Immunology Exam 2 (Part 2) -- Secondary Lymphoid Organs and Lymphocyte Trafficking

What are the 2 primary lymph organs? What do they do?

1) Bone marrow

-- B & T cells originate

2) Thymus

-- T cells develop

What are the 3 secondary lymphoid organs?

1. Lymph nodes

2. Spleen

3. Mucosal-Associated Lymphoid Tissue (MALT)

T/F: Secondary lymphoid organs have separate areas for naïve T cells and activated T cells

FALSE

Separate areas for naive T cells and naive B cells

T/F: Activated B cells travel to the helper T cell area to help activate helper T cells

FALSE

-- activated Th migrate to B cell area to help activate B cells

T/F: Lymphoid Follicles are common within all primary lymphoid organs

FALSE

-- common w/in all SECONDARY lymphoid organs

What area is the loose networks of follicular dendritic cells (FDC) with rich supply of naive B cells or memory B cells?

Primary lymphoid follicles

What area is the where replication and differentiation fo B cells (clonal expansion) occurs after antigen stimulation?

Secondary lymphoid follicles (germinal center)

Which of the two types of dendritic cells are WBCs made in bone marrow that migrate to tissues and present antigens to T cells?

AP dendritic cells (AP DC)

Which of the two types of dendritic cells are regular cells that go to lymphoid follicles and display antigen to B cells?

Follicular Dendritic Cell (FDC)

Where are Follicular Dendritic Cells (FDC) present?

Present in secondary lymphoid organs

What is the function of FDC?

Catch & display opsonized antigens to B cells w/ high affinity receptors

--> does NOT opsonize antigen, does NOT kill or ingest antigen

What are two ways in which an anitgen is opsonized?

1) Complement

2) Antibodies

T/F: Follicular Dendritic Cells are a type of WBC since they are made in bone marrow and migrate to tissues or lymphoid organs

FALSE

-- APC Dendritic cells ARE WBCs

-- FDC are NOT a WBC; made before birth in lymphoid follicle and STAY there; They are Stromal cells!!

Early in an infection, ________ proteins bind to invaders (opsonization). Once the opsonized invader comes to _________ via blood or lymph, ______ cells have receptors that will bind them and display them to _______ cells.

Complement proteins bind (opsonization)

Come to Secondary lymph organs

FDCs cells have receptors that will bind

Displays to B cells

Later in the infection battle, once _________ have been produced, FDCs can bind to the ________ region of antibodies. The FDCs will then attach and hold opsonized antigens, making sure they are held ________ to each other and allow ______ to cluster/crosslink more easily and help the signal to the nucleus to activate.

Antibodies have been produced

Fc region of antibodies

FDCs make sure antigens are held CLOSE

Lets BCRs cluster/crosslink easier

T/F: Follicular Dendritic cells phagocytose an antigen and display it on MHC II

FALSE

- APC does phagocytose; FDC doesn't

Follicular dendritic cells

A. Have complement receptors

B. Have MHC II receptors

C. Kill pathogens

D. Travel to the lymph nodes from the tissue

A. Have complement receptors

NOTE: they don't use MHC to display ANYTHING

T/F: FDCs and APC DC are the same type of cell, they are just in a different location

FALSE

Once a B cell is activated, the number of B cells can double every 6 hours, and this proliferation can cause what to occur?

Push aside other B cells and create a DARK ZONE

T/F: All B cells in the germinal center are identical clones

TRUE

What three processes occur in the Germinal Centers of secondary lymphoid follicles?

1) Somatic hypermutation

2) Career decision

3) Class switching

What is the process by which BCR genes undergo mutation and selection, creating a greater affinity of the BCR for its cognate antigen (fine tuning Fab region), and low affinity BCR B cells die by apoptosis?

Somatic Hypermutation

What is the process by which a B cell can become either a plasma (antibody factory) cell and leave the bone marrow to shower blood in antibodies, or become a memory cell?

Career Decision

What is the process by which a B cell chagnes the class of antibody it produces (GAMED) and is T cell dependent?

Class switching

T/F: Class switching occurs in the dark zone of the germinal center, while Somatic hypermutation occurs in the light zone of the germinal center.

TRUE

What are the three types of Mucosal-Associated Lymphoid Tissue (MALT) secondary lymphoid organs?

1) GALT (gut associated lymphoid tissue)

2) NALT (nasal associated lymphoid tissue)

3) BALT (bronchus associated lymphoid tissue)

Peyer's patches and the appendix are examples of what type of MALT? Tonsils & adenoids?

Peyers & appendix = GALT

Tonsils & adenoids = NALT

T/F: Only the GALT and NALT have lymphoid follicles, BALT does not.

FALSE

-- all of them (GALT, NALT, and BALT) have lymphoid follicles

What part of the lymph node anatomy surrounds the lymph node?

Capsule

What part of the lymph node anatomy is where the lymph first enters the node? What cell type is this lined with?

Subcapsular sinus (marginal sinus)

Macrophages

What part of the lymph node anatomy is under the subcapsular sinus an d is where primary and secondary lymphoid follicles are? What cell types are contained here?

Cortex

Lymphoid follicles (FDC) & B cell area

What part of the lymph node anatomy is deep to the germinal centers? What cell is contained here?

Paracortex

T cell area

What part of the lymph node anatomy is beneath the cortex and paracortex?

Medulla

What part of the lymph node anatomy is involved with brining lymph into the node? Out of the node?

In = Afferent lymph vessels

Exit = Efferent lymph vessels

T/F: Lymphocytes can only enter a lymph node via incoming lymph but can exit via blood or lymph.

FALSE

-- can enter via arteriole blood (HEV) or incoming lymph; can only exit via lymph

What is the entry point for B and T cells to enter secondary lymphoid organs form the blood?

High Endothelial Venules (HEV)

T/F: Antigens can only enter the lymph node via the blood.

FALSE

-- blood or lymph

An antigen can come in on APCs or they can arrive opsonized with antibodies and/or compliment, but opsonized agents will be captured by what cells?

Follicular dendritic cells (FDCs)

T/F: Endothelial cells in blood vessels do not overlap in order to offer more room for the passage of cells.

FALSE

-- Usually OVERLAP like shingles to offer LESS room for passage of cells

T/F: High Endothelial Venule (HEV) cells in blood vessels are columnar an doffer more room for the passage of cells.

TRUE

What is a highly vascularized organ who's major functions are to remove aging and damaged blood cells and particles, such as immune complexes and opsonized microbes, form the circulation and to initiate adaptive immune response to blood-borne antigens?

Spleen

T/F: The spleen can receive from blood & lymph

FALSE

-- just blood

(but everything in the blood is allowed to enter)

T/F: The spleen has no HEV

TRUE

At rest, ______% of cardiac output goes through the spleen, taking about ____ minutes to screen all the blood in your body?

5%

30 mins

T/F: The spleen has afferent and efferent lymphatics

FALSE

-- only efferent

(NO AFFERENT brining lymph ot the spleen)

Resident dendritic cells (AP DCs; antigen presenting) live where in the spleen? What do they display when normal? When infected?

Marginal sinus

Display MHC II; when INFECTED, display MHC I

T/F: An AP DC can travel through the blood or lymph

FALSE

-- ONLY lymph

Once activated, the activated AP DC travels to where in the spleen? What do they activate in this location?

PALS (Periarteriolar lymphoid sheath)

Activate T cells

Helper T cells that have been activated by APCs in the PALS will then move where? What cells do they help?

Move into lymphoid follicles of spleen

-- give help to B cells

The spleen has true FDCs located where? What do they do?

Lymphoid follicle

Capture opsonized antigen to display it to B cells

The Efferent lymphatic vessels drain into where?

Pancreaticosplenic lymph nodes

Blood entering the spleen is diverted to where? What two types of cells is this loaded with?

Marginal sinuses

-- macrophages and antigen presenting dendritic cells

Blood must filter back to where?

splenic vein

What is the specific region of the spleen where T cells are? B cells?

T cells --> area called periarteriolar lymphoid sheath (PALS)

B cells --> area between PALS and marginal sinuses

B cell activation via T cell independent activation occurs in the spleen in response to what? Why is this significant for those w/o a spleen?

Response to encapsulated blood born bacteria

-- those w/o a spleen are more susceptible to encapsulated bacterial infections like Streptococcus pneumoniae and Haemophilus influenzae

What part of the spleen makes up the bulk, and is a site of RBC destruction, removes old red blood cells, and recycles iron?

Red pulp

In the red pulp of the spleen, hemoglobin is broken down into what?

globin --> individual amino acids

heme --> bilirubin

T/F: The spleen holds a small amount of monocytes and macrophages since its not as involved in the inflammatory response.

FALSE

-- LARGE number of monocytes/macrophages since monocytes migrate to battle sites to become macrophages or dendritic cells, and macrophages mediate generalized systemic inflammatory responses via TNF

What part of the spleen is embedded int he red pulp, contains B cells and T cells, and helps mediate adaptive immune responses to blood-borne antigens?

White pulp

What are the 3 regions of the White pulp of the Spleen?

1) PALS (periarteriolar lymphoid sheath)

2) Secondary Follicles

3) Perifollicular Zone

Which area of the white pulp of the spleen is where cell mediated immunity is, surrounding the central arteriole, made up of T cells, and is where AP DCs migrate to activate T cells?

PALS (periarteriolar lymphoid sheath)

Which area of the white pulp of the spleen is where humoral immunity is, and has the germinal center, B cell corona, and marginal zone?

Secondary Follicles

Which area of the white pulp of the spleen surrounds both PAL and follicle?

Perifollicular zone

T/F: GALT is the MALT in the small intestine

TRUE

-- peyer's patches (adults have about 200)

-- GALT = gut-associated lymphoid tissue

T/F: Peyer's Patches have high endothelial venules (HEV) that allow lymphocytes to enter form the blood the lymphatics (afferent), while it uses lymphatics for outgoing/exit (efferent)

FALSE

-- ENTER from HEV from blood

-- OUTGOING efferent from lymphatics

NO incoming (afferent) lymphatics!

What is the antigen entry in the Peyer's patches that are easily accessible to microorganisms in the intestine in order to "sample" cells in the lumen of the intestine?

M cells (microfold cells)

What two cellular features does M cells (Microfold cells) lack?

1) Villi

2) Mucus (easily accessible to microorganism)

M cells (Microfold cells) will enclose intestinal antigens in vesicles and have contents released into tissues surrounding the intestine through what?

Endosomes

M cells (Microfold cells) are selective in what they take in, as they onlty take in what?

Only take in what can bind to the molecule on the surface of the M cell

-- lets things that would normally pass through GI tract pass through

How are Peyer's Patches much like other secondary lymphoid tissue? (2)

1) Antigens brough into distinct B cells and T cell areas

2) Lymphocytes enter through HEVs (difference is NO incoming lymph vessel)

What two ways are Peyer's Patches different from other secondary lymphoid tissue?

Specialize in making Th cells that tell B cells to make:

1) IgA antibodies

2) Th2 cytokine profile (Th2 bias in gut) --> IL-4, IL-5, IL-13

Which Th bias is geared for parasitic attack or food contaminated w/ pathogenic bacteria? What are its effector cytokines?

Th2 bias

Effector cytokines (intestintes) = IL-4, IL-5; IL-13

What is the function/goal of the IL-4 that is produced by Th Helper T cells?

1) Growth factor to proliferate T cells (releasing Th2 cytokines)

2) Growth factor for B cells that are making IgE (if in intestine outside of lymph tissue)

What is the function/goal of the IL-5 that is produced by Th Helper T cells?

Causes B cells to make IgA (antibacterial in the GI if in Peyer's patches

What is the function/goal of the IL-13 that is produced by Th Helper T cells?

Stimulates mucus in the intestine

Why would it make sense to fire up production of B cells, IgA, and IgE with the Th2 bias?

IgA = Mucosal bacteria

IgE = Parasite

What are the two ways in which an opsonized antigen be brought in? Is it marked?

Can be brought in by a dendritic cell OR come in alone

May come in marked with complement OR antibodies

SUMMARY of pathway of opsonized antigen w/ ADC

1) Area where macrophages can eat/present it (lines w/ macrophages)

2) Area where FDC can catch and present to B cells (lymphoid follicles & B cell area)

3) Area where T cells can be presented peptide antigens (activated Th go to Germinal Center to help B cells; T cell area)

4) Lymph outflow to the next secondary lymphoid tissue (activated B cells and T cells leaving)

T/F: Billions of T cells pass through secondary lymphoid organs, and many will be activated as they meet their cognate antigen

FALSE

-- only a VERY SMALL number will be activated (those that actually meet their cognate antigen)

What happens to T cells that have not met their cognate antigen in the secondary lymphoid organ?

Leave and continue to circulate to other secondary lymphoid organs

What happens to Th cells that were activated in the T cell areas?

Proliferate & travel to germinal B cell areas

T/F: B cells are APCs that take in protein presented by FDCs; they process and present it to Th cells on MHC II, re-stimulating Th cells.

TRUE

What are three features of naive T cells in T cell trafficking?

1) Have many adhesion molecules

2) Circulate (lymph/blood) every 12-24 hours

3) if do not meet their cognate antigen after about 6 weeks, die by apoptosis

What are two features about experienced T cells that are different from naive T cell in T cell trafficking?

1) Express CERTAIN adhesion molecules which limits where they travel

-- expression limited; adhesion molecule expressed depend on where T cell was activated

2) Have RESTRICTED travel

-- access to lymph organs where they were activated and access to site of infection (roll/stop/exit stragetgy)

T/F: Lymphoid follicles are islands of FDC in a sea of T cells

FALSE

- in a sea of B cells

T/F: Billions of B cells pass through secondary lymphoid organs, and many will be activated as they meet their cognate antigens on follicular dendritic cells.

FALSE

-- only a VERY SMALL number will be activated (if/when they meet their cognate antigen on FDC)

What happens to B cells if they do not meet their cognate antigen?

Leave and continue to circulate

Activated Th cells in the T cell areas proliferate and travel ________ to activate ________

Proliferate and travel to germinal B cells area

Activate B cells

Where do experienced B cells tend to settle down in to make antibodies?

Bone morrow or Spleen