• Liquifactive (destruction of cell structure)
• Coagulative (maintanence of cell structure)
• Caseous (amorphous granular debris)
• Fat necrosis (fatty debris as in acute pancreatiti)

Process of diapedesis 

(stages, important molecules/signalling factors)

• Margination -  venule low-flow causes the margination of leukocytes and therefore rolling adhesion (vasoactive compounds - PAF via GPCRs, histamine via H₁, bradykinin)
• Leukocyte rolling adhesion through epithelial expression of P selectin (histamine or thrombin mediated release from Weibel-Palade bodies), E-selectin (upregulated by TNF-α, IL-1, LPS) and L-selectin counter ligands (GlyCam-1, CD34, CD44) and leukocyte expression of L-selectin and P-selectin counter ligands (Sialyl Lewis X)
• Leukocyte activation and tight adhesion - GPCR mediated (chemokines, C5a, fMLP, PAF) activates integrin expression to interact with endothelial ICAM-1
• Diapedesis mediated by PECAM-1 (CD31) homophilic interactions

Opsonising agents

(Classes and molecules)

• Antibodies (Fc phagocyte binding)
• Complement - C3b, C4b and C1q to interact with complement receptor 1 and C1q interaction with Fc region of antibodies
• Circulating proteins - pentraxins, collectins, ficolins - secreted pattern recognition receptors that coat microbes to increase neutrophil reactivity

Neutrophil granule killing mechanisms 

(Granule types and proteins)

• Azurophilic granules (primary) - myeloperoxidase (cytotoxic), bactericidal/permeability increasing protein, defensins, serine proteases, neutrohil elastase, cathespin G
• Specific granules (secondary)- alkaline phosphatase, lysozyme, NADPH oxidase (respiratory burst - generation of superoxide anion and reactive oxygen species) collagenase, lactoferrin, histaminase, cathelicidin
• Tertiary granules - Cathepsin, gelatinase, collagenase

Receptor type and activation of macrophages

(receptor types and recognition molecules)

• Scavenger receptors - internalisation of modified self proteins and pathogens (recognise LPS, E. Coli, diacylated lipopeptide, S. aureus as well SR-A recognising polyanionic ligands such as modified LDL gram negative and positive bacteria, asbestos, silica, AGE-modified proteins)
• Lectins - proteins that recognise specific sugar residues (Dectin-1 recognises β-gylcan and facilitates uptake and TNF-α secretion, complement receptor 3, mannose receptors)
• TLRs - activate transcription factor NF-κB by Myd88 and IRAK4 signalling amd thus secretion of TNF-α, Il-1, IL-6   (TLR1:2 recognises lipopeptides and GPI, TLR4:4 recognises LPS, TLR5 recognises flagellin, TLR7/8 = ssRNA etc.)
• Opsonin receptors
• Activation by pro-inflammatory inflammatory compounds - Endotoxin, IFN-γ, Il-4, IL-13, TNF-α, IL-1, IL-6, IL-10, IL-12

Macrophage killing mechanisms

(phagosome contents)

• Oxygen dependent degradation through NADPH and production of ROS. Hydrogen peroxide and myeloperoxidase activate halogenating system to create hypochlorite 
• Oxygen independent systems through secretion of defensins, lysozyme, lactoferrin (sequestration of iron)
• inducable nitric oxide synthase produces on stimilation by IL-1, TNF-α and INF-γ to produce NO to react with superoxide to form cytotoxic peroxynitrite

Complement cascade

(classical, alternative and lectin)

• Classical cascade - C1q binding to paired IgM or IgG, production of c1s esterase to cleave c4 and c2 into c4a/b and c2a/b. C4b2b acts as a C3 convertase, while C2a is an anaphylatoxin. C3 convertase can cleave C3 into C3a and C3b. C3b binds to the surface of the pathogen and binds C4a to form C5 convertase. C5 is cleaved into C5a and C5b. This facilitates the formation of the C5b-9 complex, or MAC.
• Alternative complement pathway - spontaneous hydrolysis of C3 to form C3(H₂O) which allows binding of Factor B and in turn allowing Factor D to cleave B into Ba and Bb. Bb forms C3(H₂O)Bb, or fluid phase C3 convertase which can cleave C3 into C3b and C3a. C3(H₂O)Bb is stabilised by the binding of properdin, forming C3bBbP, which in turn can bind an additional C3b to form the C5-convertase (C3b)₂BbP to form MAC. 
• Lectin pathway - MBL forms complex with MASP1/2/3 which are similar to C1r and C1s molecules. These proteins cleave C4 and C2 to form C4a/b and C2a/b, forming the C3 convertase C4b2b

CSFs overview

(name - producer; target; function)

• G-CSF - endothelium, macrophages; neutrophil progenitor cells; growth and differentiation of neutrophils
• GM-CSF - Th cells; progenitor cells; growth and differentiation of monocytes and dendritic cells
• M-CSF - thymic epithelial cells, PMNs, chondrocytes, glomerular mesangial cells, Ishikawa cells; macrophage lineage; growth and differentiation of monocytes, enhance expression of differentiation-antigens and stimulation of chemotactic, phagocytic and cytotoxic activities of monocytes

interleukins overview

(name - producer; target; function)

• IL-1 (pro-inflammatory) - monocytes, macrophages, B cells, dendritic cells; Th cells, B cells, BK cells, others; Th cell costimulation, B cell maturation and proliferation, NK activation and various inflammation, acute phase response and fever functions
• IL-2 (haematopoietin) - Th1 cells; activated T cells, B cells and NK cells; cell growth, proliferation, activation and synthesis of antibodies
• IL-3 (multi-CSF, haematopoietin) - Th cells and Nk cells; stem cells and mast cells; stem cell growth and differentiation, mast cell growth and histamine release
• Il-4 (haematopoietin) - Th2 cells; activated B cells, macrophages, T cells; B cell proliferation, differentiation and IgG and IgE synthesis, macrophage MHC II expression, T cell proliferation
• IL-5 (haematopoietin) - Th2 cells; activated B cells; proliferation and differentiation, IgA synthesis
• Il-6 (haematopoietin, pro-inflammatory) - monocytes, macrophages, Th2 cells, stromal cells; activated B cells, T cells, stem cells, various, neurons & osteoblasts; B cell differentiation to plasma cells, T cell costimulation, stem cell differentiation, acute phase response, neuronal differentiation and bone loss
• IL-7 - marrow and thymus stroma; stem cell; differentiation into progenitor B and T cells
• IL-8 - macrophages and endothelial cells; neutrophils; chemotaxis
• IL-12 - macrophages and B cells; activated Tc cells and NK cells; Tc cell differentiation to CTLs and NK cell activation

interferon overview

(name - producer; target; function)

• IFN-α/β - leukocytes and fibroblasts respectively; various; viral replication MHC-1 expression
• IFN-γ - Th1 cells, Tc cells, NK cells; various, macrophages, activated B cells, Th2 cells, macrophages; viral replication, macrophage MHC expression, Ig class switch to IgG_2a in B cells, Th2 cell proliferation, macrophage pathogen elimination

TGF/TNF overview

(name - producer; target; function)

• TGF-β - T cells and monocytes; monocytes, macrophages, activated macrophages, activated B cells, various; monocyte/macrophage chemotaxis, activated macrophage IL-1 synthesis, activated B cell IgA synthesis, various cell proliferation
• TNF-α - macrophages, mast cells, NK cells; macrophages, tumour cells; macrophage CAM and cytokine expression, tumour cell death
• TNF-β - Th1 and Tc cells; phagocytes and B cells, tumour cells; phagocytosis, activation of effector B cells and phagocytes to infection, leukocyte adhesion to endothelial cells, peripheral lymphoid organogenesis, stimulation of B cells, cell death in tumour through inhibition of angiogenesis

Complement control proteins

• Complement receptor 1 - main system for the processing and clearance of opsonised immune complexes - regulator regulator of the complement cascade, mediation of immune adherence and phagocytosis, as well a suppression of complement pathways
• Membrane co-factor (CD48) - cofactor for cleavage of C4b by serum factor I to prevent host cell damage 
• C4b binding protein inhibits classical and lectin pathway by accelerating the decay of C3-convertase and is a cofactor for serine protease factor I which cleaves C4b and C3b. Also binds apoptotic and necrotic cells and DNA to clear damage after infection
• Decay accelerating factor (CD55) recognises C4b (classic and lectin) and C3b (alternative) fragments - interferes with conversion of C2 and therefore the formation of the C4b2b convertase, while interaction with C3b in alternative pathway prevents cleavage of B to Bb by factor D.
• Factor H - cofactor for factor I and thus cleavage of C3b, as well as accelerating decay of C3-convertase from alternative pathway
• Factor I cleaves C3b and C4b to inactivate the complement cascade
• C1 inhibitor - acute phase protein which irreversibly binds and inactivates C1r and C1s proteases as well as MASP-1/2

• IL-4 - recruitment of macrophages and activation to M2 (repair and healing), as opposed to M1, coupled with secretion of IL-10 and TGF-β to reduce pathological inflammation. Triggers release of arginases, proline and polyaminases by M2 cells to increase wound repair and fibrosis
• IL-10 - suppression of cytokine secretion, antigen presentation and CD4+ T cell activation. Inhibits LPS and bacterial product mediated indiction of proinflammatory cytokines
• IL-13 - Involved in the induction of airway disease. Anti-inflammatory propertes similar effects to IL-4, but thought to be more central mediator. Induces matrix metalloproteinases to allow clearance of dead inflammatory cellsm especially from the airway lumen.
• TGF-β - induction of Tregs (Foxp3) and pro-inflammatory Th17. Without TGF-β, Teg differentiaion is inhibited. B lymphocytes proliferation inhibited by induction of CDK inhibitor 21 and suppression of c-myc and ATM genes. Induction of apoptosis of immature or resting B cells. Stimulation of resting monocytes and inhibition of active macrophages - downregulation of inflammatory cytokine production in monocytes and macrophages through the inhibition of NF-κB

Serpins

(function & examples)

• Inhibition of proteolytic cascade (antithrombin) and the inflammatory and immune response (antitrypsin, antchymotrypsin, C1 inhibitor)
• Prevention of excess clotting, as well as damage of host cells through release of degredation enzymes by neutrophils and macrophages

Cytokines in chronic inflammation

(names and functions)

• IFN-γ released by Th1 cells to activate macrophages in mycobacterial infections attempts to overcome phagolysosome maturation. This allows presentation of killed bacteria to Th1 cells, and further activation and release of IFN-γ. Macrophages in this cycle are stimulated to produce IL-1, which recruits further macrophages. In pathological disease, this process is amplified and the macrophages and Th1 cells form a granuloma, with the macrophages walling off the Th1 cells by differentiating into fibroblast-like cells
• TNF-α produced by macrophages - increased macrophage recruitment and inflammatory cytokine release mediates cycle of chronic inflammation through much the same mechanism

Roles of molecules in repair regulation

(names and functions of cytokines and fibrinolysing agents)

• PDGF - required element in the cellular division of fibroblasts - facilitate movement past G₁ checkpoints and thus allowing division. In wound repair, this allows the extracellular matrix formation and collagen formation 
• TGF-β and FGF-7/10 also implicated in the regulation of fibroblasts
• Endothelial migration through fibronectin and proliferation through VEGF and TGF-α
• Fibrinolysis - plasminogen converted to plasmin by activators (tPA from endothelial cells and uPA from macrophages and PMNs)