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140 Cards in this Set

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  • Back
What are the molecular components of the innate immune system?
Antibacterial peptides, complement factors and their receptors, Fc receptors, Inflammatory cytokines, growth factors, histamine
What are the cellular components of the innate immune system?
Macrophages, monocytes, NK cells, granulocytes, mast cells
What are the main receptors of the innate immune system and what do they recognize?
Pattern recognition receptors (PRRs). They recognize molecular patterns often found on pathogens called pathogen associated molecular patterns (PAMPs). Examples are LPS, mannose.
What are the main receptors of the adaptive immune system?

T-cell receptor (TCR) and B-cell receptor (BCR)

What are the main molecular components of the adaptive immune system?
Antibodies, MHC molecules, TCR, BCR, lymphatic cytokines
What are the main cellular components of the adaptive immune system?
T-cells (both αβ and γδ), B-cells, antigen-presenting cells (APCs)
What are the antigen-presenting cells (APCs)?
Monocytes, macrophages, dendritic cells and B-cells
What are the main cellular components of the natural immune system?
iNKT cells, iγδT cells, MAIT cells, IEL cells, CD5+ B cells
What are the main molecular components of the natural immune system?
Natural (auto)antibodies
What is the structure of an antibody?
The dotted regions are the variable domains. The striped regions are the variable domains. The blue regions are the heavy chains, and the red regions are the light chains. On each of the variable domains, there are 3 CDR regions (12 in total).
The dotted regions are the variable domains. The striped regions are the variable domains. The blue regions are the heavy chains, and the red regions are the light chains. On each of the variable domains, there are 3 CDR regions (12 in total).
What is the structure of the T-cell receptor?

What are the CDR regions? Which one is special?
The complementarity-determining regions, or CDRs, are three short highly variable regions on each of the variable domains on an immunoglobulin. CDR3 is the most variable, while CDR1 and CDR2 are less variable.
What to we mean by how antibodies are monofunctional before binding the antigen? Which region of the antibody is involved?

Before the antibody binds an antigen, the antibody has only one function: to bind an antigen.


The Fab-segment of the antibody is involved in this.

What to we mean by how antibodies are polyfunctional after binding the antigen? Which region of the antibody is involved?
After binding an antigen, antibodies have many functions, like signal transduction, complement fixation, opsonization, immunocomplex formation, Fc receptor binding, etc. The Fc-segment of the antibody is involved in this.
What are the different classes of immunoglobulins, and which chain of the Ig do they differ by?
They are IgG, IgM, IgA, IgD and IgE. They differ by the heavy-chain only.
What are the two isotypes the light chain of an antibody can be?
Kappa (κ) and lambda (λ).
Which immunoglobulin isotypes have longer heavy chains than the others?
IgE and IgM.
What comprises the T-cell receptor complex, and what are the functions of the different parts?
The T-cell receptor complex is comprised of the T-cell receptor and CD3. The TCR will recognize and bind the antigen, while CD3 will perform the signal transduction.
What is an epitope?
An epitope is a specific site of an antigen that an antibody can bind to.
What cells produce antibodies?
Plasma cells
What comprises the B-cell receptor complex?

The B-cell receptor complex is comprised of the B-cell receptor and CD79.

Which cells express MHC I?

All cells with a nucleus, and platelets. This includes the antigen-presenting cells!

Which cells express MHC II?


Antigen-presenting cells. They are dendritic cells, B-cells, monocytes and macrophages.

Which genes code for MHC I?
HLA-A, HLA-B and HLA-C
Which genes code for MHC II?
HLA-DP, HLA-DQ and HLA-DR
What is the structure of MHC I?
Note that the microglobulin is not a part of the MHC molecule itself, but a protein found in blood that binds to the MHC I molecule.
Note that the microglobulin is not a part of the MHC molecule itself, but a protein found in blood that binds to the MHC I molecule.
What is the structure of MHC II?

What are the two major types of T-cells?
CD8+ (cytotoxic) and CD4+ (helper) T-cells
Which MHC molecule can CD8+ T-cells bind?
MHC I
Which MHC molecule can CD4+ T-cells bind?
MHC II
What kinds of peptides are presented on MHC I?

Endogenous peptides, peptides originating from within the cell

What kinds of peptides are presented on MHC II?
Exogenous peptides, peptides originating from extracellular pathogen like bacteria
What is the ligand for CTLA-4 and CD28? What cell type are they found on and what is the different between them?
The ligand is B7.1 and B7.2. CTLA-4 and CD28 are found on B-cells. CTLA-4 inhibits the cell and has higher affinity for the ligand than CD28. CD28 activates the cell.
What are the 5 big families of adhesion molecules?

Ig-superfamily, selectins, integrins, mucin-like molecules and "other".

What molecules belong to the Ig-superfamily of adhesion molecules?
CD4, CD8, antibodies, TCR, BCR, MHC molecules, CD79, CTLA-4, CD28, B7.1 and B7.2 (and many more)
What molecules belong to the selectin family of adhesion molecules?
L-selectin, found on lymphocytes, E-selectin on endothelial cells and P-selectin on platelets.
What molecules belong to the "other" family of adhesion molecules?
CD45, CD25 and CD154
What are the three different ways cytokines can signal between cells? (-crine)
Autocrine, paracrine and endocrine.
What are the two types of antimicrobial peptides?
Defensins and cathelicidins
What does opsonization mean?
Opsonization happens when antibodies or complement factors bind to the surface of a pathogen, which makes it easier for a phagocyte to phagocytose the pathogen
What are the different types of pattern recognition receptors (PRRs)?
Toll-like receptors, NOD-like receptors, RIG-like receptors and C-type lectin-like receptors.
What are the most important Toll-like receptors (TLRs) and what are their ligands?
TLR4 which binds LPS (the most important) and TLR5 which binds flagellin
On what type of bacteria is lipopolysaccharide (LPS) found?
Gram-negative bacteria
What cells produce inflammatory cytokines during an initial infection?

Macrophages

What are the inflammatory cytokines?
IL-1, IL-6 and TNF-α.
What activates the classical activation pathway of macrophages?
LPS
What activates the alternative activation pathway of macrophages?
IL-13 and IL-14
What characterizes the acute phase reaction?

After activated macrophages produce IL-1, IL-6 and TNF-α, these cytokines will travel to different parts of the body. They will have the following effects:


- They will make the liver to produce the acute phase proteins.


- They will make the brain to increase the body temperature, creating fever


- They will make the bone marrow produce more lymphocytes.

What are the most important acute phase proteins?
C-reactive protein, serum amyloid A, fibrinogen, mannose binding lectin and complement factors.
What is the function of C-reactive protein?
CRP opsonizes bacteria by binding to phosphocholine on their surface.
What is the structure of the immunoglobulin heavy chain gene before recombination?
Many V, D and J segments. Multiple constant segments follow.
What is the result of VDJ recombination on the immunoglobulin heavy chain gene?
Only one V, one D and one J will remain.
Which proteins are important in VDJ recombination?
RAG1, RAG2 and TdT.
What is allelic exclusion?
Only one of the immunoglobulin heavy chain genes are expressed. The other is turned off.
What is isotype exclusion?
Isotype exclusion means that each B-cell chooses to produce either the κ or the λ light chains, not both.

What happens during positive selection during development of B-cells?


Only B-cells that can successfully present the pre-B-cell receptor are allowed to survive.
What happens during negative selection during development of B-cells?
Self-antigens are presented to the B-cell receptor of B-cells. If the BCR will bind, the B-cell will be killed.
What is the beta-selection during T-cell development?
If the pre-T cell cannot present the pre-T cell receptor, it will be die.
What kinds of T-cells do we find in the thymus, and how do the different cells express CD4 and CD8?

Double negative T-cells - express neither CD4 nor CD8


Double positive T-cells - express both CD4 and CD8


Single positive T-cells - express either CD4 or CD8

What happens during positive selection in the thymus?
Double positive T-cells that can bind moderately to either MHC I or MHC II with their T-cell receptor are allowed to live. If they can't bind, they die.
What happens during negative selection in the thymus?
After positive selection, double positive T-cells are exposed to self-antigens. If they can bind self-antigens strongly, they are killed. If not, they're allowed to survive. The double positive T-cell will then become single positive.
What are Treg cells?

Treg, or T regulatory cells, are CD4+ T-cells that have a negative feedback on the immune response by inhibiting T-cells.




Treg express CD25, FOXp3 and CTLA4.

What are the γδ T-cells?
The γδ T-cells are a special type of double-negative T-cell found in tissue. They're synthesized mostly before birth.
Which interleukin will T-cells start to produce when activated?
IL-2
What are the subtypes of T helper cells?
Th1, Th2, Th17 and Treg.
Which cytokine induces differentiation of a naive Th cell to Th1, and what infection is this type of T helper cell involved in?
IL-12. Th1 cells are involved in viral and intracellular bacterial infections.
Which cytokine induces differentiation of a naive Th cell to Th2, and what infection is this type of T helper cell involved in?
IL-4. Th2 cells are involved in parasitic infections.
Which cytokine induces differentiation of a naive Th cell to Th17, and what infection is this type of T helper cell involved in?
TGFβ and IL-6. Th17 cells are involved in extracellular bacterial infection and fungal infection.
Which cytokine induces differentiation of a naive Th cell to Treg, and what is the function of Treg?
TGFβ, IL-2 and retinoic acid. Tregs are involved in regulating the immune response.
What are the B1 B-cells?
B1 B-cells are produced only during embryonic life. They produce low-affinity autoantibodies, mostly IgM. They're found in the serosa of body cavities.

What are the two types of B2 B-cells?


Marginal zone B-cells and follicular B-cells
What are the marginal zone B-cells?
The MZ B-cells are found in the marginal zone of the spleen. They produce mostly IgM, and are involved in T-cell independent antibody response.
What are the follicular B-cells?
Follicular B-cells are found in the blood and follicles of the secondary lymphoid organs. They constitute most of the T-cell dependent antibody response. They produce many IgD.
What is the T-cell dependent immune response?
The T-cell dependent immune response is activated in response to protein antigens, and begins with the extrafollicular reaction and ends with the germinal centre reaction. It results in the formation of high-affinity plasma and memory cells. Mostly IgG and IgM are produced.
What is the T-cell independent immune response?
The T-cell independent immune response is activated in response to non-protein antigens, like lipids or carbohydrates. It initiates the extrafollicular reaction, and does not result in formation of memory cells. Only IgM is produced.
What are the characteristics of the follicular dendritic cells?
Follicular dendritic cells, or FDCs are important in the germinal center reaction. They're not related to dendritic cells, and are originate from mesenchyme. They don't have phagocytic activity and are non-adherent. They express VCAM-1, and can store antigens for a long time in complexes called the iccosome.
What is affinity maturation?

Affinity maturation is a process which happens in the germinal centre during the germinal centre reaction. It causes random mutations in the genes for the CDR regions of the immunoglobulins. Some of these mutations yield antibodies with higher affinity than before. The result is B-cells which produces antibodies with higher affinity than originally.




AID is a protein that is important in affinity maturation.

What is isotype switching?

Isotype switching is a process that happens during the germinal centre reaction. It causes B-cells to switch the isotype of immunoglobulins they produce from IgM to something else, like IgG.




It involves cutting away the genes for the isotypes you don't want to produce that are in front of the gene of the isotype you want to produce.

What are the effector functions of antibodies?
Antibodies can neutralize, precipitate, agglutinate and opsonize pathogens and toxins.
What happens when a pathogen or toxin is neutralized by antibodies?
When antibodies bind to a pathogen or toxin, the pathogen or toxin cannot enter the cell to infect or damage it.
What happens when a pathogen is precipitated by antibodies?
The antigen-antibody complex is no longer soluble, so the complex is precipitated.
What happens when a pathogen is agglutinated by antibodies?

Agglutination is all about creating clumps of pathogens.


Because antibodies have to sites they can bind to antigen, they can bind two antigens simultaneously. If many antibodies bind multiple antigens, huge clumps of antigens can be formed, which makes them unable to infect or damage anything, while also making it easier for phagocytes to eat them.

What are Fc receptors?
Fc receptors are found on certain cells, and can bind to the Fc region of antibodies that have bound an antigen.
What are the properties of IgM?
IgM is the earliest produced IgM during an infection. It can cross epithelium to enter lumen of organs. It is important in activating the complement system through the classical pathway.
What are the properties of IgD?

IgD is never found in soluble form. It's only found on the surface of B-cell as their B-cell receptor.

What are the properties of IgG?
Multiple subtypes of IgG exist, IgG1, IgG2, IgG3 and IgG4. They are the type of antibody that are most important in entering tissue. IgG can cross the placenta. IgG antibodies are important opsonins. They can activate antibody-dependent cell-mediated cytotoxicity (ADCC) and the complement system.
What is an opsonin?
An opsonin is a molecule that can opsonize pathogens.
What are the properties of IgA?
IgA is the antibody that protects mucosa, especially the GI tract. They exist in dimeric form or in monomeric form. IgA is an opsonin.
What are the properties of IgE?
IgE is important against parasites, but also in allergy. It's the only antibody that can activate mast cells.

What is antibody-dependent cell-mediated (or cellular) cytotoxicity (ADCC)?


ADCC is the process of how NK cells and eosinophils recognize cells (bacterium or parasite) that are opsonized by IgG or IgE. This causes the NK cell or eosinophil to release enzymes like perforin and lytic enzymes that kill the target cell.

What is the complement system?

The complement is a major part of the effector system of the innate immunes system. It consists of proteins called complement factors that are found in the blood. These complement factors are activated by three different pathways: the classical, the lectin and the alternative pathways.




The activation of the complement system increases inflammation, produces an opsonin called C3b, and a molecule called MAC that lyses pathogens.

What activates the complement system through the classical pathway?
Pathogens opsonized by IgG or IgM activate the classical pathway.
What activates the complement system through the lectin pathway?
The lectin pathway is activated when a protein called mannose-binding lectin (MBL) binds to a pathogen.
What activates the complement system through the alternative pathway?
The alternative pathway is activated after some C3b proteins have opsonized the pathogen.
What are the regulators of the complement system?
C1 inhibitor and decay accelerating factor (DAF) regulate the complement system.
Why do red blood cells express C3b receptor (CR1)?
After pathogens are opsonized by C3b, the red blood cells will bind to them with their C3b receptor and carry the pathogens to the liver and spleen, where the pathogens are phagocytosed.

What are NKT cells and do they produce?

They are a special type of a leukocyte, found in tissue. They have both CD56 and TCR. They recognize microbial phospholipids and glycolipids when presented to them by other cells through CD1d.




They produce cytokines very quickly, like IL-4, INFy, IL-17 and TNFa.

How does the naive CD+ cells (CTL-P) differentiate into cytotoxic lymphocytes?

They have to bind an antigen presented on a MHC I molecule. When they do, they start to express an IL-2 receptor.


Parallely to this, a Th1 cell, which is activated by an APC, will start to sectrete IL-2.


IL-2 binds to the IL-2 receptor on the activated CTL-P cell and will cause it to differentiate into a cytotoxic lymphocyte (CTL cell).

How will CTL cells differentiate further?

They will either become effector cells or memory cells.

What is the function of CTL memory cells?

They will wait for the antigen to show up later in life. When the body is infected with the same pathogen again, with the same antigen, the memory CTL cells will be activated. They produce IL-2 by themselves and dont need Th1 cells to get activated. Therefore, they are quicker than the normal CTL cells.

Describe the effector mechanisms of CTL cells.

When a CTL cell binds to an infected cell or a tumor cell, it will form tight adhesions with this target cell.


The CTL cell will use adhesion molecules like integrins, creating a conjugate.


Further, the CTL will rearrange its granules to the side of the target vell and degranulate, releasing their granules onto the target cell by exocytosis.

What are the granules from a CTL cell and how do they kill its target cell?

The granules contain molecules like perforin and granzymes.




Perforin: creates a pore in the membrane of target.




Granzyme: Enters target cell and kills in two different ways.


1) Granzyme A causes DNA-damage which induce death of cell.


2) Granzyme B activates a protein cascade called the caspase cascade (begins with caspase 8). This is an extrinsic apoptotic pathwath. Caspase 8 activates an enzyme called CAD, which cleaves DNA and kills the cell.




Simultaneously, a protein, Fas Ligand, will bind to the Fas receptor on target cell and activate caspase 8, resulting in the same mechanism as by granzymes.


What does NK cells use to know if a cell is abnormal?

When activated, they secrete INFy. They have two unique receptors called KIR and KAR, which are important to how they recognize abnormal cells.




KIR (killer inhibitory receptor): binds to MHC I molecules (not the antigen presented on it!) If the cell is abnormal, there will be a weird MHC I or it can be absent.




KAR (killer activating receptor): Binds to KAR-ligand on the cell surface.





Describe the effector mechanism of NK cells with KIR and KAR.

KIR inhibits killing of a cell, while KAR activates it. KIR has stronger activity than KAR.




If KIR cannot bind to a MHC I molecule because its abnormal or absent, there will be no inhibitory signal.


KAR can still bind to the KAR-ligand on the infected cell, and the activating signal will therefore be enough to activate killing of the cell when the inhibitory signal is absent.

Describe the sensitization phase of a delayed type hypersensitivity.

Some pathogens will infect antigen-presenting cells like macrophages or Langerhans cells. These APCs wikk then degrade some part of the bacteria and present it on MHC II.


A naive T helper cell will bind to this antigen and differentiate into a TDTH cells.

When does the effector phase begin in delayed type hypersensitivity?

When the body cannot remove the antigen or if there is a re-exposure to the same antigen.

How does the TDTH activate macrophages in the effector phase of delayed type hypersensitivity?

TDTH cells secrete IFN-y and presents TNF-b, and both will bind to receptors on the macrophage.


The TDTH cell will bind itself to the MHC II on the macrophages.




The combination of these signals will cause the macrophage to grow in size, express more MHC II molecules, more TNF receptors and produce more reactive oxygen species.


When this is done, the TDTH will move on to the next macrophage.

What causes the pathological reaction in Delayed Type Hypersensitivity?

The ROS and the inflammatory cytokines that the activated macrophages produce.

What can cause delayed type hypersensitivity to go horribly wrong?

Prolonged DTH reactions, like with tuberculosis where the bacteria is very hard to get rid of. Many activated, enlarged and infected macrophages will fuse together into one multinucleated giant cell.


This giant cell will be surrounded by activated macrophaes and TDTH cells in a clump, making a Granuloma. These cause tissue injury (eg in the lungs).

How can Delayed type hypersensivity be caused by contant allergens?

Typical contant allergens like nickel, hair dye and poison ivy are haptens, small molecules that make complexes with other proteins that the immune system can recognize.


These complexes can activate the Langerhans cells in the skin.


The Langerhans cell will migrate from skin to lymphnode and activate T helper cells.


The T helper cells then differentiate into TH1 cells, travel back to the skin and release IL-2 and IFN-y.


This causes the skin inflammation when in contact with these allergens.

What is the primary immune response?

Its the immune response that occurs when the body first meet a specific antigen.

What is the secondary immune response?

When the body meets the same antigen after the primary immune response.

Why is the secondary immune response more effective?

The cells of secondary immune response are memory B-cells and memory T-cells, and not naive lymphocytes.




- The memory B-cells have every Ig isotype on their surface.


- More compelement receptors.


- Higher affinity to antigen due to affinity maturation.


- Bind and phagocyte antigens much quicker, and therefore present it to memory T-cells faster.




- Memory T-cells express CD45R0, that is shorter than CD45RA, and this makes binding to TCR easier.




- Memory T-cells and memory B-cells migrate to place of inflammation and live there.

Primary immune response vs. secondary: Response begins how long after pathogen infection?

Primary: 4-7 days


Secondary: 1-3 days

Primary immune response vs. secondary: Time of peak response?

Primary: 7-10 days


Secondary: 3-5 days

Primary immune response vs. secondary: Size of antibody response?

Primary: Depends on antigen




Secondary: 100-1000 times higher than primary response

Primary immune response vs. secondary: Antibody isotype produced?

Primary: Mainly IgM




Secondary: Mainly IgG

Primary immune response vs. secondary: Antigens?

Primary: T-dependent and T-independent




Secondary: T-dependent

Which cytokines are important for memory T-cells and why?

IL-15 for proliferation


IL-7 for survival

What will inhibit the proliferation of APCs after phagocytosis of a pathogen or cell, and why?

Thymidine (T in DNA) in the phagocytosed organism.




This is to make sure that the APC only migrates to lymph nodes without becoming crazy.

How can Treg cells suppress T-cells by taking away IL-2?

IL-2 is essential for proliferation and differentiation of T-cells.




Treg cells are CD25+, and CD25+ is also known as IL-2 receptor. By binding IL-2, they will reduce the levels of IL-2 present. T-cells will die due to this deprivation.

What inhibitory cytokines do the Treg cells produce to inhibit effector T-cells?

TGFβ, IL-35 and IL-10

How does the B-cell know that it has produced enough antibodies?

They have a surface protein, CD32/FcγR II.


(This is the only FcγR that is inhibitory on the B-cell).


The FcγR II has low affinity for IgG antibodies, so many antibodies that already have bound an antigen can inhibit the B-cell in response to an excess of antibodies.

What kind of immune cells can be found in the SALT?

Langerhans cells, macrophages, γδ T-cells, αβ (normal) T-cells, B-cells, NK-cells, granulocytes, mast cells and keratinocytes.

What does the Langerhans cells do?

They are specialized dendritic cells located in the skin. They become activated by phagocytosing something.


To present it for the immune system, they have to migrate to a nearby lymph node as veiled cells.

What types of cells are important in the MALT?

MAIT cells (mucosa associated invariant T-cells), NK cells, macrophages, eosinophils, mast cells and granulocytes are all important here.

What is the function of the M cells?

They are scattered among the epithelial cells of the intestines. They can take up antigens from the lumen of the intestine and transport them to APCs. The ACPs are waiting in on the basal side of the M cell.

Where will the APCs differentiate in the intestines?

In the Peyers patches

Which isotype is the most important antibody in the mucosal defense?

IgA

Where can we find IgA1 and where can we find IgA2?

IgA1 is found in the lamina propia of the intestines.




IgA2 is found in the lumen of the intestines.


It can resist the proteases found there.

What does it mean that the mucosal surfaces are innerconnected in a secretory immune system?

It means that if a pathogen is found in the intestine and gets presented to APCs, an immune reaction will occur in all the mucosal surfaces in the body, and not just at the infected site.

Describe hypersensitivity type I ( Immidiate hypersensitivity)

- Allergic reactions like pollen.


- Mediated by IgE and mast cells.


- 15-30 mins


- Begins with the first exposure to the allergen:




Macrophages and dedritic cells will meet the allergen and produce IL-4.


IL-4 indices Th into Th2 cells, and isotype switching to IgE.


A lot of IgE gets produced, and they bind on FcεR I on mast cells, sensitizing them.




Next exposion will lead the mast cells covered in IgE to bind allergens and release histamines, proteases, prostaglandins, leukotrienes and TNF.

Describe hypersensitivity type II (cytotoxic hypersensitivity)

- Allergy against medication (as Penicillin)


- Mediated mostly by IgG, but also IgM


- Response time is minutes to hours


- Penicillin can function as a hapten, that bind to proteins on RBCs.


- Proteins will be recognized as foreign because of this.


- Macrophages will phagocytose the RBC-Penicillin complex and present it to Th-cells.


- Th --> Th2 cells


- Th2 produce IL-4, and IL-4 will promote isotype switching to IgG1 (and IgE).


- IgG1 will opsonize the RBCs with penicillin on it.


- Classic pathway of complement pathway, increased phagocytosis and activation of ADCC.

Describe type III hypersensitivity (Immunocomplex disease)

- Response time: 3-8 hours


- When there is a slight excess of antigens in the body, and the body tries to get rid of them.


- Antibodies and complement factors bind to them to make small immune complexes.


- These small complexes make the macrophages struggle, since they are better at taking out large complexes.


- These small complexes accumulate in vessels (mainly) and tissues, activating complement system and causes inflammation.

Describe type IV hypersensitivity (Delayed type hypersensitivity)

- Begins 1-2 weeks after first contact with the antigen.


- APC will produce IL-2


- Th --> Th1


- Th1 cells proliferate and get sensitized.


- Re-exposure activate Th1, which will activate macrophages and other inflammatory cells.


- This takes 48-72 hours.


- Long-lasting DTH will result in granulomas.

What is true for Hypersensitivity types I, II and III?

They are all mediated by antibodies and there is usually an overlap between them.

How is the central passive tolerance established?

By negative selection of both T- and B-cells.


This will make sure that almost no lymphocyte will recognize self-antigens.

Where and how does the negative selection happen for B-cells?

It happens in the bone marrow. The bone marrow has a steady blood flow, and the developing B-cells will be in contact with blood and all the antigens there.


If the B-cells bind to any antigen found in the blood, it will lead to apoptosis.

What is the peripheral tolerance?

It involves keeping some antigens out of reach for the immune system, so that the lymphocytes wont meet the antigens at all. Like in the blood-testis barrier or the eyeball.

What is the another part of peripheral tolerance where T-cells have recognized self-antigens?

It has to stop or kills these T-cells. Treg cells that express CTLA-4 are present in all tissues and suppress the T-cells that would recognize self-antigens.


Also, IL-4, IL-10 and TGFβ are present, when there is no inflammation. These cytokines will tell APCs to not express B7 proteins that are necessary to activate T-cells.