Tissue Responses to Injury & Infection - Inflammatory Response - Midterm Notes PDF

1 1 TISSUE RESPONSES TO INJURY AND INFECTION – Inflammatory Response 1. Cause Acute Inflammatory Response: o Injury or Infec7on: Triggered by ,ssue injury (e.g., cuts, bruises, burns) or...

1 1 TISSUE RESPONSES TO INJURY AND INFECTION – Inflammatory Response 1. Cause Acute Inflammatory Response: o Injury or Infec7on: Triggered by ,ssue injury (e.g., cuts, bruises, burns) or invasion of pathogens like bacteria, viruses, or fungi. o Cellular Damage: Necro,c cells release damage-associated molecular pa?erns (DAMPs), which ac,vate the immune system. o Microbial Products: Molecules like lipopolysaccharides (LPS) from Gram- nega,ve bacteria ac,vate pa?ern recogni7on receptors (PRRs) such as Toll-like receptors (TLRs) on immune cells. Chronic Inflammatory Response: o Unresolved Acute Inflamma7on: When acute inflamma,on is not resolved, it becomes chronic. o Persistent Infec7ons: Pathogens like Mycobacterium tuberculosis can evade destruc,on and persist, leading to granuloma forma7on. o Exposure to Irritants: Con7nuous exposure to irritants (e.g., pollutants, tobacco smoke) can lead to chronic inflamma,on. o Autoimmune Condi7ons: Autoimmune diseases (e.g., rheumatoid arthri,s, Crohn's disease) trigger chronic immune responses against self-,ssues. 2. Pathophysiology Acute Inflamma7on: o Recogni7on: Immune cells like mast cells, macrophages, and dendri7c cells detect DAMPs or pathogen-associated molecular paOerns (PAMPs) on pathogens via PRRs like TLRs. o Vascular Changes: § Vasodila7on: Blood vessels widen to increase blood flow, leading to redness and warmth. § Increased Permeability: Blood vessels become leaky, allowing immune cells, fluid, and plasma proteins to enter the ,ssues, causing swelling. § Pain: Swelling puts pressure on nerves, while bradykinin and prostaglandins sensi,ze pain fibers, causing pain. o Cellular Events: § Mast Cell Ac7va7on: Release of histamine, causing vasodila,on and increased permeability. § Recruitment of Neutrophils: Neutrophils are the first to arrive, followed by monocytes/macrophages. Neutrophils perform phagocytosis and release reac,ve oxygen species (ROS) to kill pathogens, but they may also damage host ,ssues. § Forma7on of Neutrophil Extracellular Traps (NETs): Neutrophils extrude their DNA to trap and kill pathogens. o Resolu7on and Repair:  2 § Clearance of Pathogens: Once the threat is neutralized, immune cells (e.g., macrophages) remove debris and dead cells. § Tissue Repair: Fibroblasts and growth factors (like vascular endothelial growth factor, VEGF) promote ,ssue repair. Chronic Inflamma7on: o Persistent Immune Ac7va7on: Unlike acute inflamma,on, chronic inflamma,on is prolonged and o\en driven by ongoing irritants or infec,on. o Granuloma Forma7on: Infec,ons like tuberculosis cause granulomas, which are organized collec,ons of immune cells that "wall off" the infec,on. Macrophages fuse into giant cells, surrounded by a ring of lymphocytes. o Tissue Damage: Chronic inflamma,on leads to fibrosis (excess collagen deposi,on) and scarring due to prolonged immune ac,vity. 3. Transmission Not Transmissible: o Inflamma,on is a biological process, not a communicable disease. o However, certain infec7ous diseases that trigger inflamma,on (like tuberculosis) are transmissible from person to person. o Chronic inflamma,on can also be linked to non-communicable condi7ons like obesity and metabolic syndrome, but these are not "transmiOed" in the same way as infec,ons. 4. Risk Factors Modifiable Risk Factors: o Infec7on: Exposure to infec,ous agents, especially bacteria, viruses, fungi, and parasites, increases the risk of inflamma,on. o Smoking: Smoking introduces irritants into the lungs, triggering chronic inflamma,on and diseases like chronic obstruc7ve pulmonary disease (COPD). o Obesity: Adipose ,ssue releases pro-inflammatory cytokines like TNF-α and IL-6, promo,ng low-grade chronic inflamma,on. o Diet: Diets high in saturated fats, refined sugars, and processed foods can promote systemic inflamma,on. o Chemical Exposure: Chronic exposure to pollutants, industrial chemicals, and irritants can lead to persistent inflamma,on. Non-Modifiable Risk Factors: o Age: Older individuals exhibit a phenomenon called inflammaging, characterized by low-grade, chronic inflamma,on. o Gene7cs: Gene,c predisposi,on to autoimmune diseases (e.g., rheumatoid arthri7s and systemic lupus erythematosus) increases the risk of chronic inflamma,on. o Sex: Women may have different inflammatory responses due to hormonal differences, par,cularly estrogen, which influences immune func,on. Summary Table  3 Criteria Acute Inflamma7on Chronic Inflamma7on Unresolved acute inflamma,on, Cause Infec,on, injury, cell damage chronic infec,on (e.g., TB), irritant exposure Recogni,on of DAMPs, PRR ac,va,on, Persistent immune response, Pathophysiology vasodila,on, leukocyte recruitment, granuloma forma,on, chronic pathogen clearance cytokine release, fibrosis Not transmissible (except in infec,ous Not transmissible (except in Transmission diseases) infec,ous diseases) Smoking, obesity, autoimmune Risk Factors Infec,on, ,ssue injury, burns, trauma diseases, chronic infec,ons, irritant exposure