Immuno Chapter 2- Cells, Organs, and microenvironments of the Immune System

Hematopoiesis

Hematopoietic Stem Cells (HSC)

Myeloid Lineage Cells

Lymphoid Lineage Cells

Primary Lymphoid Organs

sites where immune cells develop form immature precursors

Bone Marrow

Thymus

Secondary Lymphoid Organs

the site where the mature antigen-specific lymphocytes first encounter antigens and begin their differentiation into effector and memory cells

Lymph nodes

Spleen

Barrier Tissues (MALT and skin)

Lymphatic System

Tertiary Lymphoid Tissue

T- Cell zone

B- Cell follicle

Germinal Centers

Fibroblastic Reticular Cell Conduit (FRCC) System

Follicular Dendritic Cells (FDCs)

What does a successful immune response to a pathogen depend on?

a choreographed interaction among diverse cell types.

Innate immune cells

the first line of defense against pathogens

What are the major innate immune cells?

• Phagocytic cells

• inflammatory and defense cells

• cytotoxic innate cells

What are the phagocytic cells and what do they do?

they engulf and destroy pathogens.

• neutrophils

• monocytes/ macrophages

• dendritic cells

What is the function of the neutrophils?

to eat bacteria and die quickly (which forms pus)

• these are the most abundant white blood cells (make up 50-70% of the leukocytes)

• they’re the first cells to arrive at an infection

Once the neutrophils are released into the blood from the bone marrow, what happens?

they are then released in to the blood to circulate for 7-10 hours, then migrate into the tissues (they only last here for a few days)

leukocytosis

having too many white blood cells in the blood.

• too many neutrophils in the bone marrow. - indicated infection

What is the function of the Monocytes?

they eat pathogens, clean up dead cells, and signal other immune cells

• they circulate in the blood

• they are long- lived

• There are two types of monocytes

  • inflammatory

  • Patrolling

What is the function of inflammatory monocytes?

they enter tissues quickly in response to infections

What is the function of PAtrolling monocytes?

they crawl slowly along blood vessels, monitoring their repairs

What does monocytes turn into when they enter the tissues?

macrophages

What changes does macrophages undergo once stimulated by the tissue damage or pathogens?

• They contribute directly to the clearance of pathogens from that tissue

• they act as pAPCs for T-Lymphocytes

Tissue- Specific Macrophage

macrophage that lives in a particular tissue and is specially adapted to work there.

opsonin

a molecule that “tags” a pathogen so immune cells can recognize and eat it more easily.

What are the ways that immature Dendritic cells take in antigens?

• engulf it by phagocytosis

• internalize it by receptor- mediated endocytosis

• imbibe it by pinocytosis

What is the function of the dendritic cells?

they capture antigens and present them to T cells

• they act as a bridge between innate and adaptive immunity.

What does phagocytic means?

the ability of a cell to engulf, ingest, and destroy foreign particles, microbes, dead cells, and debris through a process (known as phayogcytosis )

What are some of the inflammatory and defense cells?

• mast cells

• basophils

• eosinophils

What is the function of the mast cells?

they release histamine

• they’re found in the tissues (skin, mucosa)

• they are important in inflammation and allergies

What does histamine do?

What is the function of basophils?

they release histamine during allergic responses and help with parasites

• they’re not phagocytic (they do not engulf other cells/germs)

• they circulate in the blood

• they stain blue in H&E staining

What is the function of eosinophils?

they are important for parasite defense

• they cluster around the parasite and damage their membranes

• they’re also involved in allergies and asthma

• These cells migrate from blood and into tissues

• these stain pink in an H&E staining

Where are the eosinophils mainly located?

small intestines

• in other places, they tend to help with asthma and allergy symptoms

  • they secrete cytokines that regulate B and T lymphocytes- this influences the adaptive immune response

What is the function of Mast cells?

they fight parasitic worms and help with allergies

• these are released from the bone marrow and into the blood as undifferentiated cells

• These mature AFTER they leave the blood and go into tissues

• These are very similar to basophils

What are the cytotoxic innate cells?

the natural killer cells (NK)

What is the function of Natural Killer cells?

the kill virus- infected and cancer cells

• these do not need antigen presentation

• they can detect abnormal cells missing normal markers

What are the primary lymphoid organs?

the bone marrow and thymus

What are the secondary lymphoid organs?

the spleen, lymph nodes, and specialized sites in the gut and other mucosal tissues

Where are the hematopoietic stem cells located? What are they?

in the bone marrow - self renewing

What does the HSC (Hematopoietic Stem cells) divide into?

Myeloid and lymphoid progenitor cells

Professional Antigen-Presenting cell (pAPC)

a specialized immune cell whose main job is to show pieces of pathogens to T cells to activate them. ( this is just a characteristic of the phagocytic cells)

Why are pAPCs important?

because they form important bridges between both the innate and adaptive immune systems

What are the three major activities that occur when pAPCs encounter pathogens?

• they secrete proteins that attract and activate other immune cells

• they internalize pathogens via phagocytosis, digest those pathogenic proteins into peptides, then present these peptides on their membrane surface

• They upregulate costimulatory molecules(additional signals) that are required for the full activation of helper T cells

What are naive T lymphocytes?

Lymphocytes that have not been activated by binding antigen

What does the myeloid progenitor cell differentiates into once the cell leaves the bone marrow and enters the peripheral tissues?

Dendritic cells and monocytes

While in the bone marrow, what does the myeloid progenitor cells differentiate into?

• granulocyte-monocyte progenitor

• Eosinophil progenitor

• Basophil progenitor

• Megakaryocyte

• Erythroid progenitor

• Mast cell

What does the granulocyte- monocyte progenitor cells eventually differentiate into once the cells mature?

• monocyte- which then differentiate into either a macrophage or dendritic cell (once it reaches the tissues)

• neutrophils

What does the eosinophil progenitor cells eventually differentiate into once the cells mature?

eosinophils

What does the basophil progenitor cells eventually differentiate into once the cells mature?

basophils

What does the megakaryocyte cells eventually differentiate into once the cells mature?

platelets

What does the erythroid progenitor cells eventually differentiate into once the cells mature?

erythrocytes

Once the Lymphoid progenitor cell matures in the bone marrow, what does it then differentiate into?

• a dendritic cell

• a innate lymphoid cell

• a b-cell progenitor, which then develops into a b-cell

Once the Lymphoid progenitor cell leaves the bone marrow, then enters into the thymus, what happens?

they then mature into the T-cell progenitor, then differentiate into the helper and cytotoxic T cells

What are the two capacities that defines stem cells?

1. their ability to regenerate/ self renew

2. their ability to differentiate into diverse cell types

What can embryonic stem cells do?

they can generate almost all of the special cell types in an organism. (Pluripotent )

Pluripotent

A cell that can turn into almost any type of cell in the body.

What can adult stem cells do?

can turn into several different cell types, but only within one specific tissue or system. (multipotent)

multipotent

A cell that can become several different, but closely related, types of cells.

What are tissue specific stem cells? What harbors them?

Stem cells that live in a particular tissue and only make the types of cells needed for that tissue.

• multiple adult organs

What was the first tissue- specific stem cell identified? what is it the source of?

• Hematopoietic stem cells

• erythroid (red blood cells) cells and leukocytes (white blood cells)

Where does HSCs originate and reside? Where can some also be found?

originate in fetal tissues and reside in the bone marrow of adult vertebrates

• sometimes in the spleen and liver

What is HSC controlled by?

to keep a balance- cell division, death, and differentiation

quiescent- this happens when the immune system is just being normal.

the HSCs are resting or inactive, but still alive and ready to act if needed.

Progenitor cells

have a limited self renewal capacity and becomes more committed to a particular cell lineage.

What is the relationship of HSCs and age? What does this show?

as age increases, the number of HSCs decreased (that there is a limit to HSCs self- renewal potential)

proliferative capacity

How much a cell is able to divide and make more cells.

What were expressed by the rare HSC population (during the classic experiment box 2-1)? What did this do?

some surface proteins- CD4, Sca-1, c-Kit

• this allowed the HSCs to be isolated directly

Pluripotency

The ability of a cell to become almost any type of cell in the body.

What are the most quiescent (inactive but still alive) HSCs? What do they retain throughout the life of an organism?

Long-term HSCs

• they retain pluripotency

What type of HSC divide more frequently and happen to have limited self-renewal capacity?

short term- HSCs

What promotes the development of multipotent progenitors (MPPs)?

c-Kit receptor

• this is a receptor for cytokine SCF

Multipotent progenitors (MPPs)

early cells that come from stem cells and can turn into several different kinds of related cells, but not forever.

• this means that they have a very limited ability to self renew

  • they also proliferate quickly

• they can make lymphoid and myeloid cell lineages

Lymphoid primed, multipotent progenitors (LMPPs)

• these cells tend to go into a certain lineage, then will not be able to turn into other cells in different lineages

early lymphoid progenitor (ELP)

a young blood cell that is just starting to commit to becoming an immune cell.

• they can leave the bone marrow and enter the thymus (as T-Cell progenitors)

• They can stay in the bone marrow as B-cell progenitors

What is the lifespan of a red blood cell?

120 days

What is the lifespan of a platelet cell?

5-10 days

What is the lifespan of a neutrophil? Why?

6 hours to 2 days

• this is because they are the first responders and once they eat the germ, they die.

What is the lifespan of a monocyte?

days to months

What is the lifespan of Basophils and Mast cells?

hours to days

What is the lifespan of the lymphocytes? Why?

days to years

• this is because they are part of the adaptive immune system, taking note of what germs were previously in the body and how they were fought off- committing them to memory

How can the hematopoietic cells be distinguished visually?

Using hematoxylin and eosin stains or fluorescent markers

What all falls under the myeloid lineage cells?

• red blood cells

• granulocytes

  • neutrophils

  • eosinophils

  • Basophils

• monocytes

• macrophages

Are myeloid lineage cells innate or adaptive?

Innate immune cells

When a dendritc cell has captured an antigen, what happens?

it loses the capacity for phagocytosis and large- scale pinocytosis.

What are the two lineage commitment choices that a cell can make?

• myeloid progenitor cell (aka a common myeloid progenitor)

• lymphoid progenitor cell (aka a common lymphoid progenitor)

What does a myeloid progenitor cell do?

it creates red blood cells, platelets, and myeloid cells (granulocytes,monocytes, macrophages, and some dendritic cell populations)

What does lymphoid progenitor cells do?

they created B-lymphocytes, innate lymphoid cells (ILC’s) and specific dendritic cell populations.

Which HSC’s stay inactive and keep the ability to become many different cell types throughout life?

Long-term HSC’s

Does Long- term HSC’s make short term HSC’s?

Yes

Which HSC’s are usually inactive but divide more often and have a limited ability to renew themselves?

Short-term HSC’s

What does short-term HSC’s develop into?

multipotent progenitors (MPP’s)- they do not self-renew, yet they divide quickly and can become both lymphoid and myeloid cells.

What happens to an HSC as it progresses from a LT-HSC →ST-HSC→MPP?

it loses its ability to self-renew