immunology Flashcards
what is the innate immune system
always present and first line of defence but not specific
what is the adaptive immune system
specific to the invader but slow to act
examples of primary lymphoid organs
- thymus
- bone marrow
what is primary lymphoid organs
where cells originate
where do cells and molecules of immune system circulate
in the blood
where does immune response take place
at site of infection
where does memory specific cells reside
in the spleen and lymph nodes
what are the specific cells called
lymphocytes
what are the specific cells molecular form called
antibodies
what are other examples of secondary lymphoid organs
- adenoids
- tonsils
- Peter’s patch in small intestine
- lymphoid
where do all immune cells derived from
pluripotent stem cells
where are pluripotent stem cells generated
in bone marrow
where are T cells generated
thymus
where do both lymphocytes activate
in peripheral tissue
what can B cells become
antibodies
what is the lymphoid tissue at mucosa surfaces called
mucosa-associated lymphoid tissue
MALT
what do neutrophils defend
major first line defence against pathogens
what role do mast cells, eosinophils and basophils have
immunity to parasites
and
allergies
what do monocytes and macrophages defend against
bacteria, fungi, parasites
what do dendritic cells do
antigen presenting to T lymphocytes
what do B lymphocytes produce
antibodies
what are CD4
helper cells
what are CD8
cytotoxic
what are barriers against pathogens
- skin
- mucous
- cough reflex
- urine flow
- gastric pH
- commensal flora
what is used to monitor HIV
CD4 count
what do cytokines do
change the function of the same or other cells
what is paracrine function
modulates adjacent cells
what are endocrine effects
modulates cells and organs at remote sites
what are the main cytokines
- interferon
- interleukins
what are some types of interferons
- alpha
- beta
- gamma
what is the function of chemokine
chemotactic molecules that attract cells along a gradient from low to high
what is another feature of chemokine
ability to activate immune cells
what are the 2 parts to the immune system
- physical barrier
- blood-borne system
what is the most abundant white cell
neutrophil
what are neutrophils involved in
phagocytosis
what is the first line of defence
neutrophil
what is the least common white blood cell
basophil
what do basophils contain
histamine and heparin
what does histamine and heparin do
- vasodilatation
- anticoagulation
what are basophils involved in
parasitic defence and allergies
what are eosinophil key in
asthma
what are monocytes precursors of
macrophages and Kupffer cells
where do monocytes differentiate into macrophages
peripheral tissue
what are the 3 pathways of complement cascade
- mannose
- classical component
- classical
when does innate immune system present
from birth
what is the innate immune system mediated by interaction between
PAMPs and PRRs
does innate immune system require memory
no
when does immune system occur
immediately
does the adaptive immune response require memory
yes
how long does adaptive immune response take
1-2 weeks on first encounter
3-7 days on second encounter
what is the complement system
cascade of >40 proteins
what do lysosomes do
cleaves bacterial cell wall
what does activation of certain cells in the innate immune system lead to
activation of adaptive immune response
what forms a bridge between innate and adaptive system
dendritic cell
where are complement proteins produced
liver
what form do compliment proteins circulate in
inactive form
what are the 3 pathways of the compliment cascade
- alternative
- classical
- mannose-binding
what does C3a lead to
inflammation
what does C3b do
opsonisation of pathogens
what is the flow of cascade of classical pathway
C1 –> C2 –> C4 –> C3
what forms the MAC complex
C5b + C6-C9
what are the main functions of MAC
- promote inflammation
- recruit cells
- kill target cells
- solubilise antigen complexes and remove them
what do neutrophils do
phagocytose and kill microorganisms
how do neutrophils kill pathogens
by releasing antimicrobial compounds e.g. defensins
where are neutrophils derived
from bone marrow
what makes the bacteria more ingestible
opsonisation
what is opsonisation
bacteria being coated to make them more ingestible
what does elastase do
break down fibrous structure in extracellular matrix, facilitating progress of the neutrophil
what is another name for antibody receptor
Fc receptor
what is granule release initiated by
products of bacterial cell wall, complement proteins, leukotrienes and chemokiens
what cytokine can cause granule release
tumour necrosis factor-alpha
what do eosinophils release
pro-inflammatory mediators
what do pro-inflammatory mediators provide
immunity against parasites
where are most eosinophils
in tissues
particularly at epithelial surfaces where they survive for several weeks
what is the main role of eosinophils
protection against multicellular parasites such as worms
how is protection achieved by eosinophils
release of pro-inflammatory mediators, which are toxic
what receptors promote development of eosinophil
IL-3
IL-5
what do mast cells release
pro-inflammatory and vasoactive mediators
what do mast cells have a role in
allergy
what do mast cells and basophils contain
- histamine
what do mast cells and basophils have a high affinity for
immunoglobulin E
IgE
where are mast cells found
tissues (skin and mucosal)
where are basophils found
blood
what do both mast cells and basophils release
pro-inflammatory mediators
what are the effects of histamine
- vasodilator
- increase vascular permeability
- smooth contraction in airways
what do proteases do
digest basement membrane causing increased vascular permeability
what do proteoglycans do
anticoagulant activity
what does platelet-activating factor do
vasodilator
what do prosaglandins do
- increase vascular permeability
- bronchoconstriction
- vasodilatation
what is histamine
low-molecular weight amine
how long does histamine last in blood
less than 5 minutes
what does histamine cause
reddening (erythema)
swelling
what do C3a, C4a and C5a activate
basophils and mast cells
where are monocytes
in the blood
where are macrophages
in the tissues
what are the roles of macrophages
- ingest and kill bacteria
- release pro-inflammatory molecules
- present antigens to T lymphocytes
- immunity to intracellular pathogens
what is CD14 a receptor for
lipopolysaccharide
what is CD16 a receptor for
IgG antibodies
when in vitro what can monocytes differentiate into
myeloid dendritic cells
what is a key role of tissue macrophages
maintenance of tissue homeostasis
how do macrophages recognise pathogens
PAMPs
what is the major function of dendritic cells
activation of naive T lymphocytes to initiate adaptive immune responses
what are dendritic cells a bridge between
innate and adaptive immune system
what are the major types of dendritic cell
- myeloid
- plasmacytoid
what binds lipopolysaccharide
toll-like receptor 4
where are lipopolysaccharide found
gram negative
what PAMP does the PRR TLR2 bind to
peptidoglycan (PAMP)
what PAMP does the PRR TLR7 bind to
single stranded RNA
what can a mature dendritic cell cease
pinocytosis
what does mature dendritic cell activate
T cell
what cytokines does dendritic cells cause the release of
IL-12
how do T lymphocytes remove a pathogen
- direct kill it
- recruit B lymphocytes to make specific antibodies
how do lymphocytes orchestrate immune responses
via cell to cell interactions and cytokine release
what is the receptor on T cells
T cell receptor (TCR)
what is the receptor on B cells
B cell receptor (BCR)
what is another name for BCR
immunoglobulin
what is another name for immunoglobulin
antibodies
what are the 4 chains of immunoglobulin
- 2 heavy chain
- 2 light chain
what does each chain contain
highly variable and constant regions
what does the variable region do
binds antigens
what does the constant region of the heavy chain dictate
the function of the antibody
examples of antibodies
IgM IgG IgA IgD IgE
what’s the most dominant immunoglobulin
IgG
what immunoglobulin is first produce in immune response
IgM
what immunoglobulin is found in mucous membrane secretions
IgA
what immunoglobulin is present in allergies
IgE
what immunoglobulin is found on B lymphocyte surface membranes
IgD
what immunoglobulin has the longest half life
IgG
what immunoglobulin binds to mast cells
IgE
what immunoglobulin crosses the placenta
IgG
what immunoglobulin is helpful for diagnosis of infection
IgM
what immunoglobulin dominates in second exposure to antigen
IgG
what is IgA present in
secretions - tears, saliva, GI tract
what immunoglobulin helps protect a new born baby
IgA as present in breast milk
what does the T lymphocyte exist as
heterodimer
how many types of T cell receptor are there
2
what T receptor has alpha and beta
CD4 and most CD8
what HLA molecules does CD4 require presentation from
HLA class II
what HLA molecule does CD8 require presentation from
HLA class I
what marker is the helper T lymphocyte
CD4
what marker is the cytotoxic T lymphocyte
CD8
what is most abundant CD4 or CD8
CD4
what molecules can stop inflammatory response
programme death ligand 1 and its protein
PD-L1
what cancers are monoclonal antibodies presenting
- melanoma
- renal cell carcinoma
where are most naive T lymphocytes resident
lymph nodes or spleen
where are naive T lymphocytes activated
lymph nodes
how are T lymphocytes activated
by antigens presented to their TCR as short peptides bound to major histocompatibility complex (MHC) molecules on the surface of DCs
what is nuclear factor kappa B
pivotal transcription factor in chronic inflammatory disease and malignancy
what cytokines stimulate Th1
IL-12
what cytokines does Th1 produce
- IFN-gamma
- IL-2
- TNF-alpha
what is the function of Th1
pro-inflammatory
role of Th1 response
- organise killing
- activate macrophages to kill
- instruct CD8 cells
what cytokines cause production of Th2
IL-4
what cytokines are produced by Th2
- IL-4
- IL-5
- IL-13
what is the function of Th2
pro-inflammatory
what does Th2 have a role in
- kill parasites
- recruits eosinophils
- promotes IgE
what cytokines cause production of Th17
- IL-6
- IL-23
- TGF-beta
what does Th17 cause production of
IL-17
what is major marker of Th1
CD4
what is a major marker of Th2
CD4
what is the main role of Th2
- protect from extracellular pathogens
- role in allergic reactions
what is major marker of TH7
CD4
what is role of Th17
- protect from fungi
- role in autoimmune inflammatory disease
what is major marker of cytotoxic T lymphocyte
CD8
what is role of CD8
- kill target cells via HLA class I
- protect from viruses
how does CD4 influence the immune system
- release of cytokines
- direct cell-cell interaction
what are the major function of CD4
- licensing of DCs
- licensing of B lymphocytes (initiate and mature antibody responses)
- secretion of cytokines (growth and differentiate of range of cells)
- regulation of immune reactions
what is the main subtype of CD4 T lymphocytes
Th1
what does Th1 drive
activation of monocytes/macrophages and CTLs
what do Th1 have important pathology with
protection against intracellular pathogens e.g. viruses and mycobacteria
how are Th1 cells recognised
by their secretion of pro-inflammatory cytokines IFN-gamma and TNF-alpha
what do TH2 cells drive
antibody response, especially IgE
promote eosinophil granulocyte function
what do Th2 cells have important role in
protection from extracellular parasites
- immune response for allergic reactions
how are Th2 cells recognised
secretion of IL-4, IL-5 and IL-13
what do Th17 cells drive
inflammatory responses through recruitment of neutrophil granulocytes
what are Th17 cells important in
protection from fungal infections
how are Th17 cells recognised
by secretion of IL-17
what interleukin stops inflammation
IL-10
what are CD8 involved in
defence against viruses
when do CD8 kill viral cells
HLA class I present
where must CTL be activated
in lymph nodes by DCs
how do CD8 kill
- cytotoxic granule proteins
- toxic cytokines
- death inducing surface molecules
where are natural killer cells made
in bone marrow
where are natural killer cells present
blood and lymph nodes
what is the main surface molecule for natural killer cells
CD16
what is the role of natural killer cells
kill abnormal host cells
what do natural killer cells secrete
- IFN-gamma
- TNF-alpha
what does migration into inflamed tissue require
- an affected organ or tissue
- responding immune cells bind and adhere
what does ICAM-1 help migration
expression on tissue endothelium is sensitive to numerous pro-inflammatory molecules
allow immune cells to be guided form the blood into tissues
where are MHC molecules located
chromosome 6
what is another name for MHC
HLA
what does MHC play a role in
immune function
how many classes of MHC are there
3
what does HLA class I have a role in
presenting short antigenic peptides to T cell receptors
where is class I HLA expressed
on all nucleated cells
where are HLA II expressed
antigen presenting cells
examples of antigen presenting cells
- dendritic cell
- monocyte / mactopahges
- B lymphocytes
what is the endogenous route of antigen presenting
all nucleated cells
- comes from within
what is the exogenous route of antigen presenting
- property of antigen presenting cells
- antigens are internalised
what is cross presentation
ability of some antigen presenting cells to internalise exogenous antigens and process them through endogenous route
what is the essential component in the activation of CD8 cells
cross presentation
what is the early and rapid host response to tissue injury
acute inflammation
what does increase pathogen numbers lead to
activation of complement in the tissues
what do inflammatory mediators change
the blood flow and attract and activate granulocytes
what are some symptoms of acute inflammation
- fever
- heat
- pain
- swelling
- redness
what mediates the production of CRP in the liver
IL-6
what does lysis lead to formation of
fluid in the tissue space containing dead and dying bacteria
what is there usually at site of pathogen entry
tissue hypoxia
how can the inflammation become walled off
through local fibrin deposition to protect the host
how to antigens from the pathogen travel
via the lymphatics
how are dendritic cells activated
via the PRR-PAMP system
what does the adaptive immune response lead to
activation of pathogen specific T lymphocytes
what does adaptive immune response cause release of
IgM
what is resolution aided by
scavenging activity of tissue macrophages
what is chronic inflammation
inflammation arising in response to insults that cannot be resolved in days/weeks
examples of chronic inflammation
- viruses (Hep A, B and C)
- bacteria
- environmental toxins (asbestosis, silicon)
what does mycobacterium leprae cause
leprosy
what does tuberculosis immune response cause
nerve damage and numb patches of skin
how leprosy resolved
antibiotics
what are tests for tuberculosis
- Mantoux test
- interferon gamma release blood test
when tuberculosis becomes chronic what persists
macrophages in the lesions fuse to form giants cells and epithelioid cells
what genes are involved in inflammation for crohns disease
- NOD2
what results would indicate an inflammatory response or infectious disease
high CRP level
what result would indicate a state of immune deficiency
low concentration of IgG
what result would indicate a state of immune pathology
presence of autoantibodies or allergen-specific IgE
what does raised CRP levels indicate
infection or inflammation
what does low levels of immunoglobulins indicate
antibody deficiency
e.g. primary immunodeficiency
what does raised IgE suggest
allergy
what does raised neutrophils suggest
bacterial infection
what does low neutrophils suggest
secondary immune deficiency
what does high eosinophils suggest
allergic or parasitic disease
what does low levels CD4 suggest
HIV
what does double stranded DNA autoantibodies suggest
rheumatoid arthritis
what is ANCA for
vasculitis
what is mitochondrial autoantibodies for
primary biliary cholangitis
when does primary immunodeficiency arise
birth
what diseases can T lymphocyte deficiency cause
- DiGeorge syndrome
- AIDS / HIV
- T cell activation defects
- X-linked hyper-IgM syndrome
what disease can B lymphocyte deficiency cause
- X-linked agammaglobulinaemia
- common variable immunodeficiency
- IgA deficiency
what disease does combined T and B cell defects cause
- severe combined immunodeficiency (SCID)
what diseases does neutrophil defects cause
- chronic granulomatous disease (CGD)
- leucocyte adhesion deficiency
what are features of infections associated with immunodeficiency
- chronic, severe or recurrent
- resolve only partly
- caused by unusual organisms
do opportunistic pathogens have low or high virulence
low
examples of opportunistic organisms
- atypical mycobacteria
- pneumocystis jiroveci
- staphylococcus epidermidis
what do phagocyte defects cause
- deep skin infections
- abscesses
- osteomyelitis
what does T lymphocyte deficiency cause
- infection with fungi
- Protozoa infection
- intracellular organism
when do congenital deficiencies present
several months after birth due to 28 day half life of maternal IgG
what inheritance if only males of the family are affected
X-linked
what is Di-George syndrome due to
T lymphocyte deficiency
what is Di-George syndrome
when the third and fourth pharyngeal arches fail to develop
so no parathyroid gland, aortic arch or thymus
how does Di-George syndrome present
- at birth
- dysmorphic facies
- hypoparathyroidism
- cardiac defects
- infections
what chromosome is Di-George syndrome affected by
chromosome 22
acronym to help remember Di-George syndrome
CATCH 22
- cardiac abnormalities
- abnormal facies
- thymic dysfunction
- cleft deformities
- hypokalaemia
+
chromosome 22
what causes the lack of T lymphocytes in Di-George syndrome
no thymus
what is treatment for Di-George syndrome
- calcium supplementation
- correction of cardiac abnormalities
- prophylactic antibiotics
- thymic transplantation
what is severe combined immunodeficiencies due to
impaired T, NK, B lymphocyte
what is most common SCID defect in
IL-2 receptor
treatment for SCID
SCT preferably from HLA-identical donors e.g. siblings
what is Wiskott-Aldrich syndrome
X-linked defect in a gene involved in signal transduction and cytoskeleton function
what is chronic granulomatous disease characterised by
deep-seated infections
when is chronic granulomatous disease present
toddler age
treatment of chronic granulomatous disease
- prophylactic antibiotics
- anti fungal therapy
what is allergic hypersensitivity
binding of an antigen to specific IgE
how many phases do allergic reactions have
2
what are the late phase responses mediated by
Th2 cells
- they recruit eosinophils
what does the late phase response give rise to
chronic inflammation
what does the late phase response cause in asthma
prolonged wheezing
where do Th2 cells accumulate
around small blood vessels
how long do Th2 cells persist for
1-2 days
what do histamine and serotonin cause
- bronchoconstriction
- increased vascular permeability
what do leukotrienes do
chemoattract
what are the Th2 cytokines
- IL-4
- IL-5
what makes some allergens so powerful
they are proteolytic enzymes this allows them to cross skin and mucosal barriers
what is atopy
allergic response
how is allergic disease made
skin prick testing
treatment for allergic reactions
- avoidance = 1
- antihistamine
- corticosteroids
- CYLTs receptors
- ## omalizumab
how do corticosteroids help in allergic reaction
inhibit prostaglandin and leukotrienes mediators
cause vasoconstriction which leads to reduced cell and fluid leakage from vasculature
what do CYSTL antagonistic do
inhibit leukotrienes by blocking the type 1 receptors
what is omalizumab
monoclonal antibody that binds IgE
when is omalizumab used
in asthma that cannot be controlled by corticosteroids plus LABA
what is anaphylaxis
serious allergic reactions that is rapid in on set and may cause death
how does anaphylaxis start
as an acute, generalised IgE-mediated immune reaction involving specific antigen, mast cells and basophils
what foods can cause anaphylaxis
- nuts
- shell fish
- dairy products
- egg
- citrus fruits
other causes of anaphylaxis
- wasp, bee stings
- medications (antibiotics)
what is central to the cause of anaphylaxis
activation of mast cells and basophils
what are initial symptoms of anaphylaxis
- tingling
- warmth
- itchiness
what are late symptoms of anaphylaxis
- generalised flush
- angio-oedema
- hypotension
- bronchospasm
- laryngeal oedema
- cardiac arrhythmia
- death may occur within minutes
management of anaphylaxis
ABCDE
- lie patient flat on bed with feet raised
- ensure airway is free
- give O2
- monitor blood pressure
- find venous access
- administer IV adrenaline
- administer IV antihistamine
- administer IV hydrocortisone
what is best treatment of anaphylaxis
prevention by avoiding triggers
what adrenaline is given for anaphylaxis
epinephrine
what is autoimmunity
when the immune response turns against itself
what does IL-12 stimulate
Th1
what do cytokines recruit
effector cells (macrophages)
what is IgG4 disease
fibro-inflammatory condition with the formation of swellings in multiple sites
what is IgG4 related disease driven by
Th2 T cells
what is Addisons disease
rare chronic endocrine system disorder
who does autoimmune hepatitis usually affect
women
what are risk factors of rheumatoid arthritis
- smoking
- previous viral infections
- human herpes virus
- vitamin D deficiency
what is major criteria for autoimmune disease
- evidence of autoreactivity
- clinical response to immune suppression
- passive transfer of the putative immune effectors
what is acute organ rejection mediated by
CD4 and CD8 T lymphocytes
what do glucocorticoids do
- potent effects on monocyte production
- blockade of T lymphocyte production of IL-2
- reduced activation of a range of innate immune cells
what is an example of a purine analogue
azathioprine
how does azathioprine work
inhibits DNA synthesis in dividing adaptive immune cells
what are cytokines
pleiotropic agents
