medsci 202 > lecture 12 > Flashcards

lecture 12 Flashcards

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1
Q

describe how a local skin infection is handled by the immune system

A

e.g. infection by staph aureus on skin
1) local cells will release chemokines
2) chemokines recruit more cells to the site of infection
3) some molecules will also trigger the liver to produce acute phase proteins like complement
4) immune cells are recruited by chemokines - some are close enough to simply migrate while others travel through blood
5) vascular activation and increased permeability enables the recruitment of these immune cells from the blood

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2
Q

what immune cells are present in the blood

A
  • neutrophils
  • monocytes (which differentiate into macrophages in tissue)
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3
Q

what is extravasation

A

physical process of immune cells leaving blood vessels by squeezing through endothelial cells to reach tissues

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4
Q

what is chemotaxis

A

following extravasation, the directional movement of immune cells toward a higher concentration of chemical attractants (like bacteria or chemokines) at the site of infection

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5
Q

what immune cells are the primary responders for most forms of infection

A
  • neutrophils and macrophages
  • these will be there or will be recruited in the first couple of hours
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6
Q

describe the process of phagocytosis

A

1) bacteria is extracellular
2) the bacteria has molecules on its surface that allow it to be recognised, and immune cells have receptors that can recognise the bacteria
3) the immune cells can now detect and phagocytose the bacteria
4) the membrane then begin to wrap itself around the bacteria, internalising it so the bacteria is now inside the phagocyte in a “vesicle”
5) enzymatic and pH based destruction inside the vesicle leads to death of the bacteria
6) if the phagocyte has the ability to present an antigen, then it will do so
7) the bacteria’s debris, aka PAMPs, is released into the tissue environment to activate more immune cells

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7
Q

what are PAMPs

A

small, conserved molecular structures found on microorganisms like bacteria that act as signals for the innate immune system

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8
Q

what are the receptors present on phagocytes

A
  • pattern recognition receptors
  • opsonic receptors
  • complement receptors
  • apoptotic receptors
  • scavenger receptors
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9
Q

describe pattern recognition receptors

A
  • e.g. toll-like receptors
  • detect a broad array of molecular patterns from bacteria, fungi and viruses
  • they also detect the bacterial debris
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10
Q

what is opsonisaiton

A
  • opsonisation is the coating of bacteria with molecules that make it easier to phagocytose
  • e.g. coating with complement or antibodies
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11
Q

describe opsonic receptors

A
  • e.g. Fcγ receptors
  • bind the antibodies that coat a pathogen
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12
Q

describe complement receptors

A
  • e.g. CR1, CR3, CR4
  • bind specific complement proteins
  • can also bind factors from the ECM and acute phase proteins
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13
Q

describe scavenger receptors

A

bind bacterial products e.g. LPS

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14
Q

describe apoptotic receptors

A

bind phosphatidylserine on dying cells to “kill” them

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15
Q

how can bacteria cause damage to host

A

by secreted exotoxins

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16
Q

1 : by what mechanisms by what mechanisms is damage caused to host

A
  • electrolyte secretion
  • necrosis
  • apoptosis
  • superantigen toxins
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17
Q

what does electrolyte secretion cause

A

diarrhea by vibrio cholerae

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18
Q

what does necrosis cause

A
  • unprogrammed death of cells e.g. by S. aureus
  • swelling, redness, pus
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19
Q

what does apoptosis cause

A

programmed cell death e.g. by E. Coli shiga toxins

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20
Q

what does nerve synapse inhibition cause

A

paralysis or tetani by clostridium species of bacteria

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21
Q

what do superantigen toxins cause

A
  • cytokine release/storm
  • potential for organ failure, toxic shock etc
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22
Q

2 : by what mechanisms is damage caused to host

A
  • endotoxins
  • cell wall fragments
  • hydrolytic enzymes
  • inhibition of secretions
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23
Q

what do endotoxins cause

A

inflammatory cascade

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24
Q

describe the process of inflammatory cascade by endotoxins

A
  • e.g. LPS is an endotoxin and PAMP found on gram-negative bacteria
  • TLR4 receptors on innate immune cells bind to LPS
  • this activates an innate immune inflammatory response, causing an inflammatory cascade
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25
what do cell wall fragments cause
an inflammatory cascade
26
describe the process of inflammatory cascade by cell wall fragments
- e.g. lipoteichoic acid from gram-positive bacteria acts as a PAMP - lipoteichoic acid binds to TLR2 and activates an immune response, causing an inflammatory cascade
27
what do hydrolytic enzymes cause
tissue digestion leading to bacterial spread
28
describe the process of tissue digestion by hydrolytic enzymes
- e.g. hyaluronidase in S. aureus 1) breaks down hyaluronic acid in the host's ECM 2) this loosens tissue structure and helps bacteria move around more easily 3) injured cells release DAMPs which triggers more inflammation
29
what does inhibition of secretions cause
less stomach acid so bacteria can't be killed which can lead to ulcers
30
what can cause inhibition of secretions
pathogen Helicobacter pylori
31
#3 : by what mechanisms by what mechanisms is damage caused to host
- multiplication within cells - cross-reactive antibodies - mutation - obstruction
32
what does multiplication within cells
- damage to host tissue - cell death
33
describe the process of damage to host tissue by multiplication within cells
- when viruses, bacteria or parasites exit a host cell, they lyse it, resulting in cell death - if an immune cell wants to target a pathogen inside a cell, it needs to destroy the host cell to reach it
34
what do cross-reactive antibodies cause
immune damage to host tissue, i.e. autoimmune reactions
35
how do cross-reactive antibodies cause autoimmune reactions
- e.g. rheumatic fever caused by S. pyogenes 1) immune system produces antibodies against the that target S. pyogenes antigens 2) some antigen 3) the antibodies don't perfectly distinguish self vs bacteria so they bind to your own tissues as well 4) antibodies trigger inflammation in your tissues resulting in tissue damage
36
what can mutations cause
uncontrolled cell growth, resulting in tumours
37
how can mutations cause uncontrolled cell growth
- viral oncogenes, when infecting a human, can suppress the tumour suppressing genes and activate growth signals - this results in cells dividing repeatedly without control
38
what does obstruction cause
the blocking of blood or lymphatic vessels
39
how can obstruction cause the blocking of blood or lymphatic vessels
1) e.g. Echinococcus granulosus causes hydatid cysts 2) these form a fluid-filled cyst in organs 3) as the cyst expands slowly it presses on nearby structures 4) this leads to reduced blood flow or blocked lymph drainage
40
what are common host responses to damage caused to host
- cytokines - pyrexia (fever) - luekocytosis - acute phase proteins - endocrine changes
41
how do cytokines respond to damage caused to host
- they are pro-inflammatory mediators released by immune cells AND normal local cells - secreted into blood flow to reach other areas of the body - e.g. brain to make it aware and protect itself - e.g. liver to make acute phase proteins
42
examples of cytokines
IL1β, TNF and many others
43
how does pyrexia (fever) respond to damage caused to host
- increases temperature to ~40° as viruses don't find it optimal - inflammatory cytokines released by monocytes and macrophages
44
how does leukocytosis respond to damage caused to host
increased neutrophil and monocyte production from bone marrow
45
how do acute phase proteins respond to damage caused to host
- produced by the liver to limit tissue damage and resolve infection - e.g. complement proteins
46
how do endocrine changes respond to damage caused to host
- producing glucocorticoid steroids and other stress hormones - anti-inflammatory molecules to control the immune response
47
example of inflammation
- suppuration - abscess - ulcers - cellulitis
48
what is suppuration
- a type of inflammation - solid tissue, pyogenic (pus-forming), oozing of pus - can be more or less painful depending on where it forms
49
what is abscess
- a type of inflammation - fibroblasts form a capsule around the infected area - necrotic, pus-filed centre
50
what are ulcers
- a type of inflammation - form on epithelial surfaces and erodes it away to expose tissue - painful
51
what is cellulitis
- a type of inflammation - spreads through loose connective tissue under the skin - treated by antibiotics
52
where are ulcers common
mouth and intestines
53
when are ulcers common
when our immune system is weakened
54
what are the key visual signs of inflammation for local skin infections
e.g. pimple - redness - swelling - heat due to increased blood flow - pain - depending on severity, there can be loss of function
55
are there only visual signs of inflammation
no - increase temperature, swollen lymph glands and other symptoms can also point to inflammation
56
describe the process of an infection breaching the skin barrier
1) bacteria or injury occurs in a specific area and is detected by the immune system 2) chemicals are released and act on nearby blood vessels 3) extravasation: blood vessels become more permeable so immune cells AND plasma can leave the bloodstream 4) heat and redness due to vasodilation which = more blood flow to area 5) swelling due to leakage of plasma from blood into tissue 6) swelling is alleviated by lymphatic vessels draining excess fluid 7) activation of nerve fibres resulting in pain
57
what are dendritic cells
immune cells that capture antigens and present them to T cells in lymph nodes to trigger adaptive immune responses
58
what happens after a local skin infection has been phagocytosed
1) immune cells like dendritic cells and macrophages will go to the lymphatic vessels to travel to the lymph nodes 2) interstitial fluid containing the bacterial and host cell debris will also be carried to the lymph nodes 3) lymphatic vessels will pump the fluid to the lymph nodes
59
what is the purpose of an innate response for local tissue ifnections
- quick to resolve infection and prevent spread - raise the alarm - minimise tissue damage - provide antigens from the infection for delivery to the lymph nodes
60
how can antigens get to the lymph nodes
- immune cells can transport antigens to the lymph organs - antigen presenting cells can process and prepare the antigens for lymph organs - free/soluble antigens: as cellular debris, including host cell debris, through the lymphatic vessels - pathogens travelling to the lymphatic vessels directly
61
what are the primary organs of the lymphatic system
- thymus and bone marrow - the rest of the lymphatic system is secondary organs!
62
describe lymph nodes
- size of a thumb nail - 500-800 strategically located around the body
63
where does the adaptive immune system mostly reside
the lymphatic system
64
what is the lymphatic system connected to
1) the circulatory system leaks fluid into tissues, aka interstitial fluid 2) lymphatic vessels absorb leftover fluid as lymph 3) lymph travels through lymphatic vessels 4) thoracic duct is the main lymphatic vessel that drains lymph from most of the body back into blood
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