inflammation and hypersensitivity - block e

Question 1

inflammation triggers

Answer 1

pathogens

damaged cells

toxin compounds

Question 2

five signs of inflammation and causes of them

Answer 2

heat/redness - vasodilation, widening of capillaries heats tissues and causes redness

swelling (oedema) - fluid released into tissues, increased permeability, tenderness because of increased leukocytes in area

pain - fever and proliferation of leukocytes, systemic response

loss of function - resolution, wound healing - scar tissue (non functional) - prevents movement - further damage

Question 3

stages of inflammation

Answer 3

Inflammatory response starts when macrophages & other cells resident in the affected tissues are activated.

Innate local response – binding of PAMPs/DAMPs to PRRs

Receptor signalling – release of inflammatory mediators

Leukotrienes. Prostaglandins, Platelet activating factors. Histamine - all come from the breakdown of cell membrane phospholipids - secreted very rapidly

chemokines and cytokines and complement cascade

Pathogen-associated molecular patterns

Damage-associated molecular pattern

Pattern Recognition Receptor

Question 4

inflammation mechanism

Answer 4

injured tissue (endothelial cells), mast cells, and macrophages secrete inflammatory signals that induce vascular changes

increased blood flow to area increases delivery of beneficial proteins and leukocytes
Increased vascular permeability allows plasma proteins to gain entry to interstitial fluid

complement (C5a) enhances the process of vasodilation & helps activate endothelial cells and mast cells (resident in tissues)

Question 5

resident cells phagocytosis

Answer 5

can phagocyte bacteria (macrophages and dendritic cells)

cells are recruited to the injury site by a process called extravasation

key cellular components of inflammation include; neutrophils, macrophages, dendritic cells, and mast cells

induced and regulated by cytokines (TNFα, IL-1β, & IL-6) & chemokines (CXCL1 & CXCL8)

Question 6

leukocyte rolling and extrvaasation

Answer 6

rolling adhesion

tight binding

diapedesis

migration

neutrophils make up the first wave of cells that cross the blood vessel wall to enter an inflamed tissue

Question 7

inflammatory response - phagocytes

Answer 7

phagocytes enter area and release inflammatory mediators that induce more phagocytes

may induce fever (temp > 38)

stimulates leukocyte activity and provides a less suitable environment for some pathogens

destroys pathogens, clears dead cells, sets stage for tissue repair

Question 8

causes of immune mediated disorders

Answer 8

failure of immune response (auto-immunity)

inappropriate response to antigens that don’t pose a threat (hypersensitivity)

Question 9

two types of hypersensitivity

Answer 9

immediate - symptoms appear in a short space of time

delayed - can take 2-3 days for symptoms to appear

Question 10

classes of hypersensitivity

Answer 10

type 1 - IgE mediated

type 2 - IgG or IgM mediated

type 3 - immune complex mediated

type 4 - t cell mediated

Question 11

IgE mediated hypersensitivity

Answer 11

Ig discovered in 1960s, causes allergies

displayed by mast and basophils - binds antigen on second exposure = degranulation

vasoactive mediators = histamine, heparin, prostaglandins, leukotrienes, and proteases

IgE induces cross linking of bound mast cells and basophils with release of vasoactive mediators

includes systemic anaphylaxis and localised anaphylaxis - hay fever, hives, eczema, asthma

Question 12

IgE mediated response types

Answer 12

immediate early response - due to release of vasoactive compounds

late phase response - mediators released during the reaction cause localised inflammation

Question 13

IgG and immune complex hypersensitivity

Answer 13

induced by antigens that induce IgM and IgG

cutaneous reaction - arthus reaction

reaction time is 2-6 hours

pathology - necrotising vasculitis

effector cells - monocytes and neutrophils

secreted mediators - products of complement activation

Question 14

type ii hypersensitivity

Answer 14

antibody-mediated destruction of cells by IgG and IgM

antibody bound to cell-surface antigen can induce death of this cell by 3 mechanisms; complement system (create pores in cell membrane), antibody-dependent cell-mediated cytotoxicity (ADCC), the bound antibody can serve as an opsonin (attracts phagocytic cells to bind and phagocytose cell

when excessive or misdirected = damaging

Question 15

type ii mechanism

Answer 15

surface antigen present on target cell

IgG Fc portion bind receptor on NK, MAC, and neutrophils

IgG/IgM binds to create an immune complex

complement activated

includes blood transfusion reactions, haemolytic disease of the new born and autoimmune anaemia

Question 16

IgG type ii examples

Answer 16

Haemolytic disease of the new-born

Haemolytic disease when Rh- mother carrying a Rh+ baby

Can be prevented by the administration of Rhogam at time of delivery.

A Rh- mother pregnant by a Rh+ father – danger of developing a response to the Rh antigen that the foetus may have inherited from father

Can lead to mother rejecting the Rh+ foetus

RBCs from the foetus can enter the maternal circulation during pregnancy, but certainly at birth.

Results in the mother producing anti Rh+ antibodies

rhogam prevents b cell activation and memory formation

Question 17

immune complex hypersensitivity

Answer 17

mediated by immune complexes and results in complement activation

usually immune complexes are important or clearance of antigen by phagocytes

in some cases large numbers can result in tissue damage

severity depends on - size of immune complexes, levels of immune complexes present, and the distribution within the body

Question 18

immune complexes

Answer 18

normal part of adaptive immune response

recognised by Fc receptors on phagocytes and engulfed

cleared by RBCs in spleen or kidney and/or by complement activation which leads to lysis of the cells with the immune complexes

Question 19

type ii hypersensitivity

Answer 19

failure to clear immune complexes = disorders in phagocytotic machine or irregularities in the antigen

when they are not cleared they can be deposited into the blood vessels or tissues

uncleared complexes can bind to mast cells, neutrophils and macrophages

Question 20

Ab-Ag lattices

Answer 20

antigens create them

some have high affinity for certain tissues and are sometimes highly charged

complement elicits localised vasodilation and attracts neutrophils

results can be blood vessel inflammation (vasculitis), tissue damage (glomerulonephritis and arthritis)

Question 21

arthus reaction

Answer 21

immune complexes deposited near antigen admin site induce arthus reaction

localised event - large immune complexes precipitate close to injection site of antigen

lytic enzymes from neutrophils (frustrated phagocytosis) and tissue damage also mediated by the complement membrane-attack complex

generalised type III reactions such as serum sickness occur when immune complexes are deposited throughout

Question 22

t cell mediated hypersensitivity

Answer 22

only type that is purely cell mediated

initiated by t cells (CD4+ Th1 cells)

reaction takes 1-2 days

recruits macrophages

sensitisation phase and an effector phase (initiates on 2nd exposure)

contact dermatitis (poison ivy/oak)

Question 23

type iv

Answer 23

after sensitisation T-cells, clonally expand and differentiate into effector T-cells

effector phase – 2nd exposure – T-cells secrete a variety of cytokines;

IFNγ, TNFα & TNFβ

these cytokines recruit and activate macrophages
macrophages (professional APC) – very good at presenting antigen = exasperates the response

Th17 helper T-cells and CD8+ T-cells also contribute

Question 24

granuloma

Answer 24

the heightened phagocytic activity leads to a build-up of lytic enzymes from macrophages in the area of infection

a prolonged DTH response becomes destructive to the host and results in a visible granuloma

continuous activation of macrophages

induces them to adhere closely

fuse to form multinucleated giant cells

can displace normal tissue cells

forms nodules - continue to release lytic enzymes, destroying tissue and blood vessels, and cause necrosis