Basic Concepts of Immunology (1-6)

Question 1

What is the difference between the structures that BCRs and TCRs recognise?

Answer 1

TCRs: internal, linear structures
BCRs: external, 3D structures

Question 2

What 2 signals are needed for T cells to activate?

Answer 2

signal 1: antigen (peptide-MHC complex) from APC
signal 2: danger signal (co-stimulation- B7 on APC binding CD28 on T cell) from same APC

Question 3

What are C-type lectins (CLRs)?

Answer 3

receptors that mediate Ca2+-dependent carbohydrate binding
have diverse ligands
mainly involved in antigen uptake
cause release of ROS to kill pathogen

Question 4

What are toll-like receptors (TLRs)?

Answer 4

internal and external receptors that recognise pathogen groups
different combinations give different functions (omg skylanders swap force)
adaptor molecules initiate pathways on other side of the membrane

Question 5

What are NOD-like receptors?

Answer 5

join together to form the inflammasome, a macromolecular machine that converts ProIL to IL-1beta, an inflammatory cytokine
among other things (?)

Question 6

What are Rig-like receptors?

Answer 6

recognise foreign nucleic acids in the cytoplasm

an obstacle when generating mRNA vaccines
- can be overcome by replacing uridine w natural derivatives, eg pseudouridine

Question 7

What are the primary lymphoid organs?

Answer 7

production and maturation of lymphocytes
- thymus, maturation and selection of T cells
- bone marrow, production of lymphocyte precursors from stem cells, IgM and IgD B lymphocytes

Question 8

What are secondary lymphoid organs?

Answer 8

accumulation of mature lymphocytes where most acquired immune responses are initiated
- spleen, deals with pathogens in blood
- lymph nodes, where antigens are taken and presented
- mucosal-associated lymphoid tissues (MALT) eg gut (GALT), bronchial (BALT)

Question 9

What are the different sections of a lymph node?

Answer 9

outer layer:
- primary follicle - B cells
- germinal center- secondary lymphoid tissue
inner layer: paracortex - T cells
medulla - plasma cells and macrophages
afferent lymphatics - 10% of naive lymphocytes enter this way
high endothelial venule (HEV) - 90% of naive lymphocytes enter this way, as well as immature DC and Ag
- also known as post-capillary venules

Question 10

What are the different sections of the spleen?

Answer 10

red pulp: where the blood is filtered of pathogens and dead blood cells
white pulp:
¬ PALS - T cells
¬ marginal zone - B cells
¬ primary follicle - B cells
¬ marginal sinus
¬ germinal centre

Question 11

What ways are B cells activated?

Answer 11

T-independent (marginal zone B cells):
- Ig cross-linking of bacterial polysaccharides (TI-2)
- mitogen - LPS, bacterial products (TI-1)

T-dependent (follicular B cells)
- protein antigens (TD)

Question 12

What are the phases of B and T cell activation?

Answer 12

In a T zone, T cells interact with dendritic cells, which causes:
- IL-12 production from DC, causes differentiation of T cells into Th1
- B7 on the APC expressed due to PRR activation - costimulatory molecule that interacts with CD28 on T cell

CD40L on activated T cells to interact w CD40 on Bcell which activates B cell (along with Ag affinity)
Activated T cells then become Th2 or Tfh which activate B cells in the follicle which is important for memory and proper antibody response

Question 13

How is lymphocyte traffic mediated by cell adhesion molecules?

Answer 13

naive lymphocytes can enter lymph nodes through HEV but not the tissues

once activated they can now enter tissues but not HEV

they have specific homing receptors so they preferentially bind to vascular addressins on tissue related to origin of activation

Question 14

What are homing receptors?

Answer 14

• adhesion molecules on circulating lymphocyte
• bind to molecules expressed on vascular endothelium
• may vary with state of activation of a given cell
  (selectins, integrins, ig-superfamily)

Question 15

What are vascular addressins?

Answer 15

• molecules on vascular endothelium to which homing receptors bind
• constitutively express OR induced by soluble mediators
• often tissue-specific
  (selectins, integrins, ig-superfamily)

Question 16

What are the steps of lymphocyte migration from blood?

Answer 16

1. rolling and tethering
2. activation
3. firm adhesion
4. migration between epithelial cells

Question 17

What receptors are involved in T cell HEV migration?

Answer 17

T cell:
- L-selectin
- CCR7
LFA-1 (low affinity)

HEV cells:
- CD34
- secondary lymphoid tissue chemokine (SLC)
- ICAM-1

Question 18

What is MALT?

Answer 18

mucosal associated lymphoid tissue, which includes:
- gastro-intestinal tract (GALT)
- mammary glands
- respiratory tract
- urogenital tract

Question 19

What is humoral immunity?

Answer 19

the receptors of B lymphocytes

immunity in the fluids of the body (blood…)

Question 20

How does a membrane-bound B cell receptor cause a cell response?

Answer 20

by use of associated signalling receptors:
Igalpha = CD79a
Igbeta = CD79b

both have small intracellular components, 3 amino acids

Question 21

What is the J-chain?

Answer 21

allows IgA dimers and IgM pentamers to more easily cross mucosal membranes

Question 22

When a population of B cells is activated, what percentage form plasma cells and memory B cells?

Answer 22

plasma cell = 95%
memory B cells = 5%

Question 23

Why are memory B cells important?

Answer 23

during a secondary response, memory B cells from long-lived plasma cells which produce antibodies for months-years
found in bone marrow and epithelial tissues

Question 24

What are mast cells?

Answer 24

release inflammatory mediators (granules) after FcεR bound by IgE antibodies w crosslinked antigen

Question 25

What is the alternative pathway of the complement system?

Answer 25

1. Cleavage of C3 into C3a and C3b by C3 convertase
2. C3b binds to surface of microbe which binds Factor B which is cleaved into Bb which forms C3 convertase so more C3 is cleaved
3. This binds more C3b which forms C5 convertase, which cleaves C5 into C5a and C5b which is involved in the formation of the membrane attack complex (MAC)

Question 26

What are the functions of anaphylotoxins?

Answer 26

the ‘a’ components of cleaved proteins of the complement system:
- inflammation
- increased blood flow
- increased vascular permeability
- smooth muscle contraction
- cell recruitment

Question 27

What is the classical pathway of the complement system?

Answer 27

• Ab binds to antigen on surface of pathogen
• C1 complex binds to the Fc region of the Ab, which activates C1 serien proteases
• the proteases cleave C4 into a an b, and subsequently cleaves C2 into a and b which form C3 convertase (C4b2a), cleaving C3 into a and b
• C3b binds covalently to receptors on pathogen surface as well as Cr1 receptor on phagocytes, marking them for opsonization (enhanced phagocytosis), or it can participate in the formation of the C5 convertase

CR1 and Fc receptors work cooperatively to enhance phagocytosis

Question 28

What is the lectin pathway of the complement system?

Answer 28

• upon recognition of bacterial cell carbohydrates, Mannose-binding lectin (MBL) forms a complex with a serine protease
  this leads to a proteolytic cascade of cleavage of C4 and C2
• this generates C4a and C4b, and C2a and C2b
• this forms C3 convertase (C4b2a)

Question 29

How is the complement system regulated?

Answer 29

MCP (membrane cofactor protein): co-factor for the inactivation of serum factor I that cleaves C3b and C4b

DAF (decay accelerating factor, CD55): binds to C4b or C3b and prevents formation of C3 convertase

both act to prevent complement activation on host cell surfaces

Question 30

How does Fc receptor signalling work?

Answer 30

binding of Fc region to FcR transduces signal through membrane to γ2 subunit

receptors have motifs that can activate or inhibit kinase cascades eg ITAM, ITIM

FcRn binding allows immunoglobulins to pass through membranes

Question 31

What are γδ T cells?

Answer 31

T cells that have TCRs composed of a γ chain and δ chain as opposed to regular T cells whose receptors are composed of α and β chains

γδ T cells are found in tissues, whereas αβ T cells circulate the bloodstream

have particular cell receptors in different tissues
eg skin = Vγ5vδ1 TCR (why are immunologists like this)

can directly bind to pathogens in some instances

Question 32

What is Skint1?

Answer 32

not v strong signal and doesnt illicit a strong response
keeps γδ T cells alive and tells them cell is not under stress

downregulation of Skint1 and stress molecules such as Rae1/MICA causes to γδ to produce interferon gamma and IL-13

Question 33

how do dendritic cells activate naive T cells?

Answer 33

upregulate MHC-I and II and B7 molecules as they mature
secrete chemokines to attract naive T cells

DCs first need to be activated, this is done through recognition of PAMPs
they mature and migrate to paracortex (T zone) of lymph node

after T cell activation, clonal expansion of T cell occurs (then differentiate into Th or CTL)

Question 34

how do tissues control when to respond to and what class of response to initiate against danger signal?

Answer 34

• interferons tell innate cells to tell adaptive cells about infection
• release of cytokine specific to tissue elicits an appropriate response
• once danger goes away, the tissues tolerise immune cells by delivering signal 1 but no signal 2

Question 35

How do the complement pathways cause pathogen killing?

Answer 35

1. C3a and C5a created during complement process mediate inflammation, causing recruitment of phagocytes
2. binding of C3b to pathogen and CR1 on phagocyte surface marks them for opsonisation
3. formation of C5 convertase (C4b2a3b) causes cleavage of C5 into C5b which is involved in recruitment of many proteins in the membrane attack complex (MAC). This forms holes in the pathogen surface causing leakage of cell contents and eventually lysis