Block 2 - Immunology Flashcards
1
Q
Define the immune system.
A
The immune system is a complex network of specialised cells, tissues and soluble factors that co-operate to kill and eliminate microorganisms and cancerous cells.
2
Q
State the organs of the immune system and describe their function.
A
Skin and mucous membranes (found in respiratory tract, gastrointestinal tract and urogenital tract)
- the first line of defense, they act as epithelial barriers to infection.
Primary lymphoid tissues
- the anatomical sites where white blood cells (leukocytes) are produced, includes the bone marrow and the thymus.
Secondary lymphoid tissue
- lymph nodes are small organs that filter the lymph, they remove dead cells, pathogens and antigens; which are used to activate the adaptive immune system
- spleen serves as a filter for the blood, it removes old and damaged red blood cells and removes infectious pathogens and uses them to activate adaptive immune response.
3
Q
Outline how the immune system works.
A
Distinguishing ‘self’ molecules from ‘non-self’ molecules.
Identifying ‘danger’ signals.
Or both.
4
Q
Outline the routes in which pathogens can infect the body
A
Digestive system.
Respiratory system.
Urogenital system.
Skin damage.
Circulatory system.
Lymphatic system.
5
Q
Describe the initial response of the immune system.
A
Occurs in tissues.
Receptors are non-specific and do not change overtime.
Inflammation is induced.
Non-specific mechanisms include phagocytosis, complement activation, type 1 interferon pathway and NK cell activity.
6
Q
Describe the adaptive response of the immune system.
A
Response is specific.
Occurs in lymph nodes, where cells of adaptive response are ‘presented’ with antigens.
Specific lymphocytes proliferate and differentiate in response to pathogen detection.
Antibodies recruit components of the innate response (phagocytosis, NK cells etc) in a specific, targeted way.
7
Q
Describe the communication that occurs between the innate and adaptive responses.
A
Initial to adaptive - antigen presenting cells of the innate system interact with cells of the adaptive system.
Adaptive to initial - antibodies from the adaptive response trigger targeted innate responses.
8
Q
Outline the components involved in the innate (natural) immunity.
A
Natural/physical barriers.
Soluble factors
- cytokines
- acute phase proteins
- inflammatory mediators
- complement proteins
Immune cells
- macrophages
- mast cells
- natural killer cells
- neutrophils
9
Q
Outline the components involved in Adaptive (acquired) immunity.
A
Soluble factors
- cytokines
- antibodies
Immune cells
- B cells
- T cells
10
Q
Describe physical barriers to infection.
A
Epithelial surfaces function as protective barriers, an outer surface which is tough and impermeable to micro-organisms.
11
Q
Outline physical barriers.
A
Composed to tightly packed, highly keratinised, multilayered cells.
Constantly undergo renewal and replacement.
12
Q
Outline physiological factors involved in physical barriers.
A
Low pH 5.5 (therefore acidic).
Low oxygen tension.
Tears.
13
Q
Outline sebaceous glands and secreted products of physical barriers.
A
Secrete hydrophobic oils such as sweat.
Lysozyme.
Ammonia.
Antimicrobial peptides.
Secretory IgA.
14
Q
Describe mucus membranes lining the body cavities that meet the environment.
A
Respiratory, gastrointestinal and urogenital tracts.
Physical barrier to trap invading pathogens.
Secretory IgA prevents bacteria and viruses attaching to and penetrating epithelial cells.
Contains lysozyme, defensins and antimicrobial peptides directly kills invading pathogens. Lactoferrin acts to starve invading bacteria of iron.
Cilia directly trap pathogens and contribute to removal of mucous, assisted by physical maneuvers such as sneezing and coughing.
15
Q
Describe commensal microorganisms.
A
100 trillion bacteria normally reside at epithelial surfaces. There is >500 different microbial species. Has a symbiotic relationship with host.
16
Q
Outline the steps to the process of infection.
A
1) physical barriers are breached.
2) pathogens invade.
3) innate immune response initiated.
17
Q
Outline components in innate immune responses. (i.e. types or cells/proteins)
A
Phagocytic cells (both tissue-resident and circulatory) orchestrate initiation of the response. They recognise, ingest and kill bacteria and yeasts.
Degranulating cells (both tissue-regulating and circulatory) orchestrates initiation of the response. They damage and kill multicellular parasites and viruses.
Secreted proteins
- complement proteins (induced)
- chemokines
- cytokines
18
Q
Outline the use of macrophages in early innate immune responses.
A
Tissue resident innate immune cells recognise and respond to invading pathogens.
- phagocytosis
- pro/anti-inflammatory
- bacterial killing mechanism
- antigen presentation
- wound healing/tissue repair
19
Q
Outline the use of mast cells/eosinophils/basophils in early innate immune responses.
A
Tissue resident innate immune cells recognise and respond to invading pathogens.
- pro-inflammatory
- parasite killing mechanism
- linked to allergy and asthma
20
Q
Outline the use of natural killer cells in early innate immune responses.
A
Tissue resident innate immune cells recognise and respond to invading pathogens.
- killing of virally infected cells
- killing of tumour cells
21
Q
Outline the use of dendritic cells in early innate immune response.
A
Tissue resident innate immune cells recognise and respond to invading pathogens.
- antigen uptake in peripheral sites
- antigen presentation
- naive T cell activation
22
Q
Outline the use of neutrophils in early innate immune responses.
A
Tissue resident innate immune cells recognise and respond to invading pathogens.
- phagocytosis
- pro-inflammatory
- bacterial killing mechanisms
23
Q
Describe how innate immune cells recognise pathogens.
A
Pathogens express many common PAMPs (pathogenic associated molecular patterns).
PAMPs are recognised by specific pattern recognition receptors (PRRs) that are expressed by immune cells -> cell surface receptors, intracellular receptors.
Interaction of these ligands with their partner receptors triggers active activation of innate immune cells.
24
Q
Describe how macrophages express receptors for many microbial constituents and outline the steps.
A
Macrophages (and later neutrophils) ingest and kill invading extracellular bacteria and fungi. Via pinocytosis, receptor-mediated endocytosis, phagocytosis.
1) macrophages express a set of PRRs.
2) receptor binding to PAMPs signals the formation of phagocytic cup.
3) cup extends around the target and pinches off, forming a phagosome.
4) fusion with lysosomes to form a phagolysosome, killing off pathogens and degradation of constants (acidification, lysosomal hydrolases, proteases).
5) debris (including antigens) is released into extracellular fluid.
6) pathogen-derived peptides are expressed on special cell surface receptors (MHC-2 molecules).
7) pro-inflammatory mediators are released (e.g. TNF [alpha]).
25
Describe opsonisation.
Opsonisation
The coating of pathogens by soluble factors (opsonin) to enhance phagocytosis. Opsonins are small soluble factors that can bind to pathogens, thereby enhancing phagocytosis.
26
Outline the steps of trans-endothelial migrations.
1) margination of neutrophils to the endothelium near sites of tissues damage/infection.
2) binding of neutrophils to adhesion molecules (selectins, ICAM-1) on the endothelial cells.
3) migration of neutrophils across the endothelium.
4) movement of neutrophils within the tissue via chemotaxis.
5) activation of neutrophil by PAMPs and TNF[alpha].
27
Describe phagocytosis.
In infected tissues, pathogens release chemical signals that attract neutrophils.
Neutrophils use PRRs to bind and phagocytose these pathogens.
Kills internalised pathogens via two distinct mechanisms:
1) oxygen-independent killing
2) oxygen-dependent killing
28
Describe oxygen-independent killing.
Bacterium is phagocytosed by neutrophil.
Phagosome fuses with azurophilic and specific granules.
pH of phagosome rises, antimicrobial response is activated and bacterium is killed.
pH of phagosome decreases, fusion with lysosomes allows acid hydrolases to degrade the bacterium completely.
29
Describe oxygen-dependent killing.
NADPH oxygenase dependent mechanisms (the respiratory burst) -> production of toxic reactive oxygen species (ROS).
Neutrophil activation (PAMPs, pro-inflammatory cytokines), assembly of the NADPH oxidase complex, production and release of ROS into granules.
30
Describe degranulation.
Release of anti-microbial substances from neutrophil granules into the extracellular milieu.
Direct killing of extracellular pathogens bacteria and fungi.
Bystander tissue damage -> damaging systemic inflammation.
31
describe neutrophil extracellular traps (NETs).
Extracellular bacteria and lymphal forms of fungi can induce NET formation – a form of cell suicide.
NETs immobilise pathogens, preventing dissention of infection spreading and promoting phagocytosis.
32
Describe molecules of the immune system.
Adaptive immune responses are induced by specific structures called antigens.
And antigen is any substance which can cause an adaptive immune response by activating B cells and T cells.
An antibody (also known as an immunoglobulin) is a protein that binds to one specific antigenic epitope.
An antibody is produced in response to a specific antigen during acquired immune response.
33
Describe the complement system proteins.
Is a family of approximately 30 different proteins which are produced in the liver. They circulate in blood/tissues as inactive precursor proteins (makes up ~10% of serum proteins).
Can be activated directly or indirectly by invading micro-organisms. Complement proteins can enzymatically cleave and activate other downstream complement proteins in a biological cascade.
They play a critical role in promoting inflammation and defence against extracellular bacterial species.
34
List what cells are classified as phagocytic cells.
neutrophils, monocytes and macrophages, dendritic cells.
35
List what cells are classified as degranulating cells.
mast cells, eosinophils, basophils.
36
Describe what is meant by the primary immune response.
The primary immune response is the body’s initial reaction to a newly encountered antigen, resulting in the activation of B and T cells to produce antibodies and initiate an immune response.
37
Describe what is meant by the secondary immune response.
The secondary immune response is a faster and stronger immune response that occurs upon re-exposure to a previously encountered antigen.
38
Describe immunological memory.
Immunological memory is the ability of the immune system to ‘remember’ past encounters with pathogens and response more quickly and effectively upon re-exposure. This is the basis for a successful vaccine.
39
Describe how the immune system contributes to wound healing.
As a part of the healing process, acute inflammation via the immune system is associated with tissue repair and regeneration. Through the recruitment of neutrophils and macrophages, the early innate immune system clear cellular debris, remodels the extracellular matrix and induces the production of high levels of cytokines.
40
Describe how allergies can arise from abnormal immune responses.
Allergies arise from an overactive or abnormal immune response where the immune system mistakenly identifies harmless substances (known as allergens) as threats, triggering an inflammatory response when in is unnecessary.
41
Describe how autoimmunity can be caused by abnormal immune responses.
Abnormal immune responses can lead to autoimmunity when the immune system mistakenly identifies ‘self’ tissues as ‘non-self’ and attack them causing inflammation and tissue damage.
42
Describe how the immune system may target a transplant.
Abnormal immune responses can recognise a transplant organ as foreign, the recipient’s immune system mounts an attack against the graft/transplant (aka transplant rejection) causing inflammation and damage.
43
Outline innate VS adaptive immunity.
- Innate immune response
* First line of defence
* Non-specific
* Fast acting
- Adaptive immunity
* Pathogen specific
* Has ‘memory’
* Slower but highly effective
The innate and adaptive immune response can work together to eliminate pathogens.
44
State the requirements for adaptive immunity.
1) Lymphocytes (T and B cells) must recognise the antigen.
2) Stimulated to divide and differentiate.
45
Describe the bridge between innate and adaptive immune responses.
Antigen presenting cells (dendritic cells act as this) can bridge the innate and adaptive immune response. APCs present antigens to T cells within lymphoid organs.
The lymph nodes and the spleen
In tissue during chronic inflammation
46
Outline what T cells are.
Lymphocytes of the adaptive immune system that mature in the thymus.
Recognise specific antigens via T cells receptors (TCRs)
Require antigens to be presented on specialised surface protein (unlike B cells, they cannot bind free-floating antigens).
CD4+ are helper T cells, they are known as the ‘coordinators’ and have many subtypes.
CD8+ t cells are cytotoxic T cells are known as the killer.
47
Describe the T cell receptor.
T cells recognise antigens using a surface receptor. T cell receptor (TCR) recognises processed antigens on MHC class ll molecules.
Each T cell can express a unique antigen receptor (TCR). The outer most domains ([alpha/[beta] or [gamma]/[sigma]) are highly variable. This is achieved by V(D)J recombination to generate receptor diversity.
48
Describe V(D)J recombination in T cell receptor gene loci.
DNA segments (variable, diversity and joining genes) are randomly rearranged by RAG ½ enzymes creating unique TCRs. Ensuring each T cell express a unique antigen receptor.
49
Describe antigen recognition by the T cell receptor (TCR).
T cells only recognise parts of the antigens presented on cell surface complexes.
- Antigens from pathogens that replicate with host cells e.g. viruses.
- Antigens from material that has been phagocytosed or endocytosed.
Infected and foreign antigens can be detected by T cells. Foreign peptides must be presented on the cell surface by major histocompatibility complex (MHS) glycoproteins.
50
Describe class 1 and 2 MHCs.
Class l -> expressed on all nucleated cells including leucocytes. (CD8+), includes alpha chain and beta2 microglobulin.
Class ll -> expressed only on leucocytes which present antigen to T cells i.e. antigen presenting cells. (CD4+), contains alpha and beta chains.
51
Draw a diagram of a class 1 MHC, labelling the chains involved.
[see notes for answer]
52
Draw a diagram for class 2 MHC, labelling the chains involved.
[see notes for answer]
53
Describe antigen presentation on MHC ll complexes.
Certain cells phagocytose pathogens and can present their antigens produced from proteolysis on their surface.
This can then go on to activate naïve CD4+ cells. When CD4 and TCR bind simultaneously to the same MHC class ll peptide complex, the T cell is about 100 x more sensitive to the antigen than if CD4 were absent.
54
Describe the use of adhesion molecules in interactions between T cells and antigen presenting cells (APCs).
Adhesion molecules LFA-1 and ICAM-1 also form adhesive interactions between T cells and APC.
- T cells initially bind APC through low affinity LFA-1 – ICAM-1 interactions.
- Subsequent binding of T cell receptors signals to LFA-1.
- Conformation change in LFA-1 increases affinity for ICAM-1 and prolongs cell-cell contact.
The outcome is T cell activation.
Pairing of accessory molecules stabilises interactions (like the one above) and provides co-stimulation.
55
Outline the types of signals APCs deliver to naive T cells.
1) Activation
2) Survival
3) Differentiation
Activation of T cells (clonal selection) drives clonal expansion.
56
Draw diagrams of resting T cells and activated T cells in metabolism and the cell cycle.
[see notes for answer)
57
Draw a diagram describing how cytokine environment determines subtype differentiation.
[see notes for answer]
58
Outline the types of T cells.
Th1 -> activates macrophages by secreting IFN-[gamma] and IL-2.
Th2 -> induces B cell class switching to IgF by secreting IL-4.
Th17 -> recruit neutrophils for fighting bacteria/fungi by secreting IL-17.
Treg -> supresses immune activation by secreting IL-10 and TGF-[beta].
Tfh -> promotes B cell antibody production, class switching and affinity maturation by expression of CD40L and secreting IL-21.
59
Describe the acute phase response.
This systemic response involves changes in the plasma concentrations of specific proteins in response to inflammation.
Driven by pro-inflammatory mediators by activated macrophages.
Mediated by liver hepatocytes which produce a variety of acute phase proteins.
- C3 and MBL (complement protein system)
- C reactive protein (CRP)
->> Primes certain bacteria for destruction by the complement system and phagocytes.
->> Has a prognostic role (severity and duration of inflammation)
60
Describe C reactive protein (CRP).
A major acute phase protein in humans.
Used as a marker for inflammation.
Functions as an opsonin to enhance bacterial cell phagocytosis.
61
List the complement components.
C1, C2, C3, C4, C5, C6, C9
62
Draw a diagram outlining the how C3 begins to activate downstream proteins.
[see notes for answer]
63
Draw a diagram of the complement system pathway.
[see notes for answer]
64
Draw a diagram for the downstream complement pathway.
[see notes for answer]
65
Draw a diagram describing why C3 is an excellent opsonin.
[see notes for answer]
66
Describe how virally infected cells are destroyed.
Virally infected cells secrete cytokines called interferons (TFN[alpha]/[beta]) that induce anti-viral responses in the affected tissue.
Activated natural-killer (NK) cells recognise and destroy virally infected cells and abnormal host cells.
67
Describe how macrophages, B cells and antibodies (IgE), and CD4+ T cells respond to pathogens.
Macrophage
Recognise PAMPs and increase inflammation in response.
B cells and antibodies (IgE)
Increases antibody dependent parasites killing by mast cell degranulation.
CD4+ T cells (Th2 cells)
Promote IgE responses to parasite antigens, enhance eosinophil recruitment and activation (degranulation and killing).
68
Outline and describe lymphocytes.
o B cells
Responsible for humoral immune response
Activated by specific antigen
Produce antibodies that attack pathogens circulating in the blood and lymph.
Key role in defence against extracellular pathogens.
o T cells
Responsible for cellular immune responses.
Activated by a specific antigen.
Key role in defence against intracellular pathogens.
* CD4+ T cells -> key regulators of the entire immune system.
* CD8+ T cells -> kill virally infected body cells.
o As they develop, B cells and T cells learn to distinguish self from non-self, if they are reactive to self-antigens they are usually destroyed or inactivated.
69
Describe antigens and antibodies.
- Adaptive immune responses are induced by specific structures celled antigens.
- An antigen is any substance which can cause an adaptive immune response by activating B cells and T cells.
- An antibody is produced in response to a specific antigen during acquired immune responses.
- An antibody (also known as immunoglobulin) is a protein that binds to one specific site on an antigen.
70
Describe T cells and B cells in relation to lymphoid tissue.
Antigen-specific T cells and B cells develop in primary lymphoid tissues -> constantly re-circulate between blood, secondary lymphoid tissues and lymphatic vessels.
Naïve T cells and B cells segregate into different areas within secondary lymphoid tissues where they become activated by an antigen.
71
Draw a diagram depicting how lymphocytes encounter antigens in lymph nodes.
[see notes for answer]
72
Describe the role of dendritic cells.
Dendritic cells act as a bridge between the innate and adaptive immune system as it transports debris from destroyed pathogens (innate immune system) into lymph nodes so they are can be in contact with lymphocytes (adaptive immune system).
73
Outline what B cells are.
- Lymphocytes of the adaptive immune system that originate from the bone marrow.
- Recognise specific antigens via B cell receptors (BCRs).
- Produce antibodies.
- They can recognise free-floating native antigens.
- Unlike T cells, they do not need antigens to be presented to them on MHC.
- They can present antigens on MHC class ll to T cells.
74
Describe the way B cells can recognise antigens.
B cells recognise antigens by a surface immunoglobulin. B cell receptors (BCRs) recognise native antigens.
Immunoglobulin are synthesised and secreted by B cells.
To secrete Ig they must be activated by the binding of antigens to BCRs. (BCR is a form of the antibody that the B cell can make).
This triggers differentiation into plasma cells.
75
Draw a diagram describing how B cell receptor binding triggers clonal expansion.
[see notes for answer]
76
Outline B cell activation by BCR.
B cell activation by BCR alone is a weak stimulus.
Induces proliferation and differentiation into plasma cells.
Poor signal for formation of long-lived memory B cells.
No class switching or affinity maturation.
77
Describe the cross talk between T cells and B cells.
T cells are activated to antigens that may reside within viral peptides.
B cells that recognise a surface epitope of a virus can process and present after virus epitopes.
->> Viral specific T[FH] cell provides help to B cells that recognise a linked epitope.
78
Describe B cell interactions with T[FH] cells.
B cells can interact with T[FH] cells via antigen presentation on MHC class ll
* Antigen recognition by T[FH] cells induces signals to activate B cells.
* B-cell proliferation generates plasma-blasts that form the primary focus.
* Further differentiation can proceed to the germinal centre, resting memory cells or antibody-secreting plasma cells.
79
Describe germinal centres and the changes B cells can undergo there.
High affinity antibodies are made in germinal centres. Germinal centres are specialised microenvironments within secondary lymphoid organs (lymph nodes, spleen, Peyer’s patch) where B cells undergo:
- Affinity maturation -> make highly specific antibodies.
- Class switching -> make the right antibody class.
- Differentiation -> produce plasma cells and memory B cells.
80
Briefly discuss an overview of immunoglobulins.
Present in plasma, tissues, secretions and the lymphatic system.
They are a product of the humoral immune system.
They are secreted by activated B cells, also known as plasma cells.
Provide recognition function and trigger effector functions.
81
Outline the structure of immunoglobulins.
o All immunoglobulins are similarly structured.
- Two hinged heavy chains
- Two light chains
They are joined by disulphide bonds.
o Fab region-recognition function
- One constant domain
- One variable domain
o Fc region – effector functions
- Two or three constant domains
82
describe how the antibody system can recognise millions of different antigens.
Three hypervariable loops or complementarity determining regions in each V domain.
This is revealed by comparing sequences of different antibodies.
Hypervariable loops of CDRs form the antigen binding site
CDRs form close-lying loops at one end of the V domains.
When the VH and VL domains are paired, their CDRs create antigen binding site.
83
Describe the non-covalent interactions between antibodies and antigens.
Electrostatic forces - attraction between opposite charges e.g. NH3+ and COO-.
Hydrogen bonds - hydrogen shared between electronegative atoms (such as N and O).
Van der Waals forces - fluctuations in electron clouds around molecules oppositely polarising neighbouring atoms.
Hydrophobic forces - hydrophobic groups interact unfavourably with water and tend to pack together to exclude water molecules, this attraction alao causes van der Waals forces.
Cation-pi interaction - noncovalent interaction between a cation and an electron cloud of nearby aromatic group.
84
Describe the classes of immunoglobulin in humans.
There are 5 classes of immunoglobulins (IgG/M/D/A/E) each with unique heavy chains
- gamma
- mu
- sigma
- alpha
- epsilon
85
Describe the immunoglobulin - IgD
Predominantly found in B cell surfaces.
- very low serum concentrations
- function unclear ->> may be involved in the antibody response
- recently found to be implicated in mucosal immunity
86
Describe the immunoglobulin - IgM
Predominantly the antibody of 1[degree] responses.
- only in plasma and secretion as they are too large to enter the tissue.
- pentamer of Y-shaped units joined together by joining (J) chain and disulphide bridges.
- ten binding sites for antigen ->> very good at agglutination e.g. viruses.
- Very efficient at activating the complement system.
87
Describe the immunoglobulin - IgG
Predominantly the antibody of 2[degree] responses.
- most abundant Ig in plasma = 10 mg/mL
- 4 subclasses ->> IgG1, IgG2, IgG3, IgG4.
- Very efficient at triggering complement system and directing phagocytosis.
- Only Ig class to cross the placenta ->> protects the baby in the first few months of life.
88
Describe the immunoglobulin - IgA
Found in mucosal areas and in secretion.
- important serum Ig ->> 2-3 mg/mL
- monomeric and dimeric forms
- major antibody in seromucous secretions e.g. saliva, milk, colostrum.
- class of antibody first encountered by many invading pathogens.
89
Describe the immunoglobulin - IgE
Mediates allergy response and defence against parasitic infection.
- sensitises mast cells and basophils for degranulation.
90
Describe affinity maturation and class switching.
Mediated by activation-induced cytidine deaminase (AID).
- Somatic hypermutations that increase affinity (dark zone)
- Class switching through DNA recombination (light zone)
Changes the constant region of heavy chain without altering specificity.
Removes the Cu (IgM) region, replacing it with another constant region (IgG, IgA, or IgE).
Directed by cytokine environment.
91
Outline the fates of B cells in germinal centres.
1) re-entry into the dark zone
2) long-living plasma cell
3) memory B cell
92
Outline side effects through mutagenic dysregulation.
Burkitt's lymphoma.
Diffuse large B cell lymphoma.
Follicular lymphoma.
93
Describe differentiation of memory B cells.
Memory B cells are pre-selected for high-affinity antigen biding in the germinal centre.
Long-lived B cells that persist after an immune response, ready to respond rapidly upon next exposure to the antigen.
->> provide faster, stronger and more specific responses compared to naive B cells, BCR on memory B cells are the type of antibody they can make.
94
Describe plasma cells.
Plasma cells, derived from B cells, are specialised immune cells that produce and secrete large quantities of antibodies to fight infections and provide long-term immunity.
95
Draw a diagram depicting how resting cells in the immune system become effector cells and memory cells and their effects.
[see notes for answer]
96
Summarise the differences between immature dendritic cells and mature dendritic cells.
Immature
- decreased co-stimulatory molecules
- decreased MHC ll expression
- decreased secretion of pro-inflammatory cytokines
- increased phagocytic capacity
- decreased Glycolysis
Pathogens, cytokines, PAMPs and DAMPs cause maturation of dendritic cells.
97
Describe T cell independent antigen responses.
- Non-protein antigens
* Simple, repetitive antigens (often carbohydrates)
* PAMPs
- Induce low affinity antibody responses
- No memory B cells produced
98
Outline T cell dependent antigens. Add a supporting diagram.
- T cell epitope = short peptides
- B cell epitope = ay molecule type
- Co-stimulation provided by effector CD4+ T cells (Tfh cells)
[see notes for answer]
99
Discuss the pathway resting T cells go through to increase cell size/cycle/proliferation.
Resting T cells only express a moderate affinity IL-2 receptor (IL-2R[beta] and [gamma] chains only)
↓
Antigen and co-stimulation results in gene transcription (IL-2R[alpha] chain and IL-2)
↓
Increase in cell size, cell cycle and cell proliferation
100
Draw a diagram depicting the altered expression in cell cycle regulators between naive and 24hr activated T cells.
[see notes for answer]
INK4 and Cip/Kip are CDK-cyclin inhibitors
Numbers indicate copy numbers of each protein as determined by quantitative proteomics
101
Draw a diagram depicting dendritic cells producing CTLs.
[see notes for answer]
102
Describe how Th1 cells act to enhance macrophage killing.
Some pathogens are very efficient at evading phago-lysosomal killing by macrophages.
Th1 cells act to enhance macrophage killing of intracellular bacteria before they can escape from the phagolysosomal system.
1) Infected macrophages present bacterial peptide antigens on their surface (in complex with MHC-ll).
2) Effector Th1 cells migrate from secondary lymphoid tissues into infected tissue sites.
3) Th1 cells are re-activated by tissue-resident macrophages in an antigen-specific manner (-> express CD4OL and IFN[gamma]).
4) These co-stimulatory molecules hyperactivates macrophages, enhancing their killing activities and increased TNF[alpha] secretion.
103
Describe the differences between T cells dependent antigens and T cell independent antigens in reference to B cell stimulation.
Effector Tfh cells provide co-stimulation for B cells that are responding to protein antigens.
Antigen and co-stimulation drives B cell differentiation into antibody secreting plasma cells:
Tdep antigens
- Short- and long-lived plasma cells
- Germinal centre response:
* Memory B cells
* High affinity antibodies
* Cytokine microenvironment dictates Ig class switching
Tind antigens:
- Short-lived plasma cells
- No germinal centre response
104
Describe cellular immune responses that mediated by CD8+ T cells.
Cytotoxic T lymphocytes (CTLs or Tc cells) migrate out of the lymph node and enter sites of infection to kill infected host cells.
CTLs are selective killers
- They only kill target cells expressing the correct peptide on MHC class 1.
- Also secrete pro-inflammatory cytokines (IFN[gamma] and TNF[alpha).
CTL are efficient killers
- They can recycle to kill multiple targets.
105
Outline the components of CTL granules.
o Perforin
Polymerises to from a pore-like channels
Cylindrical structure
Lipophilic outside
Hydrophilic centre
o Granzymes
Serine proteases, at least 3 different types related to trypsin and chymotrypsin
Induce apoptosis once in the target cell
o Granulysin
Anti-microbial properties
Promotes apoptosis
106
Draw a diagram outlining how CTLs can induce apoptosis by multiple mechanisms.
[see notes for answer]
107
Outline the steps in CTL induced apoptosis.
1) CTL recognises and binds virus-infected cell
2) CTL programs target for death, inducing DNA fragmentation
3) CTL migrates to new target
4) Target cell dies by apoptosis
108
Describe the negative feedback signals between T cells and B cells.
Negative feedback signals reduce co-stimulation
- Often a consequence of prolonged T cell activation (-> exhausted T cells)
- E.g. upregulation of inhibitory CTLA-4
109
Draw a diagram describing how to reactivate 'exhausted' T cells.
[see notes for answer]
110
Draw a diagram depicting the pathway of a macrophage during phagocytosis to inducing tissue repair.
[see notes for answer]
111
Describe the different types of T cells.
Cytotoxic T cells (CTLs) aka CD8+ T cells are a type of white blood cell that directly kills infected or cancerous cells.
T helper 1 cells (TH1 cells) release a molecule that activates macrophages.
T helper 2 cells (TH2 cells) orchestrate type 2 immune responses that usually target parasites.
T follicular helper cells (TFH cells) aka CD4+ T cells play a role in developing high-affinity antibodies and memory B cells by providing essential help to B cells in secondary lymphoid organs.
