dont (9) Flashcards
L4- physiological symptoms of acute inf?
physiological response: increase blood flow symptom: heat (colo.r), redness.
vasodilation symptoms( redness (rubor) and swelling (tumor)
release of soluble mediators: pain (dolor)
extravasation of fluid: swelling (tumor), pain (dolor)
i.e: cells, fluids, proteins into intestinal space.
cellular influx (chemotaxis): pain (dolor), swelling (tumor)
increased cellular metabolism: pain (dolor), swelling (tumor), heat (colo.r)
L4- stages of acute inf?
initiation: induction of the response e.g: stepping on a nail - tissue insult leads to pain, redness and swelling.
amplification: dependent on extent of tissue injury
destruction phagocytic, enzymatic and non enzymatic mechanisms.
termination: resolution of inflammation, anti-inflammatory mediators
L4- The acute phase response?
IL-6, IL-1 and TNF cause hepatocytes of the liver to release:
- serum amyloid protein (inhibiting fever)
- C reactive protein (a marker of systemic inflammation)
- mannose binding protein which along with crp aids removal of microorganisms
fibrinogen: in blood clotting.
these are all acute phase proteins that promote repair, activate the immune system and contain infection or injury.
Inflammatory mediators produced locally at the site
of inflammation can act systemically eg on hepatocytes
of the liver leading to the “acute phase response”.
C reactive protein is used clinically
as a surrogate marker of systemic inflammation
L4- Five Inflammatory Cascades?
contribute mediators for the acute inflammatory cascade:
1. Complement
2. Coagulation
3. Bradykinin
4. Arachidonic acid
5. Free Radicals
through endothelial damage:
activation of the clotting cascade produces? plasmin which leads to complement activation.
(1)
degradation products of fibrin after thrombin will also increase vasciular permeability, neutrophils and chemotaxis.
bradykinin pathway: mediators are called kinins- potent mediators that cause pain. increased vasicular permeability, vasocdilation, pain, smooth muscle contraction. (3)
arachidonic acid: cell membrane damage releases membrane phospholipids acts on?? phospholipase. get arachdionic acid. 2 pathways after. lipoxygenase pathway producing leukotriene A4 that producesleukotrienes for neutrophil chemotaxis and bronchial smooth muscle contraction.
cycloxygenase pathway gives prostoglandins for increased vascular permeability, vascular dilation, neutrophil chemotaxis. (4)
respiratory burst after phagocytosis produces free radicals (5)
h2o2 + cl- by mpo gives ocl- +h20
2o2- + 2H+ by superoxide dismutase t h2o2 + o2
??? process is confusing for me
L4- definition of chronic inf and fibroblasts?
Self perpetuating, may develop in the course of recurrent or
progressive acute inflammation, or low grade irritants that fail to
elicit a classical acute inflammatory response.
fibroblasts: produce survival factors for t cells and b cells so promote their survival thus promoting inflammation.
L5- polymorphism of MHCs?
+ MHC gene regions?
highly polymorphic- high variation in specific allele of hla. mhc protein variants are present in the population. these proteins have the same structure but differ in 1-20 aa. most variation is in peptide binding domain. o can bind to lots of peptides and present different antigens so enhances immune system ability to recognise and respond to different pathogens.
each person has 6x mhc class 1 and 6x mhc class 2 or more. 3x on one chromosome and 3x on another.
mhc genes are on chromosome 6. ver long: 3.6x10^6 base pairs long. 224 gene loci-128 expressed and 51 in the immune system.
polygeny- multiple genes for mhc class1 and class 2. called HLA (human leukocyte antigen genes.
L5- Dendritic cells: how do they interact with T cells?
Dendritic cells are proffessional antigen presenting cells. dendritic cells in the periphery needed for recognition and ingestion of pathogens. in secondary lymphoid organs they extend long processes known as dendrites. (enhances interactions with t cells) there is antigen presentation to both cd4 and cd8 t cells.
L7- Adaptive response phases?
Antigen Recognition
B and T cells encounter specific antigen
Triggers initial immune response
Unique receptor recognizes antigen
Clonal Expansion
Lymphocytes rapidly divide
Exponential increase in antigen-specific cells
After a number of days they start differentiating.
antibodies seen at around 5 days.
Peaks around 10 days
Two immunity types:
Humoral (antibody-mediated)
Cell-mediated
Antigen Elimination
Antibodies and effector T cells attack
Remove pathogen/infected cells
Neutralize threat
Contraction (Homeostasis)
14-21 days after initial response
Majority of activated lymphocytes undergo apoptosis
Prevents excessive immune response
Memory Formation
Small population of cells survive
Become memory B and T cells
Ensure faster response in future encounters
L7- B cell signalling proppogation?
Syk phosphorylates multiple sites on the scaffold adaptor protein BLNK.
BLNK phosphorylation recruits and activates BTK, Phospholipase C-γ and G protein exchange factors (GEFs).
Phospholipase c-y (gamma) :
PLC-γ: key signalling molecule recruited following BCR/TCR activation.
Breaks down PIP2 in the cell membrane to secondary messengers: IP3 and DAG.
IP3 causes the release of Ca2+ from the ER, raising intracellular [Ca2+]
Activates Nuclear Factor of activated T cells (NFAT)
Intracellular [Ca2+] and DAG activate the NF-κB pathway via Protein Kinase C (PKC)
L7- NFAT activation?
Activated by ca release from the er. Increased ca binds to calmodulin which binds and activates calcineurin (a phosphatase). When nfat is in cytoplasm it is phosphorylated and this phosphorylation is what keeps it in the cytoplasm. So once calcineurin is activated it removes phosphate groups of nfat (dephosphorylation) allowing nfat to move to nucleus where it can induce transcription.
L7- b and t cells after activation?
Cells enter cell division (proliferation)
resting lymphocytes: in G0 of cell cycle, large nucleus, little cytoplasm, little evidence of organelle
B or T blast cell: G1/S/G2 cell cycle, increased cell size, chromatin decondensation, rough and smooth ER
Cell division – divides 2-4 times a day, clonal outgrowth
Cells differentiate
B cells become plasma cells or memory B cells
CD4+ become different T helper subsets
CD8+ become activated cytotoxic T cells
CD4+ and CD8+ can become long lived memory cells
L7- what happens when signal 1 happens?
When signal 1 is activated you get upregulation of adhesion molecules called integrins like icam1 that bind to adhesion molecule on antigen presenting cells to keep them together.
B and t cell antigen receptors and co stimulatory molecules move to centre of synapse called centra; super molecular activation cluster. Around this is a ring of adhesion molecules to stabilise this.
B cells- how do b cells differentiate in the bone marrow and the periphery?
what happens at the immature b cell stage?
bone marrow differentiation refers to the different stages from haematopetic stem cells to the mature b cell. in the periphery it refers to t cell and t cell independent activation.
Immature B Cell Stage
Immature B cells express a functional BCR (IgM) on their surface.
At this stage, negative selection occurs to eliminate self-reactive B cells through mechanisms like:
Clonal deletion (apoptosis of strongly self-reactive cells)
Receptor editing (further light chain rearrangement to produce a non-self-reactive receptor)
Anergy (functional inactivation of weakly self-reactive cells)
