Inflammation: IMMUNO Flashcards
Cytokines list
IL-1 IL-2 IL-4, IL-5 IL-6 IL-7 IL-10 IL-12 induces IFN-y
TNF-a
IFN-a
IFN-B
IFN-y
CD list
Messengers/ mediators in immune regulation. (Traffic signals that attract cells to site)
CD4+ helper T (Th) (binds MHC II + EC pathogens)
CD8+ cytotoxic/killer T (binds MHC I + IC pathogens)
CD 28
CD80, CD86
CD40L, CD40
CD19, CD20
CD 25
CDR
CD3
CDR3
Antigen presenting cells (APCs)
Dendritic cells (hematopoetic, everywhere and present IC pathogen fragments), macrophages, and B-cells
Cells involved in innate immunity
- Phagocytes! Digest particle via phagolysosome
- First to act are neutrophils in accute inflamm, use chemotaxis to find infection and spit out NET to prevent bacteria prolif
- Macrophages (monocytes in circ, and become macrophages once they enter tissues), which have many names
- NK cells (detect stim signal and MHC I to kill cell, but don’t attack RBCs, which is why malaria can hide there)
Complement system
Assists antibody activity pathways, serves to recruit phagocytes (combo of complement opsonization and antibody paths are best for getting phagocytes to act).
-C3 splits into C3a and C3b. C3a goes on to be a anaphylotoxin, meaning it recruits phagocytes (esp neutros) (C5a does this too, potent). C3b deposits on bacteria, tagging it (opsonizing it) for destruction (by macros)
Immunoglobulins list
IgG IgA IgM IgE IgD (GAMED)
Affinity vs. Avidity
AVIDITY is higher for IgM bc pentamer and contains MORE binding sites, but IgG generally has higher affinity bc binds more strongly (must undergo at least ONE rearr to produce IgM, but if single rearr produces clones then will all have same affinity)
Heavy change vs light chain rearrangement
H (mu) chain– DJ rearr, then V-DJ rearr via Rag
Light chain: kappa genes rearr, then lambda if needed
IgG
- most abundant, impt in secondary ab response
- Can cross placenta to give immunity to fetus
- Can bind to IgG Fc receptors on macrophages when ab bound to antigen to opsonize pathogens
IgA
- Dimer
- in secretions (saliva, tears, milk, mucus linings)
- Neutralizes and activates ALT complement pathway (firs to act, makes sense b/c in mucus linings)
IgM
- Pentamer
- Strong avidity bc many sites for binding
- Activates classical complement path (along with IgG)
- First ab made in resp to pathogen
IgE
- Bound to FCE receptors on basophils/mast cells
- Activating this leads to ASTHMA and ALLERGIC rxn
- can protect from helminths
- IL-4 from helper-T celsl helps with isotype switching to IgE
IgD
- can be found on B cell surface etc (can can fxn as B cell rec along with IgM)
- Express on B-cells during maturation when leaving marrow (mature but naive) before entering lymph nodes
IgG
- most abundant, impt in secondary ab response
- Can cross placenta to give immunity to fetus
- Can bind to IgG Fc receptors on macrophages when ab bound to antigen to opsonize pathogens
- In ab isotype switching, IgM may switch to this
CDR3
CDR= complementarity determining region
CDR3 is the part of the B-cell receptor (antibody) that contacts the epitope (antigen) and will send signal to let itself know that pairing between H-chain an surrogate light-chain is productive (still @ pro-b cell stage) (???), mutations here cause somatic hypermutations
PAMPS
Immune cells recognize PAMPS on pathogens and respond using PRRs (such as TLRs)
-Example: TLR-4 recognizes LPS in gram(-) bacteria, and then this PRR initiates the inflammatory response
Classical vs Alternative complement pathway
Classical: activated by antibody-antigen COMPLEX (occurs 3 days later, adapative)
Alternative: First to act, begins at C3 (always on, innate)
Th1 vs. Th2 helper T-cells
Th1: produce IFN-y which activates macrophages and opposes IL-4
- makes macrophages better, opsonize antibodies of B-cells
- high affinity TCR only req low amt of antigen to get activated to Th1
Th2: Produce IL-4 to activate B-cells and oppose IFN-y
- Makes B cells better, prob made for helminths, and IL-10 to inhib immune resp
- low affinity TCR req lots of antigen to get acitvated to Tf2
Fc region
Antibodies bind to microbe, and then Fc receptors on phagocytes usually bind to these antibodies. Fc is the portion of the cytophilic ANTIBODY that binds to FcRs on phagocytes. For example, IgE binds to FcE receptors on mast cells, triggering degranulation and immune repsonse. Fc helps with opsonization and degranulation, but is NOT needed for neutralization in Ig digestion
- Some pathogens can encode proteins that prevent this, allowing them to live bc their proteins block phagocytes from binding and digesting
- Fab region is variable
T-cell maturation steps
Recognized processed antigen (as peptide fragments)
- Thymocytes from marrow enter THYMUS via HEVs and undergo (+) selection in cortex (via cortical thymic epithelial cells, where they acquire a-B TCR and interact w/ thymus hormones), and (-) selection in medulla (via AIRE TF).
- Had a-B chain rearrangement. Cells were first DN cells, then DP cells (expressing both CD4 and 8), then expressed only one (cytotoxic or helper)
T-cell activation steps
- To become an active cell, T cell binds to self antigen,, and there’s co-stimulation of its CD28 to B7 (80 or 86) on an APC and sends signal to move on (B7 is off, but can become turned on under inflammatory state).
- Once active, undergoes CLONAL EXPANSION via IL-2 (but NOT somatic hypermutation–don’t need the affinity increased)
- Effector T-cell can become either Th1 or Th2
IgM
- Pentamer
- Strong avidity bc many sites for binding (good complement fixation)
- Activates classical complement path (along with IgG)
- First ab made in resp to pathogen
MHC I
MHC I:
- on all nucleated cells, trimer with 3 a-chains(???), binds short chain which fits in groove, genes are HLA-A/B/C, presents IC pathogen fragments to CD8 cell (IC means enters INSIDE cell, such as viruses)
- mech: in ER, calnexin and calreticulin chaperone prots fold chains and bind B2. MHC I binds TAP transport prot via tapasin enz, which peptide binds to and travels thru and binds MHC I, which now exits golgi to be recognized by CD8 cells at cell membrane
How HSV affects MHC I
HSV prevents its peptide from binding to TAP, so it cannot travel thru TAP to get to the ER, or memb, and remains undetected
