immunology exam 1 - innate immunity (inflammatory response)

portal of entry

• skin and mucous membranes that prevent pathogens from entering

• part of the innate response

time it takes for innate response to kick in

0-4 hours

inflammation

• response of the host to the presence of “foreign” bodies/injury

• characterized by key indicators due to accumulation of fluids (blood plasma) and phagocytic cells

chemotaxis

cellular movement toward the site of injury in response to a chemical concentration gradient

chemoattract

chemicals that cause cells to move in the direction of the stimulus

five sign of acute inflammation

• pain

• redness

• immobilization (loss of function)

• swelling

• heat

major inflammatory leukocytes that degranulate

• mast cells

• basophils

• eosinophils

• neutrophils

degranulation

process in which a cell release a large concentration of inflammatory mediators

major inflammatory leukocytes that phagocytose and/or opsonize

• neutrophils

• eosinophils

• activated macrophages

• activated dendritic cells

phagocytosis

• “cellular eating”

• eliminates invading cells as well as dead/damaged cells

opsonization

• process that increases the rate of phagocytosis

• can trigger the release of inflammatory mediators

chronic inflammation

caused by repeated exposure to a stimulus or a substance that the body can’t get rid of

langhans giant cells

• present when there’s chronic inflammation

• a fusion of macrophages where nuclei form a boundary to trap the foreign substance

• prevent further damage to the body because it cannot remove the substance

cellular adhesion molecules (cam)

• found on the surface of host cells to help them either stick together or stick to the surroundings

• includes selectins (E, P), mucins (sialyl- Lewis), Ig superfamily (ICAM-1, VCAM-1, and PECAM-1), and integrins (LFA-1, VLA-4)

selectins (E, P) function

• a type of cellular adhesion molecule

• binds to mucins to help cells stick to one another or other surfaces

mucins (sialyl-Lewis) function

• a type of cellular adhesion molecule

• binds to selectins (E, P) to help cells stick to one another or other surfaces

name the Ig-superfamily CAMS

• ICAM-1

• VCAM-1

• PECAM-1

Ig-superfamily CAMS function

• a type of cellular adhesion molecule

• can either bind to themselves OR integrins (LFA-1, VLA-4) to help cells stick to one another or other surfaces

soluble mediators

• released by cells, bind to receptors, and then elicit an immune response

• mediators are phosphorylated which allows for the pathway to continue

• ex: turn on/off genes via these mediators

name the soluble mediators

• JAK (Janus kinases)

• STAT (signal transducer and activator of transcription proteins)

• cytokines

overall goal of soluble mediators

• vasodilation

• endothelial permeability

• expression of CAMs

• leukocyte activation

• chemoattraction

• extravasation of white blood cells (leave the vasculature and fight pathogens in local tissue)

cytokines

• a type of soluble mediator

• three families: interleukins, interferons, and cytotoxic/modulators

name the interleukins

• IL-1, IL-2

• IL-4, IL-5

• IL-6, IL-8

• IL-12, IL-13

• IL-21, IL-22

• IL-23

name the interferons

• IFN-α

• IFN-β

• IFN-γ

name the cytotoxic/modulator cytokines

• TNF-α

• TGF-β

local effects of IL-1β

• vascular permeability

• leukocyte activation

• endothelial CAM expression

• IL-8 production

• vasodilation

local effects of TNF-α

• vascular permeability

• leukocyte activation

• endothelial CAM expression

• IL-8 production

• chemotaxis

• cytotoxic capabilities

local effects of IL-6

• vascular permeability

• leukocyte activation

• leukocyte production

systemic effect of IL-1β

• fever

• induce liver to release acute phase proteins

• septic shock

systematic effect of TNF-α

• fever

• induce liver to release acute phase proteins

• septic shock (major)

systematic effect of IL-6

• fever

• induce liver to release acute phase proteins (major)

• septic shock

fever

• an increase in body temperature that is often triggered by the immune system as a response to an invading pathogen

• induced by pyrogens

pyrogen

• chemicals that induce fever by changing the “thermostat”

• includes IL-1, TNF-α, IL-6, and arachidonic acid metabolites

benefits of fever

• increased mobility of leukocytes

• increased proliferation of t-cells

• enhanced leukocyte phagocytosis

• enhanced enzymatic function of immune proteins

• hindered growth of pathogens

• decreased function and effectiveness of pathogenic toxins

local effect of IL-8

• leukocyte CAM expression

• chemotaxis

local effect of IL-12

• activate NK cells

• activate CD8 cells

• induce the differentiation of CD4 T-cells into TH1 cells

• production of IFN-γ in NK and T cells

• released during a viral infection

IFN-γ

• type 2 interferon

• mediates both the innate and adaptive responses

• increases NK cell activity

• activates B and T cells specific to viral pathogens

• shut down viral replication cycle

• “supercharges” macrophages

IFN-α and IFN-β

• type 1 interferon

• can be released by any infected cell and are immediately effective in the area of infection

• induce resistance to viral replication in all cells, increase MHC 1 expression in all cells, increase antigen presentation in all cells, and activate NK cells to kill virally-infected cells

things that cytokines can be involved in

• chemotaxis and inflammation

• activation of white blood cells

• influence t-helper differentiation

Th1

• T-cell that specifies in microbial and intracellular pathogen immunity

• activated by IL-12 and IFN-γ

• feedback loop present when NK and CD8 cells release IFN-γ

Th2

• T-cell that specifies in extracellular pathogen immunity

• activated by IL-4

Th17

• T-cell that specifies in mucosal, extracellular bacteria, and fungal immunity

• activated by IL-1, IL-6, IL-23, and TGF-β

Th9

• T-cell that specifies in helminth (worm) immunity

• activated by IL-4 and TGF-β

Th22

• T-cell that specializes in wound healing and tissue remodeling

• activated by IL-6 and TNF-α

C3a

• complement protein

• increases vascular permeability, induce degranulation, act as chemoattracts, activate B/T cells as well as macrophages, and increase CAM expression

• same functions as C5a

C4a

• complement protein

• increases vascular permeability and CAM expression

C5a

• complement protein

• increases vascular permeability, induce degranulation, act as chemoattracts, activate B/T cells as well as macrophages, and increase CAM expression

• same functions as C3a

histamine

• vasoactive amine

• increases the permeability of capillaries

• increases swelling and inflammation

• causes blood vessels to dilate

• chemotactic and can attract white blood cells

• produce mucus to trap pathogens

formation of platelet-activating factors and arachidonic acid metabolites

• self-regulated process

• granulocytes and macrophages undergo lipid remodeling by taking a piece of the phospholipid membrane and turning it into one of these mediators

• occasionally made when cells are damaged or dying

platelet-activating factors

• formed through lipid remodeling

• increase vasodilation, vascular permeability, chemotaxis, and clot formation

arachidonic acid metabolites

• formed through lipid remodeling

• increase vasodilation, vascular permeability, chemotaxis, and fever

• includes leukotrienes and prostaglandins

name the proteins that travel to the liver for acute phase protein synthesis

• IL-6 (major)

• Il-1

• TNF-α

pentraxin family

• group of acute phase proteins

• released from the liver

• includes CRP and SAP

CRP

• stands for c-reactive protein

• complement protein from the classical pathway

• a part of the pentraxin family of acute-phase proteins

• released from the liver

• increases phagocytosis and can activate complement

percentage of liver cells that can release mediators

75% to 80%

SAP

• stands for serum amyloid protein

• complement protein from the classical pathway

• a part of the pentraxin family of acute-phase proteins

• released from the liver

• increases phagocytosis, can activate complement, and binds to mannose/galactose

collectin family

• group of acute phase proteins

• released from the liver

• includes SP and MBL

SP

• stands for surfactant protein

• complement protein from the lectin pathway

• a part of the collectin family of acute-phase proteins

• released from the liver

MBL

• stands for mannose-binding lectin

• complement protein from the lectin pathway

• a part of the collectin family of acute-phase proteins

• released from the liver

fibrinogen

• acute phase protein that is released from the liver

• aids in blood clotting

fibrin

• arises from fibrinogen

• helps with blood clotting

• also works to increase vascular permeability, vasodilation and chemotaxis

fibrinogen-derived peptide

• arises from fibrinogen

• increases chemotaxis and vascular permeability

bradykinin

• mediator that is involved in the pain response

• increases vascular permeability, vasodilation and chemotaxis

hemodynamic effects of innate immune system components

• increased vasodilation

• decreased pressure on the endothelial walls in veins (ie: decreased blood pressure)

• increased expression of CAMs

• increased vascular permeability

• blood “pooling” (contributes to immobilization)

leukocyte extravasation

• process in which white blood cells leave the vasculature

• four steps: margination, rolling, adhesion, and transmigration

margination

• first step of leukocyte extravasation

• occurs as blood flow slows

• leukocytes collect along the endothelium and potentially may stick

rolling

• second step of leukocyte extravasation

• IL-1 and TNF-α activated endothelial cells to present selectins (E, P)

• selectins (E, P) loosely bind to mucins (sialyl-Lewis) on leukocytes

• cell doesn’t stop moving, rather it slows down through bonds that are made and broken

adhesion

• third step of leukocyte extravasation

• leukocytes bind to endothelial cells and stop rolling

• integrins (LFA-1, VLA-4) on leukocytes bind to Ig-superfamily CAMs (ICAM-1, VCAM-1) on endothelial cells

• IL-8 activates the integrins on leukocytes

• IL-1 and TNF-α activates Ig-superfamily CAMs on endothelial cells

transmigration

• fourth step of leukocyte extravasation

• self-interactions between PECAM-1 on both leukocyte and endothelial cell surfaces pull the leukocyte through the endothelial wall

• leukocyte then travels to where the infection is in the body

hematoma

• forms after inflammation occurs

• a mix of fibrin mesh used to form a blood clot

complete resolution after inflammation

• hematoma is formed to help blood clotting

• leukocytes clean up the cellular damage

• fibroblasts deposit extracellular matrix that is used to rebuild tissue

• normal function is restored - no long term exposure to harmful stimulus

incomplete resolution after inflammation

• some tissue regeneration occurs

• tissue function is altered or lost because connective tissue is placed instead of endothelial cells

• occurs when there is a long-term exposure to stimulus

fibrosis

• loss of tissue function

• a result of incomplete resolution