Inflammation (5 of 5)

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:

Robbins basic pathology 9th edition…modified

From T lymphocytes and others And foreign materials

From -T lymphocytes -mast cells -eosinophils…etc.

The major role of alternatively activated macrophages

Including angiogenesis

Do not forget that macrophages also secrete TNF, IL-1, chemokines, eicosanoids…etc

Also induces macrophages to become multinucleated giant cells

Macrophage

T lymphocyte

Antigen presentation and activation (IL-12…etc.)

Activation & recruitment

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

Robbins basic pathology 9th edition

This example is a caseating granuloma

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

*Exogenous pyrogens (bacterial products, e.g., LPS) stimulate release of endogenous pyrogens (IL-1 & TNF)

eicosanoids (including prostaglandins)

Especially PGE2

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