innate immunity Flashcards
phagocytic cells
ability to eat and destroy
* myeloid (neutrophils, eosinophils, basophils)
* macrophage- monocyte
neutrophils
granulocytes, phagocytic
* rapid phagocytosis but cannot phagocytose repeatedly
* have granules which contain bactericidal enzymes
* short lived
* no ability to present antigens
Macrophages and monocytes
granulocytes, phagocytic
* slow but can phagycytose repeatedly
* contain bactericidal enzymes
* long lived
* selected cells have abilty to present antigens
lysozymes
bactericidal
myeloperoxidase
bactericidal
superoxidase dismutase
bactericidal
lactoferrin
Binds iron, therefore, iron is not
available for bacterial growth.
collagenase
Dissolves collagen when entering
tissues that have invading antigen
defensins
Inserts between lipid bilayers and disrupt the interactions of lipid molecules
neutrophilia
increase in number of neutrophils
indicative of infection
neutropenia
decrease in number of neutrophils
can be killed by pathogen
killing methods by neutrophils
- phagocytosis
- respiratory burst
- extracellular traps (NETs)
phagocytosis steps
- Chemotaxis
- Attachment
- Phagocytosis
- Destruction
chemotaxis (of phagocytosis)
- chemical messages released from site of injury/inflammation attract phagocyte to the site of pathogen/tissue destruction
- Adherence to vascular endothelial cells: Increased expression of adhesion molecules on the surface of endothelial cells favoring attachment to surface molecules on neutrophils
- increase in spaces between cells of endothelium
-
Diapedesis- Neutrophils migrate out of blood
vessel and enter injured site.
attachment (of phagocytosis)
neutrophils and antigen attach to trigger ingestion
1. Zeta Potential (both cell surface of phagocytes and antigens are negatively charged, therefore repel. The zeta potential needs to be reduced.)
2. Opsonins (are proteins that bind to antigen to facilitate phagocytosis and decrease zeta potential. The process is called OPSONIZATION. Eg. Complement components; antibody; a-fetoproteins)
opsonins
Any substances which promotes phagocytosis
e.g. Antibodies, Complement Components, Certain Liver proteins
“natural ketchup”. Proteins which
coat the antigen to facilitate phagocytosis
destruction (phagocytosis)
Fusion of phagosome with lysosome-phagolysosome
results in “dumping”of noxious antigen destroying chemicals
The trapped pathogen is now “bathed” in toxic antimicrobial fluids
“toxic shower”
respiratory burst
- binding to bacterium results in activation of NADPH oxidase
- releases an e- to O2 acceptor
- super oxide anion combines with H2O to make hydrogen peroxide and hypocholoride ion (both toxic to antigen)
- toxic products are released outside cell
Neutrophil Extracellular Traps (NETs)
- Sticky web-like nets made of de-condensed nuclear DNA
- Coated with antimicrobial proteins from granules
- Shown to trap and kill bacteria, are critical for clearing of some infections such as Salmonella & Shigella
- Neutrophils form NETs and release them as a form of apoptosis (cell death). This is called NETosis.
Eosinophil
- Larger than neutrophils
- Increased in allergies and parasitic infestation
- Granules have arylsulfatase, peroxidase, acid
phosphatase - Large crystalloid granule has core of major basic protein
(MBP) with matrix surrounded by
–Eosinophil cationic protein (ECP)
–Eosinophil peroxidase (EPO)
–Eosinophil derived neurotoxin (EDN)
eosinophil granules contain:
- arylsulfatase
- peroxidase
- acid phosphatase
Eosinophil large crystalloid granule has core of major basic protein (MBP) with matrix surrounded by:
–Eosinophil cationic protein (ECP)
–Eosinophil peroxidase (EPO)
–Eosinophil derived neurotoxin (EDN)
basophils
*Least numerous granulocyte (0.5% of blood leukocytes)
*Granules have complex of vasoactive molecules
very strong inflammatory products (nasty!)
where do all hematopoetic cells come from?
bone marrow
resting vs activated macrophage
activated is double in size
functions of macrophages
phagocytosis
* destructive enzymes
* respiratory burst
release secretory protein
* interlukens (IL)
What are the 3 tyrogenic factors secreted from macrophages?
causes fever
IL-1, IL-6, tumor necrosis factor alpha (TNFalpha)
IL-12
stim Th-1
IL-1
stim T cells (for antibody response)
induce fever
tumor necrosis factor alpha (TNFalpha)
cytotoxic
induces fever
IL-6
induce fever
promotes B cell functions
IL-10
downregulates Th-1 immune responses
promotes Th-2, B cells
fever functions
- decrease growth of bacteria
- muscle proteolysis (increased amino acids for use in immune system)
- stim fibroblast proliferation (tissue repair)
- lowers iron, zinc in blood (deprive bacteria of iron)
- stim hepatocytes (acts opsonins to enhance phagocytosis by neutrophils)
- increase # of neutrophils
- increase motility of neutrophils
- increase alternate pathway of complement
- increase lymphocyte activation (T, B, NK)
macrophages and repair of tissue
- tissue damaged by antigen
- macrophages arrive at injured site and secrete collagenase (destroy fibrillar structure of damaged connective tissue)
- secrete angiogenic factors (form new blood vessels)
- secrete growth factor, IL-1 (acts on fibroblast to produce collagen and tissue is repaired
macrophage antigen presentation
antigen is phagocytosed then processed
processed antigen (antigen pieces) presented to T cells for activation
dendritic cells
- thin membranous projections
- excellent antigen presenting cell (100x more)
- antibody coated antigens are rapidly presented to lymphocytes
- in all tissues except brain, eye, testes
- need to encounter antigen to survive or die within 2-4 days
4 types of dendritic cells
- myeloid (hematopoietic origin)
- lymphoid (hematopoietic origin)
- follicular (hematopoietic origin)
- plasmacytoid (look like plasma cell, secrete IFNalpha)
mature/immature dendritic cell
immature
* excelent at catching antigen
mature
* excellent at processing antigen, secrete cytokines like IL-12, IL-6
Natural Killer Cell
- subset of bone marrow derived lymphocytes (distinct from B/C cells)
- express FcRIII (CD16)
- have cytotoxic granules containing special proteins like perforin, protease (granzymes)
- kill microbe infected cells by lytic mechanism
- kill tumor and viral infected cells
- secrete IFNgamma
