immune system Flashcards
describe viruses
obligate intracellular parasites
hijacks host machinery to propogate themselves
ability to evade our immune defences (virulence factor)
describe bacteria
singe cell prokaryotes
extracellular/intracellular
virulence is factors they produce e.g toxins, enzymes, motility etc
what are the two types of immunity
innate and adaptive
what are the three components of innate immunity
static/anatomical barriers
soluble barriers
cellular barriers
what are examples of static barriers
skin
mucosa
stomach acid
tears
microbiome
what are examples of soluble barriers
antimicrobial peptides
complement proteins
cytokines
opsonins
what are examples of cellular barriers
macrophages
neutrophils
NKC
basophil/mast cell
dendritic cells
what are examples of the cells in the adaptive immunity
t cells (CD4 and CD8)
b cells
what do NKC do
kills by apoptosis
what do neutrophils do
phagocytose bacteria and viruses
what do basophilss/mast cells do
inflammatory response
what do macrophages do
phagocytose bacteria and viruses
what do dendritic cells do
links to adaptive immunity by presenting antigens on surface to activate t cells
what do CD4 t cells do
secrete cytokines to help other cells (t helper cell)
what do CD8 t cells do
kills by apoptosis
what do B cells do
divide and differentiate into plasma cells which secrete antibodies
contrast the innate and adaptive immune responses
innate is non specific whereas adaptive is specific
innate has already formed barriers to combat pathogens whereas the adaptive takes time to build up defence
innate recognises common components of pathogens whereas adaptive recognises any pathogen
innate has no memory whereas adaptive does
what is the intugementary system comprised of
skin and accessory organs
what is the function of the integumentary system
protection
immunity
sensation
thermoregulation
water balance
waste excretion
vit D production
what are the 3 layers of the skin
epidermis (outermost layer/epithelial tissue)
dermis (CT)
hypodermis (adipose tissue)
describe the epidermis
stratified squamous keratinised epithelium that is avascular and contains a basement membrane that attaches to CT and is semipermeable
what are the 5 layers of the epidermis
stratum corneum
stratum lucidum
stratum granulosum
stratum spinosum
stratum basal
what is the stratum basal
bottom most layer of epidermis containing single layer of epithelial cells
germinating layer (i.e stem cells where keratinocytes start to grow)
constantly dividing
tightly bound to underlying CT
what is the stratum spinosum
has spiny projections of desmosome microfilaments > maintenance and structural integrity which assist in holding the cells tightly together and giving the skin strength, resilience and flexibility
what is the stratum granulosum
thin granular layer
keratinocytes accumulate granules of keratin as they migrate towards the surface > secrete keratin into extracellular space
what is the stratum lucidum
thin clear layer of cells
starting to die
filled w intermediate form of keratin
only seen in thick skin (palms and soles)
what is the stratum corneum
outermost layer > multiple layers of dead cells embedded in keratin
waterproof barrier
desquamation > cells shed
very thick in thick skin
what are the four cell types in the epidermis
keratinocytes
langerhan cells/dendritic cells
melanocytes
merkel cells
what are keratinocytes
provide protection by producing keratin
what are langerhan cells
cells of the immune system
antigen presenting cells
derived from bone marrow
mostly in stratum spinosum
bone marrow > in blood as monocyte > differentiate into langerhan cell > ingest > digest > present antigen > lymph node > warn others
what are melanocytes
produce melanin
stratum basal
ingested by keratinocytes > moved to apex to protect nucleus > protects DNA from photo damage
what are merkel cells
mechanoreceptors > respond to stretch or torque
in highly sensitive skin
long processes that interact w cells across different layers
reside in stratum basal
describe keratinisation
as keratinocytes move towards surface of skin > increased keratin production > cells flatten + nuclei disappear > layers or keratinised cells form stratum corneum
how long does it take for skin to regenerate completely
approx 28 days
contrast thin and thick skin
thin skin covers most of the body whereas thick is palms and soles
thin skin has a thin stratum corneum whereas thick skin has a thick stratum corneum
thin skin has no stratum lucidum whereas thick does
thin skin has hair follicles whereas thick does not
why is there a corrugated interface in the junction b/w epidermis and dermis
increase SA > adds strength > ensures integrity of the joining of the two layers
describe the dermis
two layers: papillary dermis and reticular dermis
papillary dermis - loose CT
reticular dermis - dense CT w thick collagen fibres > provides strength
describe the hypodermis
layer of adipose tissue that underlines the skin
what is the function of the hypodermis
insulation
energy storage
cushioning
what are the ancillary structures in the integumentary system
nerves
sweat glands
hair/hair follicles
describe the role of nerves in the integumentary system
sensing temp, touch, pain and pressure
high density of nerve endings
each sense has its own nerve fibre
what are the two types of sweat glands in the integumentary system
merocrine (eccrine)
apocrine
describe merocrine sweat glands
widely distributed
secrete sweat directly onto skin surface
describe apocrine sweat glands
areas of hair e.g under arms
connected to hair follicles so that hair shaft can move secretions onto surface
what are the two portions of the sweat glands and what do they do
secretory portion which make and release sweat
duct portion which sweat travels along
what is the function of sweat glands in the integumentary system
thermoregulation
waste removal
what do hair and hair follicles do in the integumentary system
involved in touch sensation and thermoregulation
has sebaceous glands and arrector pilli muscles
describe thermoregulation in cold environments
cold
> vasoconstriction > blood away from surface of skin
> arrector pilli muscles contract > trap heat
describe thermoregulation in hot environments
heat
> vasodilation > blood towards surface of skin
> swear glands > sweat > evaporation
> arrector pilli muscles relax > heat escape
what is the function of barriers to infection
prevents pathogens from crossing epithelia and colonising tissues
describe the anatomical barrier mucous membranes
has mucus which is produced by goblet cells > it is highly viscous so it traps microbes
has cilia which are hair like projections > propel microbes out of tracts
describe the anatomical barrier commensal microbes
digest dietary fibres > produce metabolites, vitamins, short chain fatty acids > maintain healthy colon
competes w pathogenic microbes for nutrients and space
release antimicrobial substances (lactic acid and bacteriocins)
can commensal microbes causes disease
yes under some circumstances
for example, when the body is immunocompromised the commensal bacteria becomes opportunistic and takes over
describe the soluble barrier antimicrobial peptides (AMPs)
cationic proteins that disrupt membrane integrity or cell anabolism
e.g Defensins
produced by keratinocytes, mucosa, neutrophils, macrophages
do AMPs bind and destroy eukaryotic membranes
no
since they are cationic and bacterial membranes have a negative charge, they are more drawn to that
mammalian membranes have cholesterol which makes the membrane not have a negative charge so it doesn’t attract AMPs
describe the soluble barrier complement system
complement activation > cascade activation of complement proteins > opsonisation, initiation of inflammatory response, punching of hole in cell membranes
what are the 3 types of complement activation
classical pathway
alternative pathway
lectin pathway
what happens in the classical pathway of complement activation
complement component recognises antibody-antigen complex
what happens in the alternative pathway of complement activation
complement component binds generally on to microbe surface
what happens in the lectin pathway of complement activation
complement component binds onto sugar residues on bacteria surface
what is opsonisation
complement protein coats surface w C3b proteins to promote phagocytosis
what happens to initiate inflammatory response
release of anaphylatoxins > binds to immune cells to trigger inflammatory response / chemoattractants to phagocytes
what happens in the punching of holes in cell membranes
formation of membrane attack complex (MAC) on surface of target cells
describe the soluble barrier opsonins
they are soluble proteins
tag microbes so that it is easier fro phagocytes to eliminate
what are the professional phagocytes
neutrophils and macrophages
what is the difference b/w apoptosis and phagocytosis
apoptosis is of infected/tumour cells by NK cells
phagocytosis is of extracellular bacteria by professional phagocytes
what are the 2 major mechanisms of endocytosis
pinocytosis (non specific)
receptor-mediated (specific)
explain the process of phagocytosis
- plasma membrane expands to form pseudopods
- pseudopods retract and seal off to form phagosome
- phagosome fuse w lysosome
- lysosome release lysozymes which break down the foreign material
- broken down material excreted by exocytosis
what triggers phagocytosis
recognition of microbes directly > pattern recognition receptors (PRRs) which sense common patterns like lipopolysaccharide
recognition of microbes indirectly > opsonin receptors e.g C3bR which detects the complement protein C3b
explain the role of NK cells
- recognises tumour/infected cell
- degranulation occurs ie NK cells release cytotoxic chemical
- infected cell self destructs into apoptotic bodies
- apoptotic bodies are detected and phagocytosed by professional phagocytes
how are NK cells made in haematopoiesis
haematopoietic stem cell > common lymphoid progenitor > NK cells
made in bone marrow, mature in thymus
how are CD4 and CD8 t cells made in haematopoiesis
haematopoietic stem cell > common lymphoid progenitor > T pre cursor > CD4 and CD8
made in bone marrow, mature in thymus
how are B cells made in haematopoiesis
haematopoietic stem cell > common lymphoid progenitor > B precursor > B cell
made in bone marrow, mature in bone marrow
how are granulocytes made in haematopoiesis
haematopoietic stem cell > common myeloid progenitor > granulocytes (neutrophils, eosinophils, basophils)
made in bone marrow, mature in bone marrow
how are platelets made in haematopoiesis
haematopoietic stem cell > common myeloid progenitor > megakaryocyte > platelets
made in bone marrow
how are erythrocytes made in haematopoiesis
haematopoietic stem cell > common myeloid progenitor > erythroblast > erythrocytes
made in bone marrow
how are macrophages made in haematopoiesis
haematopoietic stem cell > common myeloid progenitor > monocyte > macrophage
made in bone marrow, mature in tissue
how are dendritic cells made in haematopoiesis
haematopoietic stem cell > common myeloid progenitor > monocyte > dendritic cell
made in bone marrow, mature in tissue
what are primary lymphoid organs
where lymphocytes undergo ontogeny
that is, they develop into mature B and T cells ie in bone marrow and thymus
what happens during lymphocyte ontogeny
B and T cells develop receptors to recognise non self antigens
what occurs at secondary lymphoid organs
mature lymphocytes encounter antigen and differentiate into effector cells (t helper cell, cytotoxic t cell, plasma cell)
what are the two secondary lymphoid organs
lymph nodes
spleen
function of the lymph node
filters tissue borne antigens
lymph enters via the afferent lymphatic vessel, filters through the parenchyma, leaves via efferent lymphatic vessel
function of the spleen
organ that filters blood-borne antigen
function of mucosal-associated lymphoid tissue (MALT)
filters mucosa-borne antigens
what are the lymph node vessels
afferent and efferent lymphatic vessels
lymphatic artery
lymphatic vein
what is the functional tissue of the lymph node known as
parenchyma
what are the major regions of the parenchyma
cortex - predominant B cells arranged in primary and secondary follicles
paracortex - predominantly T cells
medulla - populated by both B and T cells
how does lymphocyte trafficking occur
lymphocytes enter node via artery > through high endothelial venue into paracortex > T cells stay in paracortex while B cells migrate into cortex > B cells meet antigens > when it is time to leave, both B and T cells leave via efferent vessel
what are cytokines
intercellular communicators > secreted to communicate w another cell (receiver cell must have corresponding receptor)
what are the 3 cytokine actions
autocrine (self)
paracrine (neighbour cell)
endocrine (distant via blood)
what are actions of interleukins (IL)
inflammatory response
> macrophage releases TNF-alpha and IL-1 beta > binds to receptor > neutrophil binds to homing receptor > extravasates
proliferation
> CD4 releases IL-2 > autocrine > CD4 proliferates
what are interferons (IFN)
fight against virus infection
IFN alpha and IFN beta inhibits viral replication in neighbouring cells
what are chemokine
chemotactic cytokine > recruitment of cells
IL-8 released by macrophage > ‘trail’ that extravasated neutrophil follows
what MHC marker do CD8 t cells recognise peptides on
MHC 1
what MHC marker do CD4 t cells recognise peptides on
MHC 2
does MHC 1 present endogenous or exogenous peptides
endogenous
does MHC 2 present endogenous of exogenous peptides
exogenous
where are MHC 1 markers found
all nucleated cells
where are MHC 2 markers found
antigen presenting cells (dendritic cells, macrophage, B cells)
describe the process of antigen processing w MHC 1
endogenous protein > digested into short peptides > peptides taken into ER > loaded onto MHC 1 marker > MHC 1 exported to surface > MHC 1 expressed on surface of nucleated cell
describe the process of antigen processing w MHC 2
uptake of exogenous antigen > digested in endoscope > MHC 2 enters endoscope > peptide loaded onto MHC 2 > MHC 2 expressed on surface of antigen presenting cell
what is MHC 1 used for
intracellular pathogen or tumour > initiate apoptosis
CD8 T cells activate via MHC 1 > produce effector t cytotoxic cell > kill infected cell
what is MHC 2 used for
extracellular pathogens > produce antibody and phagocytosis
CD4 T cells activate via MHC 2 > production of t helper cells
immunoglobulin vs antibody
Ig = structure
Ab = function
describe IgM
pentametric
10 antigen binding sites
binds to antigen in blood and tissue
first Ig to be secreted
describe IgG
monomeric
2 antigen binding sites
binds to antigen in blood and tissue
high affinity
secreted on 2nd encounter w antigen
binds to Fc receptors on macrophage and neutrophils
describe secretory IgA
dimeric
4 antigen binding sites
binds to antigen in mucosa
protected from enzymatic degradation by secretory component
where are Ig produced
By B cells in bone marrow
what are Ig expressed on surface of B cell called
B cell receptor
what do antibodies bind to
epitopes (antigenic determinants) on antigens
> forms Ab-Ag complex (no covalent bonding)
what is the structure of Ig
4 polypeptides joined by disulphide bonds
y shaped
2 light chains
2 heavy chains
what is the function of Ig
binds specifically to antigen
base of molecule mediates biological activity
what are the 5 Ig isotypes
IgG
IgA
IgM
IgE
IgD
what are the roles of Ab
neutralisation - blocks binding to host cell
agglutination - prevents colonisation
opsonisation - enhances phagocytosis
complement activation - leads to cell death
what is Ab affinity
strength of binding of Ab to antigen
why is a higher affinity better
higher affinity means an AbAg complex can form for longer so that biological functions can take place
how does the humeral response begin
B cells made in bone marrow > circulation > moves to secondary lymphoid tissue > here, there is a B cell repertoire waiting to meet an antigen
antigen > lymph node > recognised by appropriate (specific BCR) B cell
describe the process of clonal selection
activated B cell proliferates to make clones of itself > differentiates into plasma (effector) cells and memory B cells expressing IgG
what do Plasma cells do
secrete IgM Ab into circulation to neutralise antigen
what do memory B cells do
remain in circulation in case of secondary exposure so that it can repeat the clonal proliferation process again
Do IgG also get secreted
yes they are secreted by plasma cells in the second encounter
describe the primary antibody response
1- lag period
2- initial spike of IgM
3- followed by rise in IgG
4- at the end, many B memory cels expressing IgGs are formed > primed against antigen
why is there a large lag period at the start of the primary immune response
time for B cells to meet antigen, proliferate, make plasma cells that secrete antibodies
describe the secondary antibody response
1- reduced lag period
2- initial spike of IgG 9much higher than the primary response)
3- followed by spike of IgM (similar to primary response)
4- at the end, more B memory cells expressing IgG are formed
why does the secondary response have a shorter lag phase
there are already many B memory cells present, so it takes less time for the antigens to be recognised and for antibody secreting plasma cells to be produced
describe the activation of naive CD4 t cells into t helper cells
naive CD4 meets processed Ag on MHC 2 marker on antigen presenting cell > activates > clonal expansion > differentiates > T helper cell formed
describe the activation of naive CD8 t cells into cytotoxic t cells
naive CD8 meets processed Ag on MHC 1 marker AND receives cytokines from t helper > clonal expansion > differentiates > cytotoxic t cells formed
describe the role of T helper cells
recognise peptide on MHC 2 marker on naive b cell > release cytokines > b cell activated > differentiate/proliferate > antibody production
release cytokines > activate macrophage > increased phagocytotic activity and increase expression of MHC 2
what are the local vascular changes during an inflammatory response
vasodilation
increased membrane permeability
describe the role of T cytotoxic cells
recognises peptide presented on MHC 1 on self cell > initiates apoptosis
describe the mechanism behind apoptosis
immune cell recognises self cell > forms seal with a gap > immune cell releases perforins and granzymes which go towards the self cell through the gap > perforins attach to self cell to form pores > grazymes travel through pores > initiate apoptosis
how do other immune cells contribute to cell mediated immunity
Antibody dependent cell cytotoxicity
here immune cells detects antibodies binding onto target cell > things like apoptosis, phagocytosis and lytic enzymes
what is vaccination
process of getting a vaccine
what is immunisation
process of getting a vaccine and becoming immune to the disease
what is a vaccine
a weak (attenuated) form or part of an infections agent
what does immunisation do
primes the immune system before a natural infection
lower chance of falling ill and lessens the severity due to the presence of more memory B cells and IgG
vaccination of what leads to just humoral immunity
inactivated whole organism
purified or recombinant subunit
> do not enter the cell
vaccination of what leads to both humoral and cell mediated immunity
live attenuated
mRNA
> enters cell
what are the 4 types of vaccines
live attenuated
inactivated vaccines
= whole organism
purified subunit
cloned
= part of organism
how does vaccination stimulate antibody production
vaccine > dendritic cell takes it up > presented on MHC2 to naive CD4 cells > CD4 activates and differentiates into T helper cells
B cell independently recognises vaccine > present on MHC2 > B cell also receive cytokines from t helper > B cell proliferate and differentiate into IgM producing plasma cells and IgG expressing memory B cells
describe formation of live attenuated vaccines
virus passed on from one culture to another > accumulates genetic mutations > acclimatises to new environment > becomes attenuated
what are the pros and cons of live attenuated vaccine
pros
single dose only
imparts life long humoral and CMI
cons
reversion to wild type
describe formation of inactivated vaccines
virus injected into chicken egg > viral replication > harvest virus > inactivate w beta-propiolactone
what are the pros and cons of inactivated vaccines
pros
stimulates humoral immunity
no reversion to wild type
cons
little to no CMI
more than one dose required
contains egg product
describe formation of purified subunit vaccines
break up bacteria > isolate capsular polysaccharides > conjugate to protein > vaccine stimulates production of IgM and IgG and B memory cells
pros and cons of purified subunit vaccines
pros
stimulates humoral immunity
no chance of reverting to wild type
cons
little to no CMI
more than one dose required
describe formation of cloned vaccines
isolate genetic material and produce recombinant products
pros and cons of cloned vaccines
pros
stimulates humoral immunity
no reversion to wild type
cons
multiple doses required
what is an adjuvant
substance that enhances immune response
why are vaccines sometimes administered w an adjuvant
slow release of vaccine > prevents it from being cleared too quickly > greater antibody response
what is passive immunity
transfer of ready made antibodies from one person to another > short lived and no memory
e.g breastfeeding
what is inflammation
protective response designed to rid the organism of both the cause of injury and the consequences of the injury
linked to healing/repair
what are the key components of inflammation
blood components
blood vessels and endothelium
chemical mediators
cellular and extracellular components of CT
what are the type types of inflammation
acute and chronic
what is acute inflammation
occurs directly after injury
lats for minutes, hours or days
immediate vasodilation and increased vessel permeability
what are causes of acute inflammation
infections
trauma
infarction
what are aims of acute inflammation
deliver nutrients and defence cells
destroy any infective agents
remove debris
what are clinical effects and causes of acute inflammation
redness - vasodilation and increase blood flow (hyperaemia)
heat - hyperaemia
pain - pressure on nerve endings
swelling - accumulation of exudate and hyperaemia
loss of function - direct local damage + combined effects of above
what are systemic effects of acute inflammation
malaise
myalgia
arthralgia
decreased appetite
leukocytosis
fever
what are features of acute inflammation
vascular and cellular response
chemical mediators
exudate
variable tissue necrosis
explain vascular and cellular response in acute inflammation
vasodilation and increase blood flow which then slows down > vessels become leaky and permeable > exudation > neutrophils attracts to damaged area > macrophage and lymphocytes migrate to damaged area
what is the main cell type in acute inflammation
neutrophils
what is neutrophilia
increase in neutrophil count in blood
what are some chemical mediators of acute inflammation and what do they do
histamine - vasodilation, increase vascular permeability
serotonin - vasodilation, increase vascular permeability
prostaglandins - vasodilation, pain, fever
what is exudate
protein rich fluid and cells that have escaped from blood vessels due to increase vascular permeability
contains fluid, fibrin, many neutrophils and few macrophages
what is the function of exudate
carries proteins, fluids and cells from local blood vessels into the damaged area to mediate local defences
destroy infective causative agent
breakdown and remove damaged tissue
what are the 4 types of acute inflammatory exudate
serous
fibrinous
purulent
hemorrhagic
describe serous exudate
generally less serious
thin fluid
e.g blister
describe fibrinous exudate
large amounts of fibrin
common in membrane lined cavities
e.g pericarditis
describe purulent exudate
large quantities of pus
e.g brain meningitis
describe hemorrhagic exudate
many red blood cells due to ruptured blood vessels
what are the 3 outcomes of acute inflammation
resolution
repair
chronic inflammation
describe the resolution outcome of acute inflammation
return of damaged tissue to normal
minimal damage
describe the repair outcome of acute inflammation
damaged tissue must undergo repair
scar tissue formation
healed tissue may differ from original tissue
describe the chronic inflammation outcome of acute inflammation
damaged tissue unable to repair itself bc persisting damage stimulus
what is chronic inflammation
inflammation of prolonged duration
persists until damaging stimulus is eradicated
tissue cannot undergo resolution
causes of chronic inflammation
unresolved acute inflammation
prolonged exposure to potentially toxic endogenous/exogenous agents
immune-mediated
explain unresolved acute inflammation causing chronic inflammation
e.g osteomyelitis
persistent infection in bone
explain exposure to potentially toxic agents causing chronic inflammation
e.g wear particles in prosthetic implant
degradation over time > release toxic exogenous agents > granulomatous inflammation
explain immune-mediated cause of chronic inflammation
e.g rheumatoid arthritis
autoimmune > destruction of articular cartilage
what are some common systemic effects of chronic inflammation
arthralgia
myalgia
fever
chronic fatigue
depression, anxiety
what are features of chronic inflammation
mononuclear cell infiltration
tissue destruction
attempts at healing via fibrosis and angiogenesis
what are the main cells involved in chronic inflammation
macrophage
lymphocytes
plasma cells
what are pros and cons of activated macrophages
positives
increased lysosomal enzymes
production of cytokines, growth factors, and other mediators
negatives
responsible for much of the tissue injury
what is a granulomatous inflammation
focal collections of macrophages, epitheloid cells, and multinucleate giant cells that have a amassed substance they cannot digest
how does a granulomatous inflammation occur
injury > inability to digest inciting agent > failure of acute inflammatory response > persistence of injurious agent > recruitment of macrophages w epitheloid and giant cell formation > granuloma
what are other cells involved in chronic inflammation
fibroblast
endothelial cells
eosinophils
what are the two outcomes of chronic inflammation
organisation and repair - fibrosis / healed tissue will differ from original tissue / loss of function
co morbidities - poor prognosis
chronic inflammation is a contributor to diseases such as…
cancer
Alzheimers
CVD
CKD
what are the aims of wound healing
remove damaged tissue
fill a gap caused by tissue destruction
restore structural continuity
restore function
what are the two types of wound healing
regenerative - tissue replaced w functional tissue
non regenerative - replacement of tissue w CT (scar)
which cells can undergo regenerative healing
labile cells
stable cells
what are the phases of wound healing
reactive phase
reparative phase
remodelling phase
describe the reactive phase of healing
haemostasis - platelet aggregation and clot formation
inflammation - eliminate pathogens and limit damage
describe the reparative phase of healing
epithelialisation - epithelial layer begins to grow under clot
granulation tissue forms
myofibroblasts which have contractile properties contract the wound by drawing in edges of it
describe the remodelling phase of healing
scar formation
realignment of tissue
what is primary intention healing
occurs in wounds w dermal edges that are close together
closer occurs fast (approx a week)
complete return to function w minimal scarring
secondary intention healing
sides of wound are not opposed
healing occurs from bottom of wound upwards
much larger amounts of granulation tissue > scarring
what is the function of granulation tissue
protects wound surface
fills wound from its base w new tissue and vasculature
replaces necrotic tissue
what are components of granulation tissue
new, thin walled blood vessels
fibroblasts
keratinocytes
endothelial cells
inflammatory cell infiltration of ECM
describe the sequential change in granulation tissue
- vascular granulation tissue = newly formed capillaries, macrophages and support cells
- fibrovascular granulation tissue = proliferating fibroblasts, capillaries and macrophages
- fibrous granulation tissue = fibroblasts synthesise collagen and align themselves, contraction frequently occurs
what are the four stages of fracture healing
formation of a haematoma and granulation tissue
formation of a soft callus
conversion to a hard callus
remodelling
what are factors that influence wound healing
local factors
e.g infection, mechanical factors, foreign bodies, vascular supply, size, location
systemic factors
e.g poor nutrient supply, metabolic status, circulatory status, drug therapies, age-reduced collagen and fibroblast synthesis
what is a hypersensitivity reaction
inappropriate and/or exaggerated response to an antigen
what is the consequence of a hypersensitivity reaction
over reacting inflammatory response and destruction of innocent cells
what are the 4 types of hypersensitivity reactions
type 1 - immediate
type 2 - cytotoxic
type 3 - immune complex
type 4 - delayed type hypersensitivity
describe type 1 hypersensitivity reactions
IgE mediated (anaphylaxis)
allergens
atopic patients predisposed to producing high levels of IgE > produce IL4 and IL5 in response to allergens
degranulation (of histamine and serotonin) occurs very quickly
describe asthma as a type 1 hypersensitive reaction
deep in lung
eosinophils play major role
chronic inflammation
what are treatment options for type 1 HS reactions
avoidance
histamine receptor blocking
puffer
monoclonal antibody therapy
desensitisation
describe type 4 hypersensitivity reactions
cell mediated (no antibody)
symptoms develop days after exposure
e.g contact dermatitis , granulomatous disease
how does screening/central tolerance of T cells occur
in the thymus
TCRs generated in thymocytes > screen > cells w TCRs against self are apoptosed while cells w TCRs against non self become mature/naive t cells
how does screening/central tolerance of B cells occur
in bone marrow
cells w BCRs against self are apoptosed while cells w BCRs against non self become mature/naive B cells
how do autoimmune diseases occur
some T and B cells escape the screening process during central tolerance > self reactive lymphocytes
what are some examples of autoimmune diseases and their self antigen and immune effector
T1 diabetes - pancreatic beta cells - autoantibodies and Th cells
MS - brain white matter - Th, Tc and autoantibodies
rheumatoid arthritis - CT, IgG - autoantibodies
