Test 1 Flashcards
2 forms of danger that activate the innate immune response
Cell damage or
Presence of a pathogen
The innate immune system
•Is the second level of defense after a physical barrier has been breached •The Innate system: –Goes WAY back in time –IS “HARDWIRED” WITH GERMLINE DERIVED RECOGNITION MECHANISMS –IS CAPABLE OF RAPID RESPONSE –IS SOMEWHAT INDISCRIMINATE –IS HIGHLY DESTRUCTIVE –HAS NO MEMORY OF THE ENCOUNTER
PAMPs
Pathogen associated molecular patterns
DAMPs
Damage associated molecular patterns
TLR
TOLL like receptors on innate cells that bind PAMPs and DAMPs which activate phagocytic or killings mechanisms of the cell
-‘gateway to the immune system’
Leukocytes
- defined as white blood cells.
- •As a rule, their cytoplasm contains granules that are loaded with killer/hydrolytic/oxidizing molecules that are released in response to a perceived threat. Not all cells’ granules are visible under staini g and these leukocytes are called agranulocytes as opposed to granulocytes (when granules are visible under staining).
THE ADAPTIVE(ACQUIRED) IMMUNE SYSTEM
•has four cardinal characteristics:
–Recognizes antigens (pathogen components that stimulate immune responses) with very specific receptors
–can distinguish precisely between self from non-self
–can clonally expand antigen specific cells after their activation
–can remember specific encounters (memory)
Lymphocytes
Orchestrator of the adaptive immune response. They possess the most powerful ability to recognize and target pathogenic microorganisms.
Small lymphocytes come in two types, B cells (make antibodies)and T cells(helper and killer).
Gateway to the adaptive response
Innate response
B cells
Produce highly specific antibodies
T cells
Have helper and killer functions. Also regulate immune response by controlling cytokine production.
Germline encoded defense
Innate immunity
Function is contained primarily in leukocytes of myeloid lineage
Innate immune system
Macrophages
- first responder
- terminally differentiated cells
- present in most tissues
- long lived
- derived from monocytes
- high population in damaged or inflamed tissue
NF-kappaB enters the nucleus, it does what
It activates gene transcription. Numerous cytokines and antimicrobial proteins are expressed when NF-kappaB is activated.
List the sequence of events that occurs when a TLR is activated (10 out of 11 follow this pathway)
- TRL-4 (bound by LPS and LBP) binds to the adapter protein MyD88
- MyD88 binds and activates SIIK. This initiates a cascade of TRAF6 and the kinase IkappaK
- IkappaK phosphorylates IkappaB
- phosphorylated IkappaB is degraded, releasing NFkappaB to migrate into the nucleus and activate gene transcription
- numerous cytokines and anti microbial proteins are expressed
When a TLR receptor is missing or malfunctions, what results occur
There is no innate immune response
Critical cells in the innate response that interface with the adaptive system
- dendritic cells (DC)
- natural killer cells
- NKT and some certain T cells
Dendritic cells. Describe characteristics.
In many ways the most important cell in the immune system.
– Roam freely
– Multiple PRRs
– High phagocytic activity
– Excellent APC
– Direct the type of immune responsevia based on PRR stimulaton, antigen presentation and cytokine and costimulatory molecule expression
PRR stands for
Pattern Recognition Receptor
APC stands for
Antigen-Presenting Cell
NK stands for what and does what
NK = Natural Killer cells. They cooperate with humoral immunity to kill infected cells
Humoral immunity
Humoral immunity is the aspect of immunity that is mediated by macromolecules (as opposed to cell-mediated immunity) found in extracellular fluids such as secreted antibodies, complement proteins and certain antimicrobial peptides. Humoral immunity is so named because it involves substances found in the humours, or body fluids.
Describe the steps that are needed for a NK cell to kill an infected cell
- antibodies bind antigens on the surface of a target cell
- Fc receptors of the NK cells recognize the bound antibodies
- cross-linking of Fc receptors signals the NK cell to kill the target cell
- target cell dies by apoptosis
These two cells are innate immune cells even though they are derived from the LYMPOID lineage
- NKT (Natural killer T-cells)
- delta/gamma T-cells
- they are innate cells because their T cell receptor does not undergo gene rearrangement that is necessary for adaptive immunity.
All the cellular elements of blood, including the red blood cells, the platelets and the white blood cells of the immune system originate from what cell that is located where?
The multipotent (do NOT use the word pluripotent) hematopoietic stem cells. They are located in the bone marrow.
APCs are
Antigen-presenting cells which are another name for dendritic cells. They activate T lymphocytes by presenting the antigen on the pathogen.
Primary lymphoid organs
Bone marrow and thymus
Mature form of monocytes
Macrophages. Monocytes circulate in the blood and migrate into tissues. Once they are in the tissues they can differentiate to macrophages.
Classified as granulocytes
- neutrophils
- eosinophils
- basophils
What are the three factors needed to mature the multipotent hematopoietic stem cell (before it takes either the myeloid or lymphoid path)
- SCF
- IL-6
- Flt3L
A slightly matured hematopoietic cell (exposed to 3 factors already) can become a lymphoid progenitor or a myeloid progenitor based on the presence or absence of what factor?
IL-7
- when IL-7 is present, the cell becomes a lymphoid progenitor
- when IL-7 is NOT present, the cell will become a myeloid progenitor
What 3 factors does a myeloid progenitor need present before it can mature further?
- IL-3
- GM-CSF
- IL-6
Secondary lymphoid organs. List them.
- lymph nodes
- spleen
- tonsils
- Peyer’s patches
- appendix
Tertiary lymphoid tissue
Lymphoid cells are developing in an organ where they are NOT supposed to be
Describe the thymus structure
- Origin: Ventral part of 3rd pharyngeal pouch and third branchial cleft. Endoderm and underlying mesoderm origin. Two lobes.
- Capsule of Fibroblasts that form trabeculae or septa which separate the cortex into lobules. Each lobule connected to a central running confluent medulla.
What secretes IL-7 in the thymus
Epithelial reticular cells secrete it for lymphocytes
The cortex of the thymus contains ___% of all thymocytes
80-90%
A lymph node is
Encapsulated with Type I collagen with reticular cell and fiber (Type III Collagen) stroma attached.
The Parenchyma of a lymph node is made up of
Lymphocytes
Primary lymphoid organ is
Bone marrow
What is SCF?
SCF=stem cell factor, it’s the ligand for c-KIT.
What do dentritic cells due to T cells?
They present antigens to activate the T cell
Multipotent Hematopoietic Stem Cells (MHSC) sit in a niche of either
Multipotent Hematopoietic Stem Cells (MHSC) sit in a niche of either osteoblasts or sinusoidal endothelial cells. Also require stromal cells (to release growth factors) as they differentiate.
What are the two types of stem cells in bone marrow?
There are two types of stem cells in bone marrow -multipotent hematopoietic Stem cells (MHSC or HSC) and mesenchymal stem cells (MSC)
Describe the path of maturation of a MHCS in the bone marrow.
MHSCs start in osteoblasts niche. As it receives growth factors, it will mature and come out of the osteoblast niche and receive growth factors from the stromal cells. It matures further upon receiving growth factors there and then it heads to the vascular niche where it gets more growth factors and is finally mature enough to enter the sinusoidal vessel and begin circulation. NOTE: all the growth factors are secreted by stromal cells.
List some secondary or peripheral lymphoid organs.
2° or Peripheral: Lymph nodes, Spleen, Tonsils, Peyer’s Patches, Appendix
What is tertiary lymphoid tissue?
3° Where immune responses occur outside lymphoid organs, E.g. Pannusin an arthritic joint. Tertiary lymphoid tissue is when immune cells are developing in organs where you do NOT want them. This is bad.
Define what is in the stroma and parenchyma of lymphoid organs.
Stroma: Reticular cells and fibers (Type III Collagen) except thymus. (This is the steel wool structure)
• Parenchyma: Lymphocytes, macrophages,dendritic cells, NK cells (spleen)
Nurse cells in the thymus secrete
IL-7
Hassall’s corpuscle is
These are tightly wound bundles of epithelial cells with a precipitate in the middle.
Superficial (subcapsular) of the thymus has 5% of all
thymocytes which are mainly large blasts of what kind of cells.
CD3-,4-,8- cells proliferate for 1 week
At the Mid-Cortex to Cortico-Medullary junction of the thymus what kind of cells are present for 2 weeks and what processes occur?
Mid-Cortex to Cortico-Medullary junction:
CD3+4+8+ mature for 2 weeks.
- + and then – selection eliminate unnecessary or potentially autoreactive cells via apoptosis as no inflammation. This is a selection process where thymocytes must recognize self MHC antigens but not too well.
What happens to the CD 3,4,8 cells in the cortex of the thymus as they enter the medulla?
The cells lose either a 4 or an 8 to become CD 3,4 or CD 3,8
What kind of cells are in the medulla of the thymus
10% of all thymocytes: CD3+4+ orCD3+8+ mature cells which exit to peripheral lymphoid organs.
<4% of all thymocytes produced after three weeks leave for periphery as CD3+4+ or CD3+8+ lymphocytes. Most cells die via apoptosis. Which type of cell is there more of in the end?
Twice as many CD3+4+ survive than CD3+8+.
What do the trabeculae do in the lymph nodes?
Trabecula extended from capsule and separate cortex into superficialouter cortex with follicles and an inner paracortex or deep cortex. An inner medulla leads to a hilus where blood vessels and the efferent lymphatic is found.
What is found in the hilus of the lymph node?
An inner medulla leads to a hilus where bloodvessels and the efferent lymphatic is found.
What are the three sinuses in the lymph node called?
Reticular stroma creates lymphsinuses which are called
subcapsular, trabecular and medullary.
Describe the lymph circulation in the lymph node.
- Afferent lymphatics receive lymphatic vessels from the
periphery. Have valves directed to the subcapsular sinus. Subcapsular → Trabecular → Medullary Sinuses → Efferent Lymphatic → Thoracic Duct. Sinus made up of stellate reticular cells and fibers. Macrophages extensively attach.
Describe the blood circulation of a lymph node.
Hilar artery → Cortical nodule capillaries → Deep Cortical Post – Capillary venules with a high endothelium (HEPCV) → Hilar vein.
What are the HEPCVs in the lymph node important for?
It is through the HEPCVs that the main players of the Adaptive Immune System (T and B cells) gain entrance into the lymph nodefrom the circulation.
What happens in the secondary nodule in the lymph node.
- 2° nodule with germinal center are the sites where B cells mature with the help of CD4+ T cells into either Plasmablasts or Memory Cells
Migration and Differentiation of some B blasts into the Medullary Cords to become what?
Migration and Differentiation of some Bblasts into the Medullary Cords to become Plasma Cells (short lived). Long-lived plasmablasts leave via the efferent lymphatics and go to the bone
marrow.
Inner/paracortex/deep cortex of the lymph node contains-
-Diffuse cells: 1° T, some B
• Langerhans Cell (Immature Dendritic Cell)
• High endothelial post-capillary venule (HEPCVs) function as the gate of entry of T and B cells from the circulation into the lymphnode.
What is a Langerhans Cell
Langerhans Cell (Immature Dendritic Cell)originates in the marrow and localize in the epidermis of the skin. It brings processed
antigen into the node from periphery via
afferent lymphatics and becomes a mature antigen presenting cell called an
Interdigitating Dendritic Cell. It presents antigen to T cell
Neutrophils
- most common circulating short lived white blood cell
- rapid responders
- short lived
- rarely found in normal tissue
