Case 7- immune response Flashcards
Role of Macrophages
1) Perform phagocytosis
2) Release cytokines and chemokines
Cytokines
A small protein that alters the behaviour of other cells, typically immune cells
Chemokine
A type of cytokine that stimulates the migration and activation of other cells
What do cytokines and chemokines do ?
They recruit neutrophils and monocytes from the blood stream, this is inflammation
What happens if there are a high number of pathogens?
The signalling PRR (Pattern recognition receptor) is activated, releasing cytokines to recruit immune cell reinforcements. Toll-like receptors are a family of signalling PRR’s which trigger the release of cytokines. If the number of pathogens are low only Phagocytosis will occur
What happens when the Macrophage encounters a stranger (pathogen)
If it’s a stranger the bacteria will have a PAMP which is recognised by a Toll like receptor (type of PRR), this activates transcription factors NFKB and IRF3/7. This causes the transcription of mRNA and the release of cytokines which go on to promote inflammation.
What happen when a Macrophage encounters danger?
When cells are damaged (danger) for example due to hammering your thumb, the Toll like receptor detect DAMP (Damage Associated Molecular Patterns). This is released from the damaged cell. This sets up the same signalling cascade as with a microbial injury and causes inflammation. This is because the epithelial barrier is likely to be broken so it stops an infection forming.
What do Macrophages respond to
Stranger/danger response
Roles of inflammation
- Delivery of effector cells and molecules to the site of infection to enhance and speed up killing of the invading microorganisms.
- Promotion of blood clotting at the site of infection to provide a barrier against further spread.
- Promotion of tissue repair.
Mechanism of action- inflammation
1) Binding of pathogen by tissue sentinel macrophages leads to its activation and induces the release of cytokines and chemokines.
2) Cytokines and chemokines: induce dilation of localised blood vessels and the production of adhesion molecules on the surface of blood vessels. These anchor neutrophils and monocytes which would normally flow past as the adhesion molecules make the blood vessel more sticky. They increase vascular permeability by producing gaps in the blood vessels.
3) Neutrophils and monocytes migrate into the tissue in a process known as extravasation (dipedesis and transmigration), they go through the gaps in the blood vessel. Monocytes differentiate into Macrophages during extravastion.
Major organs and tissues of the immune system
• Lymphatic system including Lymph Nodes • Bone Marrow • Thymus • Spleen The immune system is part of the lymphatic system. In the lymph system you have immunological surveilance
Bone marrow- immune system
Primary site of new white blood cell generation (haematopoiesis). It is composed of multipotent hematopoietic stem cells – which give rise to all white blood cells (+ others cell types)
Thymus- immune system
Site of T lymphocyte maturation
What is a primary lymphoid organ
Sites of white blood cell generation and maturation
What is a secondary lymphoid organ
The storage of white blood cells and where the majority of induced innate and adaptive immune reactions take place
Lymph node- immune response
Are small glands that filter lymph for harmful substances. Immune reactions, most notably induced innate and adaptive immune responses primary take place within Lymphoid nodes.
Spleen- immune response
Similar in structure to a large lymph node, it acts primarily as a blood filter for harmful substances. It is also important for white blood cell storage namely monocytes. Spleen also synthesises antibodies in its white pulp and removes antibody-coated bacteria and antibody-coated blood cells by way of blood and lymph node circulation.
What stem cell generates all blood cell
The multipotent haematopoietic stem cell in the bone marrow
What stem cell gives rise to the lymphoid’s
The multipotent haematopoietic stem cell which gives rise to the Common lymphoid progenitor which creates the lymphoid (B cell, T cell and natural killer).
What stem cell gives rise to the other blood cells?
The multipotent haematopoietic stem cell which gives rise to the common Myeloid progenitor gives rise to the rest of the blood cells like Macrophages and erythrocytes. All the Myeloid cells are a part of the innate immune response.
Mast cell generation
The myeloid progenitor gives rise to mast cell precursors in the blood, when they enter the tissues they form mast cells, they have a rounded nuclei
Types of granulocytes
Neutrophils, Eosinophils, Basophils and Mast cells. Have granules in the cytoplasm
Granulocytes (phagocytic and non-phagocytic)
Granulocytes can be split into phagocytic and non-phagocytic cells. Phagocytic granulocytes use their granules phagocyticaly to destroy the pathogen. Non- phagocytic Granulocytes undergo de-granulation.
Phagocytic granulocytes- Neutrophils
Most abundant granulocyte. Can undergo oxidative burst where the different lysosome contents are released all at once, to kill both the neutrophil and the internalised pathogens. They can eat 30 bacteria at once. They have a three lobular structure due to the nucleus. In the blood moves in tissue for inflammatory response
Phagocytic Granulocyte= Eosinophil
In the blood, enters the tissues in an immune response They eat antibody coated parasites, they are abundant in allergic disease. When stained with Eosin they are a pinky orange. They have a C-shaped nucleus.
Non-phagocytic Granulocytes- Basophils
Stained blue in a Haematoxylin dye. It instigates its response in degranulation. Has large internal granules. Live in the blood
Non-phagocytic Granulocytes- Mast cells
Sentinel cells. There is the release of granules containing histamine and active agents. Has a major role in allergic response. Found in the tissues so when imaged there wont be any red blood cells.