What is the difference in the lysosome of a macrophage compared to a neutrophil?
There is no myeloperoxidase in macrophage which makes it less effective
What does the macrophage have that the neutrophil does not?
Lipases
* This is why TB is taken care of by the macrophage (it has a thick membrane which is broken down by the lipases)
What are the 2 main functions of MHCII on the surface of a macrophage with foreign antigen?
- It presents the antigen to the rest of the immune system
- It lets the immune system know that the macrophage is self (otherwise the immune cells would try to kill it)
Interferon gamma via Th1 cells on macrophages results in 3 actions by the macrophage
- Increased phagocytosis
- Increase antigen presentation
- Increased digestion via lysosomal enzymes
Function of cytokines secreted by macrophages
IL1
Increases fever
Function of cytokines secreted by macrophages
IL6
- Pro inflammatory cytokine
- Increases liver secretions of acute phase proteins (CRP, complement, coagulation system, cirruloplasmin, etc.)
- Stimulates B lymphocytes to produce Ab
4 steps (protection) of an acute infection (like a cut)
- Skin
- Macrophages (langerhans cells)
- Neutrophils –> IL3 (bone marrow), GM CSF, M CSF, G CSF
- Increased macrophages after about 8 hours (because of signal from neutrophils)
Function of cytokines secreted by macrophages
IL8
Signal to attract neutorphils for acute inflammatory reaction
Function of cytokines secreted by macrophages
IL12
Acts on T0 and converts it to Th1 (which secretes IL2 which activates cytotoxic T cell and IFN gamma which stimulates the macrophage)
Function of cytokines secreted by macrophages
IL10
Acts on Th1, inhibiting it which will then allow Th2 to be more activie (it stimulates B cells which make Ab)
Function of cytokines secreted by macrophages
TNF alpha
- Secreted after priming by gamma interferon
- Helps release cytokines for inflammation
Function of cytokines secreted by macrophages
TGF Beta (Tumor Growth Factor)
- Causes apoptosis of many cells (T cells important especially)
- Decreases neutrophil and monocyte activation
Function of cytokines secreted by macrophages
MIP (Macrophage Inflammatory Proteins)
- CCL3 PMN cell recruiter and activator
- CCL4 Monocyte recruiter
(CC = Cysteine-Cysteine chemokine)
What enzymes do macrophages have?
- NADPH Oxidase
- SOD
- Lipases (Neutrophils don’t have these) - Used to kill TB
- Don’t have MPO (Neutrophils do have these)
What 3 CD proteins are on the surface of macrophages?
- CD14 (Works with TLR2 and TLR4)
- CD31 (for neutrophil health check)
- CD11b
What receptors are on the surface of macrophages?
- Gamma Interferon
- C3b and IgG (both opsonins -
- TLR2 and TLR4 (PRRR)
What is TGF beta?
It is a multifunctional protein that plays a crucial role in regulating cell growth, differentiation, proliferation, and survival.
What types of cells produce TGF beta?
TGF-beta is produced by many different cell types in the body, including immune cells, epithelial cells, and fibroblasts
How to Macrophages become resident cells of tissue?
- They adhere to cells via integrins
What do integrins do once the macrophage is connected to tissue?
They activate TGF beta
What does TGF beta do once its activated by integrins (attached to macrophages)?
- It binds to TGF beta receptors on the macrophage which then downregulates the macrophage’s phagocytosis and its production of cytokines
- The macrophage then sits on the tissue and waits for an invader
How is a quiescent macrophage (attached to tissue cells) reactivated?
It contacts a bacterial LPS (or a virus) via TLR and CD14
What are clusters of differentiation (CDs)?
- They are proteins on the surface of a cell.
- These proteins, which are also called antigens or markers, are important for our immune system as they help identify different types of cells, such as white blood cells, and allow them to interact with each other.
What happens once a macrophage is attached to a bacteria/virus via TLR and CD14?
- Actin is released: –> Decreased integrin attachment
- TGF beta is decreased
- Macrophage becomes active
