pathology Flashcards
what is immunology?
study of immune system
what is pathology
pathology is the study of causes/effects of diseases
what is aetiology?
the cause of a disease or condition
what is pathogenesis?
progressive changes as disease develops
example of primary lymphoid organs?
thymus, bone marrow
primary vs secondary lymphoid organs
primary is where immune cells are created and mature/educated. secondary is where immune cells are stored.
what is lymph
lymph is a celar, colourless fluid that circulates the lymphatic system. it originates from interstitial fluid.
what does lymphatic system consist of?
lymph, lymphatic vessel, lymphoid organs, lymphoid tissues, immune cells
where is thymus located?
central of body, chest area behind lungs
thymus in newborn compare to adult?
thymus is larger in newborn and decrease in size when age increase
what does thymus do?
T cell maturation and education.
(t cell is produced in bone marrow)
what does bone marrow do?
bone marrow consist of red marrow, which consist of stem cell. stem cell differenciate into immune/defence cell
production of B cell and T cell
what is the stem cell that produce blood and immune cell?
haematopoietic stem cell
which 3 secondary lymphoid organs?
Spleen, lymph nodes, lymphoid tissues (eg tonsil and adenoid)
what does spleen do?
blood filtration system
what does both innate and adaptive immune system split into?
cellular component and humoral component
give example of innate immune cell?
monocytes/macrophages, mast cell, neutrophils, eosinophils, natural killer cells, basophils
what is humoral component?
humoral component is anything (eg protein…) that is produced by cellular component
example of adaptive immune cell?
B cell and T cell
example of non-professional immune cell?
epithelial cell, endothelial cell, fibroblasts
what does monocyte differentiate into in tissue?
macrophage
what is the precursor of macrophage?
monocytes (circulate blood as monocytes, nmigrate to tissue and differentiate into macrophage)
what does macrophage do?
phagocytosis and present antigen
early responder to inflammation
what does mast cell do?
degranulation (histamine involved)
early responder to inflammation
help in allergic reaction
what innate immune cell is most numerous?
neutrophils
what does neutrophils do?
phagocytosis and degranulation
NETosis via degranulation
What cell product NET/ what cell undergo NETosis?
Neutrophil
Does basophils and eosinophils have granules?
yes
What is NETosis?
it is the production of neurtophil extracellular traps, which help traps invasive microorganism
what cell is basophils and eosinophils structurally similar to?
neurtophils
what cell does basophils and eosinophils have similar function?
mast cells
involed in allergy and undergo degranulation
roles of eosinophils?
major roles in anti-parasite immunity
what does natural killer cells do?
large granulocytes.
kill host cells that are infected (cancerous cell, viral infected cell)
have long cellular projections that detect stuff within vicinity
what does dentritic cell do?
phagocytoisis and antigen presentation
Bridge between innate and adaptive immunity, move from tissue to lymph to activate T and B cell
Where is T cell produced
bone marrow
what immunity does T cell drive?
cellular immunity
what does T cell do?
T cell recognize peptides (antigen)
where is B cell produced?
bone marrow
where does B cell mature in?
bone marrow
where is B cell stored in?
lymph and lymph nodes
where is T cell stored in?
lymph and lymph nodes
what immunity does B cell drive?
humoral immunity
what does B cell mainly do?
production of antibodies,
Antigen presentation for T cell activation
what is innate immunity?
first line of non-specific defence
what is inflammation?
inflammation is the immune system response aimed at eliminating the inciting cause/threat
examples of inciting cause that can cause inflammation
invading microorganism, particular material (allergens or prostheses), altered self cell, transformed malignant cells
examples of inciting cause
invading microorganism, particular material (allergens or prostheses), altered self cell, transformed malignant cells
stages of inflammation?
initiation (response to harm), progression (containment), amplification (modulation, starts to clear threat), resolution (acute/chronic)
what does epithelial do for immunity?
physical barrier and secretions
what does epithelial barriers produce?
example include: antimicrobial peptides, secretory IgA, lactoferrin, lysozyme, cystatins …
main antibody found in body secretion?
IgA
what cell produce IgA?
B cell
how does antimicrobial peptides work?
target microorganism. AMPs attach and disrupts its membrane and cause lysis
what is cathelicidins?
antimicrobial peptides
example of antimicrobial peptides?
cathelicidins
how does lysozyme work?
2 ways
target component of bacterial ell wall, cleave protein within cell wall and cause lysis
pass through cell wall and embed into bacterial cell membrane, then cause lysis
what is lysozyme?
enzyme found in saliva
what is virulence factor?
things (mediatorm protein, chemcial, sugar…) produced by the microorgansim
what is the main recpetor found on immune cell?
toll-like receptor
how is microorganism recognised?
immune cell have receptor for component of microorganism
how many TLR is identified in human body?
10
where in immune cell is toll-like receptor found?
can be on cell membrane, can be inside cell on specific organelles
what cell is TLR-2 found?
monocytes, dendritic cells, mast cells, eosinophils, basophils
what cell is TLR-4 found?
macrophages, dendritic cells, mast cells, eosinophils
examples of receptor found on immune cells (other than toll-like receptor)
dectin and glucan receptors, NOD-like receptors, protease-activated receptor
what does dectin and glucan receptors recognise?
fungal pathogens
what does NOD-like receptor recognise?
intracellular pathogens (viruses)
what does protease-activated receptors recognise(PARs)?
allergens
what is the collective name for receptors that recognised PAMPs?
Pattern recognition receptor (PRRs)
what is the collective name for things that PRRs recognize?
Pathogen associated molecular patterns (PAMPs)
what is the collective name of receptor on innate immune cells?
pattern recognition receptors (PRRs)
what happens to host cell after PRR is stimulated?
downstream signalling cascade in host cell
examples of effector response after microbial recognition?
production of soluble mediator, phagocytosis, antigen presentation, degranulation
is soluble mediator humoral or cellular component?
humoral
examples of soluble mediator produced by immune cell?
antimicrobial peptides, enzyme, cytokines and chemokines, complement proteins, prostaglandins and leukotrienes, immunoglobulins, growth factors, matrix metalloproteinases (MMPs)
what is cytokines?
soluble mediator produced by immune cell
small protein
signaling molecules
what is the 3 groups/family of cytokines by structure?
interleukin family, TNF family, interferons
is cytokines anti or pro-inflammatory?
can be both
3 types of cytokines by function?
autocrine (alter behaviour of cell from which they were secretes),
paracrine (alter neighbouring cell),
endocrine (released into circulation and alter distant cells)
what does autocrine cytokines do?
it alter behaviour of cell from which they were secreted (self-regulating)
what does paracrine cytokines do?
it alter behaviour of neighbouring cells
what does endocrine cytokines do?
it is released into circulation and alter behaviour of distant cells
what receptor does cytokines bind to?
cytokin receptor
what happens after cytokine receptor activation?
conformational changes–> effector response
eg more cytokines or chemokines released, degranulation, antimicrobial peptides produced…
reaction similar to microbial recognition
what is chemokines?
soluble mediator
chemotactic cytokines (protein)
what is chemotaxis?
movement of cell in a direction corresponding to a gradient of increasing concentration of a substances
ie. immune cell move towards increasing conc of chemokines
what is chemokines main role in immune response?
immune cell recruitement
directing immune cells where to go
what receptor does chemokines bind to?
chemokine receptor on immune cell
what receptor detects fungal pathogen?
dectin and glucan receptor
what receptor dectects intracellular pathogen (virus)?
NOD-like receptor
what receptor detects allergens?
protease activated receptor
what does it mean when immune cell is tissue-resident?
present regardless of infection
and they will produce chemokines during infection
what might tissue resident immune cell produce during infection?
chemokines
to recruit more immune cell
what gradient is neutrophils attracted to?
CXCL8 (IL8)
what is and what does CXCL8 do?
it is chemokines and cytokines. and it attract neutrophils to site of inflammation
what is diapedesis?
the migration of immune cells out of circulation into blood vessel walls
what is the migration of immune cells out of circulation into blood vessel walls?
diapedesis (extravasation)
types of receptors involved in diapedesis?
selectins, integrins, immunoglobulin superfamily
how does neutrophils move out of circulation?
by interaction between neutrophils receptor and ligand on endothelial cell
what immune cells undergo degranulation?
granulocytes
eosinophil, basophil, mast cell, NK cell, neutrophil
what is granules?
vesicles containing soluble mediator, like proteinases(enzyme), antimicrobials(AMP), chemical mediator(histamine)
what does mast cells and basophils cell does undergoing degranulation?
they produce and release histamine
what immune cell produce histamine when degranulation?
mast cell and basophil
what does histamine do to body?
vasodiation, increase vascular permeability (allow immune cell out of circulation)
affect smooth muscle contraction
affect bronchoconstriction
affect neurotransmission
what component is NET made of?
proteins and chromatin (DNA)
what is produce after activation of NETosis?
protein and chromatin(DNA) to form extra-cellular fibril matrix
what does NK cell do when undergoing degranulation?
ADCC (andibody-dependent cellular cytotoxicity)
release perforin and granzyme, causing apoptosis
what does NK cell release during degranulation?
perforin and granzyme
what does perforin and granzyme do?
perforin form pore within abnormal cell
granzyme destroy the cell
–> apoptosis
what is ADCC?
antibody-dependent cellular cytotoxicity
antibodies tag abnormal cell for removel, detect by NK cell and undergo degranulation
what does eosinophils do when undergoing degranulation?
ADCC
release enzyme called major basic protein(anti-parasitic toxin)
what is major basic protein?
it is a potent anti-parasitic toxin that drives cellular lysis
what cell produce major basic protein?
eosinphils
what cell produce perforin and granzyme?
NK cell
steps of phagocytosis?
recognition, engulfment, phagosome formation, phagolysosome formation, cell digestion, exocytosis or antigen presentation
example of initiating factors for phagocytosis?
opsonization by antibodies or complement
microbs recognition by PRP
efferocytosis (removal of apoptotic or necrotic cells)
what is opsonization?
tagging of cells for removal
how is antigen presented to T cell?
via MHC receptor
how many cascade system does plasma contain? and what are they?
4
complement, kinins, coagulation factors, fibrinolytic system
where is complement protein produced?
liver and by immune cells
what does complement protein drive?
opsonization and inflammatory response
leads to formation of membrane attack complex
what is membrane attack complex?
formation of pores on surface of microorganism
is complement protein pro or anti inflammatory?
pro-inflammatory
what is anaphylatoxins?
C5a and C3a complement proteins fragment
name the 3 pathway of complement? and what is the initating factor for each?
classical, lectin, alternative
classic driven by antigen-antibody complex
lectin drive by lectin (protein found on surface of microorganism)
alternative drive by component form by microorganism (virulence factor, protein…)
what does the complement pathway lead to?
production of C3
which 2 complement pathway can allergens stimulate?
classical and alternative
descript adaptive immunity?
specific and acquired
provide immunological memory
name the 3 main receptor for adaptive immunity?
T cell receptor, B cell receptor, Major Histocompatibility complex(MHC)
difference between innate cell receptor and adaptive cell receptor?
innate is highly conserved, similar in structure between individual.
adaptive is highly variable, and have huge diversity (changes in structure)
what receptor does T cell have?
T cell receptor
what is CD4 and CD8?
protein and co-receptor for t cell receptor
describe the T cell in thymus
immature T cell or thymocytes
what does CD8 binds to?
MHC I
what does CD4 bind to?
MHC II
where is MHC I found?
found on all nucleated cell in the body
where is MHC II found?
found only on antigen presenting cell
name the 2 class of T cell receptor?
alpha beta, gamma delta
name the 2 region of TCR
constant and variable region (antigen binding site)
what is the 3 gene segment that codes for T cell receptor?
VDJ
what is the process that creates the diversity of T cell receptor?
VDJ rearrangement/ somatic recombination
what is VDJ rearrangement/somatic recombination?
the process by which T/B cell receptors have different antigen binding site (diversity)
what happens to T cell in thymus?
CD4/CD8 - –> +
receptor expression
thymic education (positive and negative selection)
describe thymic education?
T cell interact with thymic epithelial cells which will present antigen.
positive selection
- make sure T cell interact with MHC
- moderate binding is gd
- no binding = apoptosis
negative selection
- make sure T cell doesn’t recognise self peptide
- ensure no self-reactive T cell leave thymus
- strong binding to MHC = apoptosis
name of non-activated T cell in lymph nodes or spleen after education
naive T cell
what is MHC I responsible to present?
endogenous protein
what is MHC II responsible to present?
exogenous protein
after APC undergo phagocytosis, where do they move to? and what do they do?
lymph nodes, mature en route (upregulate production of co-stimulatory receptor)
example of co-stimulatory receptor on APC?
CD40 and CD80/CD86
what is the 3 signal during T cell activation/priming?
- Antigen by MHC on APC and TCR on T cell
- interaction of co-stimulatory receptor on both T cell and APC
- APC producing cytokines
what does cytokines production by APC during T cell activation lead to? (for CD4 and CD8)
CD4: differentiate into subset
CD8: drive cellular lysis by degranulation
how many subset does T helper cell (CD4+) have?
5
what drive CD4+ T cell differentiation?
cytokines produced by APCs
what are function of helper T cell?
TH2: Induce antibody production by B cell, in allergic reaction
TH1: instruct macrophage to undergo phagocytosis
Treg: damp down inflammatory responces/immune suppression
important roles in barrier and mucosal immunity
what does cytotoxic T cells do?
produce pro-inflammatory response
undergo degranulation
induce host cell to undergo apoptosis
what happens to T cell after activation?
clonal expansion
what is the receptor of B cell?
B cell receptor
which 2 subset of B cell?
plasma cell, memory B cells
name the antigen presenting cell?
B cell, dendritic cell, macrophage.
where is B cell educated?
bone marrow
how does diversity of B cell receptor arise?
VDJ recombination
what is VDJ recombination?
it lead to the huge diversity of B cell and T cell receptor
what is BCR?
type of antibody (IgD, IgM)
what does B cell undergo during education?
negative selection
what happen in B cell negative selection?
make sure B cell doesn’t react with self-antigen
if strong binding between B cell and slef-antigen presented by bone marrow cell, –> macrophage engulf it
what is B cell called after education, before activation?
naive B cell
where does naive B cell move to from bone marrow?
lymph nodes and other secondary lymphoid organs
what is the 2 methods of B cell activation?
thymus dependent, thymus independent
main difference between thymus dependent and thymus independent B cell?
dependent –> activated by T cell
independent–> activated by component of microorganism
what happens in thymus dependent B cell activation?
3 signals
1st: B cell present antigen to T cell
2nd: co-stimulatory molecules interaction (CD40-CD40L)
3rd: cytokines produced from CD4+ TH2 or TfH cells
lead to differentiation of B cell
what happens in thymus-independent B cell activation?
B cell stimulated by microbial component (egLPS). Antigen stimulate BCR and PRRs on B cell
then will lead to differentiation of only plasma cell
- no long term immunity
what is class switching?
B cell switching production of one type of antibody to another
which is the first antibody produced by B cell?
IgM
how does class switch happen?
gene rearrangement within constant region of B cell receptor
what is affinity and avidity of antigen?
affinity is the strength of bind.
avidity is the amount of binding sites
which antibodies have strongest affinity
IgG and IgE
which antibodies have higher avidity?
IgA and secreted IgM
why do we need class switching?
it will lead to a stronger immune response
what function does B cell antibodies have?
neutralization, opsonization (for phagocytosis and degranulation), classical pathway of complement cascade
which pathway of complement cascade does antibody trigger?
Classical pathway
example of antibody that does neutralisation?
IgA
how does vaccination work?
when 1st exposure, body produce IgM and slowly produced IgG
memory cells form from that, and will primed to produced IgG when re-exposure
–> stronger immune response by IgG
characteristic of acute inflammation
rapid onset, short term, involes only innate immune system, localized response, complete restoration of tissue
characteristic of chronic inflammation
tend to arise from acute, long term, involve both innate and adaptive immune system, persistent inflammation, eventually tissue damage (no restoration)
what is the 5 cardinal signs of inflammation?
redness, heat, swelling, pain, lost of function
how is redness and heat of inflammation caused?
vessel diation adjacent to site of damage
endothelial cells swell and retract, and promote diapedesis
exudation, vessels become leaky and allow passage of fluid
what is the in inflammatory exudate in swelling?
fluid(lymph) and salt,
glucose and oxygen
immune cells and soluble mediator
fibrin
what cause pain in inflammation?
stretching of tissue by excessive fluid buildup
release of soluble mediator
what cell produce prostaglandins and leukotrienes? and how
macrophage and neutrophils
from product of fatty acid metabolism
arachidonic acid converts to leukotrienes and prostaglandins by lipoxygenase and cyclooxygenase respectively
what is the main role of prostaglandin and leukotrienes in inflammation?
cause vascular dilation
acts on nerve fibre (itching)
involved in chemotaxis
role in tissue remodeling
what is the 4 plasma system?
complement, kinins, coagulation factors, fibrinolytic system
what is the protein that can activate all 4 plasma system?
hagemen factor/coagulation factor XII
what is hageman factor?
serine protease (enzyme) found circulating inactive in blood
which pathway of complement system can hagemen factor activate?
classical pathway
what does hageman factor do in kinin system?
it convert precursor to kallikrein
what can convert precursor to kallikrein?
hageman factor and neutrophil
what does kallikrein convert in kinin system?
convert kininogens to kinins
what is the main example of kinins?
bradykinin
what does bradykinin do in immune system?
drive diapedesis
- Target endothelial cell in blood vessel to swell and contract –> leaky
what is the 2 pathway of coagulation system?
intrinsic and extrinsic
how does intrinsic pathway of coagulation system work?
hageman factor contact with activating surface (injury) and activates itself, leading to cascade of event
what does both intrinsic and extrinsic pathway of coagulation system lead to?
common pathway
what is needed for blood clot formation in common pathway?
fibrin, activated platelets
fibrinogen convert to fibrin by thrombin
what does thrombin do?
convert fibrinogen to fibrin
what does hageman factor does in fibrinolytic system?
it convert plasminogen to plasmin
what does plasmin do in fibrinolytic system?
it is an enzyme that breaks down fibrin and prevent excess clotting
what system can plasmin activates?
complement system
disease when too much blood clotting?
thrombosis
disease when too much bleeding
hemorrhage
what is the balance between coagulation and fibrinolytic system?
hemostasis
what is hemostasis?
the balance between coagulation and fibrinolytic system
what medication inhibits blood clotting?
warfarin, heparin
what disorder might affect plasma factor system and how?
von willebrand disease, haemophilia A, haemophilia B
they cause mutation in genes responsible for clotting factor protein
regeneration vs repair
regeneration/healing= new function differentiated cell (same as before)
repair= fibrous scar and change in tissue structure and function
name the 3 types of cell involved in healing and repair? and describe each
labile cell
- normally undergo activate cell division
- rapid regeneration
- eg immune cell, epithelial cell
stable cell
- will regenerate, but not as quick as labile cell
- eg fibroblast
permanent cell
- unable to divide or regenerate
- eg certain muscle cell of heart, nerve cell
what is the 4 stages of healing?
coagulation, inflammation, proliferation, maturation
what tissue is form in early proliferative phase?
granulation tissue
what is the formation of new blood vessel
angiogenesis
what is angiogenesis?
formation of new blood vessels
what happen in first phase of proliferation of soft tissue?
new capillaries, immune cells, and fibroblast formed
what happen in the second phase of proliferation?
capillaries regressed and replaced by collagen. collagen deposition mediated by fibroblast.
fibrous granulation tissue formed.
myofibroblasts drive contraction of surrounding tissue
what is myofibroblast and what does it do?
specialised cell found within muscle
it drive contraction of surrounding tissue
what is MMPs?
matrix metalloproteinases
soluble mediator produced by immune cell
what does MMP do?
MMPs remodeled extracellular matrix (made of protein fibres)
it helps cellular migration and aid angiogenesis
what is growth factor?
soluble mediation and signalling molecules produced by immune cell
what does growth factor do?
it binds with receptors on cell surface, and promote cell growth/differentiation
which growth factor promote angiogenesis?
vascular endothelial growth factor
2 method to form new capilaries by existing vasculature? and describe
sprouting: involve gradient of VEGF. enthothelial cell in existing blood vessel will move towards higher conc of GF
splitting: a large blood vessel splits into 2, no gradient of VEGF
what is fibrosis?
deposition of collagen and formation of fibrous connective tissue
driven by fibroblast
controlled by macrophages (M1 and M2)
what does M1 and M2 do? macrophage
M1 is pro-inflammatory, and drive inflammation.
M2 is anti-inflammatory, and will drive tissue repair (fibrosis and angiogenesis)
what happen in maturation phase of soft tissue?
new granulation tissue produced is remodeled by collagen fibres
re-epithelization happens
regain of tensile strength prostaglandins decrease fibroblast activity
what does prostaglandins do in healing and repair?
it decrease fibroblast activity
what happen in coagulation phase for healing of hard tissue?
hematoma formed, which is a blood clot within bone and surrounding tissue
what happen in proliferation phase in healing of hard tissue?
granulation tissue forms fibrocartilage callus, which is a mixture of fibroblast, chondroblast, osteoblasts
what happen in maturation phase of healing of hard tissue?
callus becomes ossified, and required constant remodelling
where does osteoclast originates from?
differentiated from hematopoietic stem cell (macrophage precursor)
where does osteoblast originates from?
differentiated from mesenchymal stem cell
how does osteoclastogenesis happens?
RANKL produed by osteoblast activates RANK of osteoclasts
what will inhibits RANKL?
osteoprotogerin (OPG)
what cell produced OPG?
osteoprotogerin produced by osteoblast
how does peripheral tolerance work?
slef-reactive T cell that escape the central toleane, will not have signal 2 or 3 for activation
as APCs doesn’t up-regulate production of co-stimulatory molecules
–> anergic T cell (mostly removed by apoptosis)
how is rheumatoid arthritis caused?
excessive citrulline, which is produced from arginine via PADs
how is rheumatoid arthritis related to periodontitis?
PADs which is an enzyme that drive formation of citruline is also produced by P. gingivalis
what factor decide whether if cell injury is reversible or irrversible?
how vulnerable the cell is, dose/injury intensity
cause of cell injury
hypoxia, ischaemia, infectious agent, physical agent, chemical drug, immulogical response, nutritional imbalance, genetic defects
the 2 microscopic observation of reversible cell injury. and describe them
cloudy swelling: less ATP, so energy depend ion channel on cell membrane not functioning, influx of Na and water –> swelling
fatty change: deposite of lipid in cytoplasm
what happen in necrosis
cell swelling, leakage of cell content –> inflammation, phagocytosis
nuclear shrinkage (pkynosis), nuclear fragment (karyorrhexis), nuclear digestion (karyolysis)
name the type of necrosis and spell
talk about each (check notes for answer)
coagulative necrosis, liquefactive necrosis, caseous necrosis, fibrinoid necrosis, gangrenous necrosis, fat necrosis
difference between necrosis and apoptosis
necrosis have inflammation and apoptosis don’t
necrosis involve cell membrane disruption, cell membrane intact in apoptosis
necrosis is cell swelling, apoptosis is cell shrinkage
pathological trigger for apoptosis
unrepairable DNA damage (p53), viral infection–> cytotoxic T cell, hyoxia/ischaemia
what is amyloid and where is it usally deposited?
amyloid is fibrillar protein that is abnormally folded
usually deposited extracellularly, eg basement membrane
what are the 3 types of amyloid and describe
AL, derived from light chain immunoglobin of plasma cell
AA, derived from protein produced in liver
Abeta, deposited in brain, related to alzheimer’s disease
two types of pathological pigmentation, describe and exmaple
build up in cytoplasm
exogenous –> pigment from outside of body
endogenous–> pigment from inside body
2 type of pathological calcification
dystrophic, metastatic
dystrophic: deposite of calcium phosphate in necrotic tissue, normal serum calcium
metastatic: increase serum calcium, no deposite. seen in connective tissue of blood vessel
caused for increased serum calcium
Increase PTH, bone destruction, excess VitD, renal failure
3 development growth disorder, too little growth
and describe
agenesis(doesn’t develop at all), aplasia(fail to develop to normal from primitive embryonic structure), hypoplasia(less tissue form)
development growth disorder, too much growth and example
hamartoma
eg mole (pigmented naevi), haemangioma, lymphangioma
developmental growth disorder, when growth in wrong place
ectopia
acquired cell growth example and decribe each
atrophy - decrease in number and size
hypertrophy - increase in size
hyperplasia - increase in number
metaplasia - change from one differentiated structure to another (eg columnar to squamous)
dysplasia - disorder growth
