5070: Inflammation

what does the immune system do?

distinguish self from non-self

when the body is injured, what does the immune system do?

inflammation

what is catabasis? when does this occur

tapering off and resolution of inflammation

endogenous activity

how quickly does inflammation occur? to what two types of cell injury?

rapidly in response to both exogenous and endogenous cell injury

what are 5 things that inflammation should be ? or be able to do? what happens when these aren’t present?

local

where and when appropriate

controlled

time-limited

capable of stopping when not needed

can be dangerous/fatal

what is the time frame of acute inflammation?

short, usually less than 2 weeks

where does acute inflammation occur?

localized to injury or infection

how long does chronic inflammation occur for?

longer period of time

where does chronic inflammation occur? is it helpful or harmful?

diffuse area, maladapdive

what is the location of a macrophage when it is called as such?

tissues

when going by the name monocytes, where are they located? what is their function?

blood

eliminate microbes, dead tissue, mediator source

what is the inflammation pathway?

injury —>

chemical mediators —>

promoted vasodilation —>

enter neutrophils and macrophages to tissue—>

phagocytosis

after injury during acute inflammation, what is activated and where do they come from?

macrophages, dendritic and mast cells, neutrophils

from local and nearby sources

during acute inflammation, what is generated after injury and activation? where are they generated? what does this result in ?

mediators

locally

vasodilation and vascular permeability

what is phagocytosed during inflammation cascade?

bacteria, debris, dead cells

if a wound is present, what seals the area?

platelets

when appropriate, this type of proteins will enter the injured and inflamed area, depositing if need be.

clotting proteins, fibrin

alongside vasodilation, what is another thing that occurs ? This allows what to enter at the site of tissue damage? what does fluid leakage through blood vessels to tissue cause?

permeability

plasma proteins, leukocytes

edema

what are the 5 cardinal signs of inflammation?

pain

heat

redness

swelling

loss of function

neutrophilia definiton. What can this be a sign of ?

higher neutrophil count in the blood

inflammation

one sign of inflammation is the liver releasing acute phase proteins in response to which pro-inflammatory cytokines?

IL-1 (interleukin-1)

IL-6 (interleukin-6)

TNF-a (tumor necrosis factor alpha)

what does the liver release after being targeted by pro-inflammatory cytokines

acute-phase proteins

what is the definition of acute-phase proteins?

a protein whose plasma concentrations increase during inflammation

innate immunity doesn’t require previous exposure to what to react?

antigen

what type of action does innate immunity have? how long usually? when does it usually resolve

rapid action

seconds or minutes

a few days to one week

what does innate immunity use to kill invading organism?

phagocytic cells (macrophages, neutrophils)

natural killer cells

protein cascade

what is acquired immunity also known as ?

adaptive immunity

what does acquired immunity require? how fast does this reaction occur? does this change?

previous exposure to antigen

slower initially

changes when it is the 2nd exposure

what does acquired immunity use to fight antigens?

T and B immune cells that are specific for one antigen

during cell-mediated immunity, what is used?

cytotoxic (killer) T cells

during humoral immunity, what is used?

B cells and antibodies

there are 2 pathways for leukocyte (WBC) development, what are they?

lymphoid and myeloid

describe the lymphoid pathway of leukocyte (WBC) development

gives rise to lymphocytes and NK cells

what does the myeloid pathway give rise to?

granulocytes, monocytes/macrophages, dendritic cells, megakaryocytes, erythrocytes

T lymphocytes are created where? where do they develop?

in bone marrow

develop in thymus

what are the 2 major forms of T lymphocytes?

Helper T cells

cytotoxic or Killer T cells

what does CD stand for in relation to T lymphocytes? what is their significance?

cluster of differentiation

critical in antigen recognition

Helper T cells have what CD attached to them ?

CD4+

what do helper T cells do?

activate other T cells and macrophages

stimulate B cell proliferation and antibody production

secrete pro-inflammatory cytokines

what 3 major types of helper T cells are there ?

TH1, TH2, TH17

What CD is associated with cytotoxic/killer T cells?

CD8+

What do cytotoxic/killer T cells do?

kill infected cells

where are B lymphocytes created and developed? what do they ultimately produce?

created and develop in bone marrow

antibodies

what do memory cells do?

produce daughter cells programmed to produce the same antibodies

what is the lifespan of B lymphocytes?

long-lived

what is another thing that B cells can do regarding differentiation? what does this allow them to do?

differentiate into plasma cells

quickly synthesize large quantities of antibodies when needed

when a B cell is exposed to an antigen, what does it stimulate the B cell to become (2 things)?

antibody secreting plasma cells

memory B cells

what is a characteristic of a B cell receptor? what does it respond to? what does it require help from?

antibody like

responds to only 1 antigen epitope

Th cells

how do T helper cells assist B cells in activation (2 ways)?

cell to cell reactions through receptors

secretion of cytokines that stimulate B cell growth and differentiation

does the B or the T helper cell present the antigen to the T cell?

B cell presents antigen

what is an alternative name for antibodies?

immunoglobulins (Ig)

how many antigens bind with an antibody?

1

what are antibodies prodcued by? what are they a soluble form of ?

B lymphocytes

BCR’s

where would you find antibodies in the body?

blood, lymph, mucus

cytokines released by T helper cells can induce what process in B lymphocytes?

what process is this important in?

class switching

allergic response

each antibody has how many polypeptide chains? what are they classified as

4 total chains

2 long heavy chains, 2 short light chains

what are the characteristics of the F ab functional component?

specific

high affinity to specific antigens

the F c component of the antibody has what characteristics?

constant region

determines the A b class and binds to complement and lymphocytes

where is the F c component the same?

in all immunoglobulin molecules of a class

F ab region is what to each specific antibody?

specific

what are opsonins? what do they do?

a type of antibody

coat the antigen and make it more recognizeable to phagocytes

what can cause a complement cascade?

antibodies bound to antigens on cell membranes

what can function as an antitoxin?

antibody

where are natural killer cells from?

lymphoid lineage

do NK cells have B or T cell markers?

no

what are NK cells considered to be part of? what do they do/kill?

innate immunity

kill tumor and virally infected cells without previous exposure

what does ADCC stand for?

antibody-dependent cell -mediated cytotoxicity

what do NK cells use receptors to do?

recognize antibody-coated cells

what is the first step of NK cells antibody-dependent cell-mediated cytotoxicity?

IgG antibody fab region binds to virus-infected cell

Fc region binds to NK cell

what is the 2nd step of NK cells antibody-dependent cell-mediated cytotoxicity?

NK cell releases enzymes that create pores in the virus-infected cell, which then activates caspase enzymes —> apoptosis of inflected cell

what are the 4 types of granulocytes?

neutrophils

eosinophils

mast cells

basophils

what are 3 types of antigen-presenting cells?

monocytes and macrophages

dendritic cells

B cells also do this but aren’t from the myeloid lineage

what is unique about antigen-presenting cells regarding the presence of B cells in this category?

they can act as an antigen-presenting cell but aren’t from the myeloid lineage

what are granulocytes?

WBCs that have cytoplasmic granules with enzymes that kill bacteria and other invaders

where can granules work?

intracellularly and extracellularly

what is an example of intracellular granular work?

breaking down pathogens that are engulfed and endocytosed

what is an example of granules working extracellularly

what can this cause (negative)

being released into environment by granulocytes

can cause tissue damage

neutrophils are a type of what?

granulocyte

what do neutrophils function as?

the primary cell type of acute inflammation

how quickly do neutrophils arrive to the site of accute inflammation?

quickly

what is the most numerous type of granulocyte?

how many are produced and consumed daily?

neutrophils

~100 billion are produced/consumed daily

how long do neutrophils remain in circulation?

6-12 hrs

colonoy-stimulating factors are used to do what?

used to increase rate of production of neutrophils during increased need

what do neutrophils do? what is the result of this?

move blood into tissues to phagocytose and kill invading organisms

apoptosis

what do neutrophils have a lot of on their outer shell?

different receptors that allow them to bind to microbes or opsonins

how do neutrophils move/what are they attracted to?

attracted to area of injury and infection by chemotactic factors like antibodies, cytokines, complement fragments

neutrophil killing mechanisms include what 2 things?

ROS generation

lysosomal proteases

what do ROS and lysosomal proteases released onto nearby tissues cause?

secondary tissue damage

when a local injury occurs, what do endothelial cells do that help WBCs move from the blood to the tissue?

upregulation of protein adhesion molecules (capture WBCs)

what is diapedesis? and what is the mechanism x 6

inflam/injury causing secretin showing

rolling with secretins

adhesion with integrins

spacious endothelium bc of infla. cytokines

neutrophil sneaks through

chemokines from invader promotes movement into tissues and platelet adhesion

what is para cellular diapedesis

neutrophil movement between gap in endothelial cells

what is transcellular diapedesis?

neutrophil movement through a pore in an individual endothelial cells

a neutrophil shift to the left is what?

when does this normally happen?

increase in the % of immature neutrophils released from bone marrow

commonly in the presence of acute bacterial infection

band forms are what?

immature neutrophils released from the bone marrow

where do eosinophils come from?

recruited from circulation

what is the mechanism of killing for eosinophils?

granules have killing agents which are meant to be exocytosed onto large targets too big for phagocytosis

what is a possible target for eosinophil action?

parasites

what is a downside or possible negative regarding eosinophils?

can injure health tissue when exocytosing granules

in allergic responses, eosinophils are important because

they are prominent in the late phase of asthma attacks

what are basophils characterized as?

a type of granulocyte