Ch.2 Chronic Inflammation Flashcards
a response of prolonged duration (weeks to months) in which inflammation, tissue injury, and attempts at repair coexist, in varying combinations delayed
Chronic inflammation
3 main causes of chronic inflmation
1. Persistant infection; difficult to eradicate (mycobacteira, some viruses fungi, and parasites)
2. Hypersensitivity Diseases; diseases that are caused by excessive and inappropriate activation of the immune system (autoimmune & allergic diseases)
3. Prolongued exposre to toxic agents they can be endo or exogenous ex. silica inhaliation.
autoantigens evoke a self-perpetuating immune reaction that results in chronic tissue damage and inflammation;
examples of such diseases are rheumatoid arthritis and multiple sclerosis
Autoimmune diseases
chronic inflammation is the result of **excessive immune responses **against common environmental substances, as in bronchial asthma
Allergic Diseases
What morphological feature of Chronic inflammation?
Macrophages, lymphocytes, and plasma cells enter site of infection
Infiltration by mononuclear cells
What morphological feature of Chronic inflammation?
____ at site of infection is induced by the persistent offending agent or by the inflammatory cells
Tissue Destruction
What morphological feature of Chronic inflammation?
replacement of damaged tissue with connective tissue, accomplished by angiogenesis (proliferation of small blood vessels) and fibrosis, culminating in scar formation
Attempts at healing
Cells which destroy foreign invaders and tissues, secrete cytokines and growth factors, and activate other cells, notably T lymphocytes.
Dominant cell in chronic inflammatory rxn.
Macrophages
diffusely scattered in most connective tissues. Circulating cells of this lineage are known as monocytes. ALso found in specific locations in organs such as the liver (Kupffer cells), spleen, and lymph nodes (sinus histiocytes), central nervous system (microglial cells), and lungs (alveolar macrophages)
Tissue Resident Macrophages
derived from hematopoietic stem cells in the bone marrow and from progenitors in the embryonic yolk sac and fetal liver during early development
Macrophages in tissues
inflammatory reactions, progenitors in the bone marrow give rise to monocytes, which enter the blood, migrate into various tissues,
What do they do after this?
Differentiate into macrophages
Microglial cells (brain) and Kupffer cells (liver) are examples of what?
Tissue resident macrophages
induced by microbial products such as endotoxin, which engage TLRs and other sensors, and by Tcell–derived mediators, especially the cytokine IFN-γ, in immune responses
Classical macrophage activation M1
produce NO and ROS, upregulate lysosomal enzymes (enhance ability to kill) and secret cytokienes that stimulate inflamation.
Eradicate infections and dominate many inflammatory reactions
M1macrophages
Clasically activated macrophages
mediators other than IFN-γ, such as IL-4 and IL-13, produced by T lymphocytes and other cells. Do what?
Alternative macrophage activation
M2
not actively microbicidal; instead, their principal function is tissue repair. They secrete growth factors that promote angiogenesis, activate fibroblasts, and stimulate collagen synthesis. **Inhibit Inflamation **
M2 macrophages
Alternative acitvated macrophages
What are some activated macrophages function?
- injestion/elemination
- Secrete inflamatory mediations (TNF, IL-1) central to propogation of inflamatory rxns
- Initate tissue repair, scar formation , fibrosis
- Antigen presentation
- Produced in bone marrow as progenitor T-cells
- Further develope in thymus in CD4+ helper or CD8+ Cytotoxic T cells
T-lymphocytes
Recognizes antigens presented on MHC molecules
TCR + CD3
TCR Complex
Used by T-cells
What cytokiene secreted by CD4+ T cell?
produce the cytokine IFN-γ, which activates macrophages by the classical pathway.
cellular response
Th1 Cells
What cytokiene secreted by CD4+ T cell?
secrete** IL-4, IL-5, and IL-13,** which recruit and activate eosinophils and are responsible for the alternative pathway of macrophage activation.
hummoral response
Th2
What cytokiene secreted by CD4+ T cell?
secrete** IL-17 and other cytokines, which induce the secretion of chemokines responsible for recruiting mainly neutrophils into the reaction.**
Th17
What cytokiene(s) secreted by CD4+ T cell defend agaisnt many types of bacteria and viruses?
Th-1 & Th-17
What cytokiene(s) secreted by CD4+ T cell defend agaisnt many types of helminthic paraisites and allergic inflammation?
Th2
*eosinophills
- antigen phagocytosed by macrophage or dendritic cell
- Present antigen on MHC Class II (on APC)
- B7 on APC binds CD28 on ____ cell and acitvate it
- Acitivated ____ cell secrete cytokienes that acitvate adaptive immunity + propgate inflamation
CD4+ T helper cells
Activates macrophages and promote B-cell class switching from IgM to IgG, promte Th1 response inhibit Th2 repsonse.
IFN-γ
TH2 secretes ____ which facilitates B-cell class switching to IgE. And section of IL-5 facilitates ____ chemotaxis and activation.
Il-4 (IgE class switch)
Eosionphil chemotaxis
Immature ____ produced in Bone marrow
Imunoglobulin rearrangment to become naive ____ that express surface IgM and IgD
B-Lymphocytes
- Antigen binds surface IgM or IgD resulting in their maturation and secretion of plasma cells
- B-cell antigen** presentation to CD4+ helper T-cells via MHC class 2 **
Two forms of B-cell acitvation
Descirbe 4 steps of secondary B-cell activation via MHC 2
1. CD40 receptor on B cell bind CD40 Ligand on Helper T cell = 2nd signal
2. Helper T cell secret Il-4 & 5 (mediate B-cell isotype swtiching + hypermutation + matruation into plasma cells)
abundant in immune reactions mediated by IgE and in parasitic infections
Eosinophills
In chronic bacterial infection of bone (osteomyelitis), a ____ exudate can persist for months
Neutrophillic
3 outcomes of chronic inflamation?
- Scarring & fibrosis
- Amyloid formation (deposition of misfolded protiens)
- Malignancy (lots of injurys, hyper, meta, dysplasia)
form of chronic inflammation characterized by** collections of activated macrophages,** often with T lymphocytes, and sometimes associated with central necrosis.
Type ___ hypersensitvity?
Granulomatous Inflammation, Type 4 Hypersensitivity (cell mediated)
In Granulomatous Inflammation:
Macrophages transform into ____ cells (pink cytoplasm) and ____ giant cells. They are surrounded by lymphocytes & plasam cells,.
Epetheliod cells and** Langerhan giant cells** (fusion of numerous acivated macrophages)
Causes Causeating granulomas
Cheese-like necrosis
Mycobacterium Tuberculosis (the ONLY causeating)
Granulomatous Inflammation may play a roll in ____ due to macrophages activaton of Vitamin D, which increased calcium absorbtion.
Hyperglycemia
Formation of a _ help TB become more resistant to drugs and immune response beccause it is very internalized
Granuloma
What disease with granulomatous inflamation?
Acid-fast bacilli in macrophages; noncaseating granulomas
skin verison of TB
Leprosy
What disease with granulomatous inflamation?
Gumma: microscopic to grossly visible lesion; surrounding wall of macrophages; plasma cell infiltrate; central cells are necrotic without loss of cellular outline
Syphyllis
What disease with granulomatous inflamation?
Rounded or stellate granuloma containing central granular debris and recognizable neutrophils; giant cells uncommon
Cat-scratch Disease
What disease with granulomatous inflamation?
Noncaseating granulomas with abundant activated macrophages
Lungs, legs
Sarcoidosis
Occasional noncaseating granulomas in the wall of the intestine, with dense chronic inflammatory infiltrate
Crohns disease (IBD)
