2-Inflammation

Which mediators are primarily responsible for the pain (dolor) in acute inflammation?

Bradykinin, PGE2, Substance P – These sensitize sensory nerves and increase pain perception.

What causes heat (calor) during inflammation, and which mediators are involved?

Histamine, Bradykinin, PGs – These vasodilators increase blood flow, causing localized warmth.

Which mediators contribute to redness (rubor) in inflammation?

Histamine, Bradykinin, PGs – Redness results from increased blood flow via vasodilation.

What is the primary mediator of swelling (tumor) in inflammation?

Histamine – Histamine increases vascular permeability, leading to edema.

How does inflammation cause loss of function (functio laesa)?

Pain and tissue damage – Both limit normal use of affected tissue.

What molecular patterns are recognized during infections to trigger inflammation?

PAMPs (Pathogen-Associated Molecular Patterns) – Recognized by innate immune receptors like TLRs.

Which molecules signal tissue necrosis and initiate inflammation?

DAMPs (Damage-Associated Molecular Patterns) – Released by dying cells to trigger a response.

How do foreign bodies (e.g., talc, sutures) cause inflammation?

By acting as non-self objects that stimulate immune cells – They physically disrupt tissues and trigger a response.

What causes inflammation in immune reactions/hypersensitivity?

Self-antigens and allergens – The immune system mistakenly targets these as threats.

What do PAMPs and DAMPs activate?

TLRs, NLRs, Mannose-binding lectin, Fc and complement receptors – These receptors detect danger and initiate inflammation.

What cytokines and factors are produced as a result of these activations?

IL-1, TNF, adhesion molecules, inflammasome activation – These propagate the inflammatory response.

Which mediators cause early vasodilation?

Histamine, PGs, NO – These expand blood vessels, increasing blood flow.

What causes increased vascular permeability?

Histamine, Bradykinin, C5a, LTB4, NO, Substance P – These disrupt endothelial junctions, allowing fluid to leak out.

What is the difference between exudate and transudate?

Exudate = high protein, inflammatory; Transudate = low protein, pressure-driven – Exudate indicates inflammation; transudate does not.

What type of pericarditis is associated with a “shaggy” pericardium and friction rub?

Fibrinous pericarditis – Caused by fibrin-rich exudate in the pericardial space.

What mediates margination and rolling of leukocytes?

Selectins (E, P) – These slow leukocytes along the endothelium.

What mediates firm adhesion of leukocytes?

Integrins – These bind tightly to endothelial ICAMs.

What molecule is responsible for transmigration (diapedesis)?

PECAM-1 – Guides leukocytes through endothelial gaps.

Name chemotactic factors for leukocyte migration.

C5a, LTB4, fMLF, IL-8, Histamine, PAF – These guide leukocytes toward the injury site.

Which cells are primarily involved in phagocytosis?

Neutrophils and Macrophages – These ingest and destroy pathogens.

Name three opsonins that enhance phagocytosis.

C3b, IgG, Mannose-binding lectin – These tag microbes for easier recognition.

What reactive species are used to kill engulfed pathogens?

ROS, HOCl, ˙OH, NO, Peroxynitrite (OONO˙) – These are toxic to microbes inside phagosomes.

What are NETs?

Neutrophil Extracellular Traps – DNA webs that trap microbes extracellularly.

What changes are seen in activated neutrophils?

Dohle bodies, cytoplasmic vacuoles, toxic granulation – Indicate high activation state.

What defect occurs in Chronic Granulomatous Disease (CGD)?

↓ NADPH oxidase → ↑ catalase+ infections – Can't make ROS to kill microbes.

What are the features of Chediak-Higashi Syndrome?

Giant granules, albinism, neutropenia – Lysosomal trafficking defect.

What deficiency leads to decreased HOCl and ↑ Candida infections in diabetics?

Myeloperoxidase deficiency – MPO is needed to convert H2O2 to HOCl.

What does histamine do?

Early increase in permeability and vasodilation – Released by mast cells.

Which mediators cause pain and permeability?

Bradykinin, Substance P – Act on nerve endings and vessels.

Which mediator causes fever and vasodilation?

Prostaglandins – Act on the hypothalamus and blood vessels.

What do leukotrienes do?

Mediate chemotaxis – Recruit neutrophils to inflammation.

What do lipoxins do?

Anti-inflammatory effects – Help resolve inflammation.

What cytokines cause systemic signs of inflammation?

TNF-α, IL-1, IL-6 – Fever, acute-phase reactants, etc.

What do NSAIDs inhibit?

COX → ↓ PG and TxA2 – Reduce pain, fever, and inflammation.

What does zileuton inhibit?

5-LO (lipoxygenase) – Blocks leukotriene synthesis.

What is the action of montelukast?

Leukotriene receptor blocker – Prevents leukotriene-mediated effects.

What are the three complement pathways?

Classical, Alternative, Lectin – Different activation triggers but converge on C3.

What is the critical step in complement activation?

C3 → C3a + C3b – C3b = opsonin, C3a = anaphylatoxin.

What do C3a and C5a do?

Anaphylatoxins → mast cell histamine release – Promote inflammation.

What does C3b do?

Acts as an opsonin – Enhances phagocytosis.

What is the function of the MAC?

Cell lysis (especially Neisseria) – Forms membrane pores.

What disorder is caused by C1-INH deficiency?

Hereditary angioedema – Unchecked complement activation.

What disorder is caused by DAF/CD59 deficiency?

Paroxysmal nocturnal hemoglobinuria (PNH) – RBC lysis due to complement.

What type of inflammation is characterized by cell-poor fluid (e.g., blisters)?

Serous inflammation – Often from plasma leakage or mesothelial secretion.

What pattern involves fibrin-rich exudate?

Fibrinous inflammation – Common in body cavities like pericardium.

What defines purulent (suppurative) inflammation?

Pus and abscess formation – Due to neutrophils and necrotic debris.

What is an ulcer in the context of inflammation?

Necrotic sloughing of epithelium – Surface defect from tissue loss.

What outcome restores normal structure?

Complete resolution – Requires minimal damage and regeneration.

What outcome involves fibrous tissue deposition?

Healing by fibrosis – Occurs after substantial tissue destruction.

What happens when inflammation does not resolve?

Progression to chronic inflammation – Characterized by prolonged immune response.

What cells dominate chronic inflammation?

Macrophages, lymphocytes, plasma cells – Unlike neutrophil-rich acute inflammation.

What are the features of chronic inflammation?

Ongoing tissue destruction and repair – Driven by immune cell activity.

What is the role of M1 macrophages?

Pro-inflammatory (IFN-γ, NO, ROS) – Activate immune responses.

What is the role of M2 macrophages?

Tissue repair and fibrosis (IL-4, IL-13) – Promote healing.

What do plasma cells produce?

Antibodies – Humoral immune defense.

What do dendritic cells do?

Antigen presentation – Activate T cells.

What is the role of eosinophils?

Fight parasites, mediate allergy (major basic protein) – In IgE-mediated responses.

What do mast cells do?

Release histamine and PGs – Trigger allergic and inflammatory responses.

What do basophils secrete?

IL-4, IL-13 – Drive allergic inflammation.

When are neutrophils seen in chronic inflammation?

In abscesses and osteomyelitis – Persistent infection.

What are epithelioid histiocytes?

Activated macrophages in granulomas – Key feature of granulomatous inflammation.

What causes immune granulomas?

Persistent microbe → IL-2, IFN-γ – T-cell mediated.

What causes foreign body granulomas?

Inert objects (e.g., talc, sutures) – No T-cell response needed.

What diseases cause caseating granulomas?

TB, fungal infections – Central necrosis present.

What causes non-caseating granulomas?

Sarcoid, Crohn, Leprosy, Cat scratch – No necrosis.

What must always be ruled out in granulomatous inflammation?

Tuberculosis – Especially when caseating.

What causes fever in inflammation?

IL-1, TNF → PGE2 – Acts on hypothalamus to raise set point.

What acute phase proteins are made by the liver?

CRP, SAA, Fibrinogen – Enhance inflammation, ↑ ESR.

Why does ESR increase in inflammation?

Fibrinogen → rouleaux formation – Stacks RBCs, settle faster.

What hormone causes anemia of chronic disease?

Hepcidin – Blocks iron release.

What causes reactive thrombocytosis?

↑ Thrombopoietin – Drives platelet production.

Neutrophilia is seen in what condition?

Bacterial infection – Typical response to extracellular bacteria.

Lymphocytosis is seen in what condition?

Viral infection – Common in mononucleosis and viral illnesses.

Eosinophilia is seen in what condition?

Allergy or parasites – Seen with IgE-mediated reactions or helminths.

Leukopenia is seen in what condition?

Typhoid, protozoa, rickettsiae – These suppress marrow or destroy WBCs.

How is Alzheimer’s disease linked to inflammation?

Microglia-driven inflammation promotes amyloid, tau, and synapse loss.

What causes inflammation in IBD?

Dysregulated immune response to gut flora.

How does inflammation promote cancer?

Drives initiation → progression → metastasis – Examples: HCV → HCC, H. pylori → gastric CA, IBD → colon CA.

What health disparities are associated with chronic inflammation?

Elevated CRP and IL-6 in chronic stress and poverty.