Theme 1 - The Immune System Flashcards
What is an antigen, usually? 2
Something that the immune system responds to. Usually a protein
What is an antigen receptor?
What recognises the antigen
What is the difference between innate and adaptive antigen receptors?
Innate - Germline-encoded pattern-recognition receptors
Adaptive - Antigen-specific T and B cell receptors
What are the two types of compact cells with reference to immune cell lineage?
Myeloid and lymphoid
Appearance and function of neutrophil?
globular nucleus
phagocytosis
Appearance and function eosinophil?
sunglasses,
fuck knows
Appearance and function monocyte?
large mono nucleus cell in blood stream (pre cursor to macrophage)
Phagocytosis
Antigen presentation
Appearance and function dendritic cell?
clear cell with dendrites
antigen presentation
Appearance and function basophil?
granular nucleus
fuck knows
what 5 immune cells are in the myeloid lineage?
neutrophil basophil eosinophil monocyte dendritic
What immune cells make up adaptive immunity?
B cells
CD4 &CD8 T cells
Characteristics of immune cells in lymphoid lineage?
Similar size to RBC
Little cytoplasm with few granules
4 types of intercellular signalling?
Endocrine
Paracrine
Autocrine
Juxtacrine
What are cytokines?
small proteins released by cells that have an effect on another cell
What is the main role of chemokines?
temporal and spatial organisation of cells and tissues
3 key features of innate antigen receptors?
Do not recognise antigen specifically Pattern recognition receptors’ (PRRs) Recognise ‘pathogen associated molecular patterns’ (PAMPS) Genome-encoded Not clonally distributed
6 features of adaptive antigen receptors?
Recognise antigen specifically
T cell receptor, B cell receptor (antibody)
Produced by random somatic recombination events between gene segments
Huge receptor diversity
Clonally distributed
Permit specificity and memory in immunity
What is compliment?
serum proteins that mark pathogens with a molecular flag and also recruit effector cells
What do the two components of compliment do?
One covalently bonds to pathogen the other attracts the effector cell
outline the process of inflammation addressing calor, dolor, rubor and tumor
Cells damaged release cytokines
Cytokines induce local dilation of blood capillaries (calor&rubor)
Vasodialtion causes gaps between cells in endothelium to widen, increasing leakage of plasma into tissue. Odema (tumor)
Swelling puts pressure on nerve endings (dolor)
4 induced barriers to infection?
Innate immune cells
Pattern recognition
Receptors (PRRs)
Interferon
The first time an adaptive immune response is made to a given pathogen is known as what?
primary immune responce
What is lysozyme and how does it work?
An antimicrobial enzyme in blood and tears.
Disrupts bacteria cell wall by cleaving bonds between the sugars that make up peptoglycan.
In terms of antigen recognition, what is the difference between a B and t cell receptor (antibody)?
B cell recognises intact antigen
T cell recognises processed antigen
Physical barriers to infection
Skin, hair, nails
Mucosa of GI, respiratory, genital tracts
3 soluble barriers to infection?
Compliment
Defensins
Collectins
4 induced barriers to infection?
Innate immune cells
Pattern recognition
Receptors (PRRs)
Interferon
What are defensins and how do they work?
Antimicrobial amphipathic peptides peptide. They have both a hydrophillic and hydrophobic region on their cell surface. Enter the lipid bilayer of the icrobe and form a pore.
What is lysozyme and how does it work?
An antimicrobial enzyme in blood and tears.
Disrupts bacteria cell wall by cleaving bonds between that make up peptoglycan.
Which type of bacteria is lysozyme most effective against?
Gram positive
3 examples of antimicrobial peptides?
Histatins
Defensins
Cathelicidins
5 features of antimicrobial peptides?
Cover epithelial cells, found in saliva
secreted by epithelial cells, neutrophils and paneth cells
Kill bacteria in mins by disrupting membrane
Also attack fungi and viruses
Inhibit DNA and RNA synthesis
What are histatins and where are they found?
antimicrobial peptide, found in the mouth. active against fungi.
What are defensins and how do they work?
Antimicrobial amphipathic peptides peptide. They have both a hydrophillic and hydrophobic region on their cell surface.
What does collectin do?
Binds to surface sugars of bacteria. Targeting them for opsination
How does ficolin work?
recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls
name the three compliment pathways
classical
lectin
alternative
where is complement made?
liver but also produced by monocytes, macrophages and epithelial cells of the intestine and urinary tract
What 4 effects are mediated by compliment?
Lysis
Opsonisation
Activation of an inflammatory response
clearance of immune complexes
What complement protein is associated with the classical pathway?
C1
What does C1 bind to?
Fc region of an antibody usually IgM
How many Fc regions must C1 bind to, what is the significance of this?
At least 2
Therefore IgM most effective at activating compliment as it has 5 Fc domains
Why does C1 not bind with serum IgM?
Serum IgM cannot bind C1 as it has a planar conformation, the shape changes on binding antigen to reveal binding sites for C1q
Draw the classical pathway
Binding C1q with the Fc domain causes a conformational change in C1r C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
What is the lectin pathway activated by?
Antibody independent, activated by ficolins and mannose binding lectin (MBL)
Draw the lectin pathway
Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases)
Active complex cleaves C2 and C4
What is the alternative pathway activated by?
Solid surface of bacteria. C3 spontaneous hydrolyses into C3a and C3b
Draw the alterantive pathway in relation to the other pathways.
c3 to c3b + c3a
What complement components initiate the membrane attack complex?
C5b binds C6 initiating the formation of the MAC
How does the MAC distrupt a cell?
MAC forms a pore that inserts into the membrane allowing diffusion of ions and small molecules, water moves into the cell killing it
Why doesn’t the MAC destroy the body’s own cells?
Human cells have soluble and cell surface associated proteins that prevent MAC formation
3 examples of compliment inhibitors?
C1 inhibitor
membrane bound c3 inhibitors
memebrane bound inhibitirs prevent actibation of MAC
Example of compliment inhibitor deficiency?
Heridatory angiodema - C1 inhibitor deficiency
What is the overall conseqience of complement deficiency?
recurrent infections
What does defiency in MBL typically cause?
serious pyogenic infections in neonates and children
A defiency in which type of complement is the most severe?
C3 most severe, leading to successive severe infections
What are patients deficent in compliment component C8 prone to?
Neisseria meningitis infections
What do 90% of people with C4 deficency develop?
systemic lupus erythematosus
In terms of phagocyte recruitment, what are the 4 stages of rolling and extravasation?
Rolling
Activation
Arrest/adhesion
Transendothelial migration
During phagocyte recruitment what molecules assist in the adhesion process?
ICAM-1 and ICAM-2 are upregulated on the endothelium
3 examples of opsonins
Complement components (C3b)
Collectins (mannose-binding lectin)
Antibodies
4 examples of phagocyte receptors
Complement receptors
Fc receptors
mannose receptor
Scavenger receptors
What are the 6 mechanisms of action utilised by phagocytes?
Acidification Toxic Oxygen derived products Toxic nitrogen oxides Antimicrobial peptides Enzymes Competetors
What are Neutrophil Extracellular Traps (NETs)? 2
When activated some neutrophils undergo a special form of cell death termed ‘NETosis’
nuclear chromatin is released from cells trapping microorganisms
What are pattern recognition receptors and what do they recognise?
Receptors able to recognise conserved structures
They recognise patterns termed:
pathogen-associated molecular patterns (PAMPs)
What are DAMPS
Damage associated molecular patterns, molecules released from necrotic cells
What are the 4 types of Pattern Recognition Receptors?
Toll-like receptors (TLRs)
NOD-like receptors (NLRs)
Rig-I like receptors (RLRs)
Cytosolic DNA sensors (CDS)
What do Toll Like Receptors recognise 4 examples?
bacterial prodiucts - Lipopolysaccharide
Flagellin
viral products - ssRNA
DNA
How is an Acute phese response measured?
Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP (a pentraxin)) are characteristic of an acute phase response and are used clinically to detect inflammation
6 Examples of where PRRs could be useful clinical targets, either as agonists or antagonists
Infection Autoimmunity
cancer Sepsis
Allergy cancer
A defect in Cytosolic DNA sensors
would result in what condition?
(STING)-associated vasculopathy with onset in infancy (SAVI)
Where do T and B lymphocytes develop?
B - Bone marrow
T - Thymus
Give 4 examples of inflammatory cytokines?
IL-1beta
IL-6
IL-12
TNF-alpha
Give an example of a chemokine and state it’s use?
CXCL8 - chemoattractant
What do NOD like receptors recognise?
bacterial degradation prodcuts in the cytoplasm
Individuals with defficient Mannose Binding Ligand (MBL) succeptible to what type of infection?
Neisseria meningitidis
In terms of immunophenotyping what is expressed by T and B cells?
B cells - CD19
T Cells - CD3, 4 and 8
In terms of B and T cell development, what is positive selection?
positive selection identifies cells that can bind antigen (in the case of T cells, MHC bound peptide) and signal through their receptor (B cell receptor or T cell receptor)
the signalling promotes their survival.
In terms of B and T cell development, what is negative selection?
Negative selection involves the binding of self-
antigen to the B-cell receptor or T-cell receptor, which results in deletion of the cell by apoptosis·
What MHC molecules do the differtn T cells recognise?
CD4- MHC II
CD8- MHC I
What is VDJ recombination?
the genetic recombination of a variable region with a
diversity region and a joining region.
The key enzymes responsible for VDJ recombination are?
Reactivating genes RAG 1 and RAG 2
What is somatic hypermutation?
A further refinement of B cell receptor recognition to antigen
What enzyme is critical to somatic hypermutation?
activation induced cytidine deaminase (AID)
What is Antibody class switching or class switch recombination?
A step in the B cells response to an antigen. Determines what type of antibody is produced.
During B cell class switching, what is NOT affected?
The affinity of the B cell receptor for antigen
What occurs during class switching?
The constant region of the antibody is replaced so that it can interact with different effector molecules
What 2 alternative isotypes of immunoglobulin are expressed by naive B cells?
IgM & IgD
Why are IgM and IgD not produced by class switch recombination in naive B cells?
Because the cells have not experienced antigen
How is IgM and IgD produced in naive B cells?
By alternative mRNA splicing
Why do T cells need to work with antigen presenting cells?
Because their receptors can only recognise the processed components of a pathogen
What are the two alternative pathways for antigen processing?
Exogenous
Endogenous
What stops the MAC from destroying own cells? 3
enzyme MCP o the surface of the bodies own cells clips to an inactive form.
Decay Accelerating Factor (DAF) accelerated destruction of covertase.
Protectin removes almost completed MACs from cell surface.
How does the lectin pathway work?
Mannose binding lectin in blood has another protein MASP bind to it.
MBL attaches to a pathogen and the MASP then functions like a convertase to cleave C3 in the blood
What is iC3b and what does it do?
Inactive C3b.
Binds to surface and marks it for phagocytosis.
To what cells do MHC I and II belong and who do they advertise to?
MHC I - Found on most cells. Billboards for killer T cells
MHC II - Antigen presenting cells - Helper T
What 3 PAMPS do the TLR located on the outside of the cell membrane recognise?
lipopeptides 1&2, 2&6
flagellin 5
lipopolysaccaride 4
What 3 PAMPS do the TLR located within the cell recognise?
dsRNA 3, 10
ssRNA 7, 8
CpG DNA 9
What 6 DAMPs are recognised by TLRs?
HSP70 Fibrinogin Fibronecctin dsRNA ssRNA DNA
What 2 pathways are associated with TLR signalling?
MyD88
TRIF
Give 2 examples of diseases linked to defects in PRRs or their signalling pathways?
Waldenstrom macroglobuleima - MyD88 gain of function
MyD88 deficiency - childhood infections but later compensated for
What disease would you typically get if you were deficient in in TLR-3?
Herpes Simplex Encephalitis
Two examples of NLRs, and where are they found?
In the cytoplasm NLRC1 and NLRC2
What do NOD1 and NOD2 (NLRC1 and NLRC2) recognise?
Components of peptoglycan. iE-DAP and muramyl dipeptide respectively.
NOD2 gain of functionwould result in what type of disease?
Sarcoidosis
NOD2 loss of function results in what disease?
Crohns
What 2 diseases are a mutation of NLRP3 associated with?
Muckle Wells syndrome
Familial cold inflammatory syndrome
A mutation of NLRP3 causes an over production of what and how can this be treated?
IL-1
IL-1 receptor antagonist - anakinra
What activates NLRP3? 3
K+ efflux
reactive oxygen species
lysosomal damage
What receptor ids linked to inflammasome?
NLRP3
What does inflammasome activate and ultimately produce?
Caspase 1 then IL-1 and IL-18
What do RIG-I and MDA5 receptors look out for?
Cytoplasmic RNA
Give an example of a cytosolic DNA sensor, what does it’s products interact with?
cGAS
what it produces interacts with STING on ER
What does a STING gain of function result in?
SAVI - chronoc inflammation of skin, lungs
5 long term side effects of prednisolone?
Diabetes Osteoperosis Cushingoid syptoms/appearnace Cateracts Proximal muscle weakness
What is the tiny region on the BCR that actually binds to the antigen?
epitope
In terms pf lymphocyte development, what type of cells in involved in their development?
Stromal cells
Where in the body does VDJ recombination take place?
Bone marrow
Where does the “stimulation by foreign antigen” component of lymphocyte maturation take place?
peripheral lymphoid tissue
What are the two types of B cell antigen?
T dependent
T independent
What 2 types of substances are being recognised by B cells when they recognise T independent antigens?
Lipids
Polysaccarides
T dependent antigens are typically what type of molecule?
Proteins, peptides
What happens in T independent antigen B cell interaction to become activated?
Crosslinking of many epitopes will result in activation.
Broadly, what happens regarding T dependent antigens to result in B cell activation? 5 marks
BCR binds to antigen Antigen processed Presented as MHC II Recognised by CD4 T cell CD4 cell activates B cell May require additional CD40 signal
What proteins are associated with co-stimulation of B cells by a helper T cell?
B cell - CD40, CD80, CD86
Th Cell - CD40L, CD28
What cytokines are secreted by Th cells during B/Th interaction?
IL-4
When first activated what is the type of antibody produced by B cells?
IgM
What region of the antibody needs to be altered in order for class switching to occur?
Fc
How many C1 complexes need to come together in orfer to activate the classical complement pathway?
2 or more
What type of antibody is involved in the classical pathway of complement?
IgM
What determines the type of antibodies that are produced by B cells?
The cytokines released by Th cells can switch B cells from making IgM to another type of antibody.
In terms of B cell receptors, what is essential for C cell activation?
Crosslinking
How does complement influence B cells
B cells have a complement receptor.
Which amplifies signal from BCR activating the B cell
I cross linking alone enough to activate the B cell?
No, it requires a co stimulatory signal
What are the proteins involved in Th dependent activation, and what would a deficiency in these proteins mean?
CD40L &CD40
Inability to mount a T dependent antibody defence
What causes B cells to class switch and change the type of antibody they produce?
Cytokines released by Th cells
What part of the BCR is affected by somatic hypermutation?
Antigen binding region.
Why to B cells ununfluenced by Th cells usually not undergo class switching or hyper mutation?
These processes require cytokine release from Th cells
What is the protein found on antigen presenting cells involved in co stimulation?
B7
Define immunisation
Immunisation is an artificial process by which an individual is rendered immune
Define passive immunisation - 2 examples
Immunity conferred without an active host response on behalf of recipient
VZV prophylaxis
snake venom anti-serum
Define active immunisation
Immunity conferred in recipient following the generation of an adaptive immune response
What is herd immunity?
Vaccination of sufficient numbers impacts the transmission dynamic so that even unimmunised individuals are at low risk
Describe a classification system for active vaccines
Whole Organism - Live attenuated or Inactivated
Subunit
Up to 9 examples of live attenuated vaccines
Measles Mumps Rubella Polio (Sabin) BCG Cholera Zoster VZV Influenza
4 Pros of live attenuated vaccines
Replication within host, therefore produces highly effective and durable responses
In case of viral vaccine, intracellular infection leads to good CD8 response
Repeated boosting not required
In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live-attenuated vaccine strain eg polio
3 Cons of live attenuated vaccines
Storage problems, short shelf-life
May revert to wild type
Immunocompromised recipients may develop clinical disease
Difference between Salk and Sabin vaccine
Salk - Injected inactivated polio virus
Sabin - Oral live-attenuated virus
What is an inactivated vaccine and what does it stimulate?
Entire organism used, but physical or chemical methods used to destroy viability (eg formaldehyde)
Stimulates B cells, and taken up by antigen-presenting cells to stimulate antigen-specific CD4 T cells
Up to 6 examples of inactivated vaccine
Influenza Paratyphoid Typhus Cholera Plague Rabies Polio - Salk
3 pros and 3 cons of killed vaccines
No potential for reversion
Safe for immunocompromised
Stable in storage
Mainly CD4/ antibody response
Responses less durable then live vaccines
Generally boosters required
Higher uptake generally required to achieve herd immunity
Why are influenza vaccines produced annually?
The target antigens are prone to mutation (antigenuc drift)
What is antigenic shift?
When more major changes in a pathogenic virus occur eg human strain recombines with with animal strain causing a pandemic
What are subunit vaccines?
Vaccines that use only a critical part of the pathogen in order to generate an immune response
What type of immune responses are illicited by a subunit vaccine
CD4 and antibody
What are subunit toxoid vaccines?
Toxins that are typically produced by bacteria are detoxified to become toxoids. These then stimulate ab antibody response.
3 examples of toxoid vaccines
Corynebacterium diphtheriae
Clostridium tetani
Bordatella pertussis
What are subunit polysaccharide vaccines?
Thick polysaccharide coats of Streptococcus pneumoniae and Neisseria meningitidis make them resistant to phagocytosis
Vaccines for these organisms formed of purified polysaccharide coats
Vaccines formed of purified polysaccharide coats; aim to induce IgG antibodies that improve opsonisation
Whats is the drawback of subunit polysaccharied vaccines, what can be done to counter this?
Polysaccharide is weakly immunogenic. So protein conjugates are added
What is vaccine conjugation?
Protein conjugate is added to polysaccharide
Antibody recognises polysaccharide and both are internalised
conjugate processed by MHC class II pathway
CD4 cell recognises peptides
CD4 cell activates B cell to produce antibodies
What is a recombinant protein subunit vaccination? 2 examples
HPV
Hep B
3 pros and 3 cons of subunit vaccines
Extremely safe
Work well where primary infection may be prevented by an antibody response
Works when the virus cannot easily be cultured eg HPV and Hep B
Development requires detailed knowledge of virology, pathogenesis and immunology
Specialised and expensive production
Weaker immune responses – boosting often needed and response rate varies
What are adjuvants and what do they do?
Helpers that boost immune response to vaccine.
Work by binding to pattern-recognition receptors on antigen presenting cells
This enhances co-stimulation and cytokine secretion, which ensures a robust T/ B cell response
What are the 3 main components of a vaccine?
Antigen
Adjuvants
Excipients
Two examples of novel vaccines
DNA vaccines
Viral vector vaccines
Describe the steps of TB infection
MTB enters lungs
establishes infection in macrophage phagolysosome
antigen presented on MHC II
TH cells relaease IFgamma
more magrophages attracted to from granuloma
Secondary infection is reactivation of this
What is the vaccination against TB
BCG
M.bovis
Aims to increase IFgamma release from Th1 cells
Limitations of BCG?
Only really effective in children against disseminated TB or TB meningitis
Works less well in adults
No protection against pulmonary TB
give 2 examples of a subunit vaccine utilising polysaccharide capsules
Streptococcus pneumoniae
Neisseria meningitidis
What’s the principle behind DNA vaccination?
Don’t give the antigen but instead the DNA plasmid that encodes the antigen
What is Di-George syndrome and what is the consequence of this?
Children born without thymus
No T cell responce
What is MHC restriction?
Positive selection
Epithelial cells in cortical region of thymus check that T cells recognise self MHC molecules
If not they apoptose
In terms of T cell maturation, what is meant by double positive and double negative?
Immature T cells arriving at thymus express neither CD4 nor CD8.
As they mature in cortex of thymus they then expree both CD4 and CD8
Why is MHC restriction important?
Ensures that T cells recognise antigen presented by antigen presenting cells. Otherwise antigen presentation won’t work.
Where in the thymus does the T cell “tolerance of self” take place?
Medulla
At what point do maturing T cells become single positive?
During or soon after positive selection
What 2 cells are involved in negative selection of T cells?
Thymic dendritic cells
Thymic medullary epithelial cells
What is tolerance of self also known as?
Negative selection
During negative selection what is tested by the thymic dendritic cells?
Does the T cells recognise any of the self antigens presented on my MHC molecules? Anwer should be no
How does strength of interaction between TCRs and MHC relate to positive and negative selection?
During positive selection weak interaction signal survival
During negative selection a strong interaction signal apoptosis
How does the “traffic pattern” of naive T cells aid tolerance of self antigens?
naive T cells remain in secondary lymphoid tissue so the will ahve been exposed to same abundant self antigens in the thymus.
Other self antigens too rare to trigger activation here
What gene expression is associated with Tregs
Foxp3
How do natural Tregs aid tolerance induction?
provide protection against the T cells that have the potential to react against self antigens
How are inductible Tregs cells different from natural Tregs?
Inductible Tregs prevent overeaction to foreign antigens and use cytokines rather than cell to cell interaction.
What is peripheral immunity?
T cells that recognise antigen on self tissue
Do not receive co-stimulation
T cell anergized and can no longer function
What checks are in place to ensure T cell tolerance?
MHC restriction - positive selection Tolerance induction - negative selection Tolerance by ignorance - doesn't see rare self antigens Treg cells - natural and inducible Peripheral tolerance Inactivation from chronic re-stimulation
Give 3 examples of cytokines that interfere with viral replication
IFN-alpha (made by lymphocytes)
IFN-beta (made by fibroblasts)
IFN-gamma (made by lymphocytes & NK cells)
Examples of cytokines involved in haematopoiesis of myeloid cells
EPO - erythrocytes
GM-CSF - neutrophils
G-CSF - neutrophils
IL-6 - mast cells
Example of cytokine involved in haematopoiesis of lymphoid cells
IL-2
Two examples of TNF mediated diseases
Rheumatiod arthritis
IBD
What are the three strategies in which cytokines can be inhibited?
Receptor antibodies - anti TNF, IL-1R
Cytokine antibodies - Anti IL-6
Soluble receptors - soluble TNFR
The cytokines responsible for imflamation are usually produced by what type of Th cell?
Th1
Give an example of the type of cytokine produced by each type of T cell
Th1 - TNF, IF gamma
Th2 - IL-4
2 cytokines released by Treg cells?
IL-10
TGF beta
What effect does the interaction of B7 with CTLA-4 have when compared to CD28?
Makes it harder for the R cell to be activated
In terms of the STRENGTH of interaction between TCRs and MHC, what results in positive and negative selection?
Survival of positive selection - weak interaction
Survival of negative selection - strong interaction
What cells within the thymus are involved in positive and negative selection and where are these located?
Cortical Thymic epithelial cell
Thymic dentritic cell
Medullary Thymic epithelial cell
What “question” is posed during positive selection?
Do you recognise these MHC molecules?
Answer better be yes
What “question” is posed during negative selection
Do you recognise any of the self peptides displayed on my MHC molecules?
Answer better be no
What is MALT, BALT and GALT?
Associated lymphoid tissue
Mucosal, Bronchial, Gut
3 main defence strategies in mucosa of intestine and oropharaynx?
Commensual flora
Epithelium and mucus
Regionalised immune system
What’s specialised about the epithelial cells of the intestines with regard to inflammation?
They provide defence without inflammation
hat specific structures exist in the intestine to aid the immune system?
Peyers patches
Goblet cells
Epithelial cells
Paneth cells
What do the following cells do?
Goblet cells
Epithelial cells
Paneth cells
Goblet cells - mucus production
Epithelial cells - express TLRs
Paneth cells - produce defensins
What do Peyers patches do?
Sample antigens from the intestine by transporting those antigens through the M cell
What tissue collects lymph and antigens from the intestinal mucosa and is the main site for oral tolerance induction?
Mesenteric lymph nodes
What are the homing receptors associated with Peyers patches and mesenteric lymph nodes?
a4b7
CCR9
What are the 2 effector sites of immune responce in the gut?
epithelium
lamina propria
What is the Gell and Coombes system of classification?
mechanism based approach of classifying immunocologicaly mediated disease
What are the 4 different Gell and Coombes classifications?
1 - IgE vs anitgen (allergy)
2- Pathogenic antibody directly causes disease
3 - Antibody/antigen complex disease
4 - Inflammation directly mediated by T cells
What is given to others to prevent Haemolytic disease of the newborn?
Anti-D IgG antibodies binds to foetal RBC in mothers circulation preventing sensitisation.
Examples of type 1, 2, 3 & 4 hypersensitivity
1 - allergy
2 - Haemolytic disease of the newborn
3 - Serum sickness, lupus
4 - Delayed type hypersensitivity - contact dematitis
Draw a picture of an indirect immunofluorescence system and a solid-phase immunoassay system for the detection of antibodies in blood
Antigen
Pt serum
Marker antibody
check for flourescence
Draw a picture of a direct immunofluorescence system for the detection of antibodies bound to tissue
Sample of tissue
Marker antibody
check for flourescence
describe the steps of an ELISA experiment
Direct and indirect
What are the two classifications of autoimmune disease?
Organ specific - insulin dependent diabetes
Non-organ specific - Lupus
With regard to autoimmunity what do mutations in IRE genes result in?
Failure of negative selection
Strongly associated with autoimmune disease
With regard to immune cell numbers what will DI George syndrome result in?
No/v low T cells due to thymic aplasia
What is molecular mimicry?
epitopes relevant to the pathogen (following an infection) are shared with host antigens
2 examples of molecular mimicry
Autoimmune haemolysis after Mycoplasma pneumoniae
Rheumatic fever: inflammatory disease occurring after streptococcal infection affecting heart, joints, skin and brain
2 examples of molecular mimicry
Autoimmune haemolysis after Mycoplasma pneumoniae
Rheumatic fever: inflammatory disease occurring after streptococcal infection affecting heart, joints, skin and brain
2 examples of molecular mimicry
Autoimmune haemolysis after Mycoplasma pneumoniae
Rheumatic fever: inflammatory disease occurring after streptococcal infection affecting heart, joints, skin and brain
A deficiency in CD40/CD40L is likely to result in what? 2
Unable to mount T cells responce
B cells secrete mainly IgM
People suffering from SCIDS lack what type of immune cell?
T and B
People suffering from SCIDS lack what type of immune cell?
T and B
What are the main classifications for immunodeficiency?
Primary Immunodeficiency syndrome - immune defect is intrinsic to the immune system itself
Secondary Immunodeficiency - secondary to anither disease process
4 characteristics of infections due to immunodeficiency
Opportunistic
Unusual
Severe
frequent
Causes of secondary immunodeficiency
Extremes of age malignancy (myeloma and lymphoma) Iatrogenic - steriods, chemotherapy Diabetes Infection - HIV
What are the 3 IMMUNOLOGICAL classifications of immunodeficiency?
Innate
“Antibody/humoral” - B cells eg bacterial infections of resp tract
“Cellular” - T cells eg HIV, viral, fungal
What are the immunideficincy syndromes called when they affect both the antibody and cellular component?
Combined immunodeficiency
What is immune dysregulation?
Uncontrolled inflamation in immunodeficiency
In antibody deficiency what type of antibody is significant?
IgG
Two Secondary causes of antibody deficiency
IgG loss through burns and nephrotic syndrome
Impaired production via immunosuppressive drugs
Two primary causes of antibody deficiency?
X linked agammaglobulinemia
X linked hyper IgM syndrome
What is Transient hypogammaglobulinemia of infancy?
Physiological antibody deficiency
Period when the portenction afforded to them by mother IgG drops as the pordcution of their own antibodies catches up
At ahat age would infants with antibody deficiency present and why?
after 3-6 months as up unitl this point they are portected by their mother IgG
What is X linked agammaglobulinemia?
A primary cause of antibody deficiency
Deficiency of Bruton’s tyrosine kinase. so no downstream signalling so B cells undergo apoptosis.
No B cells
What is X linked hyper IgM syndrome?
failure of B call maturation
Normal or high IgM
No IgA or IgG
No CD40 ligand
What is cellular immunodeficiency?
CD4 T cell deficiency
What is severe combined immunodeficiency?
rare life threatening primary immunideficiency
No T cell or B cell function
graft vs host rash
3 causes of SCID
Common gamma chain deficiency
JAK3 deficiency
RAG1/2 deficiency
What are patients with Terminal complement deficiency succeptible to?
Neissera infections
What are the indications for Azathioprine and Ciclosporin?
Immunosuppression for
Crohns
SLE
RA
What type of drug is methotrexate and what are its indications?
antimetabolite
Crohns
RA
What are the indications for rituximab and infliximab?
Crohns - infliximab only
RA
Example of an antihistamine
Chlorphenamine
