Defenses and Deficiencies Part 4 Flashcards
If a patient has a deficiency in TLR 4 receptors, what are they in danger of?
Infection by gram negative cells.
What are the 6 steps of diapedisis?
- Macrophage phagocytoses a bacteria/ Mast cell degranulation
- Cytokine production from macrophage.
- Macrophage upregulate cell adhesion molecules (selectins) and integrins.
- Leukocytes bind to endothelial wall.
- Leukocyte spreads out on endothelial wall
- Leukocyte squeezes between endothelial cells.
What are in the primary granules of neutrophils?
Myeloperoxidases(H202,OH-,Cl- into bleach), proteases, lipases nucleases.
What is the difference between neutrophils and macrophages?
Neutrophils die along with the bacteria from the bleach that they make; This forms pus.
What is pus?
Dead pathogens and dead neutrophils.
How are eosinophils like neutrophils?
They can perform diapedisis and phagocytose pathogens.
Which cytokine can recruit an eosinophil? Who produces it?
IL-4; Produced by Mast cells.
What is the role of the eosinophil?
Play a role in asthma, and the destruction of helminths.
How are eosinophil activation similar to mast cell activation?
They are activated the same way Mast cells are activated; Causes degranulation.
How is eosinophil activation different to mast cells?
In addition to IgE receptors, they have IL-5 receptors that also need to be engaged before granules are released.
What are the contents of the eosinophil granules?
Major Basic Protein, Acid phosphatase, Elastase, Eosinophil peroxidase, and eosinophilic cationic proteins.
What does Major Basic Protein do?
Induces mast cell degranulation and digests sulfated proteoglycans, parasite cutilcles (their shell).
What does Acid phosphatase and elastase do?
Degrade tissues like epidermis of helminthes, yeast and fungi
What does eosinophil peroxidase do?
Catalyses respiratory burst in eosinophils.
What does Eosinophilic cationic protein do?
Digests RNA and ribosomes; Anti-viral
What can eosinophils do that mast cells cant do?
Phagocytose and release antihistamines; Negative feedback for mast cells.
What is Septic shock?
The end result of sepsis; Widespread activation of mast cells and macrophages through TLRs. Acute response to bacteremia.
How do you recognize septic shock?
High serum levels of TNF-a and IL-1; Systemic mast cell degranulation, Vascular permeability, HYPOTENSION (shock)
What is the effect of septic shock on body temp and WBC numbers?
Body temperature rises and more WBCs are created.
What are some immunodeficiencies of the innate immune system?
Chronic granulomatosis disease, Leukocyte adhesion deficiency 1&2, Chediak-Higashi sydrome, and complement deficiencies.
Describe chronic granulomatosis disease.
Defective production of ROS by phagocytes; Mutation in phagocyte oxidate. Pathogen is PROTECTED by macrophages that are unable to do their job. Causes granulomas.
Describe LAD1.
Absent or deficient expression of Beta 2 integrins, causing defective leukocyte adhesion.
Describe LAD2
Absent or deficient expression of leukocyte ligands for endothelial E&P selectins; Failure of leukocyte migration out of vessel.
Describe Chediak-Higashi syndrome.
Defective lysosomal function due to premature fusion during development in neutrophils, macrophages and dendritic cells. Defective granule function in NK cells and CD8. Partial albinism, defective platelets. Phagocytosis is not affected. Autosomal recessive.
Describe Sporadic Congenital Neutropenia.
Due to mutations in the genes involved in granulocytic hematopoiesis and cell maturation; Severe arrest of granulopoiesis at promyelocyte stage. Neutrophil counts are low with severe onset of bacterial infections in infancy.
Describe Lazy Leukocyte Syndrome.
Slow moving leukocytes as a result of defective cytoskeletal protein polymerization; Presents with constant bacterial infections of skin, mucous membranes, and urinary tract.
What is the major characteristic of LAD?
There is LITTLE TO NO PUS in infected tissues.
What is the common treatment for these innate immune deficiencies?
Bone marrow transplant
