1
Q
what is the difference between innate and adaptive immunity
A
Innate - Immediate response - Bind a wide range of molecules - Ligands are PAMPs - No memory - On re-exposure; same response as before Adaptive - 5-10 days for clonal expansion - Highly specific for a single structure - Can potentially bind to any protein lipid or carbohydrate ligand - Long lived memory - On re-exposure; rapid response tailored to the pathogen
2
Q
where are T lymphocytes developed
A
developed in the thymus
3
Q
what are the types of T lymphocytes
A
CD4+
CD8+
4
Q
Where do the B lymphocytes develop
A
they develop in the bone marrow
5
Q
what do the B lymphocytes develop into
A
plasma cella that produce antibodies
6
Q
what are the cells of the adaptive immune response
A
T and B lymphocytes
7
Q
is NK a adaptive cell or innate cell
A
innate
8
Q
where is NK cells derived from
A
the same cells as T and B cells
9
Q
describe the uncertainty under NK cells
A
- Derived from the same cells as T and B cells although act in an innate fashion
- While It is agreed that CD34+ NK cells progenitors reside in the BM there is a less clear view on whether seeding of these cells into other organs generates organ specific NK cell maturation or whether a predefined CLP or MLP with specific developmental and homing characteristics would exit under certain conditions from the BM and specifically seed into the final sites of maturation
10
Q
what is a T cell receptor made out of
A
alpha and beta chain combined
11
Q
CD4 is
A
- CD4 is the defining marker of helper T cells
12
Q
what are the antigen presenting cells
A
dendritic - this is the most important antigen presenting cell
- macrophage
13
Q
describe how the naive T cell is activated by dendritic cells
A
- TCR and CD4 bind MHC Class II on the surface of dendritic cell
- The naïve T cell is then activated by the dendritic cells
14
Q
what are the conventional T cells
A
CD4+ - helper T cells
CD8+ cytotoxic T cells
15
Q
what are the unconventional T cell
A
intraepithelial lymphocytes (IELs)
NKT cells
gamma(circle with pony tail) cells
16
Q
there are the same amount of ..
A
conventional T cells as there are unovnentional T cells
17
Q
what type of T cell does HIV affect
A
CD4+
18
Q
what happens in HIV
A
CD4+ Cells are progressively lost
- Get a slow increase in virus RNA as there is a lack of T helper cells
- In the primary infection there is a dip then they recover and then they decrease again till they reach 0
- Then develop AIDS – get rare cancers, wasting chronic diarrhoea
19
Q
step wise progress of the immune response
A
- Primary lymphoid organs. - bone marrow thymus
- Secondary – were immune response initiation
- Cut arm
- Inflammation neutrophils( 2hours later), macrophages(6 hours later) and NK cells
- Dednritive cells go to the drianign lymph nodes by crawling through the tissues
- Dendritic cells come across dead pathogens and pick up the pieces of the dead bugs and become activated – PRR such as toll like recepotrs,
- Become activated and mature
- They stop crawling
- Start processing what they take up, chop up protein into peptides
- Put peptides on MHC
- Then go to draining lymph nodes
- Dendritic cell holds out peptide son MHC
- Say to lymphocytes if they recognise it
- Only 50-100 cell that recognise this pathogen, few
- They then have clonal expansion of CD8+ BY MITOTIC division
- CD4 t cells also expand
- Need to make sure the right set of cell is involved in getting rid of the right pathogen
- CD4 T cells. More complex then CD8, they have to differentiatie all the CD8 cells only have to expand in number
20
Q
How do CD4 become activated in lymph node
A
- Antigen presented by MHC on an antigen presenting cell, e.g dendritic cells and macrophage
- Activates CD4 T cells
- Cell division and clonal expansion
- IL-2 (INTERLUEKIN – 2) CD4 secrete and response = autocrine loop
- As they stop they differentiate and change into different cells
21
Q
How is the CD4+ T cell activated
A
- The cytokines released by the local cells and dendritic cells depend on the type of pathogen present
- The naïve CD4+ T cell can take several forms depending on the cytokine released
- The different forms of CD4+ T cells give a response tailored to the specific pathogen
22
Q
what are the CD4 T helper cells
A
TH1
TH2
TH17
TREG
23
Q
what are the cytokines that TH1 make
A
IFN - gamma
TNF - alpha
24
Q
what do TH1 cells do
A
- These induce cell mediated immunity – cells that are needed to get rid of pathogens that are inside cells (intracellular pathogens) intracellular bacteria such as TB, listeria
- Cell mediated immunity
- Helps function of CD8+ Cytotoxic T cells and macrophages
specialised for mediated immunity; viruses and intracellular bacteria
25
name some intracellular bacteria
- TB
| - Listeria
26
what are the cytokines that TH2 release
IL-4
IL-5
IL-13
27
what do TH2 cells do
Humoral immunity (extracellular pathogens), activate B cells to help them produce antibodies, mast cells and eosinophils cells (secrete things that worms and cells dont like), the response linked to allergies and Atopy, helminths
28
if you don't have any macrophages you do not..
scar, this is because macrophages lead to a scarring effect
29
describe how TH1 helps macrophages
- Viruses and bacteria have evolved mechanisms to live inside macrophages – once inside the macrophages digest and get rid of bacteria and viruses as it kills them
- TH1 cells make IFN- GAMMA, activates the macrophages giving them maximum killing ability which can then kill the bacteria and virus, also helps in the recruitment of cytotoxic T cells
- macrophages have to be controlled as they are only allowed to be activated by TH1 cells as they are dangerous
30
what cytosine causes a naive T cell to be converted to TH1
IL-12
| IL-23
31
whats an example of an intracellular bacteria that TH1 destroys
TB
- 98% of people with TB do not have symptoms
- If you make the correct response TH1 cells and macrophages are let loose, and in the lung the macrophages that are infected with TB but they can’t kill them easily, so they produce a wall around the infected area and wall it off, this is called a caseating granuloma – formed in the lung, round them are TH1 cells that guard the site
- If you become immunodeficient later in life and CD4 stop functioning the caseating granuloma break down and the TB spreads kills you
- Don’t get symptoms because rest of lung is functional and you don’t use all the lungs
32
describe how TH2 helps B cells become activated
- the dendritic cell takes up antigen and processes it which means the protein is broken up into lots of different fragments
- the fragments are placed on the MCHII receptors on the dendrite cell surface
- CD4+ T cell sees these fragments become activated via the T cell receptors
- in order to become activated the T cell recognises small part of protein and the B cell antibody recognise different part of the antigen, they both recognise the same thing
- the antigen binds to the antibody
- B cell can also take the antibody into the cell once it is bound to the antigen
- the B cell breaks down the antigen protein by the same mechanism that the dendrite cell breaks down the antigen so you get the same peptide
- the peptide is Placed on MHCII on B cell so TCR receptors on the T cell recognises it
Then you get all of the antibody responses as B cells differentiate and become plasma cells
TH2 helps several B cells recognise the proteins
33
different cytokines released by the CD4 cell causes
different antibodies to be produced
34
what is the classic example of a T cell releasing a cytokine to activate an antibody
; IL-4 induces B cells to make IgE
35
What makes IL-4
mast cells
36
what causes naive T cells to differentiate into TH2 cells
IL -4
37
What makes IL-12 and IL-23
dendritic cells that have seen bacteria and virus
38
what are the two types of leprosy
TH1 - Tuberculoid leprosy
| TH2- lepromatous leprosy
39
what are the two types of leishmaniasis
TH1 - cutaneous leishmaniasis
| TH2 - visceral leishmaniasis
40
what are the two types of TB
TH1 - lepromatous TB
| TH2 - Millary TB
41
all disease with TH1 are
limited (less harm)
42
all diseases with TH2 are
disseminate (more harm)
43
describe what happens in tuberculoid leprosy
- TH1
- macrophages are activated and bacteria are killed
- collateral damage - nerve damage, loss of sensation, limb deformity
- limited
cytokines - IFN gamma
- low number of organisms
44
what happens in lepromatous leprosy
- TH2 is dominant
- get large numbers of antibodies that are not the right kind
- massive bacterial load in tissue
- disseminated
cytokines - iL-4 IL5 IL-13
- hyperglobulinemia
- high number of organisms
45
what happens in cutaneous leishmaniasis
- TH1
| - limited disease
46
what happens in visceral lesihmanesis
TH2
| disseminated disease
47
what happens in lepromatous TB
- TH1
| - limited disease
48
what happens in milary TB
TH2
- disseminated disease
- not contained can leave lung and infect the brain which results in inflammation and death
49
describe how allergies are caused
Allergies
- Th2 responses lead to IL-4 which leads to IgE which causes allergies
- This might be because – hygiene hypothesis – immune system is infected to be challenged in the gut and you don’t get continual challenge then you are badly educated
- Can activate the immune system switch Th2 to TH1 like iL12 would
50
describe an example of an allergy
Eczema
| Classical IgE-mediated allergy (Type-I hypersensitivity)
51
what are the TH-17 cytokines needed for differentiation
- IL-6 and TGF-beta
52
what are the TH-17 cytokines produced
- IL-17 (same as IL-17a)
| - IL-22
53
what are the pathogens that TH17 cells are specialised for
- Extracellular bacteria
- Multiple inflammatory and autoimmune conditions
- The play a role in host defence against extracellular pathogens by mediating the recruitment of neutrophils and macrophages to infected tissues this is commonly defence of mucosal surfaces
54
what are the cytokines needed to differentiate Treg
- TGF-beta
55
what are the cytokines that Treg produces
- IL-10
56
what do Treg T cells do
- Immunoregulation and peripheral tolerance
| - Controsl the immune system can lead to autoimmunity and cancer if fails
57
what is immunological memory
Immunological Memory is the ability of the immune system to respond QUICKER and BETTER to pathogens that have been encountered previously
58
what are features of adaptive immunity
- highly specific
| - immunological memory
59
what does immunological memory work quicker
This is because a group of T cells activated in the initial response become memory T cells and can react specifically and rapidly on the pathogens return
- Several 100 thousands memory cells, they are there at the site of infection so they can response immediately when they see the infection again
- The memory cells are sent to the tissues and clonally expand and make cytokines immediately therefore there is no long wait
