Immunology Flashcards
1
Q
What are the 2 types of acquired immunity?
What type of cell is responsible for each?
A
Humoral (Ab-mediated) - B cells
Cell-mediated - T cells
2
Q
What can happen when the immune balance is tipped off?
A
- Over-reaction (Reaction to self/ Autoimmunity, Allergies)
2. Under-reaction: Infections, Cancer
3
Q
When is natural and adaptive immunity present?
A
Natural: From birth
Adaptive: By presence of foreign materials; environment-dependent
4
Q
How fast do innate and acquired immunity respond?
A
Innate: Rapid, first to respond (0-96hrs)
Acquired: Slow, lag time from exposure (>96hrs)
5
Q
Which immunity has memory and is specific?
What does immunological memory help it to do?
A
Acquired immunity.
Memory allows it to respond faster and more powerfully subsequently
Specific and unique response to each antigen
6
Q
What helps to self-regulate the acquired immune system?
A
Regulatory T-cells; to maintain tolerance to self-antigens, and has immunosuppressive function)
7
Q
What does loss of tolerance to self-antigens result in?
A
Autoimmunity
8
Q
Which immune system is able to discriminate from self and non-self?
A
Both
9
Q
In the following immune cells and factors:
Macrophages, B cells, Mast cells, NK cells, Neutrophils, T cells, Antibodies, Complement.
Which immune system do they each fall under?
A
Innate: Macrophages, Mast cells, NK cells, Neutrophils, Complement
Acquired: B cells, T cells, Antibodies
10
Q
What are 4 positive acute phase proteins and 2 negative acute phase proteins?
A
Positive: IgG, C3b, CRP, Mannose-binding lectin
Negative: Albumin, Transferrin (Values decreases when there is inflammation)
11
Q
Which immune system does physical barriers fall under?
A
Innate
12
Q
Which system does pathogen usually attack? (2)
A
Circulatory and lymphatic
13
Q
What are physical/ structural factors of the skin as a natural barrier? (4)
A
Tightly packed
Multi-layered (Stratified squamous)
Highly keratinised
High turnover
14
Q
What are 2 physiological factors of the skin for it to act as a natural barrier?
A
pH5.5 (Acidic) - Sweat, saliva, urine, gastric acid
Low O2 tension
15
Q
What are 5 secretions of the skin to prevent pathogen entry?
A
Hydrophobic oils from sebaceous glands Ammonia Enzymes (Lysozyme in tears and sweat to digest bacteria cell wall) Defensins Anti-microbial peptides (Directly kills)
16
Q
Where does mucous membrane line?
A
Body CAVITIES in contact with environment
17
Q
What are 3 components of the mucous membrane as a natural barrier?
A
Mucus - traps bacteria and removed by ciliated cells via sneezing/ coughing
Secretory IgA (DIMER): prevents attachment and penetration
Lactoferrin: starve pathogens of iron
18
Q
Other than skin and mucous membrane, what else exists as part of the physical barrier as a first line of defence?
A
Commensal bacteria - competes with pathogen for resources
They also produce fatty acids and bactericidins
19
Q
How do hair and earwax contribute to natural barrier?
A
Traps pathogens
20
Q
What are 2 tissue-resident innate immune cells and what are their roles?
A
- Macrophages - bacteria killing, phagocytosis, antigen presentation (Pro-inflammatory), wound healing and tissue repair (anti-inflammatory)
- Mast cells - parasitic killing (pro-inflammatory)
21
Q
What is the process of coating pathogens to enhance phagocytosis?
What are 3 factors that help coat?
A
Opsonisation.
Opsonins: IgM/G, C3b, CRP
22
Q
What signature molecular motif do pathogens express and what receptors bind to these motifs? Which cell expresses these set of receptors?
What happens upon binding?
A
Pathogens express PAMPs
Macrophages have PRRs that binds to specific PAMPs
Cytoskeletal rearrangement -> phagosome formation -> fuse with late endosomes and lysosomes -> mature phagolysosomes -> killed internally and contents digested by proteases and hydrolyases
23
Q
What happens to the degraded products in the phagolysosome?
A
Antigens - released into ECF
Pathogen-derived peptides - expressed on MHC-II molecules
24
Q
What can induce phagocytosis? (2)
What are released in the process? What do they cause?
A
PAMPs and opsonin binding
Pro-inflammatory mediators causing localised, acute inflammation
25
5 examples of pro-inflammatory mediators
TNFa, NO, Prostaglandins, Leukotrienes, Histamines
26
What happens when parasites invade?
Too large to be phagocytosis thus:
Damaged cells send out danger signals to mast cells and/or PRR and PAMP binding --> activate --> degranulate (pre-formed pro-inflammatory substance released) and gene expression (produce new pro-inflammatory substance) --> extracellular pathogen killed
27
What are the 5 hallmarks of ACUTE inflammation?
1. Redness - arteriole vasodilation, increased blood flow
2. Oedema - increased post-capillary venule permeability and fluid accumulation in extravascular space
3. Pain - stimulation of nerve endings
4. Loss of function - due to pain and swelling
5. Fever - temperature set point raised in hypothalamus
28
What are the 3 complement pathways?
Classical, Mannose-binding lectin, Alternative
29
What plasma cascade system produces protein to sustain vasodilation and other physical inflammatory effects?
Kinin system
30
What activates C5 convertase?
Active C3b on cell surface
31
What is formed at the last step of the complementary system?
MAC complex
32
How is C3 convertase activated in the mannose binding pathway?
Mannose-binding lectin (MBL) binds to mannose and peptidoglycan on bacteria causing MBL to change conformation and complex which then activate C3 convertase
33
What does the alternative complement pathway involve?
Amplication and positive feedback of C3 convertase by re-using C3b from cleaved C3
34
Why does C3b not causing any downstream complement effects on human cells?
Have inhibitory proteins against C3b
35
Does C5b or C5a go on to form the MAC?
C5b
36
What are anaphylatoxins? What are their effects (3)
C3a and C5a.
Changes local vasculature, acute inflammation and leukocyte recruitment by activating and degranulating mast cells an acting directly on local blood vessels
37
What vascular changes does inflammation promote?
Vasodilation of post-capillary venules thus losing tight junctions and causing redness and oedema
38
How are neutrophils (monocytes) recruited, activated/ mobilised during inflammation? (5)
Margination due to increased viscosity and slower flow AT POST-CAPILLARY VENULES
Binding to adhesion molecules on endothelial cells (Selections, ICAM-1)
Migration across endothelium via diapedesis
Movement within tissue via chemotaxis along chemotactic gradient
Neutrophils killing mechanism activated by PAMPs
39
How do neutrophils navigate within tissues?
Its integrins bind to extracellular matrix proteins
40
What promotes expression of Selectins on endothelial surface. What neutrophil movement does it cause?
Histamine and TNFa.
| Weak binding to neutrophil surface causes it to roll along endothelium
41
What does ICAM-1 bind to? What is required for firm binding?
LFA-1 receptor
Chemokines from damaged cells needed to fully activate LFA-1 receptor to firmly bind to ICAM-1 for stable adhesion and aggregation
42
Neutrophil activation enhanced in presence of?
Pro-inflammatory mediators
43
LFA-1 deficiency is due to defective?
| What mode of inheritence is this?
Defective CD18 - neutrophils cannot migrate out
| Autosomal recessive
44
What are the 3 roles of neutrophils?
Phagocytosis
Degranulation
Neutrophil extracellular traps
45
How do neutrophils kill internalised pathogens? (2)
1. Phagolysosomal killing - pH rise to activate antimicrobial response and pH drops for acid hydrolases to degrade bacterium
2. ROS-dependent: NADPH-oxidase complex assemble to release ROS into phagolysosome
46
What damage does neutrophillic degranulation cause? (3)
| What is it limited by? (1)
Directly kill nearby bacteria and fungi and causes bystander tissue damage
Limited by proteinase inhibitors
47
What induces Neutrophil extracellular traps?
| What does NETs do?
Extracellular bacteria and fungi.
Release of intra-nuclear contents (DNA, histone, granular proteins, neutrophil elastase) to immobilise and trap pathogens to stop them from spreading.
48
What is the best antigen presenting innate immune cell?
Dendritic cell
49
What is the best innate immune cell for TNFa production, killing and degradation?
Neutrophil
50
How long is the T1/2 for CRP?
Short
51
Can viruses be phagocytosed?
No, too small for recognition
52
What do viral infected cells release? Are these virus specific?
IFNa/B.
| No, they are host specific
53
What does IFNa/B signal neighbouring infected (1) and uninfected (3) cells to do?
Uninfected - destroy own RNA, slow protein synthesis and increase surface MHC I to activate T-cells
Infected - undergo apoptosis
54
What innate immune cell is activated during viral infection? How is it activated?
```
NK cells (Longer lived Large granular lymphocytes)
Activated when MHC I is downregulated/ absent (in cancer/ pathogens) --> releases cytotoxic granules (perforins and granzymes) along with IFN-y and TNFa at close-proximity leading to apoptosis
```
**Lysis will lead to virion release
55
Other than responding to MHC I levels, what other pathogens do NK cells kill?
Ab-bound pathogens
56
Where do T-cells mature?
Thymus
57
What happens to B or T cells if they react to self-antigens in a normal immune system?
Destroyed or inactivated
58
What kind of pathogens do B and T cells defend against?
B cells - extracellular and intracellular
| T cells - intracellular
59
What is an antibody made of?
2 heavy + 2 light polypeptide chains
60
What do antibodies bind to?
1 specific antigenic epitope
*1 antigen has many antigenic epitopes
61
How to distinguish between different classes of Ab?
By constant region of heavy chain
62
What can membrane-bound Ab on B-cells do?
Act as B cell receptor (IgM or IgD) to bind to specific antigenic epitope
63
Individual T/B cells express _ ____ type of antigen receptor which binds to only _ ____ antigenic epitope
1 specific
64
What are the 5 secondary lymphoid tissues where B and T cells are usually activated by antigens?
```
Lymph nodes - tissue infection
Spleen - blood borne infection
Mucosal-associated lymphoid tissue - throat/GI infections
Peyer's patches (Ileum)
Tonsils
```
65
How do naive T and B cells enter LNs?
| How long do they stay there?
Migrate trans-endothelially via high endothelial venules.
| A few days
66
How do lymph enter the lymph nodes?
Afferent lymphatics via high endothelial venules
67
What are the 2 zones in the lymph nodes?
T cell zone - centre; paracortex
| B cell zone (Germinal centre) - In stromal cells at the periphery follicles
68
What kind of junctions do high endothelial venules have?
Permanent gap junctions and vasodilated
69
If B and T cells do not encounter antigens in the lymph nodes, how do they return back to circulation?
Via medullary sinus --> efferent lymphatic vessel --> subclavian vein
70
What happens when naive or memory B cells are activated?
Clonal proliferation and differentiation into 2 effector cells
- Plasma cells - Short-lived (3-4 days), secrete soluble, antigen-specific antibodies, large in size due to highly active machinery
- Memory B cells - long-lived
71
What kind of BCRs do daughter cells express?
BCR with same antigen-specificity as parent B cell
72
What do highly proliferative cells form within the B cell zone (Germinal centre)?
Secondary follicle
73
How many signals are needed to fully activate a naive/ memory B cells?
What are these signals? (4)
2.
Antigen bound to BCR
Helping signals from Th cells
Signal 1 from BCR + Signal 2 from PRR + PAMP
Antigen with repetitive antigenic epitopes (e.g. peptidoglycan) - Signal 1 + 2 from multiple BCRs
74
Where do naive B cells clonally proliferate upon activation?
Germinal centre in stromal cells
75
Why is there a lag period before IgM is produced?
| How long is this lag period?
7-10 days
| Due to time for phagocytosis, transport to LN, activation, proliferating and differentiation of B cells
76
How long does a plasma cell exist?
3-4 days (Short-lived)
**Can be long-lived under TFH cell regulation
77
What is the process that selects for the antibody that binds most tightly to the pathogen called?
Somatic hypermutation
78
What is the first Ab secreted by plasma cells? Is it high or low affinity?
Low-affinity IgM Ab
79
What helps B cells switch from low to high affinity Ab production at the germinal centre?
Th cells
80
What Ab receptors do phagocytes have to?
Have IgG receptors to Fc region of IgG to deliver opsonised pathogens
*No IgM receptors
81
Do different Ab classes have the same antigen specificity?
Yes
82
Other than Ab isotype switch, what other functions do Th cells help B cells to gain? (2)
1. Differentiating into LONG-LIVED plasma cells (Stays in bone marrow to secrete Ab for extended period - e.g. vaccine)
2. Antigen-specific memory B cells
83
When does IgM and IgG intercept? (IgM fall, IgG rise)
2 weeks from antigen exposure
84
What is critical for protection during the lag period before Ab is produced?
Innate immune system
85
What site of the antibody binds to the antigenic determinant?
Variable binding site
86
What do the heavy chain constant region interact with?
Effector molecules such as complement, Fc receptors
87
What does membrane-bound IgM do? What configuration is it?
It is a monomer, acting as a BCR
88
What configuration is IgM in plasma and secretory fluids?
| Why is it not found in tissue?
Soluble pentamer.
| Due to its large size
89
What are the functions (3) of IgM?
1. Agglutination - immune complex formation
2. Complement system activation (classical pathway)
3. Opsonisation
90
What function does agglutination of Ab-Ag serve? (3)
1. Increases efficacy of elimination by enhancing phagocytosis
2. Different Ab that recognises different Ag can work together -> easier target
3. Neutralises viral particles to prevent binding and entry
91
What happens when a specific Ag binds to IgM Ab to undergo complement?
Fc region conformation change from planar to staple form -> expose multiple C1 binding sites -> C1 binds to stably to at least 2 Fc sites -> Fc region change conformation to expose more binding sites -> eventually C3 convertase production
92
How many IgM and IgG needed to activate complement (recruit C1)?
1 IgM- can bind multiple Ag
| Several different IgG - to closely located Ag
93
Why is IgM considered an opsonin even though it cannot bind to phagocytes?
More efficient at activating complement due to pentameric structure
94
What is the most abundant Ig?
IgG
95
Which Ig has the longest T1/2?
IgG
96
What is the configuration of IgG?
| How many subclasses are there and how are they differentiated?
Monomer.
| 4 sub-classes with different heavy chain
97
What are the 6 functions of IgG?
1. Agglutination
2. Complement activation
3. Foetal immune protection via placental transfer
4. Neutralisation - aggregate viral particles to prevent entry/ binding
5. Opsonisation
6. NK cell activation (Ab-dependent cell-mediated cytotoxicity)
98
How long does the foetus rely on maternal IgG?
| What happens when it wanes?
Conception to first 6 months after delivery.
| May develop Transient Hypogammaglobulinaemia of Infancy (THI) - risk of infection
99
What is the term for the immunity that maternal IgG provides?
Passive immunity
100
What kind of bacteria in particular does IgG help to enhance phagocytosis?
Encapsulated species such as Gram Negs, S. Aureus and S. pyogenes with hyaluronic acid
101
Which cells have Fcy receptors for IgG?
NK cells, Phagocytes
102
What happens when IgG bound to Ag binds to NK cells?
Apoptosis of infected cell and pro-inflammatory mediator production
103
What are NK cells activated by?
IFNa/B from infected host cells
104
What is the configuration of IgD? What does the membrane-bound form do?
How much of it is found in blood?
Monomer.
Serves as BCR to activate B cell.
Extremely low concentration in blood.
105
What is the second most abundant Ig?
| How many subtypes are there and what is its configuaration?
IgA.
2 subtypes.
Monomeric form in serum for neutralisation and dimeric form in secretory fluids (majority)
106
What is the dimeric IgA connected by?
| How is it secreted?
J peptide chain
| Actively transported across epithelial surface into secretions
107
What roles (2) do dimeric sIgA carry out?
1. Neutralisation at mucosal sites (IgM and IgG cannot be secreted across)
2. Neonatal immune protection via colostrum and breast milk to protect GIT of neonates
108
What does IgE trigger and what does it protect against?
| What is its configuration?
Allergic responses.
Against large extracellular parasites.
Monomer.
109
IgE binds to what on what immune cell to cause??
binds to FcE receptors on mast cell/ basophils/ eosinophils causing them to degranulate
110
What kind of antigens do TCR recognise?
Only peptide antigens presented by MHC molecules
111
Do B cells require MHC peptide antigens to be activated?
No, they can respond to non-protein antigen
112
How many unique TCRs does each T cell have? And how many antigens does it respond to?
Only 1 copy of unique TCR and each T cell respond to only 1 specific antigen
113
In who are MHC variants the same?
IDENTICAL twins
114
What is the difference between MHC Class I and II in terms of expression and presentation?
MHC Class I: ALL nucleated cells, presents peptide Ag to CD8+ T cells
MHC Class II: ONLY on APCs (Dendritic cells, macrophages, B cells), presents peptide Ag to CD4+ T cells
115
What stabilises the interaction between TCR and MHC I?
CD8 protein
116
What are antigen presenting cells (3)?
Dendritic cells, macrophages, B cells
117
```
What is the cell that bridges the innate and acquired immune system?
What functions (2) does it have?
```
Dendritic cells.
Phagocytosis and antigen-presentation to T cells
118
What interaction is involved in phagocytosis by dendritic cells?
PAMPs and PRRs
119
What effect does TNFa have on dendritic cells?
Causes them to mature and increase expression of co-stimulatory molecules on surface
120
Do APCs express MHC I or II?
Both
121
What are the 2 signals that are needed for T cells to fully activate (clonal proliferation and differentiation)?
1. Peptide Ag/ MHC complex presentation
| 2. Co-stimulatory molecules
122
Naive CD4+ T cells become Th0 cells which differentiates into?
Effector Th cells
123
What do activated CD4+ T cells secrete and express?
| Via what kind of signalling?
Secrete T cell growth factor (IL-2) and express IL-2 receptor.
Autocrine-mediated cell proliferation
124
IL-2 is used by which T cells?
Used by both antigen-activated CD4+ and CD8+ T cell to proliferate
125
What happens to the reactivated Th1 cell activated by MHC II?
Secretes pro-inflammatory cytokines, stimulate ROS production and enhances macrophage mediated intracellular killing (super-activated macrophages)
126
What are 3 microbes that can evade phagolysosomal killing?
Listeria, Salmonella, Mycobacteria
127
What happens to effector TFH cells as it move into the B cell zone?
Stimulated by MHC II on B cells where TFH cells will stimulate B cells to clonally proliferate and differentiate into long-lived plasma cells and memory cells
128
What do CD8+ T cells differentiate into upon IL-2 stimulation?
cytotoxic T lymphocytes
129
How do CTLs kill virally infetced host cells?
Specific TCR recognises MHC I viral peptide by infected cell --> releases perforin directly to target cell surface to form a pore, granzymes and granulysin into cell to induce apoptosis
**Minimises bystander damage
130
How do CTLs not react with self?
MHC I also displays self-peptides thus CTLs should not react with these cells
131
How long is the T1/2 of T cells?
Very long (up to 15 years) - prolonged immunity against viruses
132
When do macrophages switch to its anti-inflammatory role and what does it carry out? (3)
After pathogen elimination.
Phagocytose and degrade apoptotic cell debris, secrete anti-inflammatory IL-10 and aid tissue repair
133
What are the 2 primary lymphoid tissues for lymphocyte production and maturation?
Red bone marrow and thymus gland
134
Where do lymph not reach? (2)
Cartilage and epidermis
135
What helps to transport lymph? (5)
valves, breathing, muscle contraction, arterial pulsation, external compression
136
Where are complement proteins produced?
| In what state does it exist in circulation?
Liver.
| Inactive.
137
How long is the T1/2 for cytokines?
Short
138
What are the granular cells that defend against large antibody-coated pathogens that cannot be phagocytosed?
Mast cell (tissue-resident), Eosinophils, Basophils
139
Where do monocytes differentiate?
After migrating into peripheral tissues
140
What do multi-potent haematopoietic stem cells differentiate into? (2)
```
Lymphoid progenitor (Large/NK cells and small lymphocytes - T/B cells)
Myeloid progenitor
```
