Cells of the Immune System Flashcards
What two cell types comprise the HSC niche? What is the purpose of the niche?
The HSC niche consists of osteoblasts or sinusoidal endothelial cells. Even though HSCs have the ability to self-renew, they must be surrounded by this niche in order to do so.
The niche supplies growth factors and other regulatory molecules that support HSC-self-renewal.
Can HSCs be found in circulation?
Yes
What causes HSCs to home to their niche?
Chemical signals pull HSCs out of circulation and into their niches in the bone marrow so that they can grow
What are stromal cells?
Stromal cells are located within the niches and provide factors for HSC maintenance and differentiation.
What is the timing of return of HSCs to circulation?
HSC return to circulation is controlled in a circadian manner
How far along can stromal cells push HSCs towards differentiation?
Stromal factors can push HSCs to differentiate into progenitors (common myeloid or lymphoid) cells. Further differentiation is determined by stimulating factors and cytokine availability.
What cells are derived from common lymphoid progenitors?
NK cells, B-cells and T-cells.
All others are derived from the myeloid progenitor
What two cells can be derived from the monocyte?
macrophages and dendritic cells
What two factors are commonly involved in the HSC differentiation for common myeloid progenitors?
IL-3 and GM-CSF
What factor is commonly involved in HSC differentiation for common lymphoid progenitors?
IL-7
What factor stimulates differentiation into basophils?
IL-4
What factor stimulates differentiation into neutrophils?
G-CSF
What factor stimulates differentiation into eosinophils?
IL-5
What factors stimulate differentiation into monocytes and macrophages?
GM-CSF and/or M-CSF
What factors stimulate differentiation into dendritic cells?
Flt3L
What factors stimulate differentiation into T-cells?
IL-2 and IL-7
What factors stimulate differentiation into B-cells?
IL-3 and IL-7
How might a cytokine/differentiation factor be used clinically to help a patient?
Example: give patients G-CSF to help stimulate neutrophils to come out of the bone marrow and fight infection
Where are most immune cells in the body?
Most immune cells are constantly on the move, circulating through the blood, hoping for a chance encounter with a pathogen.
How do naive lymphocytes enter lymph nodes?
Through the blood (through HEVs)
How do antigens from sites of infection reach a lymph node?
Through lymphatics- they are taken from the site of infection by immune cells and travel through the lymphatics until they reach the lymph nodes
What happens to naive lymphocytes that don’t match their antigen in a lymph node?
After spending time in the lymphoid organ, the lymphocytes return to the blood circulation by traveling through the lymph system. They will then keep looking for their matching pathogen.
What happens to a lymphocyte that does find their match in a lymph node?
Naive T-cells will be activated and leave the and go to the site of infection via the bloodstream if they met their specific pathogen in the lymphoid organ.
Name 4 “lymphoid depots” where lymphoid cells may meet their specific antigen
- Lymph Nodes
- Spleen
- Peyer’s patches in the mucosal lymphoid tissue (like the intestine)
- Tonsils/adenoids
Do activated lymphocytes reach the site of infection via blood or lymphatics?
Blood- the lymphocytes will enter the systemic circulation via thoracic duct –> left subclavian vein
What is another name for neutrophils? Why?
polymorphonuclear cells (PMN’s). They are identified by their multi-lobed nucleus
What is the appearance of neutrophils when stained with H&E?
Neutrophils are one of the granulocytic myeloid cells, so they have cytoplasmic granules that are neither basic nor very acidic. They appear light pink or “neutral” on H&E staining
Which cells are the most abundant white blood cells?
Neutrophils. They are the most important front-line defense of the innate immune system.
Discuss the ability to fight off infection with neutropenia.
Low neutrophils make it difficult to fight off basic infections. Without neutrophils or other antibiotics, you would die of an otherwise non-lethal infection
What are neutrophils main job?
Phagocytosis and activation of bactericidal mechanisms
What is the lifespan of a neutrophil?
Neutrophils are very short lived, and usually die after 1 round of phagocytosis.
How do neutrophils kill microorganisms that are too large to ingest?
Extracellular killing mechanisms: they can spill the contents of their antimicrobial granules into the extracellular milieu, which, in addition to being microbial, can also cause local tissue damage
What are “NETs”?
neutrophil extracellular traps- full of granular enzymes and killing molecules + DNA elements which act to immobilize pathogens to decrease spreading and help with phagocytosis
What is the main component of pus?
Dead neutrophils
What is the primary role of macrophages?
Phagocytosis and intracellular killing
Differentiate primary vs secondary neutrophil granules
Primary: direct toxic/enzymatic activity
Secondary: Free radical formation
What are the three ways neutrophils kill invaders?
Nets, phagocytosis, extracellular killing
What organelle is overly represented in macrophages and why?
Lysosomes- macrophages phagocytose pathogens and kill them through formation of a phagolysosome
How do macrophages involve the adaptive immune system in a response to an invader?
Macrophages present antigens to T-cells in the lymphoid tissues
Which cells are important for the release of inflammatory cytokines?
Macrophages
Briefly, how to macrophages recognize foreign invaders?
Through pattern recognition receptors (e.g. TLRs, mannose receptors, LPS receptors, and glucan receptors)
Name three pro-inflammatory cytokines released by macrophages at the site of an infection
IL-1 beta
TNF-alpha
IL-6
What is the primary focus of a dendritic cell?
Antigen presentation. Dendritic cells degrade pathogens, but for the purpose of presentation (not killing)
Which cells provide the crucial link between the innate and adaptive immune system?
DCs: without them, a robust T cell response toward new microbes probably wouldn’t exist and we would never form life-long memory towards infections that we have previously encountered
What two ways can dendritic cells pick up antigen?
phagocytosis and macropinocytosis
Why is it so important that dendritic cells can recognize an incredible diverse set of antigens?
Because of dendritic cell versatility in the antigens they can present, there is very little that can escape recognition by immune system
What is the appearance of eosinophils upon H&E staining?
Bright pink due to their highly basic granules. They usually have a bilobed nucleus
Eosinophils are granulocytes
What is the main role of eosinophils?
Eosinophils are charged with the job of neutralizing and destroying large parasitic invaders
Why is it important that eosinophils are tightly regulated?
In order to kill a parasite, eosinophils release many enzymes and molecules that cause tissue destruction to not only the pathogens, but the surrounding tissue.
In what type of tissue are eosinophils normally found?
subepithelial connective tissue
What is the role of eosinophils in an allergic reaction?
The granules release by eosinophils can augment and help sustain allergic responses causing them to be chronic. The damage down to surrounding tissue can be significant and permanent
.Describe the appearance of mast cells
Mast cells are large, mononuclear cells that are filled with dark, basophilic granules containing mainly acidic histamine.
What is the main job of mast cells?
Open the vascular doors. This allows the recruited white blood cells to enter the site of infection.
This is accomplished through release of vasoactive substances upon activation
What are some of problems associated with non-pathogen mast cell activation?
Locally: local damage
Systemically: vasodilation and vascular permeability leads to loss of blood pressure, airway constriction and swelling of the epiglottis.
What is allergic urticaria?
Hives: caused by slowly absorbed ingested allergens that reach the skin, which then activate mast cells and cause large, itchy,, red swellings (hives)
Which cells are known as “the accomplice to mast cells and eosinophils”?
basophils
What is the role of basophils?
anti-parasitic and allergic responses
What is the appearance of natural killer cells?
NK cells are easily identifiable as large cells that are mononuclear and have a very distinctive granular cytoplasm compared to the previous granulocytes
What is the primary role of nk cells?
NK cells primarily attack virus infected cells or tumor cells and release their granules that cause their target cell to undergo apoptosis
How are NK cell surface receptors different from B and T cells surface receptors?
They are invariant- they do not rearrange and become specific for one type of antigen
What is the role of activated B cells?
Production of antibodies
What are plasma cells?
Soluble antibody-making machines (effector B-cells)
Which cells are the “commander and chief” of the immune system, and why?
T-cells; they help to orchestrate the antibody and macrophage response appropriate for the specific type of infection/pathogen.
