Chapter 2/3 Flashcards
Which cells are polymorphonuclear leukocytes?
Mast cells, basophils, eosinophils, and neutrophils
What do all PMN leukocytes contain?
Granules filled with lysosomes filled with nucleases, lipases, proteases, toxic peroxides, superoxide radicals for microbial killing
What are in mast cell granules?
Histamine. Mast cells are primary responders in allergic reactions
Which progenitor cells generate dendritic cells (DCs)?
We don’t actually know, but we group them with lymphoid progenitor cells right now
What is the ratio of RBCs to WBCs? How does this change during infection?
1000:1. However, during infection, the WBC count increases.
How long do PMN cells live? Monocytes?
2-3 days. Monocytes live for months.
What is neutrophilia?
Abnormally high number of neutrophils/ Greater than 7500/microliter
Describe what “left shift” is in context of neutrophils
It’s the premature release of neutrophils. Occurs when demand for mature neutrophils exceeds supply
What can cause neutrophilia?
Stress (physiologic), hemorrhage hemolysis, some drugs, metabolic disorders, neoplasms (abnormal tissue masses)
What are the blood percentages of neutrophils, lymphocytes, monocytes, eosinophils, and basophils?
Neutrophils = 62%
Lymphocytes = 20-30%
Monocytes = 2-8%
Eosinophils = 2.3%
Basophils = 0-2%
In which acute inflammation scenarios is neutrophilia present?
Splenectomy, appendicitis, nervousness (epinephrine), heart attack, burns…etc
Describe neutropenia
Abnormally low neutrophil count. Less than 2000 cells/microliter
Consequences of neutropenia?
Severe prolonged infections bc supply can’t meet demand
Abnormal distribution and sequestration
Decreased bone marrow production (caused by chemo, aplastic anemia, radiation)
Increased destruction (caused by splenomegaly, immune reaction)
What is granulocytopenia?
Drastically low levels of all 3 granulocytes!
What percent of granulocytes do neutrophils comprise?
95%
Which is the biggest granulocyte?
Basophil. But lowest count of all WBCs
Distinguish primary and secondary granules
Primary granules = bigger and contain killing enzymes
Secondary granules = smaller and contain molecules for maintaining homeostasis
What does FMLP stand for? What is its function? Which cell type secretes it?
N-formyl-methionyl-leucyl-phenylalanine. Functions as positive chemotactant for neutrophils. Secreted by bacteria. SUPER positively chemotactic even at tiniest concentrations
Describe eosinophilia
Abnormally high eosinophil count. Greater than 450 cells/ul
What problems is eosinophilia associated with?
-Type I allergic disorders
-Dermatologic disorders
-Parasite infestation
-Some malignancies
-Some drugs
What is eosinopenia?
Abnormally low eosinophil count
What problems is eosinopenia associated with?
Stress responses (surgery, shock, trauma, burns, mental distress)
Cushing’s syndrome: excess glucocorticoids, which is drug induced.
Describe basophilia
Abnormally high basophil count.
What issues are associated with basophilia?
It’s rare in humans, but can experience inflammation and fast hypersensitivity.
Myeloproliferative disorders and found in veterinary medicine (heart worm disease)
Describe basopenia and why this one is weird
Abnormally low basophil count, but hard to tell because normal range is 0-2%. Can be associated with hyperthyroidism, pregnancy, ovulation, stress, and long term steroid therapy
How many nuclei do neutrophils, basophils, and eosinophils have?
Neutrophils are trilobite, so 3 nuclei.
Eosinophils and basophils have 2 nuclei
Where are mast cells found?
Connective tissue
Contrast basophil vs mast cell granules
Right before releasing histamine, the bigger mast cell granules clump together. Basophil granules are smaller and do NOT clump
Basophil granules contain more _________ than T cells, which cause B cells to start making _____ and are responsible for _________
IL-4
IgE
Allergies
Macrophages enter blood as ______ from ______
Monocytes
Bone marrow
Macrophages are part of ____, also known as the _____. What is this system’s function?
Reticuloendothelial system (RES), all known as the mononuclear phagocyte system (MPS)
Functions to trap and expose foreign antigens (APC) for phagocytosis
Functions of macrophages?
Recycle trapped antigen materials to simple sugars, aa, lipids, nucleic acids. Also to process and present antigens to specific T cells
Describe the different types of macrophages that monocytes differentiate into and anatomical site
Kupffer cells = liver
Alveolar macrophages = lungs
Peritoneal macrophages = free-floating in peritoneal fluid in abdominal cavity
Microglial cells = central nervous tissue in brain
Dendritic cells = spleen and lymph nodes
Where are monocytes located?
Along capillaries
How long are monocytes in the blood before entering tissue?
8 hours after exiting bone marrow. Then go to tissue
Which cells are involved in extra cellular killing?
Natural killer cells of innate immune system and cytotoxic T cells of adaptive immune system
How to NK cells know who to kill?
Cell-to-cell contact by engaging killer-cell inhibitory receptors (KIRs) with target cell. If it binds MHC-1 (self antigen), then NK cell activation is inhibited and degranulation occurs. No destruction. If the KIRs are unable to bind MHC-1, then NK cell activates and kills target cell.
Hallmarks of inflammation?
Redness, swelling, heat, pain, loss of function
What causes inflammation?
Tissue necrosis, bone fracture, cut, burn, chemical exposure, infection, hypersensitivity reaction
Inflammation causes release of what? Give example.
Acute phase proteins such as C-reactive protein (CRP). It binds bacteria and activates complement system, which can lead to lysis enhanced by phagocytosis
Acute phase protein that is marker for inflammation?
C-reactive protein
MHC-1 is expressed on ALL cells. True or False?
False. Only present on nucleated cells. Meaning erythrocytes don’t have them bc lack nucleus
NK cells have antigen specific receptors. True or False?
False. Have self antigen receptors but nonspecific killing
Describe bradykinin
Best example of kinin superfamily. Stimulates nerve endings -> pain during inflammation. Vasodilator
Which protein family becomes activated during tissue damage? Through which pathway?
Kinins activated through blood clotting cascade
Which protein leads to kinin production?
Hageman factor (AKA coagulation factor XII) generates Kallikrein, which makes kinins
Kinins are responsible for what during inflammation?
Pain and itching
Explain kinin role in vasodilation
Act on vascular endothelial cells to make them contract (get smaller) and vasodilate vessels, thus making the vessels leaky. Also induce CAM expression so that leukocytes can adhere.
Steps of leukocyte adhesion
Tethering, rolling, activation, adherence and crawling, transendothelial migration
Types of CAMs
ICAM-I and selectins
Which cells are present at site of inflammation? Within what time frame?
PMN cells show up within 30-60 minutes to phagocytose intruder
Which cells arrive if intruder persists after neutrophils arrive?
Mononuclear cells
Role of monocytes during inflammation?
Produce cytokines when activated with antigen. Process antigen.
Key inflammatory cytokines?
IL-1, IL-6, TNFalpha, IL-8
What do inflammatory cytokines do?
Induce CAMs for adhesion by neutrophils, monocytes, and lymphocytes
Key role of IL-8?
Positively chemo-attract leukocytes to increase phagocytosis
Chemotactic factors for leukocytes?
Bacterial products
Complement
Chemical mediators
Fever is commonly present in ____?
inflammation
Bacterial products cause monocytes to release which cytokines that travel to hypothalamus to trigger fever?
IL-1
Bone marrow is what kind of lymphatic organ?
Primary and secondary
Describe parts of thymus and T cell populations that reside there
Cortical/outer/cortex region contains immature T cells.
Medulla/central region contains mature T cells that interact with APC for clonal selection
T cell maturation occurs when?
During fetal development and 1-2 years after birth
What percent T cells survive and leave thymus?
Only 5-10%
List secondary lymphoid organs
Bone marrow, spleen, lymph nodes, Peyer’s patches, tonsils, appendix
Where are Peyer’s patches found?
Ileum of small intestine
What happens in secondary lymphoid organs?
Lymphocytes interact with antigen and synthesize antibody. Trapping and concentrating antigens
What are MALT, GALT, and BALT?
Mucosa-associated lymphoid tissue = GI tract, salivary glands, eyes, skin
Gut-associated lymphoid tissue = Peyer’s patches
Bronchus-associated lymphoid tissue = bronchial tree
Which is the largest secondary lymphoid organ? Components? Function?
Spleen. White pulp (B and T cells) and red pulp (RBC and macrophages). Functions to filter dead cells and bacteria in blood
After antigen exposure, which cells proliferate in spleen?
Plasma cells
Describe parts of lymph node
Cortex, medulla, and outer capsule of connective tissue.
Cortex has lymphoid follicles that enlarge when stimulated with antigen
Why do lymph nodes enlarge?
B cells undergo mitosis
Describe B and T cell populations throughout lymph node
Mature but naive B cells undergo mitosis at germinal centers in cortex
Mature but naive T cells in paracortex
Mature and clonally selected B cells in medulla
Hilus receives antibody
Describe fate of antigen in bloodstream
Antigen enters blood -> APC such as DC, macrophage, or B cell interaction in spleen -> APC interacts with T cells that lead to T and B cell activation -> acquired immune response
