Session 6 - Adaptive immune system Flashcards
1
Q
What are the three main features of an antigen presenting cell?
A
• Strategic location of B and T cell interaction
• Pathogen capture
Diversity in pathogen sensors
2
Q
Where are antigen presenting cells found?
A
- Skin
- Mucous membrane
- Lymphoid organs
- Blood circulation
3
Q
Why is diversity in pathogen sensors required?
A
- To detect extracellular pathogens (bacteria)
* To detect intracellular pathogens (viruses)
4
Q
Give four antigen presenting cells
A
- Interdigitating dendritic cells
- Langerhans’ cells
- Macrophages
B cells
5
Q
Where are interdigitating dendritic cells found, and to what do they present?
A
• Lymph nodes
T cell and B cells
6
Q
Where are langerhans cells found, and to what do they present?
A
- Skin
* T cells
7
Q
Where are macrophages found, and to what do they present?
A
- A whole range of tissues
* B and T cells
8
Q
Where are B cells found and to what do they present?
A
- Lymphoid tissues
* T cells
9
Q
What is HLA? (human leukocyte antigen)
A
- Also known as MHC, protein holders expressed on cell surface which hold and “present” specific bacterial or viral peptides to T cells
- HLA class 1 - Binds intracellular microbes, recognised by (CD8) cytotoxic T cells
- HLA class 2 - Binds extracellular microbes, recognised by (CD4) T helper cells
10
Q
Give three types of antigen presenting cells which express HLA’s
A
- B cells
- Dendritic cells
- Macrophages
11
Q
How are extracellular microbes (bacteria) dealt with by antigen presenting cells?
A
- Bacteria phagocytosed
- Broken down in phagosome
- Processed and placed on HLA class 2
- Presented to CD4 T cells
- Provides humoral immunity
12
Q
How are intracellular microbes (viruses) processed?
A
- Proteosomes (activated by interleukins) find and destroy virus, collect peptide
- Peptide presented on HLA class 1 to cytotoxic CD8 T cellls
- Cell dependent immunity
13
Q
What are two types adaptive immunity?
A
• Humoral
Cell mediated
14
Q
What is humoral immunity?
A
• Aspect of immunity mediated by macromolecules found in extracellular fluids, such as antibodies and complement
15
Q
What is cell mediated immunity?
A
• Involved phagocytes, cytotoxic T-lymphocytes and cytokines instead of antibodies
16
Q
What types of HLA’s is found on all cells?
A
- HLA-1
* Expression of internal peptides. All cells contain peptides, so all cells have HLA-1.
17
Q
What are the two different types of T cell?
A
- Cytotoxic CD8 T cells, which kill cells (cell dependent immunity)
- B cell activating CD4 T helper cells (humoral immunity)
18
Q
How are T cell receptors diversified to be able to recognise any antigen put to them?
A
• Not enough space on genome for individual genes
Genetic recombination produces diversity of receptors required
19
Q
What is a danger of T cell recombination?
A
• Malignancy
20
Q
How does binding of a HLA molecules to a T cell receptor cause activation of the T cells effects?
A
• Once enough HLA molecules bound, T cell activates kinases which trigger transcription factors within the cell
21
Q
Why is it important for the population to have a variety of different types (polymorphic) of HLA for each class?
A
- Type of HLA determines what antigen (peptide) can be expressed
- Diversity in HLA means that there will always be a member of the population who can express a particular microbial antigen and thus mount an immune response
22
Q
How are HLA genes expressed?
A
- Co-dominant
* Both parental genes are expressed, increasing number of potential HLA molecules
23
Q
How many different genes are there for class 1 HLA?
A
3
24
Q
How many different genes are there for class 2 HLA?
A
6/8
25
Outline the features of a HLA?
* Peptide binding cleft - variable region with highly polymorphic residues
* Broad specificity
* Causes response in T cells (Class 1 - CD8 T cells, Class 2 - CD4 T cells)
26
What are bacterial peptides presented by and presented to?
* HLA class 2 peptides
* Presented to CD4+ T cells
* Humoral immunity
27
What are viral peptides presented by and presented to?
* HLA class 1 presenting viral peptides
* To CD8 T cells (cytotoxic)
* Cell dependent immunity
28
What is a slow progressor in terms of a patient response to HIV?
* Right HLA presented to CD4 cells due intrinsic HLA polymorphism
* T cell response generated as antigen presented
29
What is a rapid progressor?
* Homozygote HLA-1 marker, less HLA polymorphism
| * Weak T cell response due to lack of presentation of antigen
30
Give three clinical problems concerning HLA molecules
* Organ transplant rejection
* Autoimmune disease
* Cross reactivity between microbial and host antigens
31
What is a major cause for organ transplant rejection?
* HLA molecules mismatch between donor and recipient (allograft)
* T cells present in donor tissue attack recipient's tissue with different HLA markers
* Graft versus Host reaction
32
Give two conditions in which there is a HLA association and autoimmune disease
• Ankylosing spondylitis - HLA B27 found in 90% of patients
Insulin dependent Diabetes mellitus - HLA DQ2 found in 50-75% patients
33
What is cross reactivity?
Antibodies can sometimes combine with more than one antigen, if the antigens are similar. This can cause an immune response against host cells if things go awry.
34
Give three conditions which come about as a result of cross reactivity between microbial and host antigens
* Rheumatic heart disease
* Guillian-barre syndrome
* Type 1 diabetes
35
What is the cross reactivity in rheumatic heart disease?
• Streptococcus pyogenes
Antigen in cardiac muscle
36
What is the cross reactivity in diabetes type 1?
* Coxsakieviruses
| * Pancreatic islet cells
37
Where are T cells matured?
• Thymus
38
What do T cells produced to aid in defence against infection long term?
• Memory cells
39
What do CD8+ T cells do
• Protect against intracellular pathogens
40
What do CD4+ T cells do?
• Provide help for antibody production and regulate immune response
41
Outline the structure of a T cell receptor
• Possess A and B chain, each with variable sections
42
What factors are required for a T cell to become activated?
* Must bind to HLA molecules
| * Must bind to specific antigen
43
What happens after T Cells are exposed to appropriate stimulatory factors?
They begin to mature
44
What are the three types of helper cells a naive CD4+ T cells can mature into?
• T helper cells (Th1/Th2)
Memory cells
45
What is a naive T helper cell?
• One which has never encountered an antigen
46
What is the difference between a TH1 and a TH2 helper cell?
* A TH1 helper cell activates cytotoxic t cells and is involved in cell mediated immunity
* A TH2 helper cell is required for priming B cells to produce antibodies - Inolved in humoral immune system
47
What are the two main types of cells a CD8+ cell can differentiate into?
* Cytotoxic T cells
| * Memory cells
48
What are the three main functions of CD4+ TH1 (TH1!!!) cells?
```
• Killing of infected cells
○ Cytotoxic T cells
○ Natural killer cells
• Phagocytosis
○ Macrophages
• Antibody production (B cells)s
```
IgG
49
What are the four functions of CD4+ TH2 cells (TH2 SILLY)
```
• Killing of parasites
○ Eosinophils
• Antibody production
○ B cells
• Mast cell activation
○ IgE
• Mucosal protection
```
IgA
50
How do cytotoxic T cells (CD8+ T cells) kill virus infected cells?
* Detect HLA 1 with the viral content
* Perforins granzymes released
* Destroys viral cells
51
What T cells fight bacteria?
• CD4+ TH2 cells
| ○ Humoral immunity
52
What T cells fight viruses?
• CD4+ TH1 cells
• CD8+ T cells
○ Cell dependent immunity
53
Where are B cells formed?
• Bone marrow
54
What is the antigen receptor for B cells?
• B cell receptor
55
Do B cells make memory cells?
• Yes
56
What are the two main functions of B cells
* Protection against extracellular pathogens
* Antigen presentation to T cells
* Produce many different types of antibody
57
What is the main difference between B cells and T cells?
• B cells can be activated by proteins, lipids, nucleic acids, along with T cell binding to HLA 2
T cells can only be activated by small peptides
58
How do B cells mature?
Plasma cells produced via replication
59
How are B cells primed?
* Recognises antigen on infected tissue
| * TH2 helper cells
60
What is the fate of activated B cells?
* Become plasma cells or
| * Memory B cells
61
Give four characteristics on humoral response
* Faster
* Stronger
* Longer duration
* Higher affinity iostype switch
62
Name four important types of antibodies in the order they are produced
* IgM
* IgG
* IgA
IgE
63
What does IgM do?
* First antibody produced during an immune response
* Neutralises toxins
* Activates complement via classical pathway
64
What does IgG do?
* Main antibody secreted into blood after class switching
* Opsonise bacteria for phagocytosis
* IgG pumped across placenta in large quantities and present in mothers breast milk, giving babies extra passive immunity
65
What does IgA do?
* Produced late in immune response
* Found on mucosal surfaces
* Forms a secretory dimer which protects it from enzymes, important in gut mucosa
66
What does IgE do?
* Binds to mast cells even when antigen absent
* Causes mast cell degranulation, releasing granules, histamin and cytokines (allergic response)
* Used against parasitic worms
67
What is the difference between passive and active immunity?
* Passive - Transfer of active antibodies from individual to another. Maternal transfer to foetus is a key example.
* Active - Host is exposed to antigen and generates own immunological response and antibody production.
68
What are vaccines intended to do?
• Aim to produce memory B and Th2 cells, which produce large amounts of antibody on exposure to antigen.
69
Give three vaccines given at two months?
* Tetanus
* Haemophilus
* Menigococcus C
70
Give a vaccine given at 1 year
• MMR
71
Give a vaccine given at 10-14 years
• BCG
72
Give a vaccine given in elderly and high risk patients
• Influenza
73
Give three types of vaccines
* Live attenuated vaccines
* Dead vaccines
* Subunit vaccines
74
What is an attenuated live vaccine?
• Contains pathogens that have been weakened to the point they will not cause disease
75
Give an advantage and a disadvantage of liver attenuated vaccines
* +'ve - Live inside cells and present on HLA class 1 molecules
* -'ve - Can spontaneously revert to wild type, and can cause disease in immunodeficient patients
76
What is a dead vaccine?
• Dead micro-organism given. Antigens stimulate immune response
77
Give an advantage and disadvantage of dead vaccines
* +'ve - No chance of reverting to wild type
* -'ve - Less potent that live attenuated vaccines as cannot get inside cell
-'ve - New vaccines sometimes have to synthesised every year, due to drift and shift
78
What is a subunit vaccine?
• Vaccines derived from cell components or excretory products
79
Give an advantage and disadvantage of subunit vaccines
* +'ve - Do not replicate and rarely cause side effects
* -'ve - Require adjuvants
-'ve - may not prevent infection, just common complications
