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Year 1 - Semester 1 > Week 7&8 - Inflammation and Immunity > Flashcards

Week 7&8 - Inflammation and Immunity Flashcards

1
Q

What are the two types of irreversible injury?

A

Apoptosis

Necrosis

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2
Q

What is necrosis?

A

uncontrolled cell growth
does not require energy
damages surrounding cells

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3
Q

what is coagulative necrosis?

A 
dry gangrene
gangrene is coagulative necrosis in extremities 
lack of nuclei
ghost cell outlines
ischemia
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4
Q

what is liquefactive necrosis?

A 
wet gangrene 
infection
in CNS due to ischemia (only place it doesn't cause coagulative)
cell proteins digested
pus (neutrophils)
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5
Q

what is caseous necrosis?

A

granulomas are a cause (however granulomas don’t always have necrosis)
complete loss of structure
will look like there are lots of blue, powdery grains in it
TB a main cause

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6
Q

what is fibrinoid necrosis?

A

in smooth muscle walls of arteries

eosinophilic/fibrinous deposits (bright, almost hot, pink)

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7
Q

what is fat necrosis?

A

fat undergoes necrosis
releases fat from cells
chalky deposits (white patches on histology)

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8
Q

what is apoptosis

A

controlled cell death
requires energy
everything remains bound in membranes

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9
Q

what are the two types of apoptotic initiation?

A

Intrinsic - aka mitochondrial pathway - related to growth factors
higher levels of pro apoptic BLC2 proteins than anti apoptotic - leads to caspase 9

Extrinsic - ligand binds to extracellular aspect of death domain receptors leading to intracellular conformational change
FAS - first apoptotic signal
TNF - tumour necrosis factor
these activate caspase 8

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10
Q

what happens when apoptosis is initiated

A

caspase 3, 6, 7 activated

apoptotic bodies form - eaten by phagocytes

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11
Q

what do necrosis/apoptosis look like on gel electrophoresis?

A

necrosis - smear

apoptosis - like rungs on a ladder

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12
Q

what is exudate?

A

composed of serum, fibrin, and white blood cells

what leaks from the bloodstream to a site of inflammation

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13
Q

what is a cytokine?

A

any small protein that is involved in cell signalling (not hormones)

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14
Q

what is a chemokine?

A

a type of cytokine. They are able to attract nearby cells, getting them to move to where they need to be. This can be either towards or away from the chemokine. This process is called chemotaxis.

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15
Q

What are integrins?

A

receptors

They’re important in adhesion between cells and the extracellular matrix

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16
Q

what are opsonins?

A

any molecule that has the ability to mark an antigen or dead cell as requiring phagocytosis. They bind to the cell or antigen and make it easier for phagocytes to reach the cells by overriding the charge repulsion between the phagocyte and the target

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17
Q

What is the complement system

A

a system of proteins that enhances the effects of antibodies and phagocytes to clear microbes and damaged cells.
part of the innate immune system
produced by the liver and circulated the blood

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18
Q

What is Substance P?

A

a polypeptide that acts as a neurotransmitter and a neuromodulator

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19
Q

what is inflammation?

A

the reaction of viving, vascularised tissue to injury

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20
Q

what are the primary lymphoid organs

A

Bone marrow - WHERE ALL B AND T CELLS ARE MADE

Thymus - where t cells develop

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21
Q

what are the secondary lymphoid organs?

A

lymph nodes and spleen

also tonsils and appendix

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22
Q

what is the anti-viral state?

A

produce interferon alpha and beta to tell neighbouring cells to start upregulating anti-viral proteins and downregulating RNA production and protein translation

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23
Q

What are PAMPs

A

Pathogen-associated molecular patterns

such as lipopolysaccharide

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24
Q

What are DAMPs

A

Damage-associated molecular patterns

such as DNA, ATP and RNA

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25
Q

What are PRRs

A

Pattern recognition receptors
Detect PAMPs and DAMPs
e.g. toll-like receptors - 10 types
TLR3 binds to double stranded viral RNA
TLR4 binds to lipopolysaccharide, as found in bacterial cell walls
TLR5 binds to flagellin, a protein found in bacterial flagella

release cytokines like IL-1, IL-6 and TNF

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26
Q

why is cleavage of caspases important?

A

caspases cleave proteins, so need to be controlled.
only want caspases to be activated when they need to be i.e. apoptosis
so they are inactive and are cleaved to be activated

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27
Q

what diseases can inflammation worsen/cause?

A 
Cancers
Atherosclerosis
Obesity, type II diabetes
Neurodegenerative diseases
stroke/myocardial infarct
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28
Q

which immune cells are found in the blood?

A

monocytes
NK cells
resident liver macrophages

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29
Q

which immune cells are found in tissues?

A

pericytes
mast cells
tissue macrophages
dendritic cells (especially near blood vessels or surface barriers such as skin and GI tract)

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30
Q

Triggers of inflammation

A

Lack of self - Cell surface molecules that prevent immune attack e.g. MHC class I, complement inhibitors

Perturbed cellular homeostasis (effector-triggered immunity) - e.g. ion balance

Pattern triggered - PAMPs or DAMPs

Mild physical trauma - degranulates mast cells - releases histamine - vasoactive - makes blood vessels leaky -dilation
serotonin acts similarly to histamine - vasoactive

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31
Q

indicators of inflammation

A 
redness
swelling
pain
loss of function
heat
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32
Q

types of exudate

A

Pus -Neutrophil and enzyme rich

Fibrinous - Few cells, greyish sticky fibrin coating

Serous - Few cells, serum-like, little fibrinogen/platelets

Haemorrhagic - Vascular destruction

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33
Q

describe how immune cells get out of the blood to a site of inflammation

A

Margination is the process of neutrophils (and other white blood cells) accumulating near the vessel wall. Slow flow of blood along with the presence of more RBCs in inflammation leads to more margination. They then roll along the wall of the vessel. Histamine, DAMP and cytokines cause endothelium to expose sticky selectins on its surface. Rolling is associated with selectins. Cytokines increases surface adhesion molecules which firmly bind neutrophils. This is called firm adhesion and is associated with integrins. The process of a cell squeezing its way through the endothelium is called diapedesis. Neutrophils are guided out of the venule by pericytes. They then respond to DAMPs and have a transcriptional burst (respiratory burst as there is a generation of ATP), release cytokines, chemokines and growth factors and migrate around the tissue and screen it. Fibrin matrix helps them get around. Phagocytes need a matric to crawl over for directed migration.

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34
Q

neutrophil chemotaxic agents

A 
Self - Coagulation products
        - Complement C5a, C3a 
        - IL-8
Non-self
         -Bacterial endotoxin 
         -F-met-leu-phe peptides (bacteria have this tag on all their peptides)
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35
Q

how do resident macrophages shield trivial injury?

A

“cloak” general wear and tear by covering it
saves energy by stopping immune response
too much injury and it cannot be covered - neutrophils undergo cell death and immune response is initiated

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36
Q

what molecules are involved with pain?

A 
Bradykinin - makes nociceptors more sensitive to pain
ATP
serotonin
histamine
proteases
Prostaglandins
amines
cytokines
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37
Q

what are the three activations of the complement system?

A

Classical pathway - when the body already has antibodies to an antigen

mannose-binding lectin pathway - mannose is not found in human cells - lectin is a class of protein which binds to sugars

alternative pathway - spontaneous activation of C3 - human cells deactivate it but pathogens don’t

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38
Q

what happens when the complement system is activated?

A

all 3 form a C3 convertase which breaks it into C3a (changes blood vessel endothelium and degranulates mast cells) and C3b (opsonin) - C3b also activates C5b which activates the lytic pathway - leads to membrane attack complex MAC which makes pores in pathogen - swells and bursts

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39
Q

what are neutrophils?

A

most common WBC
recruited rapidly
good at killing but dies quickly
makes up pus

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40
Q

what are macrophages?

A 
differentiated monocytes
Good at everything 
Multipurpose
Can kill bacteria but only if activated
involved in healing
Clearance of dead cells. Will eat dying cells
ANTIGEN PRESENTING CELLS
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41
Q

what are eosinophils

A

granulocytes, with granules containing DNAses and RNAses
involved in allergy
stain bright red
bind to IgE on the surface of multicellular parasites, which causes them to degranulate and release compounds which are toxic
perform ETosis (similar to NETosis)

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42
Q

what are basophils

A

BLOOD
granules which release histamine and heparin when activated, causing vasodilatation. These cells act in allergies or parasite infections

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43
Q

what are mast cells

A

TISSUE
granules which release histamine and heparin when activated, causing vasodilatation. These cells act in allergies or parasite infections

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44
Q

what are dendritic cells

A

differentiated monocytes
phagocytes but not very good at it
not very many of them
MAIN ANTIGEN PRESENTING CELLS

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45
Q

what are natural killer cells

A

largely antiviral and anticancer, and kill cells that have been marked for killing by forming pores in them and inducing apoptosis
attack cells which have downregulated MHC I because this is a common strategy of viruses to avoid detection

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46
Q

describe phagocytosis

A

engulfs pathogen to form phagosome

  • Lysosome fuses with phagosome - lysosome contains toxic products to kill/degrade pathogen such as proteases, nitric oxide and hypochlorite (only neutrophils)
  • Now called phagolysosome
47
Q

difference between afferent and efferent lymphatics

A

Afferent lymphatics is where stuff comes into lymph node.

Efferent lymphatics is where stuff leaves the lymph node.

48
Q

how are macrophages activated

A
  • Activation can come from danger signalling or cytokines, especially interferon gamma
  • Interferon gamma is produced by a number of cells including T cells
49
Q

what are NETs

A

Neutrophil extracellular traps
the neutrophil can extrude its own genomic dna.
This works well to trap pathogens which an prevent pathogen disseminating throughout the host and also its extremely inflammatory.

50
Q

what are the possible outcomes of inflammation ?

A

RESOLUTION
extravasation diminishes

pro-inflammatory mediator are catabolised
macrophage phagocytosis of apoptotic neutrophils (efferocytosis) triggers anti-inflammatory cytokine synthesis

Stress hormones inhibition– cortisol, catecholamines, vagus nerve effects
Anti-inflammatory cytokines attenuate sickness behaviours

Immunoresolvant lipid mediators – lipoxins, resolvins, protectins from apoptotic neutrophils
 Suppress extravasation and cytokine release
 Stimulate macrophage clearance and efflux to lymph

After resolution – epigenetic changes alter how some tissues and macrophages respond again to injury for weeks-months

ORGANISATION
tissue replaced with granulation tissue which can be problematic as sticky fibrin adhesions can stick serosal surfaces together e.g. bowel loops

CHRONIC INFLAMMATION

DEATH

51
Q

describe the hazard gradient

A

Infection is very hazardous in sterile vital tissues/blood, compared with “friendly” microbes at epithelial surface such as in the gut
Checkpoint model- in more vital tissues, fewer critical checkpoints can trigger inflammation

  • Extent of cell injury and resident macrophage density (cloaking)
  • Soluble vs particle (multiple PAMP, phagocytic processing)
  • Viability (bacterial/viral nucleic acid)
  • Virulence (system surveillance)
52
Q

what happens when inflammation regulation goes wrong?

A

cytokine storm
Vasodilation throughout body – blood pressure drops
Hyperactivated inflammation but with suppression of the adaptive immune system – run out of immune cells etc – susceptible to another infection
coagulation
In sepsis, this happens in the whole body. Depletes clotting factor, inflammatory and immune cells and platelets in the blood. – unable to clot properly – disseminated intravascular coagulation – leads to capillary haemorrhages – bleeding all over the body into soft tissue
Pro-inflammatory tissue damage – susceptible to secondary infections
vicious cycles of tissue ischemia and necrosis

53
Q

how can phagocytosis be avoided?

A
  • Slippery prey – ie pneumococcus capsule -waxy surface difficult to phagocytose
  • Decoy foreign body such as sutures and catheters
  • Frustrated by slime – secreted by organisms which make it difficult for phagocytes to move around
  • Intracellular organisms evade - tuberculosis
54
Q

how does chronic inflammation occur?

A

persistant infection
presence of a foreign body such as a catheter
autoimmune disease where the inflammation itself is the problem

55
Q

what cells are most involved in acute/chronic inflammation

A

neutrophils most important in acute

macrophages most important in chronic - have a role in the formation of new connective tissue and the remodelling of present connective tissue
frustrated phagocytosis leads to granulomas

56
Q

what are granulomas

A

a mass of granulation tissue formed after frustrated phagocytosis
not vasularised - granulation tissue usually is
body’s way of walling off what it can’t get rid of
macrophages often form giant (multinucleated) cells
if there is necrosis, it is caseous

57
Q

what is an abscess?

A

granulation tissue around pus.
it can heal or discharge in two ways
1 direction - sinus
2 directions - fistula

58
Q

what is a pinoidal sinus?

A

a small hole in the skin that can become infected, forming an abscess

59
Q

what is an inflammatory sinus?

A

a blind ending pit lined by granulation tissue that opens up onto an endothelial surface.

60
Q

what is a fistula?

A

an abnormal linkage between 2 different epithelial surfaces.
Can form between any 2 epithelia surfaces which can be linked.
can happen in Crohn’s disease

61
Q

what is an ulcer?

A

when the top layers of the epithelium are lost from necrosis and lower layers are exposed, which then begin to be worn away themselves - open sore
serious in the stomach as there is no basement membrane to heal from so it must come from the side and the conditions of the stomach make this difficult. can lead to perforating gastric ulcer - potentially fatal haemorrage

If the loss isn’t full thickness this is called an EROSION

62
Q

what do you call lymphocytes which haven’t been activated?

A

naive cells

63
Q

what do B and T cells arise from?

A

from haematopoietic stem cells (HSC) in bone marrow

64
Q

describe B cells

A

• Once activated, become plasma cells
• Plasma cells produce antibodies
• Antibodies are Y-shaped soluble secreted molecules that circulate in body fluids
o Bind to pathogens and kill them/mark them to be eaten/prevent them from spreading
o Used in pregnancy tests, marking specific cells in the lab

65
Q

describe T cells

A
  • CD8+ cytotoxic T lymphocyte (CTL) – kills infected/mutated cells
  • CD4+ helper T cells (Th) – organise immune responses – produce different cytokines- differentiate into different types -Th1, Th2, Th17, Treg
66
Q

what do B and T cells have in common?

A

T and B cells express receptors of random specificity – each T/B cell bears receptors of a single specificity- unique
When the T/B cell binds to its specific antigen, it activates and proliferates
Daughter cells express identical receptor to parent (hence clonal)
Expanded population mediated immune responses and are maintained at higher precursor frequency- ready to respond next time

67
Q

describe T and B cell receptors

A

they have:
• Variable regions at tip which bind to antigen
• Constant regions which do not vary
The BCR is a Y-shaped receptor with a heavy chain and 2 light chains, the variable regions with antigen binding sites being on the end of the light chains. The TCR has an alpha chain and a beta chain, the variable regions with the antigen binding sites occurring on the end of both chains.

68
Q

describe the structure of lymph nodes

A

lymphoid follicles around the edge (primary follicles with mostly B cells and secondary follicles that contain germinal centres with lots of proliferating B cells), then T cells in the parafollicular/paracortical area. In the centre there is the medulla, with blood vessels.

69
Q

describe primary receptor diversity

A

there are multiple copies of 3 types of DNA sequence that contribute to the antigen-binding site: the variable (V) segment, diversity (D) segment, and joining (J) segment.
Somatic recombination occurs - wherein one copy of each type of segment (so 1 V, 1 D, 1 J) are selected and expressed on any given lymphocyte. Light chain just V and J
Because of how many segments there are in the germline, there are billions of possibilities of combination. This is combinatorial diversity - diversity, generated from combining different gene segments.
there are also
• Different Heavy/Light chain (BcR) combinations
• Different alpha/beta chain (TcR) combinations

Junctional diversity - Sometimes, the DNA breaking and rejoining involved in generating combinatorial diversity has mistakes - it’s a very inaccurate process. This allows new nucleotides to be inserted or present nucleotides to be lost as the “wrong” section is joined, or nucleotides have to be deleted by DNA repair machinery. Although these are technically mistakes, and they can cause frameshift or nonsense mutations that lead to the kind of non-functioning or poorly functioning lymphocytes that are killed off, it does massively increase the diversity of T and B cells available to us.

70
Q

what are the three types of regeneration?

A

LABILE cells - renewal - constantly replacing themselves such as in the GI tract and skin

STABLE cells - compensatory - such as in the liver and kidney, which aren’t constantly proliferating in the body’s normal homeostasis, but are capable of regenerating after injury and necrosis. Scarring will still happen if these mechanisms can’t keep up with the extent of the damage.

PERMANENT cells - none - such as in cardiac myocytes or neurons - scar formation

regeneration is tightly controlled by growth factors and physical stimuli from the matrix they sit in

71
Q

what happens when a tissue cannot regenerate?

A

fibrous scar production (fibrosis) to patch damaged tissues

72
Q

what are the stages of healing by scarring?

A
  1. bleeding
  2. clot formation
  3. acute → chronic inflammation
  4. fibroblast infiltration: neomatrix – matrix changes
  5. angiogenesis – blood vessel growth; fibrillar collagen
  6. scar maturation
73
Q

what are the stages of scar formation?

A
  1. fibroblast migration and proliferation
  2. extracellular matrix deposition
  3. tissue remodeling
74
Q

describe fibroblasts

A

• resident mesenchymal cells – non-polar – don’t have an “up and down”
• source of connective tissue
• migration and proliferation triggered by growth factors
• more production and less degradation
• collagens – types 1-3 are fibrillar, type 4 is basement membrane
also put down elastin, proteoglycans, glycoproteins

75
Q

describe the remodelling of scars

A

The remodelling and maturation of the scar requires the newly formed ECM to be degraded by enzymes called matrix metalloproteinases (MMPs)
The action of these MMPs are mediated by tissue inhibitors of metalloproteinases, or TIMPs

76
Q

what is fibrosis?

A

very similar to scarring but it involves the thickening of the connective tissue in response to continuous injury. This can lead to the loss of function of the organ that it is attempting to protect. End stage scarring occurs when continued injury and progressive scarring leads to irreversible scarring that can render an organ non-functional such as that which we see in liver cirrhosis.

77
Q

what does a BcR recognise?

A

recognise soluble antigen in its normal (native) form. Antigen can be sugar, lipid, chemical or protein

78
Q

what does a TcR recognise?

A

has to have the antigen “presented” to them on Major Histocompatibility Complex (MHC) molecules on another cell

79
Q

what happens to protein antigens?

A

chopped up into peptides and “loaded” onto MHC to be presented

80
Q

what are haptens?

A

antigens which are sugars, lipids etc which need to be bound to a large carrier protein to illicit an immune response

81
Q

describe Class I MHC

A

CD8+ only bind to antigens on this type (think 1 x 8 = 8)
on all nucleated cells (not RBCs) except neurons
Presents only endogenous antigens = from within cell

Single alpha chain (with alpha 1, 2 and 3 subunits) and a beta 2 microglobulin polypeptide , alpha 1 and alpha 2 form a peptide-binding cleft

82
Q

describe Class II MHC

A

CD4+ only bind to antigens on this type (think 2 x 4 = 8)
Only on specialised Antigen Presenting Cells (APC) -most important of these are dendritic cells
Presents exogenous antigens – from outside cell
Extracellular pathogens, environmental proteins, food proteins, self proteins

alpha and beta chain – form similar shape to class 1 but have alpha 1, alpha 2, beta 1 and beta 2 subunits. alpha and beta 1 form the cleft

83
Q

Where do the peptides bind on MHC?

A

via anchor residues on the peptide binding cleft

each MHC molecule can only bind a few peptides

84
Q

How do we get diversity in MHC

A 
Polygeny – multiple independent genes for each MHC type
Co-expression-  alleles inherited from mother and father – potentially 6 different types of MHC class I and MHC class 2 being expressed
Polymorphisms- multiple variants of each gene within the human population (most polymorphic of all genes – mainly in the peptide binding chain)
85
Q

what is the downside of MHC diversity

A

major cause of transplant rejection

1 in 100,000 chance of matching an unrelated donor

86
Q

what does HLA stand for?

A

Human leukocyte antigen

87
Q

what is central tolerance?

A

T cells are selected on their ability to bind to MHC

negative selection - self antigens presented and if T and B cells bind too strongly then they receive apoptotic signals and die off - to prevent autoimmunity
too weak - undergo apoptosis

Low affinity – fail selection and die
High affinity- negatively selected and deleted
In the middle are positively selected and survive
Some self-specific T cells escape death and become Tregs

selection of T cells is very wasteful - 95% are delete

88
Q

what is peripheral tolerance?

A

B and T cells require costimulation to be activated, not just an antigen
if a naive lymphocyte responds to signal 1 (antigen) but does not receive signal 2 (costimulatory verification), it undergoes anergy (hyporesponsive to antigens)

this is immune regulation from Tregs (regulatory T cells)
also receive signal 3 – (tells T cell what kind of pathogen it is and comes from innate immune cells)

89
Q

types of Tregs

A 
Natural Tregs (nTregs) – recognise self antigens – arise in thymus
Inducible Tregs (iTregs) – recognise self or environmental antigens – arise in periphery
When activated, CD4+ Tregs switch off adaptive or innate immune responses
o	Produce cytokines that dampen immune responses (IL-10)
90
Q

what does Th1 do?

A 
T helper (CD4+)
viruses and intracellular bacteria
91
Q

what does Th2 do?

A

T helper (CD4+)
parasitic worms and allergy
IL-4, IL-5, IL-13

92
Q

what does Th17 do?

A 
T helper (CD4+)
extracellular bacteria, fungi and yeast infections
93
Q

what is amyloid

A

insoluble protein - build up of acute phase reactants - can polymerise and can be deposited around the body - component of alzheimer’s

94
Q

what is the order of activation of lymphocytes?

A

antigen presenting cell activate CD4+ which direct B cells and give costimulatory verification to CD8+

95
Q

what is independent B cell activation?

A

they don’t require a T helper cell to activate them
For T independent antigens, the costimulatory signals come from microbes, cytokines and APCs.
This activation will cause the B cell to produce IgM, which is the dominant antibody in the initial immune response. This response is rapid

96
Q

what is somatic hypermutation?

A

when a B cell is activated by a CD4+, it proliferates and its BcR genes undergo very high rates of mutation.
Largely driven by substitutions of single bases in the heavy chain of the BCR and the variable “V” region of the light chain.

97
Q

how do cytotoxic T cells kill?

A

Firstly, CTLs release cytotoxins like perforin and granzyme. Perforin forms a pore in the target cell, allowing the granzyme to enter. The granzyme is a protease enzyme that activates caspases to induce apoptosis.
Secondly, they can use Fas ligation, where FAS is a ligand that binds to a FAS receptor.
a method of directly stimulating the cells to undergo apoptosis.

98
Q

what is affinity maturation?

A

the stronger binding B cells after somatic hypermutation are selected. Those with lower affinity die off
This very important for those monomeric antibodies where you have just 2 binding sites like IgG, need to generate very strong binding antibodies.

99
Q

what is class switching?

A 
where CD4+ signals to the activated B cell to produce a different class of antibody 
only on constant region
 The B cell will produce IgM first, but will undergo gene rearrangement to produce a different one (IgG, IgA or IgE) depending on what is needed
This can’t occur in T-independent activation, therefore you’ll just produce IgM from it
100
Q

IgM

A 
pentamer in structure (where the Y shaped proteins are the monomers making it up), making it the largest antibody. It’s the first to be released and isn’t very specific. 
10 binding sites
responsible for complement activation
neutralise toxins
in blood
bind to Fc-alpha/mu
101
Q

IgG

A 
monomer (2 binding sites)
responsible for complement activation
antibody-dependent cell cytotoxicity (opsonizes for cytotoxic killing by NK cells)
only antibody isotope that can cross the placenta
neutralise toxins
bind to Fc-gamma
Extra mucosal
4 sub classes
second to be released after IgM
102
Q

IgE

A

monomer (2 binding sites)
involved in activating innate immunity in the form of allergy by activating mast cells and basophils
bind to Fc-epsilon

103
Q

IgA

A

IgA is a dimer. (4 binding sites)
neutralise toxins
bind to Fc-alpha/mu
Mucosal

104
Q

IgD

A

monomer (2 binding sites)
makes up a small percentage of antibodies - in blood
activates basophils and mast cells

105
Q

what is neutralisation?

A

blocking binding of toxin to receptor on tissue cells by antibodies (e.g. as in tetanus, diphtheria, cholera, flu)

106
Q

What is type I sensitivity?

A 
Classic allergy - antibody mediated
Host has pre-existing IgE to allergen
2nd response involves cross-linking on mast cells which degranulates them
Localised response
o	Hives, blisters, nasal discharge
o	Hayfever, asthma
Systemic response
o	Anaphylaxis
107
Q

what are allergens?

A

Proteins, often proteases
Low molecular weight and highly soluble – diffuse into mucous
Very stable – can survive in desiccated particle
Contain peptides that can bind MHC class II (T cell priming

108
Q

what is anaphylaxis?

A 
Profound systemic response to allergens 
Vasodilatation due to histamine etc.
Hypotension (low BP) OedemaBronchoconstriction (histamine, bradykinins)
Treatment is symptomatic 
o	Adrenaline 
o	β-agonists 
o	IV Fluids
o	 Corticosteroids
109
Q

what are autoimmune diseases?

A

failure of self-tolerance due to:
• Genetic susceptibility
• Environmental triggers

110
Q

what is type II sensitivity?

A

IgM/IgG - antibody mediated
bind to host cells - phagocytosis, antibody-dependent cellular cytotoxicity and complement-mediated lysis

haemolytic anaemia/rhesus reaction/myasthenia gravis/graves disease

111
Q

what is type III sensitivity?

A

Immune complexes (antibody+antigen) - antibody mediated
Often deposited in tissues with high blood filtration pressure
o Kidneys & joints
o Skin & blood vessels
Immune complex-mediated inflammation & tissue damage
• Acute inflammation with inflammatory cell recruitment, platelet aggregation, vasodilatation, vasculitis, fibrinoid necrosis.

SLE (systemic lupis erythematosis) - failure in self tolerance of B and T cells - DNA and RNA bind to receptors

Vasculitis 
	Glomerulonephritis 
	Pericarditis
	 Butterfly rash 
	Arthritis 
	Pleural effusions
112
Q

what is type IV sensitivity?

A

delayed type - T cell mediated
response 1-3 days after contact with antigen
tuberculin - CD4+ and macrophage accumulation and associated cytokine expression IRN gamma and TNF
leads to granuloma with lymphocytes around the outside

113
Q

which sex is more likely to develop autoimmune diseases?

A

females - endocrine factors

114
Q

how can T cell tolerance be bypassed?

A

Modification- neoantigen generated by binding of a pathogen to a self component
Inflammation- immunostimulatory environment activates self-reactive T cells
Molecular mimicry- antibodies of T cells generated in response to infection cross-react with self because the antigens are similar

Year 1 - Semester 1 (9 decks)

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