Microbiology and Immunology 3300B Study Guide - Final Guide: Phagocytosis, Mannose, Tlr9
DepartmentMicrobiology and Immunology
Course CodeMICROIMM 3300B
Immune Study Notes Lecture 6
1. What is inflammation?
Body sends fluid, plasma proteins and immune cells to the site of tissue damage –
can be acute or chronic, local or systemic effects and could be a part of the innate
2. What are the cardinal signs of inflammation?
Calor – heat
Dolor – pain
Rubor – redness
Tumor – swelling
3. What are the blood vessels associated with inflammatory sites?
Post-capillary venules that come after capillaries; slow movement of RBC. They are
lined with endothelial cells.
4. What happens when there is tissue damage?
PAMPs or DAMPs will be present in the tissues; macrophages will recognize and
emit chemokines or cytokines – this causes a change in the endothelium = sticky;
immune cells roll a long and will go through the cells to the tissue where they will
undergo chemotaxis to the area of damage.
5. What happens when chemokines get into the blood stream?
Can go to the brain = fever, can go to liver = acute phase response, can go to the bone
marrow to cause an increase in hematopoeisis or macrophages can be APC within
6. What is the first step when damage occurs?
Detection: there are two ways to detect damage; the first is through different
receptors. Mitochondria produce formyl peptides that bind fMLP receptors, and also
have CpG DNA that binds TLR 9. There are metabolites produced by pathogens in
the IC areas such as heat shock protein and HMG, as well as metabolites such as uric
acid and ATP. Seocnd way is through immune cell binding – certain receptors such
as mannose, lipids, complement, scavenger and dectin.
7. What is the second step?
Activation of resident immune cells: macrophages take up the antigens and produce
chemokines or cytokines – after this occurs there are multiple different effects.
Cause cell differentiation and proliferation (monocytes into macrophages), dolor
(pain), local affects anti pathogen response (stop transition or translation),
activation of vascular endothelial and increased permeability.
8. How does activation of the endothelium occur?
Through integrrins/ICAMs/Selectins and chemokines – ICAMs are high affinity
adhesion molecules – stick leukocytes to endothelial cells on the luminal side.
9. What is the next step?
Leukocyte recruitment: P-selectin binds sialyl lewis on the leukocyte – causes
rolling (slow movement). Chemokines activate GPCR which eventually activates a
cluster of integrins – once this happens ICAM molecules are present and they cause
a strong bond; leading edge goes through the endothelial cells and goes to the site of
10. What is the next step?
Chemotaxis: specificity – gets them to the site of infection
Killing through phagocytosis
Systemic response: Acute phase response: IL1 beta, IL6 and TNF alpha
produce the responses
In acute phase response – macrophage binds bacteria and produces IL6 which
causes hepatocytes in the liver to make acute phase proteins to opsonize: mannose
binding lectins, SP A/D, C-reactive proteins, serum amyloid proteins (c-reactive
binds phosphocholine). Fibrinogen also made in order to clot
Changes in bone marrow epithelium to mobilize neutrophiles for phagocytosis.
Hypothalamus to increase heat so that viral transcription ceases, antigen processing
increases, fat/mscule for increased heat for the immune system – energy from fat
and proteins; dendritic cells as well for immune response (maturation)
13. Next step?
Activate adaptive immunity – usually innate can kill but sometimes we need
adaptive immunity to step in – immune cells will pick up antigens and present them
to the lymphnodes to start immune response
Resolution of Inflammation: TNF alpha and INF: no longer seeing immune cells so
wont tell them to have an immune response (short have life – no more inflammatory
signal so it stops) and wont triggor productions of chemokines.
Have inhibitory receptors – TNFR and IL-1RA which stop the production of
Immune cells have a short half life so they die through apoptosis.
IL10 and TGFbeta and lipotoxins shut down immune response when TFNalpha is
low (usually overwhelmed).
Resolvins and protectins block neutrphil recruitment and increase their apoptosis.
15. What happens in sepsis?
TNFalpha secreted into blood stream so that immune response occurs systemically.
-if the nuetrophils are in the blood cells and they aren’t leaving; going all over and
secreting harmful chemicals to essentially kill nothing – massive damages to those
blood vessels = blood clots that go to organs after breaking off – 50% chance
survival = chronic inflammatory disorders; die from MODS – liver/kidney/lungs
- a lot of different diseases where inflammation goes wrong
16. What happens with viral inflammation?
Regular neutrophils cant fix this because they are not cytotoxic – instead we have
NK cell reruitment which triggors a response at the targeted site of infection – can
usually fix viral inflammation without immune response.