IT’S THE IMMUNE SYSTEM

BOGGUSRL@email.uc.edu

BEFORE WE BEGIN:

• Share this with others. It’s the most amusing thing I have seen in some time:

http://www.dvo.com/newsletter/monthly/2004/august/pinkey.wmv

Pinkey, pet of the week. Gotta love it.

First a request from last time

Overview

• Where do all cells that constitute the immune system come from?

• What percentage of WBCs are monocytes?

• What do they become in tissue?

Overview

• Where do all cells that constitute the immune system come from?– From a self-renewing stem cell in

the bone marrow• What percentage of WBCs are

monocytes?– 2-8%

• What do they become in tissue?

– macrophages

Lymphocytes

• What percentage of WBCs are lymphocytes?

• What are the two broad categories of lymphocytes?

Lymphocytes

• What percentage of WBCs are lymphocytes?– 20-30%

• What are the two broad categories of lymphocytes?– T-cells and B-cells

B-cells

• What do B-cells give rise to?

• How can you ID them in H&E, EM?

B-cells• What do B-cells give

rise to?– Plasma cells

• How can you ID them in H&E, EM?– H&E— beer belly

and golgi ghost– EM—lots of RER,

hypertrophied golgi• Remember they

synthesize antibodies

• No storage granules b/c ab secreted

T-Cells

• What are the three categories of T-cells?

T-Cells

• What are the three categories of T-cells?– Helper T cells– Cytotoxic/killer T cells– Suppressor T cells

The Immune System

• What is the major responsibility of the immune system?

• What initiates the immune response?

The Immune System

• What is the major responsibility of the immune system?– The discrimination of self from non-

self• What initiates the immune

response?– Antigen-presenting cells (APCs)

• What are the two arms of the immune system?

• What happens once an immune response is initiated (generally speaking)?

• What are the two arms of the immune system?– T-cell (cell mediated), B-cell (humoral)

• What happens once an immune response is initiated (generally speaking)?– Both arms generate effector cells and

memory cells– Effector cells are involved in elimination of

“non-self”– Memory cells go to lymph tissue and

hibernate

T-Cell mediated immunity

• What is it synonymous with and an give an example of each

T-Cell mediated immunity– Delayed-type Hypersensitivity

• think TB test at Holmes – you have to go back to get it read in 2 days to see if there is a rxn…. Or never go back like me

– Allograft rejection• Transplant rejection

– Contact Sensitivity• Poison ivy

– Graft-vs-Host Disease• Bone marrow transplant – the donor

attacks the host cells

B-cell function

• What are the five classes of immunoglobulins and their functions?– IgA—secretory antibody (mucosal

immunity)• Secreted by transcytosis, has secretory

component– IgD—function unknown– IgE—allergic Ab… think mast cells– IgG—serum antibody – in BLOOD– IgM—first and largest antibody –

PENTAMERIC (in groups of 5)

Major Histocompatibility Protiens

• What cells express Class I MHC?

• What do cells of the immune system have?

Major Histocompatibility Protiens• What cells express Class I MHC?

– All nucleated cells– Class 1 MHC presents antigens that are

present INSIDE the cell. Makes sense that all cells express MHC 1 because any cell can be invaded by bacteria

What do cells of the immune system have?– Either class II MHC proteins or

receptors for Class II MHC proteins– Makes sense because class 2 presents

EXTRACELLULAR antigens and only phagocytes can engulf the extracellular bacteria

Definitions

• Syngenic

• Allogenic

• Xenogenic

Definitions• Syngenic

– Genetically identical

Allogenic– Genetically dissimilar individuals

within the same species (i.e. siblings)

• Xenogenic– Genetically dissimilar and from

a different species (man and mouse)

Generation of Cytotoxic T-cells

• What are the stages of generation of cytotoxic T-cells?

Generation of Cytotoxic T-cells• What are the stages of

generation of cytotoxic T-cells?– ACTIVATION: Precursor CT-

cells bind novel hybrid antigen on surface of APC

– MATURATION: Cytokines and lymphokines secreted by Th1 drive maturation to Tc

– KILLING: Activated Tc cells find infected target cells and deliver perforinapoptosis

NOTE

• Activation of T cells requires MHC class II

• Killing requires MHC class I

Activation of B cells

• Uncommitted B cells express bound IgM

• Encounters foreign epitope• Internalizes and processes

antigenAPC• Before transformation to plasma

cell it needs lymphokines from Th2 cells.

Lab stuff

• What constitutes mucosa?

• What is the lamina propria

Lab stuff• What constitutes

mucosa?– Epithelium and lamina

propria and sometimes a layer of smooth muscle or elastic fibers

• What is the lamina propria– Layer of loose CT

under epithelium of mucosal surfaces, where lymph tissue is found between red arrows

Diffuse Lymphoid tissue

Peyer’s Patches

• Have germinal centers– Inner light

zone surrounded by dark rim of lymphocytes

Palatine Tonsil

• You will differentiate it because it has stratified squamous epithelium on one side or just CT on the other!

• Note CT septa and crypt (gap in middle of tonsil)!

Macrophages

• “starry sky” appearance – i don’t see this but whatever

Pharygeal tonsil

• ANY pseudostratified ciliated columnar epithelium on a tonsil makes it a pharyngeal tonsil

What is the major product of this cell type?

ID major product of this cell type?

• First what is the cell?– Note “cartwheel”

appearance of nucleus

– Lots of RER and Golgi

– Nucleus not centrally located

– THIS IS A PLASMA CELL

• What do plasma cells make? Antibodies!

Identify

• Hints:– Size of cell– Multi-lobed

nucleus

MEGAKARYOCYTE

Identify

• Hints:– It has a germinal center evident and

its dark purple– Look at the epithelium!

– PHARYNGEAL TONSIL because of the pseudostratified columnar epithelium

Identify

• Continuous capillary– Notice

endothelial cell and pericyte (shared basal lamina)

Identify

• Hints:– Epithelium– Germinal center

– PALATINE TONSIL

• Ideally you would look at the epithelium all the way around to make sure there was no pseudostratified columnar

Identify what is indicated

• Its part of a tonsil

• It’s a big gap

• It’s a crypt!

The Thymus

• Allograft

• Isograft

• What is the basis for allograft rejections?

The Thymus• Allograft

– Tissue graft between members of the same species but different genetics

• Isograft– Tissue graft between members

within a single species with the same genetic identity

• What is the basis for allograft rejections?– MHC class I antigens

Nude Mice

• The thymus is responsible for T cell existance.

• Athymicno T cells– No allograft rejection

Feels exposed

Thymus

• Located just above the aortic arch

• ENCAPSULATED• Multilobulated

– Each lobule has cortical and medullary portion

• Hassall’s corpuscles present – these are the key

More lovely thymus

• What happens in the thymus

• Where are T-cells “born”?

• How do T cells get into the thymus?

More lovely thymus• What happens in the thymus

– T-cells taught to discriminate self from non-self

• Where are T-cells “born”?– In the bone marrow

• How do T cells get into the thymus?– They express a T-cell receptor

(TCR) on membranes• It’s a glycoprotein recognized by

endothelial cells within the thymus

More T CELL Univ.

• What are Epithelial Reticular Cells (ERCs)?

• What do they do?

• What happens when you fail out of T cell University?

More Thymus… of DEATH!!!!!!!• What are Epithelial Reticular Cells (ERCs)?

– Stromal elements of the thymus—arise from ENDODERM and aren’t involved in fiber formation, have lots of RER and have granules that contain thymosin

• What do they do?– Provide education to the T cells—express a

bunch of self antigens to T cells and teach self-non-self discrimination

• What happens when you fail out of T cell University?– Apoptosis… greater than 90% of T cells die – lets

all take a second and be glad we don’t go there

Diffuse Lymphoid Tissue

• Either fixed or transient aggregations of immune cells– E.g. peyer’s patches and tonsils are

fixed but parenchymal cells are transient – the bunches of dark lymphocytes

• BALT, GALT, and SALT

Lymph Nodes

• ENCAPSULATED• Cortical

– Lymphoid follicles• and Medullary

regions

NO HASSALS CORPUSCLES

Cortex capsule Medulla

Lymph nodes

• How can lymph enter the nodes?• How does lymph leave the nodes?

Lymph nodes• How can lymph enter the nodes?

– 1) lymph collected in periphery and brought to nodes via afferent lymphatics

– 2) lymph enters nodes via High Endothelial Venules (HEVs) in cortical region

• How does lymph leave the nodes?– Via efferent lymphatics that originate

at the hilus

Spleen

• Filters blood• Has red pulp and

white pulp• Is NOT dark

purple• Has a thick

capsule– Gives rise to

trabeculae

Spleen

• What is the order of blood flow through the spleen?

Spleen• What is the order of blood flow

through the spleen?– Enters through the splenic artery

which branches to follow the trabeculaetrabecular arteries these branch to enter spleencentral arterioles branching from these penicillar arterioles a few capillariescollects in venous sinusestrabecular veinssplenic vein

Spleen

• What is the red pulp?• What is the white pulp

Spleen

• What is the red pulp?– Filtration part of the spleen– Contains splenic cords of billroth

• What is the white pulp– The lymphoid function of the spleen

• T-cells form Periarteriolar lymphoid sheath (PALS)

• B cells form lymphoid follicles

Identify the region indicated

– That’s where the efferent lymphatics are

• The hilus

Identify the regions outlined

• First, what organ are you in… – Do you have any germinal centers? NO. so

you are in either the medulla of a lymph node, or a section of spleen or thymus that doesn’t have any B cells

– Color? Red would suggest spleen• Dark purple or hassal’s corpuscles would

suggest thymus• Since you don’t have either of those you are in

the lymph node

• The red are the medullary sinuses• The blue are the medullary cords

What is enclosed in the blue line?

• What has a capsule?– Thymus, lymph

node, spleen• Does it look like

spleen?• Does it look like

thymus?• NO, so it’s a

lymph node

• Subcapsular sinus of a lymph node

Identify the organ

• It has a capsule• It has RED and purple

• It’s the spleen!

Identify

• What organ?• What specifically

are we looking at?

• Central artery– The white pulp

usually surrounds the central artery

Identify

• Hassel’s corpuscle• Therefore you are looking at the

thymus

Identify

• Thymus of..……

YOUR MOM!!!!no, seriously

• As you age the thymus gets replaced with fat

• Also the hassel’s corpuscles become calcified

Macrophage terminology

• In the liverkupffer cells• In the lungdust cells• You’ll learn more later aren’t you

excited!?

LETS REVIEW SOME PICS, SHALL WE???

Identify the tissue

• Spleen– Notice the

red area surrounding the lymphoid follicle and the central artery within the lymphoid follicle

Identify the tissue

• EPITHELIUM– Lymph tissue

• Palatine tonsil– Stratified

squamous epithelium

Identify

• Lymph node

Identify

• Thymus– Note hassel’s corpuscles

Identify

• Germinal center– Light ring surrounded by dark rim of

lymphocytes

– What causes the dark ring around the outside?

• Immature lymphocytes pushed out to the side

Identify the area indicated

• The cortex of the lymph node– You know because it has germinal

centers• You know it’s a lymph node because it

has a capsule, a cortex and a medulla and a hilus and no hassel’s corpuscles

Identify

I don’t know?!?! Is it poop????

Well no, it actually isnt…..

• Your mom’s thymus– Lots of adipose tissue

DIFFUSE LYMPHOID TISSUE

Just a nice little lymphocyte gathering in the lamina propria

Reticular cell

Note the heavy BRANCHING

• What cells are where?

• Orange = b cells turning into plasma cells

• Blue = b cells and t cells – called corona…….. Like the BEER, our good friend

• Have both light center and dark rim so this is a SECONDARY germinal center – if it were ALL DARK it would be primary

• I would HIGHLY recommend that you go through and fill out the chart in your lab manuals about the various lymph organs and whether they are encapsulated have efferent/afferent lymphatics etc. Last year we had a bunch of questions on both parts that that chart helped A TON!

Now time for some fun friday night studying. Yay!!!!

Boggusrl@email.uc.edu