Immunity* Flashcards
Antigens - definition? epitope definition?
Definition:
- any substance capable of triggering an immune response
Epitope is the area of the antigen which the antibody attaches to (gives identity either self or non-self)
Physical barriers - skin definition? mucus (production? produced from? composition? immune characteristics?) self-tolerance definition?
Adaptive and Innate (no answer and cells?)
Skin:
- is a barrier between internal and external
Mucus:
- produced by goblet cells in the resp tract and transported by cilia
- consists of 95% water, 2% salts and 2% mucin and is sticky
- also contains antimicrobials such as growth inhib, enzyme inhib, lysins and abs
Self-tolerance:
- elim lympho which react with self antigens during early development to be destroyed
Non-specific humoral factors - growth inhibitors (function? examples? dependent?) enzyme inhibitors (function and example?) lysins (function and example?)
Growth inhibitors: - deprive microbes of nutrients for growth - Transferrin (bind iron) and Interferon (antiviral) - temp dependent Enzyme inhibitors: - prevent enzymes from doing their job - poison or drugs Lysins: - lysis - lysozyme and complement
Complement system - classical? alternative? lectin?
(describe each pathway) MAC?
Alternative pathway: - C3 clipped and forms C3a and C3b - C3b reactive (neutralised by H2) - C3b stabilised and binds to prot B - prot B clips B to form C3bBb - C3b can bind C3 convertase forming C3bBbC3b - C5 convertase Classical: - C1 formed from C1q/r/s - C1q binds Ab and C1r/s are proteases - bind to C1q; act of C1r and act of C1s - C1s cleaves C4 to C4a/b - C4 homologous to C3 - C2 binds to C4b forming C4b2b - C3 convertase - C3 bind to C3b2b making C4b2b3b - C4 convertase Lectin: sugar binding prot - triggered by Ab absence - needs plasma mannose-binding lectin - ficolins (similar to C1q) bind lectin assoc serine proteases (sim to C1r/s) and cleave C2/4 - then identical to classical MAC: membrane attack complex - C5 convertase clips C5 - C5 binds with C6/7/8/9 to form MAC - C9 pore and the rest the stalk - C5 converts C5 into C5a/b, but stays on cell surface - C7/8/9 bind in succession to C5b - C5b/6/7/8 and C9 form MAC
Membrane attack complex - safeguards for self cells? opsonisation? chemo-attactrants?
Safeguards: - decay acceleration factor (DAF) which accelerates breakdown the C3bBb - CD59 compete MAC before attachment Opsonisation: - C3b clipped by a serum prot to form iC3b - macrophages can bind to iC3b Chemoattractants: - C3a/C5a recruit macro and neutrophils - anaphylatoxins
Pathology defintion - understanding and provide basis?
The study of disease:
- understanding how they develop and progress
- provide basis for treatment selection
Understanding disease - key words?
Aetiology
Pathogenesis
Prognosis
Aetiology defintion?
Cause of disease:
- genetic and environmental factors
Pathogenesis defintion?
How an individual disease develops and progresses
Mechanisms of disease (inflamm, neoplasms and circulatory disorders)
Types of basic pathological mechanisms (inflamm? Neoplasia? Circulatory disorder?)
Inflamm: - acute - chronic Neoplasis: - benign - malignant Circulatory disorders: - thrombosis - embolism - infarction
Inflammation - acute vs chronic?
Acute: - neutrophils polymorph mediated - healing and repair - abscess formation Chronic: - lymphocyte - macro - plasma cells
Neoplasia - benign vs malignant?
No cancer
Cancer
Diagnostic pathology - what gives them info? Can aid to give a?
Macroscipic, microscopic and molecular examination of tissue samples
- biopsies
Clinco-pathological correlation
Professional phagocytes - types? function?
Types: - monocytes - macrophages - granulocytes - dendritic cells Function: - phagocytosis
Phagocytosis - process?
Process:
- engulfs the bacterium into a small vesicles called a phagosome
- phagosome fuses with a lysozyme to form a lysosome
- lysosome kills the bacterium
- also release debris
Macrophages - differentiate from? Differentiate into? Found in the? Travel to? Activation causes? 3 states of readiness?
From: - bone marrow stem cells Differentiate into: - monocytes then macrophages on the tissues Found: - in the tissues Travel: - into the capillaries and hang around waiting for pathogens Act: - chemicals released causing redness and swelling Readiness: - resting (low MHC 2 levels) - primed (higher MHC 2 levels) - APC (engulf pathogen)
Neutrophils - most abundant? Name derivative? Profession phagocyte? Life span? Fucntion? Not APC? Acute inflammation (follow what?)
Most: - WBC Name: - neutral pink Professional: - most important Life span: - 5 days Function: - phagocytosis but not APC Acute inflamm: - migrate towards site of inflamm via BVs CIA interstitial fluid, following trail of chemokines via chemotaxis
Natural killer cells - differentiate from? types of NK cells? Found where? Function and kill what? 2nd function (FasL?) Cell recognition? Activation of NK cells (given off by?) Cooperation (macrophages secretion? LPS? IL-12? IL-2?)
Diff:
- stem cells in BM
NK types:
- have diff properties
Found:
- blood and spleen
Function:
- kill tumour cells, virus infected cells bacteria, parasites and fungi
- form a MAC (secrete perforin)
2nd function:
- FasL interact with Fas in target cell connectiong and causing the cell to die
Cell recog:
- activation and inhibition receptors
- inhibotry receptor recognises MHC I, found on all human cells
- activated of the target cell doesn’t express MHC I
Activation:
- IFNa/b givej off by cells under viral attack
- secrete IFN-y
Cooperation:
- LPS creates hyperact of Macro
- macrophages produce IL-12 and TNF to increase IFN-y secretion to increase activation
- NK produce IL-2 (GF) and Macro induce receptor on NK
Inflammaptey response - defintion? Acute vs chronic?
Def:
- battle that macrophages, neutrophils and other immune systems wage against invader
Acute:
- initial response of body to harmful stimuli
Chronic:
- progressive shift in type of cells at inflamm site characterised by simultaneous destruction and healing of tissue from inflamm process
Adaptive immunity - defintion? recognition of antigens (B and T lymphocytes recog specific epitopes?)
Def:
- specific and immunological memory
Recognition:
- B and T lymphocytes
- B cells recog free organic antigen via BCR (surface IgM)
- T cells need to be shown antigen with MHC via TCR
T lymphocytes - Name? Function? Types? CD4 (functions?) CD8?
Name: - thymus derived T cell Function: - CD4 stimulate B cell to produce antibodies - CD8 are cytotoxic CD4: - activate other immune cells - B cell ab class switch - activation and growth of Tc CD8: - exposed to infected cell release perforin forming a proe and release granzyme B and induce apoptosis
Function of MHC I and II - found on? presents what (act which response)?
Found on:
- MHC I; all nucleated cells
- MHC II; all APCs
Present:
- MHC I; present virally induced peptides to CD8 T cells and trigger cytotoxic response
- MHC II; present Ag to CD4 T cells and activate macro and B cells
T cell selection - basis? positive? negative selection? Clonal expansion process? T cell memory?
Basis:
- must learn to not recognise self antigens
Positive:
- thymocyte undergoes TCR gene rearrangement
- positive selection of receptors for MHC (CD3/4/8)
- forming CD4 and CD8
Negative:
- death of cells with high affinity for self antigens
Process:
- immature T cell binds to an APC forming CD4 abd CD8
- CD4 can activate B cells or activate more macrophages
Memory:
- from fully differentiated T cells
B cells and antibodies - cell type? production of? b cells express? Tolerance?
Type: - from BM and mature into plasma cells Production: - for abs production B cells: - express sIg on the B cell Tolerance: - tolerise T cell than B cell because B cells can't produce abs without T cell help
Antibody structure - 2 parts? light chain types? heavy chain (function? regions? 5 types of heavy?) flexibility?
2 parts: - ag binding region (Fab) - fc region Chains: - light; lambda and kappa - heavy; define Ig, constant region (same for all Ig class) and a variable region (differ between B) - gamma, delta, alpha, u and backwards 3 Flexibility: - hinge region allows flexibility
Antibody classes - IgM? IgG? IgA? IgE? IgD? - (function of each?)
IgM: - fixing complement and opsonisation IgG: - opsonisation IgA: - protect mucosal surface and resistant to stomach acid IgE: - defends against parasites causes anaphylactic shock and allergies IgD: - naive B cell antigen recep
Functions of abs - neutralisation? opsonisation? complement activation?
Neutralisation:
- abs neutralise the biological effects of the antigen (stop antigen binding)
Opsonisation:
- chemically modified to have stronger interactions with cell surface receptors on phagocytes and NK cells (C3d bind to pathogen act B cell)
Anaphylactic shock - cell type? express recep? allergic act? release of?
Cell:
- mast cell
Express recep:
- IgE
Act:
- inactive until an allergen binds to IgE
- binding of 2 or more IgE required to act mast cell
- clustering of the IgE causes a complex sequence of reactions (release of histamine and heparin)
Immunological memory - secondary response features? why it occurs? memory B better?
2nd response:
- rapid
- larger and often qualitatively different
Why:
- each exposure causes an expansion in the clone of lymphocytes and differentiate to memory cells
B:
- memory B cells produce abs but with higher affinity than naive and rapid
Active and passive immunity definitions? subtypes of active and passive (natural and artificial?)
Active: - conferred by a host response to a pathogen Passive: - conferred by adoptive transfer of abs or T lymphocytes specific for the pathogen Natural active: - during infection Artificial active: - injection or orally (long lasting immunity) Natural passive: - mother to child Artificial passive: - abs given for a fatal disease Passive: - memory cells only temp
Autoimmunity - definition? treatment? theories (clonal deletion? clonal anergy? idiotype network/)
Def:
- triggered to attach the tissues of the host
Treat:
- immunosuppression
Clonal deletion:
- self-reactive lymphoid cells destroyed during development of immune system
Clonal anergy:
- self-reactive T/B cells become inactivated in normal individuals
Idiotype network:
- network of bas capable of neutralizing self reactive abs naturally within the body
Vaccinations - inactivated? acellular? attenuated? subunit? DNA? (definitions?)
Inactivated: - pathogen particle destroyed and can't divide but can be recognised and evoke immunity Acellular: - cellular material with antigenic parts Attenuated: - reducing pathogen virulence Subunit: - part of virus DNA: - injecting genetically engineered DNA
Functions of the lymphatic system?
Drainage of tissues
Absorption and transport of FAs and Fats
Immunity
Lymphatic vessels - lymph formation? movement of lymph (intrinsic and extrinsic)? external route drainage (organs?) intrinsic route drainage (organs?)
Form: - when interstitial fluid from the blood enters the initial lymphatic vessels Move: - moves along vessels by intrinsic contractions of lymphatic passages or extrinsic compression of vessels by external tissue force External: - head, limbs and body cavity walls Internal: - thorax, abdomen and pelvic cavities
Oedema - definition? clinical signs?
CS:
- abnormal accumulation of fluid in interstitium
- severe pain
- swelling
Spleen - red pulp? white pulp? function? lymphoid follicles (content? germinal centres function? release in response?)
Red:
- CT known as cords of Billroth
White:
- contain lymphocytes
Function:
- filter blood of antigens, microorganisms and defective/old RBCs
Follicle:
- white pulp contains plasma cells, lymphocytes and lymphatic nodules called follicles
- germinal centres are sites of lymphocyte production
- releases macrophages in response to foreign antigen
High endothelial venules - definition? found where? function? lymph nodes definition (source?
Def:
- specialised post-cap venous swelling characterised by plump endo cells
Found:
- all secondary lymphoid organs (except spleen)
Function:
- enable lymphocytes circulating in the blood to enter directly to a lymph node (addressins)
Lymph:
- consists of an outer cortical and inner medullary par
- source of lymphocytes
Peyer’s Patch - found? function? role mucosally?
Found:
- lowest portion of SI and distal jejunum and ileum
Function:
- facilitate generation of response within mucosa
Role:
- pathogens enter intestinal tract encounter immune cells
Tonsils - definition? infection?
Def:
- areas of lymphoid tissue in throat involved in defence from infection of upper resp tract
Infect:
- asymmetrical tonsils can indicate problems
Lymphocyte trafficking - definition? cellular adhesion molecules of T cells?
Def:
- process of lymphocytes getting into secondary lymphoid organs
Cellular:
- L-selectin binds GlyCAM-1 on HEV of lymph
- a4b7 binds MADCAM-1 on HEV Peyer’s patches and lymph nodes
Primary lymphoid organs - function? examples?
Function:
- places where blood cells are produced and receive their training
Examples:
- BM and thymus
Thymus - description? content?
Description:
- bi-lobed organ and site of T cell maturation
- divided into outer cortex and inner medulla and contrian stromal thymic epith cells
Lymphatic system and cancerous cells - spread? cancer of lymphatics? types of lymphatic cancers? Lymphangitis (what is it?)
Spread: - via the lymphatic system causing metastasis Cancer: - lymphoma Types: - thymus - multiple myeloma (BM) - leukemia (BM) - tonsillar - adenoidal Lymphangitis: - infection of lymph vessel walls - acute pyogenic infection - inflammation
Acute inflammation - definition? stimuli causing inflammation (physical? irritant? infection? immune? tissue necrosis?) Cardinal signs of inflamm?
Def: - immediate and early response to injury undergoing a series of protective changes occurring in living tissue Stimuli: - physical such as heat and cold - irritant via chemical - infection via bacteria, virus or fungi - immune such as allergy - tissue necrosis via ischemia Signs: - heat - redness - swelling - pain - loss of function
Acute inflammation - pathogenesis (stimuli? changes in vessels? blood cells?) chemical mediators (complement function? kininis function? other examples? collective effect?)
Patho:
- chemically initiated
- changes in vessel radius and vessel wall permeability (flow and exudation)
- movement of neutrophils from vessel to extravasc space
Mediators:
- complement act MAC
- kinins (vasoactive increase pain)
- prostaglandins, arachidonic acid and leukotrienes?
- platelet act factor
- cytokines
- vasodil, chemotaxis, increased permeability, neutrophil adhesion + itch and pain
- acute phase proteins
Acute inflammation - vascular changes (flow? permeability? endo cells?)
Flow:
- transient vasoconstriction
- arteriolar vasodilation
- neutrophils (VIP)
- blood flow slows losing laminar flow causing red cell aggregation and so neutrophils found near endo
Permeability:
- movement of plasma (transudate)
- movement of protein-rich fluid (exudate)
- thicker blood and stasis
- gaps between cells
Endo cells:
- contraction in response to histamine, bradykinin and leukotrienes
- retraction in response to TNF and IL-1 (lasts longer)
Acute inflammation - extravasation of leukocytes (margination and rolling -sticking?) (adhesion and transmigration - adh molecules? integrins? diapedesis? platelet adhesion mol? degrad of BM?) chemotaxis and activation (migration to injury? induces?)
Margination and rolling: - leukocyte accumulation at periphery - interact with endo - stick via E/L/P-selectin (upregulated by TNF and IL-1) Adhesion and transmigration: - ICAM and VCAM mol (induced by TNF and IL-1) - integrins act leukocytes with high affinity binding after conformational change - diapedesis via intercellular spaces - PECAM-1 (CD-31) (platelet adh) - degrad via collagenases Chemotaxis and activation: - exo/endo attractants - bacteria - complement system (C5a) - leukotriene B4 and IL-8
Cyclooxygenase and inflammation - process?
- Phospholipids converted to arachidonic acid via PLA2 (PLA2 activated y thrombin, complement, bradykinin and abs)
- Arachidonic acid converted to either leukotrienes by lipoxygenase or prostaglandins via cyclooxygenase
- Prostaglandins are converted to prostacyclin via prostacyclin synthase via endothelium or into thromboxane A2 via thromboxane A synthase via platelets
Painkillers - NSAIDs (mechanism of action? action?) Paracetamol (MoA? action?) Opioids (examples? MoA? action?) Nerve block (example? MoA? action? use?)
MoA: - inhibit COX pathway - reduce prostaglandin level and inflammation Paracetamol: - inhibit COX2, poor affinity at inflamm site, reduces PGE2 - metabolite inhibits anadamide uptake (cannabinoid pathway) - blocks Na chs Opioids: - natural (morphine) - semisynth (oxycodone) - synth (fentanyl) - act via endog path but don't alter inflamm directly Nerve block: - lignocaine - Na ch blocker - prevents AP
Neutrophils - functions (phagocytosis? degranulation? consequences?)
Phago; - recog antigen - move towards via chemotaxis - adhere to organism (opsonins) Degranulation: - posses oxidants (H202) and enzymes (proteases) Consequences: - neutrophils die after degranulation - progresses the inflammation
Plasma proteins - examples and function?
Examples:
- fibrinogen a coag factor forms fibrin and clots exudate (localises inflamm)
- Ig specific to antigen (humoral)
Resolution of acute inflamm - process (agent? epith? blood cells? vasc) benefits of acute inflamm (area? plasma prots? speed?) outcomes of acute inflammation (why?)
Process: - agent destroyed - macrophages phagocytose and leave - epith regenerate - inflamm exudate filters away - vasc return to normal Benefits: - rapid response - transient protection of area - agent destroyed - plasma prots localise process - resolve quickly Outcomes: - resolve - abscess (excess exudate) - organisation (excess necrosis) - advance to chronic inflamm (agent remains)
Chronic inflammation - definition? primary chronic inflammation (causes?)
Def:
- inflammation of prolonged duration in which active, tissue destruction and attempts at repair are proceeding simultaneously
Primary:
- resistance of agent to phagocytosis (TB)
- endog (hair)/exog (prosthesis) materials
- autoimmune (RA)
- diseases of unknown aetiology (ulcerative colitis)
- granulomatous diseases (Crohn’s)
- acute progression (osteomyelitis)
- recurrent acute episodes (chronic cholecystitis)
Chronic inflammation histology - macroscopic and microscopic appearances
Macroscopic appearances: - chronic ulcers - chronic abscess cavity - thickening of wall of hollow viscus - granulomatous inflammation - fibrosis Microscopic: - cellular infiltrate (lympho, plasma, macro and eosino) - multinucleated giant cells - prod of fibrous tissue - continued destruction
Macrophages - migration? activation? cell size and secretion? action (fibrosis and tissue injury)?
Mig:
- monocytes migrate into extravascular tissue in early acute inflamm
Act:
- by IFN-y (from T cell), endotoxins and chemical mediators
Cell:
- increased size and lysosomal enzyme release
Action:
- fibrosis (GF and angiogenesis)
- tissue injury (proteases, coag factors and NO)
Lymphocytes - T? B?
Plasma cell - from? function?
Eosinophils - mediated by? secrete? Mast - secrete and produce? neutrophil - type of cell?
T : - cell mediated immunity - act macrophages B: - abs prod Plasma: - diff B - abs Eosinophil: - mediated by IgE and parasites - release TGF, VEGF and PDGF Mast: - release histamine and produce arachidonic acid oxidation Neutrophils: - phagocyte
Inflammatory cascade by activation of (factors)?
Kinin Coagulation Complement Fibrinolytic system Leukocyte mediators Uric acid
Granulomatous inflammation - what is it? characterised by? examples (infectious and noninfectious)?
Granulomas - what are they? content?
Immune granulomas - what is it? immune response process?
Granulomatous inflammation:
What:
- distinctive pattern of chronic inflammation
Characterised by:
- focal accumulation of activated macrophages which often develop epith-like pattern
- TB and syphilis (infectious)
- RA, Crohn’s and sarcoidosis (non-infect)
Granuloma:
- large vesicular nuc, folded nuc mem, plentiful eosino granular cytoplasms and indistinct cell borders
- more secretory
Immune granulomas:
- insol particle induce cell mediated immune response
- macro enguld, process and present to T
- T lymph produce IL-2 act other T and IFN-y act macro
Giant cell - what is it? formation?
Foreign body - what is it? centre?
Langhans’ giant cell - found? appearance (nuc)? cytoplasm type?
Giant cell: What: - form whe foreign particles are too large to be ingested by 1 macro Form: - fusion of macrophages (multi nuc) Foreign body: - too big to be digested by 1 macro - foreign material at centre Langhan's giant: - found in TB - peripheral nuc rim - eosinophilic cyto
Oral manifestation of -sarcoidosis? Crohn’s? pyogenic granulomata?
Sarcoidosis - are multinodular painless ulcers of mucosa, labial mucosa and palate Crohn's: - angioedema - mucogingivitis - cheilitis - glossitis - aphthous ulcers - pyostomatitis Pyogenic: - caused by irritation, trauma, hormones or poor hygiene - ulcerated and bleeds readily
Organisation (healing and repair) - what occurs?
Organisation: - specialised tissue repair - mature fibrovasc CT - dead tissue removed by phago - granulation tissue contracts, accumulates collagen Causing remodelling and scar formation
Products of granulation tissue - scar? fibrosis problem?
Scar: - fibrous tissue Fibrosis: - can cause further disease Ongoing process of chronic inflammation
Wound healing - sequence of events? factors which influence wound healing (impairing and favouring?
Callus formation process (osteo stim? new bone? remodel?)
Sequence: - injury, clot, acute inflamm, fibrin - granulation tissue growth (angiogen) - phago of fibrin - myofibroblasts move in and lay down Col - contraction of scar - re-epith Impairing: - age - diabetes - poor nutrition and cleanliness - location - abnormal cholesterol meta Favouring: - clean - nutrition - normal mechanisms Callus formation: - granulation tissue stims osteoblastic and osteoclastic - osteoblasts lay woven bone - remodelling as osteoclasts remove dead bone, woven replaced by lamellar and reforming cortical and trabecular bone
Differences between acute and chronic?
Acute: - rapid - cardinal signs - neutrophils - vasc damage - more exudate - little fibrosis Chronic: - slower and prolonged - low cardinal signs - lymphocytes - neovasc - less exudate - high fibrosis
Definition of inflammation?
A localised, protective response to injury or infection, characterised by pain, heat, swelling, redness and loss of function and which is mediated primarily by cells present in the bloodstream
Purpose of inflammation?
Protection
Increase blood flow to site allowing increased defence cells to site
Substances secreted during inflammation - cytokines (definition and examples)? prostanoids (definitions and examples)? NO? bradykinin? histamine?
Cytokines:
- released from cells assoc with immune system that exhibit autocrine/paracrine activity (IL, chemokines, tumour necrosis factor)
Prostanoids:
- substances produced via action of COX (prostaglandins, prostacyclins and TXA2)
NO
Bradykinin
Histamine
Acute inflammation - primary and secondary response overview (secretion type?)
Primary response: - paracrine - assoc with response of local BVs Secondary response - autocrine - assoc with intracell response of cells involved in inflamm response
Primary inflammatory response - primary role? cytokines? cell secretion? actions (vasodil? permeability? cascade? adhesion?)
Primary role:
- specific, local vascular response to IL-1 and TNFa released from active neutrophils and macrophages
Actions:
- vasodilation of precapillary arterioles
- increased permeability of post-cap venule (clotting, fibrinolytic, kinin and complement cascades activated)
- Increased cell adhesion to endothelial wall
Secondary inflammatory response - primary role? cytokines? signalling pathways? NF-kB inhibition?
Primary role: - downstream, molecular effects of TNFa and IL-1 response Signalling pathways: - stimulated to activation of transcription factor NF-kB (COX2 and iNOS) NF-kB: - inhibited by IkB - on IL-1 and TNFa binding releases IkB - allowing NF-kB to be transcribed
Cyclooxygenase pathway for inflammation - phospholipids? arachidonic acid? leukotrienes? prostaglandins? prostacyclin? TXA2?
Pathway:
- phospholipid converted into arachidonic acid by PLA2 (act by bradykinin and thrombin)
- arachidonic acid converted to leukotrienes by lipoxygenase
- arachidonic acid converted to prostaglandins by COX
- prostaglandins converted into prostacyclins by prostacyclin synthase (secreted by endothelium)
- prostaglandin can also be converted into thromboxane A2 via thromboxane a synthase (from platelets)
COX isoforms - COX1? COX2 induced by? found where? COX3? COX2 products causing inflammation?
COX1: - constitutive COX2: - inducible - induced by IL-1 and TNFa COX3: - paracetamol target COX2 products: - prostanoids (PG and TXA2) - GPCR - pro-inflammatory (vasodil, hyperalgesia and reduced platelet aggregation) - directly on precapillary arteriole, post-cap venule and indirectly on C fibres
Process of fever - stimulus? pathway?
Stimulus:
- toxins released by cateria activate macrophages (IL-1)
Pathway:
- IL-1 activates COX2 converting arachidonic acid forming PGE2 causing a reset on the body thermostat
Inhibition of COX - glucocorticoids (functions? endogenous and synthetic forms? binding? PLA2?
Glucocorticoids:
- regulate glucose meta and potent anti-inflamm
- endog: cortisol/hydrocortisone and prednisolone
- synthetic: dexamethasone and betamethasone
Binding:
- intracellular receptor change gene expression
- inhibit NF-kB transcription
- block IL-1 and TNFa coding
PLA2:
- activate macrophages to release more annexin which inhibits PLA2
NSAIDs - function? side effects?
Function: - inhibit COX directly - inhibit prostaglandin synthesis Side: - anti-pyrogenic
iNOS and NO - NF-kB? expressed by? function? treatment?
NF-kB: - increased expression Expressed: - by cells in response to inflammatory response Function: - vasodilation - increased vasc permeability - increased production pro-inflamm prostanoids - inhib of platelet aggregation - cytotoxic Treatment: - iNOS inhibitors
Bradykinin - function? isoforms? byproduct of? pathway?
Function:
- potent pain producing agent (sensities nociceptive fibres)
Isoforms:
- B1 (inducible) and B2 (constitutive)
Byproduct:
- of clotting cascade
Pathway:
- Factor XIIa converts prekallikrein into kallikrein
- HMW-kininogen converted by kallikrein into bradykinin
Histamine - stored in? stimulated release? different isoforms and functions?
Stored in;
- found in granules of mast and basophils
Stimulated:
- by inflammatory stimuli and complement proteins
- released by exocytosis
Isoforms:
- H1 contract SM but relax vasc SM causing vasodil and itching
- H2: gastric acid secretion
- H3: plasticity in CNS
Why does inflammation occur - what’s it trying to achieve?
Process:
- increased BF and vessel perm
- increases defence cells
- increased phago potential and lymphocytic activity
- eliminating the pathogen
Outcomes of inflammation - successful and unsuccessful?
Successful:
- removal of pathogen, heal/repair and return to health
Unsuccessful:
- chronic inflamm
