CD3 is expressed and detected on...
T-cells
CD19 is expressed and detected on...
B-cells
What is X-linked agammaglobulinemia?
A mutation in the BTK enzyme (Bruton's tyrosine kinase) that is essential for normal B-cell development.
During B-cell development BTK is necessary for receiving signal at the pre-B-cell receptor. This is important because this signal....
Is a survival signal (do not self destruct)

Inhibits RAG-1 and RAG-2 rearrangement genes upon one succesful mutation (allelic exclusion).

Promotes proliferation

Initiates light chain rearrangement.
The term immature B-cell refers to...
A B-cell with a normal unbound IgM receptor.
The term mature B-cell refers to...
A B-cell with an IgM and and IgD expressed at the surface.
The process by which we eliminate autoreactive B-cells is called.....
Central tolerance
T-cell progenitor (thymocyte) development happens in..
bone marrow
T-cell progenitor (thymocyte) differentiation into t-cells happens in...
the thymus
The main difference in the selection process for B-cells and T-cells is that...
T-cells undergo both positive and negative selection.
In a normal patient which do we have more of , CD4+ or CD8+ t-cells?
CD4+
T precursor cells bearing a TCR that interacts best with class I HLA will become....
CD8+
T precursor cells bearing a TCR that interacts best with class II HLA will become
CD4+
In the context of T-cell development, what is negative selection?
Negative selection is the process by which thymocytes bearing a TCR with specificity for self peptides bound to HLA are deleted
In the context of T-cell development. What is positive selection and why is it important?
Positive selection is the mechanism which permits the continued development of thymocytes bearing a TCR that has some affinity for self HLA.
Positive selection of T-cells and differentiation into CD4+ or CD8+ happens in...
The cortex of the thymus.
It is mediated by cortical epithelial cells.
Negative selection of T-cells happens in....
The medulla of the thymus.
It is mediated by dendritic cells and macrophages.
How is the congenital absence of class II HLA (HLA-DR or DQ deficiency) linked to the absence of functional CD4+ T cells?
In the absence of class II expression, there is no positive selection of CD4+ T cells.
PAMP's stands for...
Pathogen associated molecular patterns.
Where are naive T-cells activated?
The preripheral lymphoid sites.
What do activated CD8+ T-cells do?
Target cells for destruction in which cytoplasmic localized pathogens (e.g., viruses) are present.
What do CD4+ Th1 cells do?
activate macrophages to kill vesicle-bound pathogens (e.g., Mycobacteria) and enhance the expression of certain IgG isotypes (e.g., IgG2a)
What do CD4+ Th2 cells do?
promote the activation of B cells and the expression of certain IgG isotypes (IgG1 and IgE).
What are the activation requirements of CD8+ T-cells?
Initial interaction with dendritic cell via adhesion molecules.

Recognition of epitope in the context of class I HLA.

CD8 association with class I molecule

CD28 association with CD80/86
When a CD8+ T-cell becomes an armed effector cell does it require CD80/CD86 to kill cells?
No
After activation of a T-cell, what cell surface protein expressions does it change?
CD40 ligand and the high affinity IL-2 receptor CD25.

It also makes cytokines.

These changes are propagated to its offspring.
What cell surface protein is essential for Th2 T-cells to activate B-cells?
CD40 Ligand
Induction of CTLA-4 on T cells results in ...
Decreased sensitivity to dendritic cells and decreased production of IL-2.
Which T cells express high affinity IL-2 receptors?
Only those that have interacted with a dendritic cell bearing an epitope bound to HLA that is recognized by the T cell.

This allows for clonal expansion of T cells that recognize pathogen epitopes.
IL-2 signalling on the high affinity IL-2 receptor causes....
Proliferation of that particular cell.
Th1 and Th2 cells can be differentiated by..
Their cytokine production.

Th-1 cells will make IL-2, INF-g and TNF-a
Th-2 cells will make IL-4,5,6,10 and 13
IL-12 (from macrophages) and interferon-g (from Th1 and NK cells) cause...
Enhanced Th-1 cell differentiation from Th-0.

Inhibited Th-2 cell differentiation from Th-0.
IL-4 (from Th2 cells or NK T cells) causes...
Enhanced Th-2 cell differentiation from Th-0.

Inhibited Th-1 differentiation from Th-0 .
The T-cell effector pool can be divided into which two groups...
SLEC (short lived effector cells driven by high levels of inflammation)
MPEC (Memory precursor effector cells that undergo genetic differentiation into memory cells from day 8-30 because they are not exposed to much inflammation)
What is a plasma cell?
Terminal B-cell that pumps out antibodies.
What type of antigen is LPS?
Thymus independant.
B cells can attack it without T helper cells.
What component of LPS is a TLR-4 agonist?
Lipid A
IL 4, IL-5, IL-6, and IL-13 are examples of...
B-cell activating cytokines
If a T-cell and B-cell are to interact...
They must bot recognize the same epitope.
Can normal plasma cells proliferate?
No
Where are most memory B-cells found?
Bone marrow.
Isotypes other than IgM or IgD are induced by ....
T cell-derived cytokines.
What immunoglobulin is abundant on mucosal surfaces?
IgA
IgE binds the receptor..
FCeR1
Can Fc receptors bind free immunoglobulins?
No
What sort of vaccine is the smallpox vaccine?
Live attenuated vaccinia is closely related to variola but not as virulent.
Why do Children under the age of 2 not respond well to Conjugate Acellular Polysaccharide Vaccines
Limited T cell-independent B cell function.
What type of immune response does vaccine for poliovirus try to create?
Neutralizing antibody to prevent virus from reaching central nervous system
What type of immune response does vaccine for smallpox try to create?
Circulating neutralizing antibody and CTL
What type of immune response do vaccines for enteric and respiratory pathogens try to create?
mucosal IgA and IgG
The only currently FDA approved vaccine adjuvant is...
Alum
It causes the death of cells which release chemicals that mature dendritic cells.
Very low doses of antigen in vaccines tend to favor...
Th-2 type responses
In order to generate cytotoxic T-cells with a vaccine we want to stimulate the...
Endogenous pathway
Flagellin, a new potential adjuvant stimulates....
TLR-5
What is a type 1 hypersensitivity reaction?
Allergen (Antigen+TLR agonist) induces production of IL-4 and IL-13.

IgE is produced.

IgE binds to mast cells on FC receptors because they have affinity for the epsilon heavy chain of IgE.

Allergen crosslinks IgE on mast cell surface.

Mast cells produce Histamine, prostglandins, leukotrienes, cytokines etc.

Early and late phase responses occur.
Eosinophils in the nasal mucosa are almost diagnostic of...
Allergies.
Atopic individuals exhibit higher than normal levels of circulating ...
IgE and eosinophils
The majority of IgE in the body...
Is fixed in the tissues (bound to mast cells)
Which immuno globulins are bound to MAST cells?
IgG and IgE
Type 1 hypersensitivity is mediated by...
IgE
Type 2 hypersensitivity is mediated by...
IgG
Which cytokine is particularly good at promoting eosiniophil production?
IL-5
In the acute phase type 1 response. Allergen binding and crosslinking of FceRI, causes MAST cells to rapidly release preformed...
Prostaglandins
Leukotrienes
Platelet activating factor (PAF)
Histamine
IL-5
TNFa
IL-4 and IL-13 are critical in type hypersensistivity because they....
Induce class switching to IgE
IL-4 is made by...
NK1.1 T cells and subsequently by activated Th2 cells and mast cells.
IL-13 is produced by...
Th2 cells and mast cells.
The most important mediator of hypersensitivity released by eosinophils is...
Major basic protein.
Apart from allergic responses IgE is important for fending off...
Parasites and worms.
IPEX is a...
mutation in fox3p that is expressed in Treg cells.
Immunologic tolerance is mediated by...
Regulatory T-cells
Fox3p is expressed at high levels only in ...
CD4+ CD25+ T cells
(T-reg cells)
What is a unique feature of T-reg cells ?
They can be activated by dendritic cells in the absence of TLR signaling.
What do T-reg cells inhibit?
Th-2 cells.
What promotes the generation of T-regs
TGF-b
Drug-induced hemolytic anemia and
Hemolytic anemia of the newborn are examples of...
Type 2 hypersensitivity reactions (IgG mediated)
Type 4 hypersensitivity or DTH is..
Th-1 cell dependant.
NOT antibody related.
Classic examples are tuberculin skin test and poison ivy contact dermatitis.
What are the two mechanisms for preventing T-cell autoreactivity?
Negative selection for auto-reactive thymocytes.

Induction of anergy when presentation occurs in the absence of co-stimulatory signals (CD80/86 and cytokines)
What is Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) ?
an autoimmune disease that is due to a mutation in the autoimmune regulator gene (AIRE). It damages the thymus selection process.
What are potential mechanisms for autoreactive T-cells escaping the thymus?
Thymocytes with TCRs that have a low affinity for self-antigens may escape negative selection.

Inflammation may expose self-antigens that are normally sequestered.

Cross-reactivity with microbial antigens.

Loss of regulatory T cell function.

Enhanced activation of Th17 T cells in the presence of TGF-beta and IL-6
By what mechanism do T-reg cells supress other T-cells?
They make cytokines TGF-b and IL-10
The T-cells that are not supresseed by TGF-b and IL-6 but stimulated by them are...
Th-17 cells
Mice lacking the ability to generate Th17 T cells are...
Less susceptible to a number of induced autoimmune diseases.
Penicillin and procainamide can both induce....
autoimmune hemolytic anemia
What accounts for the sexual bias of auotimmune disorders?
Women exhibit a Th2 bias in their immune responses

Sex hormone receptors are present on immune cells

Cytokine receptors are present on hormone-producing cells

Males are more susceptible to infection than females
Graves disease involves autoantibodies against...
TSH receptors.
Causes hyperthyroidism
Myasthenia Gravis involves autoantibodies against...
Acetylcholine receptors.
Progressive weakness at NM junction.
Lupus is a type III reaction, what does this mean?
Immune complexes are formed in solution and migrate to sites of ultrafiltration.

Anti-double stranded DNA and Sm antibodies are diagnostic
What is Hashimoto’s thyroiditis?
Autoantibodies against thyroglobulin and thyroid peroxidase; cytotoxic T cells, NK cells, Th1 cells and macrophages involved in thyroid acinar cell destruction.
What is pernicious anemia?
Autoantibodies against intrinsic factor (reducing vitamin B12 absorption) and parietal cells; Th1 cells and macrophages are major mediators of immune damage to the stomach.
What is the autoimmune mechanism of rheumatoid arthritis?
Rheumatoid factors (IgM, IgA and IgG autoantibodies directed against Fc region of IgG)
Enbrel and Remicade are...
Anti TNF-a drugs sometimes used for rheumatoid arthritis;
A syngeneic graft is...
Between identical twins or inbred animals.
An allogeneic graft is...
Between genetically distinct individuals.
A xenogeneic graft is...
Between different species.
Foreign HLA and minor histocompatibility antigens are collectively called...
Alloantigens
What are two mechanisms by which T cells recognize alloantigens?
Direct alloantigen recognition
Indirect alloantigen recognition
The difference between direct and indirect alloantigen recognition is that...
The direct recognition is of HLA on the foreign cell surface.
Indirect involves processing and presentation of the foreign
HLA on native APC's.
What is hyperacute transplant rejection?
Results from circulating antibodies against ABO or HLA antigens.

Within 48 hours of transplant.

Results in complement activation, thrombosis, neutrophil infiltration, necrosis and organ shutdown.
What is acute transplant rejection?
Response to foreign HLA histocompatibility antigens.

7-10 days after transplant but may occur after 6-12 months.

Mediated by cytotoxic T cells, macrophages and antibodies.
What is chronic transplant rejection?
Response to minor histocompatibility antigens.

May occur up to several years following transplant.

Mediated by macrophages and Th1 cells.

Characterized by progressive vasculitis, DTH or ischemia caused by damage to blood vessels.
What are some post transplant immunosupressive therapies?
Cyclosporin A: prevents cytokine synthesis in T cells by inhibiting the transcription factor, NF-AT.

Corticosteroids: Inhibit synthesis of HLA antigens, cytokines and adhesion molecules.

Anti-CD3 monoclonal antibodies: Deplete circulating T cells.

Azathioprine and mycophenolate mofetil: anti-metabolites that inhibit lymphocyte proliferation by interfering with the synthesis of nucleotide precursors for DNA synthesis.
What is Graft versus Host Disease?
Immunocompetent donor T-cells recognize the immunocompromized recipient HLA as foreign and attack the host.
7-30 days post-transplant.
Big problem in bone marrow transplant.
What are the characteristics of regulatory T-cells?
CD4+CD25+ T cells
Constitutively express CTLA-4
Activated by IL-2
Suppressed by IFNg
Suppressive function occurs via cell-cell contact and perhaps release of TGFb and IL-10