Immunology 2 Flashcards
(118 cards)
1
Q
Define antigen
A
Anything that causes an immune response, usually foreign material but can be our own tissues
2
Q
Define hapten
A
A small chemical group that lone is non-immunogenic, but when attached to a larger carruer protein can act as an antigenic determinant and elicit antibody or cellular immune responses
3
Q
Define carrier
A
Foreign proteins to which small non-immunogenic molecules (haptens) can be coupled to stimulate an immune response. Self proteins can serve as carriers
4
Q
Define adjuvant
A
Any substance which , when mixed with an antigen, enhances the immune response to that antigen (common in vaccines)
5
Q
What is the importance of antigenic drift and shift?
A
Allows variation and therefore improved immune response evasion. Pathogens exist as multiple strains
6
Q
Describe antigenic drift
A
- Point mutations in DNA, lead to coding change in amino acid
- Subtle variation in protein structure
7
Q
Outline the effect on immune response to a pathogen that has undergone antigenic drift
A
- Some antibodies bind to antigens which are unchanged, giving partial protection
- No antibodies recognise drifted epitope
- Therefore immune response is partially, but not fully protective
- Modulation of clinical signs as pathogenic particles are reduced but not cleared
8
Q
Outline the process of antigenic shift
A
- Co-infection of 2 viruses which then exchange genetic material
- Reassortment of segments in genome between different strains of same pathogen
- Leads to dramatic changes in protein expressed
- change is radical
9
Q
What are the consequences for the immune response to a pathogen that has undergone antigenic shift?
A
- Protein not recognised by antibodies
- Immune response not protective
10
Q
In what situations is antigenic shift particularly important?
A
Where individuals live in close proximity
11
Q
What are the consequences of antigenic shift and drift?
A
- Clinical disease more severe
- Multiple (consecutive) infections with the same pathogen
- Mild epidemic due to drift
- Pandemic due to shift
- Difficulty regarding vaccination
12
Q
What are the different types of vaccine that can be used?
A
- Inactivated pathogen
- Modified live pathogen
- Immune stimulating complexes (liposomes)
- Individual purified recombinant proteins
- +/- adjuvants
13
Q
What is the role of Th1 cytokines?
A
Enhance the cell mediated (cytotoxic) response
14
Q
What is the role of Th2 cytokines?
A
Enhance differentiation of B cells into plasma cells and therefore the antibody (humoral) response
15
Q
Name the antigen presenting cells
A
- Dendritic cells
- Macrophages
- B-cells
16
Q
Which APCs are involved in the naive or the primed immune reponse?
A
- DCs involved in both
- Macrophages and B cells involved in primed only
17
Q
Which APCs present to naive or memory T cells?
A
- DCs present to both
- Macrophages and B cells present only to memory T cells
18
Q
What method of antigen capture is used by which APCs?
A
- DCs and macrophages use multiple methods
- B cells only by B cell receptor
19
Q
What is the importance of the location of the lymphocyte regarding immune response development?
A
- Location and whether naive or primed cell dictates where the immune response develops and its speed
- Affects vaccines
- E.g. if vaccine given IM but the pathogen invades at mucosal surface, this is not ideal
20
Q
Explain why the primed immune response is more efficient than the naive response
A
- In naive, DCs captre antigen, travel to local lymph node, where will then activate T cells
- In primed, antigen can be captured, processed and presented locally and efficiently e.g. by MALT
- Memory cells present in body, more sensitive to restimulation, produce cytokines more quickly = more efficient
21
Q
What method of antigen capture do B cells use?
A
Binding to sIg and endocytosis (extracellular virus or bacteria)
22
Q
What method of antigen capture do macrophages use?
A
Phagocytosis (but this is inefficient with soluble antigens. Extracellular)
23
Q
What method of antigen capture do dendritic cells use?
A
Non-specific macropinocytosis and phagocytosis (efficient with soluble antigens from extracellular fluid)
24
Q
Give the processing method, MHC restriction, predominant outcome and location of response for a vaccine consisting of an inactivated whole virus, administered IM
A
Processing: Exogenous
MHC: II
Outcome: Antibody response
Location: systemic
25
Give the processing method, MHC restriction, predominant outcome and location of response for a vaccine consisting of a live whole virus administered IM
Processing: endogenous
MHC: I
Outcome: cytotoxic T cell activation
Location: systemic
26
Give the processing method, MHC restriction, predominant outcome and location of response for a vaccine consisting of a viral vector encoding a single pathogen protein administered IM
Processing: endogenous
MHC: I
OUtcome: cytotoxic T cell activation
Location: systemic
27
Give the processing method, MHC restriction, predominant outcome and location of response for a vaccine consisting of ISCOMS administered IM
Processing: endogeous
MHC: I
Outcome: cytotoxic T cell activation
Location: systemic
28
Give the processing method, MHC restriction, predominant outcome and location of response for a vaccine consisting of recombinant, inert protein administered IM
Processing: exogenous
MHC: II
Predominant outcome: antibody
Location: systemic
29
Give the processing method, MHC restriction, predominant outcome and location of response for a vaccine consisting of live whole virus administered intranasally
Processing: endogenous
MHC: I
Outcome: cytotoxic T cell activation
Location: local (mucosal)
30
Give the processing method, MHC restriction, predominant outcome and location of response for a vaccine consisting of inactivated whole virus administered intranasally
Processing: exogenous
MHC: II
Outcome: antibody
Location: local (mucosal)
31
What are ISCOMS?
Immune Stimulating Complexes
32
Outline the veterinary relevance of antibodies
- Vaccine responses
- Diagnostics
- Immune mediated diseases
- Immunodeficiency
- Tolerance
- Protection of neonate via passive immune transfer
- Therapeutic monoclonal antibodies
- Monitoring for presence of disease
33
What immunoglobulins are present on B cells?
- IgM
- IgD
- Are attached to the surface
34
What immunoglobulin is secreted by plasma cells?
IgG
35
What are the 3 signals required for the activation of naive B cells?
- Binding of antigen to surface Ig and internaisation
- Molecular interaction with Th2 cells
- Costimulation by cytokines from Th2 cells
36
What does the presence of IgM indicate regarding the phase of the antibody response?
Indicates that the acute phase of antibody response is occuring
37
What happens to the B cell immunoglobulins once the cell is activated?
IgM replaced by IgD
38
What events occur in B cells following activation?
- Class switching
- Clonal proliferation
- Transformation into lymphoblasts then plasma cells
- Formation of memory cells
39
What cytokines promote the antibody synthesis by plasma cells?
Il-6, Il-11
40
What region of the receptor is altered in class switching?
Only the Fc region, antigen recognition is the same
41
Where are multiplying plasma cells found?
In germinal centres of lymph nodes
42
Where do the final stages of B cell maturation take place?
Ileal Peyer's patches (ruminant and dog) or the Bursa of Fabricius in birds
43
Where does antigen presentation take place in the lymph node?
In the light zone of the germinal centre
44
Describe the appearance of plasma cells
- Typical acentric nucleus
| - Basophilic
45
Outline the immunological characteristics of memory B cells
- More rapid Ab synthesis
- Increased Ag affinity
- Increased expression of MHC class II and co-stim molecules
- Interact with armed T cells at lower Ag dose
46
What determines the class of immunoglobulins?
The Fc region's arrangement of carbohydrate groups
47
Which immunoglobulins can form multimers? hat is the benefit of multimers?
- IgM and IgE
| - Improve binding to antigens and phagocytes
48
What is the consequence of alterations in the Fab region of immunoglobulins?
Alters the binding specificity of the antibody for the antigen
49
What are the functions of the Fc region of immunoglobulins?
- Actively transport Ig to specific locations
- Bind to complement and promote opsonisation
- IgG Fc region can bind to PMNLs (neutrophils), macrophages, host tissues facilitating phagocytosis
50
List the functions of antibodies
- Soluble Ab binds pathogen/toxin directly
- Formation of Ag-Ab complexes
- Free antibody binds to cell antigens
- Antibody on surface of B cells binds
51
What is the result of a soluble antibody binding directly to a pathogen/toxin?
Pathogen is neutralised and so further infection is blocked
52
What are the results of Ag-Ab complex formation?
- Opsonisation by complement leading to phagocytosis
- Binding to FcR on phagocytes leading to phagocytosis
- Persistence may damage organs (thrombus formation)
- Crosslinking of IgE receptors leading to degranulation of mast cells (more allergic symptoms)
53
What is the result of antibodies binding to antigens on cells?
Recognition by specialised lymphocytes leading to cytotoxicity
54
What is the result of an antibody on the surface of B cells binding to antigens?
Exogenous antigen presentation to Th2 cells, promotes plasma cell formation
55
What is the chicken equivalent of IgG?
IgY
56
Describe the functional relevance of IgG immunoglobulins (where predominates, type of immune response, functions)
- Secondary immune response
- Dominant in serum
- Transudates into tissues
- Fixes complement
- Binds to FcR
- Opsonisation
- Neutralises toxins/pathogens
- Diagnostic
57
Describe the functional relevance of IgA immunoglobulins (where predominates, type of immune response, functions)
- Mainly mucosal surface, also serum and secretions
- Prevents conlonisation
- Can neutralise
- Weak opsonin
58
Describe the functional relevance of IgM immunoglobulins (where predominates, type of immune response, functions)
- Pirmary immune response
- Serum dominant
- Large so can't transudate easily
- Fixes complement
- Effective agglutination
- Diagnostics
59
Describe the functional relevance of IgE immunoglobulins
| where predominates, type of immune response, functions
- Serum and tissues
- Anti-endoparasitic response
- Binds via FcR to mast cells and basophils
- Involved in Type I hypersensitivity
60
Describe the functional relevance of IgD immunoglobulins
Rare, expressed only on the surface of naive B cells
61
What is meant by the primary antibody response?
The first encounter with the pathogen i.e. B cells are naive
62
What is meant by the secondary antibody response?
The encounter of a "known" pathogen i.e. B cells are primed
63
What immunoglobulins predominate in the primary response?
IgM
64
What immunoglobulins predominate in the secondary response?
IgG
65
What occurs in relation to the memory cells in a secondary response?
- Activation of memory cells
| - Differentiate into effector cells
66
Compare the primary and secondary response to a pathogen
- Secondary (aka anamnestic) is quicker, greater magnitude, longer duration
- IgG in secondary, IgM in primary
- Primary initiated in local lymph nodes but secondary in local lymphoid tissues
- In both, memory cells are established
67
What is meant by seroconversion?
Change in predominance of immunoglobulin i.e. switch from IgM in primary, to IgG in secondary
68
Describe the immunoglobulin profile on a B cell following class switching
Will only express a single type of immunoglobulin on its surface i.e. after will only have IgG, IgA or IgE
69
Describe the immunoglobulin profile of plasma cells
Identical to that of the B cell from which it differentiated
70
Which maternal antibodies delivered by the colostrum remain in the gut and which are absorbed?
IgA remains in the gut, IgG absorbed
71
What is the function of passive antibody transfer via colostrum?
Provides immunological protection against pathogens to which the mother has been exposed for several months
72
What is the function of colostral IgA?
Protects the gut epithelium against bacterial invasion until the newborn's own IgA production starts
73
Name the immunological components of colostrum
- IgG, (major component), IgA, IgM, IgE
- Cytokines (e.g. bovine IFNy, TNFa, IL-6, IL-6b)
- Trypsin inhibitors
- Lymphocytes, majority T cells
74
What is the function of trypsin inhibitors in colostrum?
Prevent protein degradation
75
By what mechanisms can IgG be absorbed from the colostrum?
Passive transudate or active transport
76
Describe the active method of IgG transport across the gut epithelium
- IgG transport protein, Fc receptor neonatal (FcRn) expressed on gut epithelium
- 2 molecules of FcRn bin one molecule of IgG
- Binding is via Fc region of IgG
- Endocytosis follows to reach local capillaries
77
List the factors influencing the success of passive immunity transfer
- Type of placenta
- Infection and vaccination history of mother
- Maternal immune response to vaccines
- Concentration of Abs in mother's serum and hence colostrum
- Colostrum loss pre-parturition
- Number of young
- Teat conformation
- Vigour of offspring
- Patency of gut epithelium to antibodies
78
Outline how placental type affects Ig transfer
- More invasive placenta has more transfer during gestation
- e.g. lots of transfer in primates, minimal transfer across endotheliochorial of dog and cat, but no trasnfer in epitheliochorial (horse) and syndesmochorial ruminant)
79
How can Ig transfer into the neonate be tested?
- Turbidity test using precipitation of Igs
- Single radial immunodiffusion
- Latex agglutination
- Brix refractometer with milk or serum in cows, colostrometer in cows
80
Briefly describe the turbidity test for assessing Ig transfer
- Chemical and serum, quantify with spectrophotometer and standard curve
- Zinc sulphate, glutaraldehyde, sodium sulphite can be used
81
Briefly describe single radial immunodiffusion for assessing Ig transfer
- More accurate and specific
- Agar gel, antisreum to IgG and serum
- Result within 18-24 hours
82
Briefly describe latex agglutination for assessing Ig transfer
- reliable and rapid
- Latex particles coated with anti-IgG and serum
- Leads to agglutination
- Takes ~10 mins
83
How much and in what time frame should calves receive colostrum?
- First feed of 3 litres/10% body weight within 2 hours
| - Then similar size feed within 12 hours of birth
84
What is the function of neutrophils in the innate immune response?
- Phagocytosis
- Release of granules that aid cell destruction
- Amplification of immune response by release of cytokines leading to chemotaxis
85
What is the function of eosinophils in the innate immune response?
- Release granules (e.g. major basic proteins, enzymes) that that destroy cells
- Release cytokines to amplify response
- Mainly for allergens and parasites
86
What is the function of lymphocytes in the innate immune response?
- Only natural killer cells involved in innate immune response
- Target and lyse cells presenting non-self antigen
87
What is the function of monocytes in the innate immune response?
Phagocytic with some antigen presentation
88
What are the main PAMPs of Gram -ve bacteria?
- Mainly LPS
- Also flagella and peptidoglycan
- DNA CpG motives (unmethylated)
89
What are the main PAMPs of Gram +ve bacteria?
- Mainly peptidoglycan
- Lipoteichoic acid, flagella
- DNA CpG motives (unmethylated in bacteria)
90
What is the role of TNFalpha in inflammation?
- Mainly produced by macrophages
- Regulation of immune cells
- Endogenous pyrogen, induces apoptotic cell death
- Activates vascular endothelium
- Increases IgG, complement and fluid drainage to lymph
- activates NNfkappab MAPK pathways
91
Outline the origin and role of IL-6 in inflammation
- Secreted by T cells, macrophages and neutrophils
- Pro-inflammatory cytokine, anti-inflammatory monokine
- Lymphocyte activation
- Antibody production
92
Outline the origin and role of IL-1beta in inflammation
- Neutrophils
- Activates vascular endothelium
- Local tissue destruction
- Stimulates IL-6 production
- Result of above is increased access for effector cells
93
Outline the origin and role of IL-8 in inflammation
- Released by neutrophils
| - Attracts neutrophils, basophils and T cells to site of infection
94
Outline the origin and role of IFNy in inflammation
- Produced by T cells, NTKs
- Most immune cells have appropriate receptors
- Upregulates MHCI expression on cells
- Activates class switching to IgE
- Activation of macrophages
- Pro-inflammatory
95
What is required in order for infection by pathogens to occur?
- Entry into host
- Invasion and colonisation of tissues/cells
- Evasion of host immunity
96
What are the consequences of infection by pathogens?
- Tissue injury, functional impairment
- Disease caused by host cell destruction/toxin production
- Host response to pathogen causing tissue damage and disease
97
Name the innate immune receptors
- Toll-like receptors
- N-formyl-methionyl receptor
- Mannose receptor
- Scavenger receptor
98
What is recognised by toll-like receptors?
- Microbial PAMP
| - Ligands
99
What is recognised by N-formyl-methionyl receptors?
Microbial chemotactic peptides
100
What is recognised by Mannose receptors?
Microbial carbohydrates
101
What is recognised by Scavenger receptors
Microbial diacylglycerides
102
Which cytokines inhibit the microbicidal function of macrophages?
IL-10, IL-4, IL-5
103
Outline the immune responses to extracellular bacteria
- IgA at epithelial surface blocks attachment
- Complement activation
- Adaptive humoral neutralising antibody response
- Th1 response
- Stimulation of B cells and antibody by LPS and polysaccharide (T-independent)
104
Outline immune responses to intracellular bacteria
- Innate: macrophages and NK cells
| - Adaptive: Th1 and CTLs, delayed hypersensitivity reaction and granuloma formation
105
What cytokines mediate the interactions between phagocytes/NK cells and intracellular bacteria?
IL-12, IFNy
106
How may extracellular bacteria evade the immune response?
- Inhibition of complement (sialic acid rich sAgs inhibit alternative pathway)
- Resistance to phagocytosis (polysaccharide rich capsules)
- Antigenic variation in surface antigens (e.g. Haemophilus spp LPS variants)
107
How may intracellular bacteria evade the immune response?
- Inhibition of phago-lysosome fusion
| - Escape to cytosol (e.g. Listeria spp)
108
Outline the innate immune response to viruses
- Infected tissue production of type I IFNs (TLR recognition of viral DNA and RNA)
- NK cells active where virus inhibition of MHC class I CTL response or where CTLs not induced
- Apoptosis,, mediated by host PKR kinase
- Complement, removal of lipid envelope
- I.e. is mediated by type I IFNs and NK cells
109
Outline the adaptive immune response to viruses
- Neutralising antibody, prevents virus entry (e.g. IgA) and removes free virus
- CTLs, MHC-1
- Antibody and complement mediated opsonisation for phagocyte clearance
- I.e. mediated by antibodies and CTLs
110
Outline the CTL activity in response to viral infection
- When CTL recognises infected nucleated cell, molecules are released that allow CL to bind with infected cell
- Perforins punch hole in cell and allow granzymes into cytoplasm = apoptosis
- Fast Fas-mediated target cell apoptosis
111
Outline immune evasion by viruses
- Inhibition of antigen presentation
- Antigenic variation e.g. flu virus haemaglutinin
- Inhibition of interferons
- Latency or provirus (proviruses integrate DNA into host cell)
112
In what ways may viruses inhibit antigen presentation?
- Inhibition of MHC-I synthesis
- Decoy MHC molecule production
- Inhibition of proteosomal activity (Herpesvirus)
113
Outline innate immune response to endoparasites
- Phagocytosis of protozoa
| - But helminths generally resistant to phagocytes and complement due to thick tegument
114
Outline adaptive immune response to protozoa
- CTL killing of infected cells
- Neutralising antibody
- For those in macrophages (e.g. Leishmania), Th1 CMI and macrophage activation (IFNy)
115
Outline adaptive immune response to helminths
- Th2 mediated immunity (IgE, mast cells, eosinophils)
- Can also involve Th1
- Production of neutralising IgG antibodies
116
In what way may increased production aid removal of helminth infection?
Helminth less able to penetrate epithelium, increased chance of destruction by eosinophils
117
Outline immune evasionsmethods used by protozoa
- Antigenic variation (different life cycle stages)
| - Stimulation of Tregs (immunosuppression)
118
Outline immune evasion methods used by helminths
- Large size, different life cycle stages, thick cuticle
- Resident in gut or lung
- Immunosuppressive factors
