Immune system cells and organs: cap #2

Dr. Claribel Luciano-Montalvo claribel.luciano@upr.edu

Hematopoiesis
Is the formation and development of both erythrocytes and white blood cells A precursor cell known as stem cell can differentiate in a myeloid or lymphoid cell Only this precursor is capable of cell division
Way to control mutation rate

Hematopoiesis generation
Occurs inside the large bones
Bone marrow Restricted to different bones during development Prior birth is restricted to liver and spleen Up to 25 years occurs in the long bones During all ages occurs in cranium, pelvis, sternum

Hematopoiesis activity

Hematopoiesis regulation
Done at genetic levels Transcription factors promote the expression of proteins that all hallmark of the different cells types Studies with Knockouts have been essential to understand the importance of these transcription regulators

Cell death
Types
Apoptosis
Controlled cell death No inflammation

Necrosis
Cell burst and cause tissue damage Inflammation is promoted

Important regulators of apoptosis

p53 is responsible for cell cycle controlling
When inhibited cell with damage will continue their cell cycle

FAS/FASL
Can promote activation of caspases to induce apoptosis

BCl-2
Inhibits apoptosis in large amounts Can translocate to the Ig heavy chain and be transcriptionally activated

CD proteins or cluster of differentiation

proteins found on the surface of white blood cells (leukocytes) at various stages of their development Help the white blood cells interact with the body's tissues and attack invaders Some CD genes play a role in cell signaling and the development of the nervous system.

How to separate hematopoietic stem cell

Using Ab you can separate the progenitor cells in order to use them to reconstitute radiated mice Cells are separated by labeling their CD with Ab and then removing labeled cells This process is repeated and finally when stem cells are extracted are used to reconstitute hematopoiesis

Ab for stem cells enrichment

Sca-1
stem cell antigen-1. Murine cell surface antigen is called also Ly6A/E or Ly6D (Lai et al, 1998).

CD34
Protein encoded by this gene may play a role in the attachment of stem cells to the bone marrow extracellular matrix or to stromal cells. This singlepass membrane protein is highly glycosylated and phosphorylated by protein kinase C.

B cell
Specialized for the production of immunoglobulins after differentiation into plasma cells B-cells process and present antigen via surface MHC class II Usually require T-cell help to respond to antigen (interleukins) but can also recognize antigen directly through surface Ig B cells mature in the bone marrow

T cell
Cell-mediated immunity especially intracellular organisms, protozoa & fungi 70-80% of total lymphocytes Long-lived memory cells (some up to 20 years) Activity is by cytokine production Th - CD4+: Respond to antigen in association with MHC Class II Tc - CD8+: Respond to antigen presented via MHC Class I Antigen MUST be peptide

Macrophages and monocytes

Macrophages
long-lived widespread distribution they express receptors for Ig and are activated by complement components which they use to take up immune complexes

Monocytes
In blood Precursor of MO

NK
classed as part of the lymphoid system particularly effective against virus-infected and tumor cells They are larger than T and B lymphocytes, have distinctive cytoplasmic granules NK cells are activated in response to interferons or macrophage-derived cytokines Kill cells with low MHC-1

Neutrophils
Travel through blood Phagocytic cells and granulocyte First cells to arrive to infection site Increase neutrophils can indicate infection The move by extravasation Induced factors in the site of infection serve as chemotaxis agents http://multimedia.mcb.harvard.edu/flash/extrav asation.swf

Eosinophils
Granulocytes Phagocytic cells Associated with parasitic infections Secrete granule content to destroy invaders

Basophils
Granulocytes Do not perform phagocytosis They primary function in hypersensitivity reactions mediated by IgE Can be activated in parasitic infections (Lantz et al 1998, Nature)

Mast cells
They are restricted to tissue Highly specialized to act during hypersensitivity reactions Contains histamine granules that are release upon allergen triggering

Lymphoid tissue
Small B and T lymphocytes that have matured in the bone marrow and thymus but have not yet encountered antigen are referred to as naive lymphocytes. Both are considered primary lymphoid tissue These cells circulate continually from the blood into the peripheral lymphoid tissues

Lymphoid tissue
In the event of an infection, lymphocytes that recognize the infectious agent are arrested in the secondary lymphoid tissue There cells proliferate and differentiate into effector cells capable of combating the infection. Mature lymphocytes recirculate continually from the bloodstream through the peripheral or secondary lymphoid organs

Peripheral lymphoid tissue

Spleen, which collects antigens from the blood Lymph nodes, which collect antigen from sites of infection in the tissues Adaptive immune responses are initiated in these peripheral lymphoid tissues

Thymus: T cells' school

Thymus
Select and maturate T cells 90-95% of the entering thymocytes are eliminated Cells in this stage develop TCR to recognize a broad amount of Ag
done by genetic recombination

T cells high specificity is acquire after Ag encounter

Lymphatic system
extensive system of vessels that collects extracellular fluid from the tissues and returns it to the blood. This extracellular fluid is produced by filtration from the blood, is called lymph. The vessels are lymphatic vessels or lymphatics

Lymphatic system and lymph node

In the lymph nodes, B cells are localized in follicles and T cells in the paracortical areas Antigen-bearing cells and antigens from infected tissues travel to these nodes

Spleen
Collects antigen from the blood It also collects and disposes of senescent red blood cells Two major areas are the red pulp and white pulp

All the ALTs

gut-associated lymphoid tissues (GALT), which include the tonsils, adenoids, and appendix, and specialized structures called Peyer's patches in the small intestine
collect antigen from the epithelial surfaces of the gastrointestinal tract

bronchial-associated lymphoid tissue (BALT) mucosal-associated lymphoid tissue (MALT) nose-associated lymphoid tissue (NALT) vulvovaginal-associated lymphoid tissue (VALT)