Immunology Flashcards
1
Q
Describe the structure of the thymus
A
Bi-lobed
Packed with proliferating lymphocytes
Medulla and cortex
2
Q
What happens to the thymus during infection
A
No obvious change
3
Q
What are Hassall’s corpuscles and where are they found
A
Fibroblasts for regulatory T cell development found in the thymus
4
Q
What happens to the thymus with age
A
Decrease in output of new lymph (but total does not decrease)
5
Q
Describe the bone marrow
A
Site of B cell and RBC production
Yellow fat surrounded by red marrow
6
Q
What happens in the bone marrow during infection
A
Increase in white blood cell production
7
Q
Describe the lymphatic system
A
Drainage system to collect antigens and filter through the nodes and return fluid to the blood
Antigen is likely to enter the lymphatic system
8
Q
Draw/describe a lymph node
A
Kidney shape
Medullary sinus is surrounded by the T cell area with many germinal centres surrounding this
Lymphoid follicle surrounds this
9
Q
What is a germinal centre
A
Area where B cell proliferate
10
Q
What happens to the lymph nodes during infection
A
Lymph nodes become enlarged/swollen
11
Q
What is the purpose of high endothelial venues and where can they be found
A
causes cells to move from the blood to lymph
Found in the lymph nodes
12
Q
Which secondary lymphoid organ does not have many HEV
A
Spleen
13
Q
What is the function of the spleen
A
Filters for antigens in the blood
14
Q
Describe the structure of the spleen
A
White pulp (WBC) Red pulp (RBC) Germinal centres
15
Q
What happens to the spleen during infection
A
Larger follicles
16
Q
Describe how epithelium is a secondary lymphoid organ
A
Mucosal and skin as a physical barrier
Mucosae-associated lymphoid tissue (MALT)
Lymph drains in villi
17
Q
What are Peyer’s patches and where are they found
A
Large aggregates of B cells that contain germinal centres important for immune response found in the gut epithelium
18
Q
What are microfold cells and where are they found
A
Cells that sample antigens to pass them to the Peyer’s patch in the gut
19
Q
Which immune response cells are found in the skin
A
Epidermal langerhans cells
T lymphocytes
Macrophages
Dermal dendritic cell
20
Q
Describe the process of extravasion
A
- Naive T cells rolls along the endothelium
- They bind to proteins and carbs along the epithelium
- HEV has chemokine bound to the cell surface
- Lymphocytes have receptors for this and binds to the receptor
- Lymphocytes deliver a signal to the T cell, changing the structure of integrin
- Integrin becomes high affinity binding and binds to the epithelium to stop movement
- Transport through epithelium
21
Q
Describe a neutrophil
A
Phagocytosis 40-75% of leukocytes short-lived circulates the blood First cells recruited
22
Q
What are NETs
A
neutrophil extracellular traps
Release of granules and chromatin to form extracellular fibres
23
Q
Describe eosinophils
A
phagocytosis and granule release
Defence against parasites
Helps B cells in GALT (IgA production)
24
Q
Describe basophils
A
Granule release
Acts as an APC for type 2 immunity
25
Describe monocytes
phagocytosis , killing, cytokine release, APC
less abundant
dispersed in tissue
Signal infection to soluble mediators
Become macrophages when the leave the blood
26
Describe mast cells
Phagocytosis, granule release (pro-inflammation), histamine and leukotrienes
Mucosal in the lung or connective tissue in the skin
Activation by complement products (anaphylatoxins)
vasodilation (red skin) and increased vascular permeability (inflammation)
27
Describe dendritic cells
APC and cytokine secretion
migration to lymph node
network site of infection
adaptive
28
Describe natural killer cells
10% of blood
Infected cell lysis, secretion of interferon gamma, activating and inhibitory receptors (NO antigen receptor), binds to opsonised cells
Large granulated lymphocytes (cytotoxic)
Bind to opsonised cells
Cancer and viral infections
29
What are soluble mediators
Small secreted proteins important in cell-cell communication that are generally local acting
Effective even in low concentration
30
What are the types of soluble mediators and what are their functions
```
Interleukins - leukocyte communication
Interferons - anti-viral
Chemokines - chemotaxis
Growth factors - proliferation and differentiation
Cytotoxic - tumour necrosis factor
```
31
What is complement
Complex series of 30 proteins and glycoproteins
Major role in complimenting the activity of specific antibodies in lysing bacteria
Triggers enzyme cascade systems to give a rapid and highly amplified response
32
What are the secondary effector functions of immunoglobulins after binding
Complement activation
Opsonisation (promotion of phagocytosis)
Cell activation via antibody-binding receptors (Fc receptors)
33
What are hyper variable regions
there are 3 in antibodies: CDR 1,2,3)
| CDS = complement determining regions that acts as binding sites for antigens
34
Define antibody affinity
The strength of the total noncovalent interactions between a single antigen binding site and a single epitope on the antigen
35
Define antibody avidity
The overall strength of multiple interactions between n antibody with multiple binding site and a complex antigen with multiple epitopes
Better measure of binding capacity
36
Give examples of antibody-cross reactivity
Vaccination with cowpox induces antibodies which are able to recognise smallpox
ABO blood group antigens
Antibodies made against Microbial antigens on common intestinal bacteria may cross-react with carbs on RBC
37
Describe IgG
```
gamma heavy
Most abundant
Has 4 subclasses
Actively transported across the placenta
Major activator of the classical complement pathway (1&3)
Blood and extracellular fluid
```
38
Describe IgA
```
alpha heavy
2nd most abundant
2 subclasses
Occurs as a monomer or dimer
secretory
Protects mucosal surfaces from pathogens
Across epithelia
```
39
Describe IgM
```
Micro heavy
First Ig synthesised after exposure
Multiple low affinity binding sites
Large pentamer
Agglutination and complement activation
Blood
```
40
Describe IgE
```
E heavy
Allergic reactions
Parasitic infections
Binds to mast cell receptors and basophils to release histamine
Very low levels
```
41
Describe IgD
Delta heavy
Expressed in B cell development and activation
very low levels
42
Give the actions of antibody-antigen
```
Neutralisation
Agglutination
Opsonisation
Complement activation
Bound by cells expressing Fc receptors (innate immunity: phagocytes, NK cells)
```
43
Describe the process of T cell dependent B cell activation
1. Phagocytosis of the pathogen
2. Pathogen broken down and displayed on the B cell and the dendritic cell via MHC II
3. T helper recognises the presented antigen on the dendritic cell then finds the B cell with the same antigen
4. Co-stimulatory molecules (CD28) provides more signalling
5. T cells produce cytokines
6. Lymphokine secretion
7. B cell enters the cell cycle and produces clones with identical BCR
44
What does class switching involve
```
IgM and IgD are "weak"
When signals (lymphokines) are given from T helper there is a class switch
```
45
Where does affinity maturation occur
Germinal centres
46
Describe the process of affinity maturation
AID enzyme causes a mutation in the antibody coding genes of the B cells (somatic hypermutation)
Cells can become worse -> apoptosis
Cells can become better -> stronger antibodies -> plasma or memory cell
47
Explain clonal selection
From a large population, 1 cell is activated via antigen binding to BCR which leads to proliferation (clonal selection). Division and differentiation is clonal expansion
48
Describe the T cell independent activation pathway
A repetitive bacterial polysaccharide acts as the first signal
Microbial constituent or accessory cell provides second signal e.g. LPS
49
What causes differences in Ig for T cell independent and dependent
No lymphokines released in T cell independent
50
Describe the TCR
The Fab region of an antibody, top is variable, bottom is constant. One alpha and one beta and a cytoplasmic tail.
51
What is the difference between the alpha and beta chains of the TCR
```
alpha = V and D and 1 recombination
Beta = V, D and J and 2 recombinations
```
52
What are CD4 and CD8 and where are they found
Co-receptors that bind to MHC.
| CD4 is found one T helper cells while CD8 is found on T cytotoxic cells
53
What is HLA and where is it found
Human leukocyte antigen - genes found in all vertebrates that code for MHC. polygenic
Chromosome 6
co-dominant expression
54
Relationship between HLA and MHC
```
MHC class I = A,B,C
MHC class II = DP, DQ, DR
```
55
What is haplotype
Group of MHC alleles on 1 chromosome
56
Describe the endogenous MHC pathway
MHC I. Synthesised in the cytoplasm
1. TAP transports protein to RER
2. calnexin and calreticulin and tapasin fold and stabilise the MHC
4. molecules transport to the golgi
57
Describe the exogenous MHC pathway
MHC II. Antigens from external environment
1. invariant chain stabilised the MHC complex
2. transport to the golgi
3. invariant chain is digested to leave a CLIP
4. Antigen is endocytose and broken down
5. Peptide presented on MHC
6. MHC exocytosed
58
Why may antibodies be inefficient
```
Pathogens:
Can hide within cells
Can change antigen shape
Can coat the antigen with antibodies
Can produce fake antigens
```
59
What are T cells defined by
inputs (STAT) and outputs (cytokines)
60
How do killer T cells induce apoptosis
Granule release - Perforin, granzyme, granulising
Fas ligand - binds to Fas receptor on the cell
Release of caspases to drive apoptosis
61
What are the activation steps of a naive T cell
1. TCR/CD8 - MHC I Binding
2. CD28 co-receptor activation
3. cytokines from infected cell
62
What is Th1 involved in
Macrophage activation
Delayed type hypersensitivity
B cell activation
Regulation
63
What occurs when the macrophage cannot kill the pathogen e.g. tuberculosis
1. Cytokine release
2. endothelial cells express proteins
3. Monocyte and Th1 migration
4. Th1 activates monocyte and macrophage
64
What is the process of Th1 amplification
1. Activated Th1 binds to MHC II and CD40 on the B cell
2. Secretion of IFN gamma
3. Upregulation of MHC II, CD40 and tumour necrosis factor alpha
4. Increase in TNF alpha secretion (autocrine) from macrophages
5. amplification
65
Give features of Tfh
Activation by dendritic cells
Stimulates B cells
Generation of isotope-switched antibodies
66
Describe tuberculosis
Ingested by macrophages
TB inhibits phagosome -lysosome fusion and lives in macrophages
Granuloma formation contains the infection
67
What is the role of Th2
Targets and stimulates eosinophils
Trigger in tracheal epithelia
Travels from dendritic to naive
68
What CD marker is expressed on naive memory T cells
CDC45RA+
69
What CD is expressed on central memory cells
CCR7
70
What is the function of Treg
Regulation of T cells and tolerant of self-antigens
| secretes immune-suppressive cytokines and inactivates dendritic cells
71
What is the function of Th17
Interleukin 17, bacterial control and neutrophil recruitment
72
Describe the process of T cell development
Produced in the bone marrow (CD4-CD8-TCR-)
In the cortex = CD4+CD8+TCR+
In the medulla = CD4+CD8-TCR+ vice versa
73
Describe selection in the thymus of T cells
Thymocyte can't bind = apoptosis
Weak binding = survival (+ve selection)
Strong binding = apoptosis (-ve election)
Prevents autoimmunity risks
74
What is the purpose of Interferon type 1
Activation of NK
75
What is the purpose of interferon type 2
Produced by T cells pre-inflamamtion
76
Define cytokine storm
Over production of cytokines and accumulation of cells
77
What are the main modes of pathogen transmission
Respiratory - large SA
GI tract - large SA
Zoonosis
Sexually transmitted
78
Define pathologic
Immune response against a self antigen, often classified under immune mediated inflammatory diseases
79
Define pathogenesis
susceptibility genes and environmental triggers
80
Describe hypercytokinaemia
Too much immune response
positive feedback loop
pathogens enter the wrong compartment e.g. the blood (Sepsis) or failure to regulate response to the correct level
81
What is the 3 signal model
Licensing a response
1. Antigen recognition
2. Co-stimulation
3. Cytokine release
82
How is immune response controlled
Responses against pathogens decline as the infection is eliminated
83
Compare central to peripheral tolerance
central - destroys self-reactive T or B cells
| peripheral - destroy or control self-reactive cells that do enter circulation
84
What is AIRE
AutoImmune Regulator
| A gene for a specialised transcription factor that allows expression of genes in peripheral tissues for self tolerance
85
What is the function of IL-10
```
Master regulator
Shuts down dendritic cells
Pleitropic (multifunctional)
Blocks pro-inflammatory cytokine synthesis
Downregulates macrophages
```
86
What are the main mechanisms of peripheral tolerance
Anergy - APC presents the antigen but the T cell is shut down
Deletion - apoptosis of the T cell
Ignorance - less APCs
Regulation - regulation of the response by cytokines from Treg
