12 - leukocytes: morphology, kinetics and functions (E2 start) Flashcards
neutrophil morphology: bands vs mature
photo
what are granulocyte granules
lysosomes containing hydrolytic enzymes and antibacterial agents
when do primary granules appear
in late myeloblast/early promyelocyte stage
where do secondary granules appear
in myelocytes
what are heterophils
granulocytes equivalent of neutrophils, but variably stained red granules
- can be a challenge to differentiate from eosinophils, especially in histopath
what happens to lymphocytes, eosinophils and monocytes
lymphocytes recirculate to tissue from blood
some tissue eosinophils may return by lymphatics
some monocytes my shuttle back to bone marrow
what is the half life of neutrophils in blood
half life in blood about 5-10 hours normally
– they survive a few days in tissues normally
—- spontaneous apoptosis if they remain in blood
what happens to the neutrophils when there is epinephrine release or marked exercise in the body
what are the half lives of eosinophils and basophils in blood
eosinophils: less than one day
basophils: 2-3 days
what is the tissue survival time of eosinophils and basophils
eosinophils: weeks to months
basophils: a few days
what is the half life of monocytes in blood
1/2 to 3 days normally
- develop into macrophage and dendritic cells in tissues where they survive weeks to months
what do monocytes and lymphocytes do in the lungs
marginating poll within lung capillaries
where are most lymphocytes
most lymphocytes are in lymphoid organs
how much lymphocytes are in blood
2-5% of total lymphocytes in blood
what are most blood lymphocytes
naive T and naive B lymphocytes
add photo
explain the recirculation of lymphocytes
- half life in blood about 30 mins
- about one day to migrate through a lymph node
- memory lymphocytes favor return to a similar type of tissue
- proliferating calls exhibit minimal migration
something about homing
what are the half lives of lymphocytes in blood (T, B and NK cells)
T-lymphocytes - years
B- lymphocytes - 2-3 weeks individual calls, proliferating clones for years
NK cells - half life 1-2 weeks in the circulation
what are the functions of neutrophils
- defense against invading microorganisms primarily bacteria
- recognize chemoattractants, migrate through the tissues and destroy invading bacteria
- requires various surface adhesion molecules
—- adhesion and spreading
—- haptotaxis (like chemotaxis except surface bound movement)
—- phagocytosis
neutrophil activation
explain haptotaxis (chemotaxis)
receptors for chemoattractants increased following activation
crawl using B1-3 integrin molecules binding to appropriate adhesion molecules within extracellular matrix
list some chemoattractants
- IL8 and other chemokines
- C5a, PAF, leukotriene B4
- bacterial products recognized by toll-like receptors
what is leukocyte rolling
mechanism of killing
what are neutrophil extracellular traps (NETs)
neutrophils release NETS composed of processed chromatin fibers containing histones, proteins form granules, and selected cytoplasmic proteins
what do NETs do
NETs can bind and kill bacteria, fungi, parasites, and possibly some viruses without phagocytosis
what is NETosis and what does it require
an active form of cell death that is different from apoptosis or necrosis
- NETosis requires the production of superoxide free radicals
what other cells also release extracellular traps
eosinophils and mast cells also release extracellular traps
what do band eosinophils look like
Where are most eosinophils in tissue
most tissue eosinophils in GI mucosa
what are the functions of eosinophils
have little phagocytic ability, with poor defense against bacteria and viruses
Have type 2 cytokine-induced inflammation ??
what are type 2 cytokine-induced inflammation
- produces type 1 hypersensitivity allergic reactions
- host defense against helminths (rounds and flukes)
how does the body try to kill helminths
organisms to large to phagocytize
so the body uses oxygen metabolites and major basic protein, eosinophil cationic protein and eosinophil neurotoxin from granules damage/kill helminths (worms and flukes)
basophils vs mast cells
add photo
what are the functions or basophils and mast cells
basophils recruited to sites of inflammation after exposure to allergens, helminths ectoparasites
- release histamine and other mediators following antigen-IgE binding
why are the granules in basophils and mast cells purple
granules: histamine bound to polyanions such as heparin giving granules purple color
how do basophils and mast cells contribute to inflammation
expulsion of parasites and eosinophil recruitment
what are the functions of monocytes
-phagocytosis, antigen presentation to T lymphocytes, cytokine production (inflammation, hematopoiesis)
- rapidly mobilized from marrow in response to inflammatory conditions
- chemoattractants are similar to neutrophils
- less effective against bacteria than neutrophils and more effective against viruses, protozoa, fungi
what happens with monocytes migrate to the tissue
monocytes migrate into tissue to become macrophages and dendritic cells
what does M-CSF do to monocytes
M-CSF promotes transformation of monocyte to macrophages
– increase in size, granules (lysosomes), mitochondria, phagocytic capacity
what are M1 macrophages
antimicrobial
what are M2 macrophages
wound repair and tissue remodeling
how are macrophages different from from neutrophils
migrate slower than neutrophils
most staying power (synthesize new membranes and lysosomes than neutrophils
more effective in viral, fungal, protozoal, helminth infections and less effective in bacterial infections
how to macrophages link innate and adaptive immunity
- toll-like receptors recognize bacterial molecules (ex LPS)
- Fc and complement receptors for opsonized microorganisms
what are the antimicrobial properties of macrophages
NADPH oxidase, but less myeloperoxidase than neutrophils
nitric oxide more important free radical for killing
macrophage scavenger receptors
how do macrophages accomplish immune modulation
- antigen processing
- tumor cell killing after sensitization by T lymphocytes
- synthesis of various cytokines
what do macrophages do to erythrocytes
degradation of phagocytized erythrocytes and iron release/stores
what do intravenous macrophages do
removal of blood borne pathogens - intravenous macrophages (liver/spleen, pulmonary)
other than being the clean up crew what do macrophages do
wound healing
what is the function of T lymphocytes
cellular immunity
—– CD4+ TH lymphocytes and CD8+ cytotoxic T lymphocytes
- produce cytokines that have effects on hematopoiesis
what do CD4+ TH lymphocytes do
provide defense against pathogens and neoplasia by recruiting and activating various immune cells
what do CD8+ cytotoxic T lymphocytes do
they are antigen dependent cells that destroy target cells (ex virus infected cells, neoplastic cells)
what are the functions of B lymphocyte functions
immunoglobulin production with participation form T lymphocytes, dendritic cells and macrophages
how are immunoblasts and plasma cells produced
Intact antigens recognize and bind to B cell receptors (BCRs)
- following activation Ig-producing immunoblasts and plasma cells are produced
what immunoglobulins are produced
IgM initially and then IgG continued antigenic stimulation
Explain NK cell function
– Generally appear as granular lymphocytes
activated NK cells bind to target tumor cells and virus- infected cells and induce apoptosis similar to cytotoxic T lymphocytes
