Why is blood usually sterile after a few passes through the liver, spleen or lymph nodes?
They have fixed phagocytic cells which lie within them
Usual role of macrophages:
Normally separate from immune system.
Clean cellular debris such as remnants of apoptotic cells
After activation of macrophages by PAMPs or some other signal, what do they do?
Secrete pro-inflammatory cytokines, some of which chemotaxis -> neutrophils enter first -> then monocytes (can be converted to macrophages)
How long does it take for neutrophils/monocytes to perform extravasation or diapedesis with an intact basement membrane?
up to 30 minutes.
Process of phagocytosis:
Endocytosis into -> vacuole (phagosome) -> lysozyme merges with vacuole -> Digested -> waste undigestible material is excreted
If a lysozyme releases it contents too early what happens?
It releases digestive enzymes.
These are proinflammatory.
phosphatidylserine and the immune response:
Phosphatidyl serine is normally on the inside of cells.
It is flipped to the outside in cells undergoing apoptosis.
it signals “eat me” to macrophages
It also acts to suppress the immune system
Why does phosphatidylserine suppress the immune system?
To limit collateral damage when macrophages are eating phagocytic cells
Endogenous Pyrogen:
Exogenous pyrogen:
Endotoxin
So endotoxin signals for our immune cells to make fever
Process of fever generation:
Macrophage encounters endotoxin -> produces interleukin-1 -> travels to hypothalamus -> sets thermostat higher
How does the hypothalamus increase body temp in response to pyrogen?
Causes shivering
Causes vasoconstriction via sympathetic innervation of skin, reducing heat diffusion
What happens to iron levels during fever?
Why?
They fall.
Bacteria need iron.
Interferon:
Produced by infected cells.
Signal for other cells to produce antiviral proteins
Gamma interferon is produce by what?
Helps to treat what?
Natural killer cells.
Infection and Cancer
What size are antigens normally?
Why?
10000 daltons (fairly large) Must be large enough to be unique
Ability to function as an antigen depends on:
Size
Complexity of structure
Antigenic Determinants:
Hapten:
Immunoassays:
tiny polystyrene beads are coated with antibodies to a specific antigen.
These beads will agglutinate into visible balls if the antigen is present, this is an immunoassay
Lymphocytes arise:
Myeloid tissue of the bone marrow by stem cells
- Other “seeded locations”:
spleen, thymus, lymph nodes
- What happens at a seeded location:
Mitotic division and proliferation of immune cells
What does the T in T cells stand for?
Thymus-dependent
T-cell differentiation:
- How predominant are they?
Stem cells divide -> Lymphocytes which seed thymus become T lymphocytes -> Mature cells (matured in thymus)
~75% of lymphocytes are T lymphocytes
What does the B stand for in B cells?
What do we call it in people?
Bursa dependent
Bursa equivalent