Immune Cells & Organs -- Chapter 2

9/11 Lecture

Hematopoiesis

formation and development of all blood cells (RBC, thrombocytes: platelets, WBC)

Steady state

10 billion WBC and 200 billion RBC a day

RBC are called

Erythrocytes

WBC are called

Leukocytes

Lymphocyte

type of leukocyte (T cells, B cells, NK cells)

Hematopoietic stem cells (HSC) have the ability to…

Regenerate and differentiate into specialized cells

Stromal cells

Produce factors that aid in differentiation of HSCs 

Type of stromal cells

Endothelial cells, macrophages, osteoblasts

Induction (in relation to HSCs)

HSCs huge multiplying capacity during infection

Totipotent stem cells

Cells that can become anything including fetal & placental cells

Pluripotent stem cells

Cells that can make any specialized cell except placenta & embryonic

Multipotent stem cells

Cells that can create diverse cell types within a specific lineage (ex: hematopoietic → blood)

Cluster of differentiation

Specific marker for identification and developmental changes

CD3 is a marker for… 

T Cell co-receptors 

CD4 is a marker for…

Helper T cells

CD8 is a marker for…

Killer T cells

CD19 is a marker for…

Expression of B cells

CD34 is a marker for…

Hematopoietic stem cells

Purpose of the panning experiment

Believed HSCs are unlikely to express “markers” of mature blood cells on surface

Steps of the panning experiment

Human blood is injected into an animal, the animal generates Antibodies (abs) against foreign human blood, the antibodies coat the well, a bone marrow suspension with a mixture of cells is added and the well is shaken leading to mature blood cells binding to the antibodies 

How was negative selection done in the panning experiment

The mature blood cells that binding to the antibodies are removed since they were Lin+ markers and the Lin- cells are kept 

Purpose of negative selection 

Keep cells that don’t have mature receptors 

Positive selection

Choosing cells that are fluorescent

HSC Treatments

Restoration of immune system in immunodeficient people, replacement of defective immune cells with healthy ones, personalized medicine (fixing genes) 

Progenitor cells

Committed to a given lineage (myeloid or lymphoid lines) with little capacity for self renewal but can multiply into many different cells 

Terminally differentiated population

Nondividing cells with limited lifespan at the end of their developmental path

Myeloid progenitors can become…

Monocytes (macrophages, dendritic cells), granulocytes, erythrocytes (RBCs), megakaryocytes (form platelets = thrombocytes) 

Monocytes appearance

1 kidney shaped nucleus

Monocyte function

Make cytokines, mild phagocytosis, antigen presentation

Do monocytes have granules? 

No

What is the marker for monocytes

CD14

What do monocytes do when in tissues?

Differentiate into macrophages and dendritic cells 

Macrophages function

Phagocytosis, cytokine production

Dendritic cells function

Present antigens to naive T lymphocytes for initial activation

Dendritic cells appearance

Long protrusions

What are dendritic cells known for?

Ultimate pAPC (professional antigen presenting cell)

What do pAPCs do?

Present antigen to T cells

What do dendritic cells do when inactivated?

Monitor the body while performing mild phagocytosis

What do dendritic cells do when activated?

Dendritic cells become activated when they capture an antigen and they mature, decreasing their phagocytotic capability and moving to lymphoid tissue to present the antigen to T cells 

Name for macrophages in brain tissue

Microglia

Name for macrophages in lung tissue

Alveolar macrophages

Name for macrophages in liver tissue 

Kupffer cell

Name for macrophages in skin tissue

Langerhans cells

What are granulocytes?

Cells with granules which have enzymes that release during infections

What is degranulation?

Process of releasing chemicals in granules into extracellular environment

Types of granulocytes

Neutrophils, basophils, mast cells, eosinophils

Neutrophil appearance and function 

Multiple nuclei and perform phagocytosis and degranulation

Basophil appearance and location

Nuclei surrounded by small dots found in blood

Mast cells appearance and function

Nuclei surrounded by small dots found in epithelial tissue (tissue that lines the body) 

What are basophils and mast cells involved in?

Inflammation

Eosinophils location and purpose

Tissue and anti-parasite

Granule components

Proteases, antimicrobial proteins, histamines, cytokines, chemokines, lipid mediators 

Major myeloid effector functions

Phagocytosis, degranulation, cytokine production, pAPCs

Name the lymphoid progenitor cells

B cells, T cells, innate lymphoid cells

B cells function

pAPCs with B cell receptors unique to each B cell

What can activated B cells become?

Plasma B cells and memory B cells

What is a plasma B cell? 

Secretes antibodies against specific pathogens 

What is a memory B cell?

Recognizes same pathogen for faster antibody production

How are B cells activated?

Antigen contact and conformation from T cells

What do T cell receptors do?

Recognize processed pieces of antigen on molecules

What do activated T cells proliferate into?

CD4+ helper cells and CD8+ killer cells

What do CD4+ helper cells do? 

Release cytokines that aid in activation of B cells 

What do CD8+ killer cells do?

Have the potential kill cells that are damaged or infected

What are the primary lymphoid organs

Bone marrow and thymus

Bone marrow function

• origin of B cells, T cells, and stromal cells

• where B cells mature 

Where are HSCs found within the bone marrow?

Perivascular niche of the medullary cavity

Defects in the thymus

Nude mouse, digeorge’s syndrome, smaller thymus as you age

What is nude mouse

genetically mutated mouse with no thymus thus no mature T cells

What is DiGeorge’s syndrome?

Small or no thymus present from mutation in chromosome 22 thus increased sensitivity to infection 

What are the secondary lymphoid organs?

Lymph nodes, spleen, mucosa-associated lymphoid tissue (MALT)

Secondary lymphoid organ function

Where lymphocytes and myeloid cells wait to encounter antigens, present antigens, become activated, undergo clonal expansion, and differentiate into effector cells 

Lymph nodes function

Trap antigen from local tissues and bring immune cells together

Where are lymph nodes mostly clustered?

Neck, armpit, and groin

How are lymph nodes connected?

Lymphatic vessels

What are the lymph nodes’ structural components

Follicles: where B cells reside

Paracortex: where T cells reside 

Capsule: connective tissue dividing outside and inside of lymph node 

Spleen function

Filters blood and responds to blood-borne pathogens

What is the spleen connected to?

Circulatory system

Components of the spleen

• white pulp (follicles) = immunologically active portion of spleen rich in B and T cells 

• Red pulp: site of erythrocyte death

• Marginal zone: separates white and red pulp and made up of special B cells that contain TLRs