Inflammation (5 of 5) Ali Al Khader, M.D. Faculty of Medicine Al-Balqa’ Applied University Email: ali.alkhader@bau.edu.jo

What will we discuss today? Chronic inflammation Granulomatous inflammation Systemic effects of inflammation

Chronic inflammation…In general Days/weeks to years Conditions causing chronic inflammation: -Persistent infections…-TB (What is the microorganism?) -Treponema pallidum (What does this microorganism cause?) -Some viruses -Some fungi -Immune mediated hypersensitivity diseases…acute and chronic reactions… but in general: chronic -Prolonged exposure to toxic agents…mention 2 examples (one endogenous and one exogenous) -Diseases that chronic inflammation is one of their mechanisms…e.g, Alzheimer, DM type 2, some cancers…etc

Cells and mediators of chronic inflammation The major two types of cells: These are the dominant here

Macrophages Resident macrophages in tissues have special names: -in liver: Kupffer cells -in spleen and lymph nodes: sinus histiocytes -CNS: microglial cells -in lung: alveolar macrophages 24-48 hours of acute inflammation…they predominate after being recruited to the tissue (they were monocytes in blood) Longer life span and better phagocytosis than blood monocytes

2 major pathways of macrophage activation: From T lymphocytes and others And foreign materials Also induces macrophages to become multinucleated giant cells Do not forget that macrophages also secrete TNF, IL-1, chemokines, eicosanoids…etc From -T lymphocytes -mast cells -eosinophils…etc. The major role of alternatively activated macrophages Robbins basic pathology 9th edition…modified Including angiogenesis

Activation & recruitment Macrophage Activation & recruitment Antigen presentation and activation (IL-12…etc.) T lymphocyte

Lymphocytes B cells…can develop into plasma cells…secrete immunoglobulins (antibodies) T cells: -Cytotoxic (CD8+) -T helper (CD4+) -Regulatory T cells These are especially important in chronic inflammation

CD4+ helper T cells TH1 cells IFN-γ activates macrophages in the classical pathway TH2 cells IL-4, IL-5, and IL-13 -recruit and activate eosinophils -alternative pathway of macrophage activation TH17 IL-17 recruitment of -neutrophils -monocytes Important in allergy and helminthic infections

Other cells of chronic inflammation Eosinophils: -parasitic infections -allergy …secrete major basic protein…special action against parasites, but also injures tissues Mast cells: -allergy…in cooperation with IgE release of histamine and eicosanoids -secrete cytokines…TNF, chemokines…etc In some conditions…neutrophils are still activated and present in large numbers = “Acute on chronic”

Granulomatous inflammation A pattern of chronic inflammation Aggregates of activated macrophages + scattered lymphocytes This example is a caseating granuloma Robbins basic pathology 9th edition

Granulomatous inflammation, cont’d Mechanisms: -Persistent T cell responses to certain microbes chronic macrophage activation -Some autoimmune mechanisms…example? -Due to foreign bodies…= foreign body granulomas -Sarcoidosis

Systemic effects of inflammation = acute phase reaction *The most important here are: -TNF -IL-1 -IL-6

Acute phase reaction, clinical & pathological changes Fever …pyrogens synthesis of prostaglandins …prostaglandins stimulate release of neurotransmitters In vascular and perivascular cells of the hypothalamus Especially PGE2 *Exogenous pyrogens (bacterial products, e.g., LPS) stimulate release of endogenous pyrogens (IL-1 & TNF) eicosanoids (including prostaglandins) They reset the temperature set point at higher level

Acute phase reaction, clinical & pathological changes, cont’d Elevated plasma levels of acute-phase proteins -C-reactive protein (CRP) -Fibrinogen -Serum amyloid A (SAA) protein **What is erythrocyte sedimentation rate (ESR)? Synthesized by hepatocytes …especially due to IL-6

Acute phase reaction, clinical & pathological changes, cont’d Leukocytosis…? …What is “shift to the left”? …What is leukemoid reaction? …What is neutrophilia? …What is eosinophilia? …What is leukopenia?

Acute phase reaction, clinical & pathological changes, cont’d * heart rate & blood pressure * sweating *Chills and rigors…What are these? *Anorexia *Somnolence *Malaise

Thank You