Immunology Flashcards
Acute phase protein levels change in response to what?
Tissue injury
“The personal identifier molecule”
MHC
A dead vaccine is safer that a live vaccine, why?
It has less residual virulence than a live vaccine
ADCC
Antibody-dependent cell mediated cytotoxicity
As well as acting as an activator of the MAC what other function does C3b serve?
Combines with IgG to cause strong opsonisation of the pathogen
Attachment of IgE to parasites wall causes activation of the IgE Fc receptor leading to which consequences?
- Mast cell degranulation
- Worm expulsion
- Increased gut motility - smooth muscle
- increase mucus production
- Cuticle breakdown
- Eosinophil release of NO, MBP and other oxidants toxic to the parasite
- Platelet and macrophage release
Avidity
The number of bonds made by an antibody determines its strength
B cells are most useful in which type of infection?
Extracellular
By which methods can the alternative pathway be activated?
Direct activation of C3
Non-pathogenic - AgAb complexes, carbohydrates etc
Pathogenic - pathogen cell walls, selected viruses and parasites
C-reactive proteins cause what process to make bacterial cells more “tasty”?
Opsonisation
Chemotaxis
Increased cell motility in response to chemical release
C3a and C5a have no effect on the MAC complex when they are formed. What is their end action?
Activation of mast cellsChemokines
Describe a site of action of IgE.
IgE molecules bind to their specific receptors on mast cells
Dead vaccines need less doses to confer immunity to the host than live vaccines.True or False.
False
Describe the mechanical aspects of innate immunity.
Body surfaces - skin and furRespiratory tract cilia Air movement in the respiratory tractMucus secretionLiquid secretion flushes
Describe an instance in which MHC 1 May not be present on the surface of a cell. What is the consequence of this?
Some tumours and infections cause down regulation of MHC1, this means that they are unable to be targeted by cytotoxic T cells.This causes activation of NK cells which apoptose the affected cell
Draw the structure of a lymphnode. How do pig lymphnodes differ to those of other mammals?
Pig structure is “backwards”
Draw a single unit of the spleens white pulp, label the whereabouts of the two types of lymphocyte found in it.
Corona = b PALS= t
Draw a C1 complex molecule.
C1q - six binding sitesC1rC1s
Epitome
The part of the pathogen which is recognized by the immune system
Exogenous Ag processing causes activation of cytotoxic T cells and endogenous Ag process causes activation of helper T cells.True or false + correct if necessary
FalseVisa versa
How are immunoglobulins absorbed in the neonate gut?
The stomach has low enzyme concentration at this point therefore FcRn receptors on the wall of the small intestine absorb the Ig.
Extra components of the complement process can cause which immune processes?
Chemotaxis - C5b
Opsonisation
Activation of mast cells
How are useful T cells selected for in the thymus?
Their affinity for MHC molecules - useful T cells have only a low affinity for MHC 1 and 2
How do a capsule and a slime layer differ in the bacterial cell?
Capsule is well defined compared with a slime layer.
How do APCs process antigen?
Endogenous - express full processed Ag on cell surface via MHC1Exogenous - Macrophage breaks down Ag and expresses parts of it on its surface or allows other APCs to pick up and express it via MHC2
How do antibodies act in a viral infection?
Prevent viral adhesionViral agglutinationMacrophage engulfmentAntibody dependent cell cytotoxicityComplement mediated lysisPrevents viral absorption
How do bacteria evade the immune system?
Avoid adaptive immunity
- Mimic host Ag
- Biofilms
- IgA proteases
Survive phagocytosis
Avoid phagocytosis
- A proteins
- M proteins
- Capsular molecules
Manipulate cytokine secretion
How do commensal bacteria act as part of the innate immune system?
They provide a barrier to the gut mucosa for other pathogenic bacteria.
How do protozoa parasites evade the host immune system?
Hide - coat themselves with host protein
Block dendritic cells
How does colostrum become rich in immunoglobulin in the udder?
Fc receptors in the mammary tissue pull Ig from the serum into the gland as it passes through, this is secreted in the milk.
How does the secretory piece of an IgA molecule function?
It protects the IgA molecule from the harsh environment of mucosal surfaces where IgA has its action. Prevents break down by proteinases.
How is the body protected from complement mediated damage?
Complement proteins breakdown easily - LabileCells have specific complement receptorsFactors I and H cleave C3 - reduce reactionRBC’s have c3b receptors which mop up excess complement proteins
How many litres of colostrum should the neonate receive in the first six hours?
1L
How would low immunoglobulin levels in the neonate be treated in cases which are over and under 15 hours old?
Over 15 hrs = IV Ig Under 15 hrs = Oral colostrum
Humoral immunity is mediated by which type of lymphocyte?
B cells
Interleukin 10, which causes inhibition of TH1 interferon gamma release, is released by what cell?
TH2
Lymphocytes are produced in the _____ _______, a _______ lymphoid organ . Once produced T cells are moved to the ________ for maturation.
Bone marrow - primaryThymus
Label this bacterial cell.
MHC
Major histocompatibility complex
Name and state the producing cells of the different types of interferon.
IFNa/b - fibroblasts IFNgamma - T cells and NK cells
Name the four major components of the T cell receptor molecule.
Alpha subunit Beta subunitCD3 complexEither CD4 or CD8 molecule
Name two types of mucosa associated lymphatic tissue.
Peyers patches Tonsils
Name two types of animal which are know to suffer with complement deficiency disorders.
Finnish landrace lambsBrittany spaniels
NO is produced by which phagocytotic cell to cause oxidative damaged in bacterial cells?
Macrophages
Outline and briefly explain the potential outcomes of a viral infection.
Cell division - viral tumoursCell lysis - destruction of host cellPersistent infection - slow release of viral particlesLatent infection - delay between infection and symptoms
Outline the characteristics of the ideal vaccination.
Provides strong immunityLong-termConferred to foetusMinimal side effectsCheap/stableDIVA testable
Outline the formation of the membrane attack complex in the classical pathway.
C1q/r/s complex binds to Ab/Ag complex > C1 cleaves C4 and C2 into a and b molecules > C4&2b attach to nearest bacterial protein > c3 binds and is cleaved to a and b > b cleaves c5 to a and b > b causes binding of c6/7/8/9 this forms the MAC
Outline the process of complement activation via the lecithin pathway.
Mannan-building lecithin binds to pathogen surface via PAMPs C4 and C2 bind to MBL and dissociate to a and b molecules causing activation of the C3 molecule
Outline the process of phagocytosis.
Attachment of microbe to phagocyte receptorPseudopodia engulf the microbe and form the phagosomeThe phagosome fuses with the lysosome Lysosome digests microbeMicrobial proteins are expelled from the phagocyte
Outline the role of the high endothelial venules in the lymphnodes.
They grab lymphocytes using integrins from the blood and pull them into the lymphnode.
PAMP
Pathogen associated molecular patterns
PRR
Pattern recognition receptors
T cells are useful in which type of infection?
Intracellular - they destroy infected cells
The C1 complex is vital in the activation of which complement pathway?
Classical
The membrane attack complex is made up of which 5 complement proteins?
C5bC6C7C8C9
The PALS of the white pulp of the spleen surround what and contain which type of lymphocyte?
Central arteryT cells
The primary response to a pathogen is ____ than the secondary reponse.
Smaller
The variable region of antibodies can also be known as what?
The antigen binding site The functional site
These types of cytokines regulate immunity by acting on lymphocytes.
Interleukins
This interleukin inhibits the release of interferon gamma therefore causing the upregulation of B cell production.
Interleukin 10
This PRR can be found on monocytes, macrophages, mast cells and Bcells and has a non-specific manner of detecting PAMPs.
Toll-like receptors
This type of Bovine Viral Diarrhoea causes abortion and malformation of the foetus.
Cytopathic.
This type of interferon causes secretion of NO and therefore prevents viral growth in cells and also activates macrophages.From which cells does it originate?
Type 2 - IFNgammaT cells and NK cells
This type of interferon increases MHC1 expression of antigen, what effect does this have?
Type 1 - IFNa/b Causes activation of cytotoxic Tcells
This type of T cell prevents auto-immunity by “turning off” CMI.
Treg cell
This type of vaccination contains an attenuated pathogen created by modification of the pathogen by heat, chemical etc or gene knockout or deletion.
Live
This vital organ is an example of secondary lymphoid tissue. Explain what is meant by this.
SpleenAn area of proliferation and differentiation of lymphocytes
Valence
The number of bonds made
What action do interferons have on the body?
Protect cells and their neighboring by binding and blocking viral receptors.
What action of an immature B cell causes its apoptosis in the bone marrow?
If it produces self recognizing antibodies
What are defensins an example of, how do they work?
Molecular innate immunityThey insert into microorganism membranes and cause cell lysisThey are found in epithelial cells and phagocytes
What are Langerhanns cells? How do they aid subcut vaccination effectiveness?
Precursors of dendritic cells. They transmit Ag from the subcut to circulating t cells.
What are the critical properties of vaccines?
Stimulate b and t cellsActivate APC’s Stimulates several epitomesPersistent vaccine antigen
What are the effects of TH2 driven immunity to helminths?
- IL5 mediated activation of Eosinophils
- Macrophage supression
- Mast cell degranulation
- IL4 release
- IgE coat the parasite
What are the sites of action of IgG and IgM molecules?
Lymphoid organsIn circulationIn tissue
What are the types of outcome of complement mediated protection?
Cell lysis - MAC Chemoattraction of phagocytesOpsonisation
What cytokines released by T cells stimulate NK cell action in later stages of viral infection?
TNF, IL12, IL2
Pyrexia and pH changes within the body are examples of what type of immunity?
Physiological innate immunity
What does the Zinc Turbidity test measure?
It estimates IgG in serum based on its precipitation when added to a zinc-containing solution. Precipitation generally occurs when levels are over 400–500 mg/dL
What functions does the bone marrow have in production of B cells?
Ag receptor constructionDevelops specificityKills self reactive B cellsSends useful cells to the periphery Production of antibodies?
What innate cytokines stimulate NK cell action in early viral infection?
IFNa/b and IL12
Th2 cells produce which cytokine to cause the proliferation of B cells?
IL4
What is a basic unit of immunoglobulin made from? Draw one & label it.
Two light and heavy chains joined together by disulfide bonds
What is a cytokine?
A cellular hormone
What is an adjuvant?
An agent which modifies the effect of another agent. They enhance the ability of a vaccine to stimulate the hosts immune system.
What is meant by immune tolerence?
Failure to mount an immune response to an antigen.
What is meant by polyclonal?
Has many epitomes, stimulates many different B cells
What is the common molecular goal of the three complement pathways?
C3
What is the difference between serum and plasma?
Serum is the fluid extracted from contracting blood clots whereas plasma is the fluid spun off anticoagulated blood
What is the function of an APC? Name three types of APC.
APCs present antigen to T cells to cause their activationDendritic cells MacrophagesB cells
What is the method of action of NK cells?
They recognize cells with low MHC1 and destroy them.
What is the quaternary structure of IgM like? How does IgM function biologically in the body?
A circular pentamer.IgM is the main antibody found in the primary response to a pathogen, it is the most efficient antibody
What is the T to B cell ratio?
80 T: 20 B
What percentage of T cells remain once selection within the thymus is complete?
5%
What causes blue eye during an adenovirus infection?
Antigen antibody complexes forming and collecting in the eye.
What products of myeloperoxidases are used to kill pathogens?
Hypochlorite and single oxygen free radicals
What type of relationship exists between Th1 and Th2 cells? Explain.
AntagonisticLike a see-saw, each releases cytokines which inhibits the other cell type
Where in the body are the complement proteins produced?
Liver
Where in the body is mannan-building lecithin produced?
Liver
Which antibodies are most effective in a viral infection?
IgG, IgM, IgA
Which antibodies cause activation of the complement system?
IgG IgA
Which antibodies cause opsonisation of pathogens? What is the effect of this?
IgG attracts phagocytes
Which antibodies neutralize pathogens by recognizing and binding to them?
IgG IgMIgA
Which antibody causes cytotoxicity of pathogens by activation of NK cells?
IgG
Which aspect of arthropod mediated disease causes an immune response in the host?
Parasite saliva
- TH1 activation - infiltration of basophils
- TH2 activation - IgE and inflammatory response
Which aspects of innate immunity are vital in parasite immunity?
Host factors
- Age
- Sex
- Health status
Parasite specificity
- Species of parasite are specific to host
Which cells of the body are considered parts of the innate immune system?
MacrophagesPolymorphic granulocytesMast cellsNK cells
Which class of MHC molecule is found on the surface of APC’s, macrophages, B cells and activated T cells?
MHC 2
Which interleukin is released by macrophages and causes activation of TH1 cells?
IL12
Which of the complement a molecules is considered the strongest Chemokines?
C5a > C3a > C4a
Which of the immune system structures develops first in the neonate?
Thymus
Which oxidative species are produced by neutrophils to destroy bacteria?
H2O2
Which part of the C1 complement protein binds to the antigen-antibody complex in the classical pathway?
C1q
Which physiological changes in the host also decrease likelihood of parasitic infection?
Increased goblet cell number
Mucin secretion
Water influx into intestinal lumen
Increased intestinal motility
Which structural molecule to lysozymes act upon?
Peptide glycine of the bacterial cell wall.
Which enzyme which is part of the innate immune system is mainly found within cellular lysosomes in macrophages?
Myeloperoxidase
Which type of B cell makes antibodies?
Plasma cells
Which type of T cell expresses CD4 on its T cell receptor?
Helper T cells
Which type of T cell recognizes MHC1 molecules?
Cd8 cells - cytotoxic T cells
Which type of T cell recognizes MHC2 molecules?
Cd4 cells - helper T cells
Which types of bodily secretions can lysozymes be found in?
- Saliva
- Tears
- Mucus
Which types of equipment do we use to assess colostrum quality?
- Colostrometer
- Refractometer
Which types of test do we use to assess Ig levels in the neonate?
- Radial immunodiffusion
- Zinc turbidity test
This virus uses antigen variation though genetic drift to evade the hosts immune system.
Influenza
Outline the methods by which viruses evade the immune system.
- Immunosuppression - destroy APC’s, induce tolerence, alter the helper T cell balence
- Antigen variation - genetic drift
- Spread too quickly for immune system to act
- IFN interference
- Inhibit antigen processing
- Non-neutralising antibody production
- Latent infection
How does Herpesvirus interfere with interferons of the body?
Produce a IL-10 analogue which inhibits IFNgamma
This virus type inhibits viral antigen processing through MHC1.
Bovine Herpes Virus
- What are the cellular factors which can cause tumours to occur?
- Which molecules are they presented on in the cell?
- Causes - products are expressed on MHC1
- Tumour supressor gene malfuction
- Viral
- Oncogenes
- Mutated normal genes
- Overproduction of normal proteins
- Foetal proteins
- Mutated glycolipids
- MHC1
How do benign and malignant tumours differ?
- Benign are at a single site
- Malignant metastisise and form secondary tumours elsewhere
How does ADCC act in tumour immunology?
- NK, monocytes, pmn’s and eosinophils bind to FcR on Ab leading to cell death
- Antibodies from abnormal cells become antigens
- Tumour antigens - proteins acting abnormally
How do cytotoxic T cells recognise and destroy tumour cells?
They recognise viral Ag bound to and MHC1 molecule and produce granulozymes, perforins and FAS(L) molecules which cause cell lysis or self apoptosis of the cell. They also release IL2 which stimulates the action of NK cells.
Describe the origination of NK cells.
They make up 15% of lymphocytes. They are a type of T cell which has become part of the innate immune system.
- Interferon gamma is released during tumour immunity by which cells?
- What does it release cause?
- Tumour cells themselves and due to NK and Tc cell activation
- Causes further activation of NK cells and stimulates phagocytosis of tumour cells by macrophages.
Which cytokines produced by macrophages cause increased activity of Th cells and NK cells?
TNF and IL1
How can tumour cells evade the bodies immune systems?
- Activate Treg cells
- Cause lymphocyte apoptosis
Immunotherapy
Stimulate the immune system to attack tumours
How can immunotherapy be used to combat tumours?
- Passively - using interferons
- Active - attempts to stimulate the host’s intrinsic immune response
- Specific - focus on specific cancer generated antigens to stimulate CMI and Ab
- Non-specific - general immune response using cytokines
- “Educated dendritic cells” - which target tumour proteins
- Activated Tc or NK cells which are returned to the host
How are tolerent B and T cells disposed of in the body?
B cells:
- Clonal abortion - immature
- Functional deletion - apoptosis, Treg, no TH cells
- Clonal exhastion - no further proliferation of plasma cells
T cells:
- Thymic deletion
- Post-thymic - suppression, abortion and deletion of self reactive cells
This type of hypersensitivity is caused by the production of IgE as a secondary response to a pathogen rather than IgA/ IgG.
What is the response to this?
Type I hypersensitivity
Causes mast cell degranulation leading to inflammation.
What clinical conditions are caused by type I hypersensitivity?
- Food allergies
- Parasite allergies
Sytemic Anaphalaxis is characterised by what symptoms?
- Respiratory stress
- Diarrhoea
- Collapse
- Increased blood pressure
What is type II hypersensitivity?
Name some clinical conditions which are caused by this.
Antibodies produced by the body attach to the host cells causing antibody dependent cell cytotoxicity
- IMHA
- Foal haemolytic disease
Blue eye is an example of which type of hypersensitivity?
Define this hypersensitivity.
Type III hypersensitivity.
Immune complexes form/ deposite in tissues causing complement reactions, frustrated phagocytosis, cytokine release.
Frustrated Phagocytosis
Release of phagocytitic enzyme into the tissue environment due to the inability of a phagocyte to phagocytose a cell (too big etc)
Define type IV hypersensitivity.
Delayed hypersensitivity - sensitised Tc cells react to a specific antigen and release cytokines which induce inflammator reactions and attract and trap macrophages leading to granuloma formation.
eg TB and TB testing
Differenciate between primary and secondary immunodeficiencies.
Primary immunodeficiencies are inherited defects whereas secondary have extrinsic causes
Immunodeficiency
Increased susceptibility to opportunistic infections and increased risk of tumours.
Define Chediak-Higashi syndrome.
- Enlarged cytoplasmic granules burst
- Increased bleeding
- increased susceptibility to infection
How do Leucocyte Adhesion Deficiencies work?
Failure of granulocytes to leave the blood and enter infections.
Absence of CD11B/18 receptor on leucocyte membranes.
BLAD and CLAD disorders are caused by mutation of what amino acids?
- BLAD - Asp - Gly
- CLAD - Cys - Ser
Pelger Huet abnormality
Is it fatal?
Neutrophil nucleus fails to segment
No.
Canine cyclic haematopoiesis
Cyclic neutropenia and other cell deficiencies (11-12day cycles)
Seen in grey collies
Name the aquired immunity defects.
- Lymphocyes defects
- Severe combined immunodeficiency
- Foal immunodeficiency syndrome - low B cells - Dales and Fells
- Nude cats - T cell deficiency
- IgM deficiency - Low IgM
- Ehler - Dalos syndrome - skin defect
Describe the different types of SCID in equines and canines.
- Equines - Arabians - DNA repair failure - T and B cells are present but don’t work
- Canine
- Bassett hound - No response to IL-2 - No IgG/A, low T cells, lack of TH cells
- JRT - No Ig’s and non-functional T and B cells
Name secondary aquired defects and the viruses they are caused by.
Describe each of them briefly.
- Parvo
- Distemper - CMI and AB depressed, cytokine interuption and lymphocyte lysis.
- Lentiviruses - FIV, HIV, SIV
- FeLV - lymphopenia, kidneys and tumours
DID
Double immunodiffusion - Measures the simmilarity between know and unknown complexes.
RID
**Radial Immunodiffusion **- Quantify Ag or Ab response
Immunoelectrophoresis
Normal vs patient comparisons
How does serology allow us to measure Ab response?
Relies upon Ag/Ab binding complexes. Lattice formation causes visible complexes.
How do DIVA tests work?
Vaccines contain markers which are detected by the DIVA test .