Lecture 8: Adaptive Immunity and Immune Recognition

Question 1

What are the general features of adaptive immunity?

Answer 1

evolutionarily relatively new
slow, but highly specific response directed against antigen
forms immunological memory = results in a rapid 2˚ response

Question 2

What are the soluble factors of adaptive immunity?

Answer 2

antibodies

Question 3

What are the cell-associated factors of adaptive immunity?

Answer 3

B cell receptors, T cell receptors and MHC molecules

Question 4

What are the specialised cells of adaptive immunity?

Answer 4

B cells (B1/B2)
T cells (Th1, Th2, Th17, Tfh, Th17, Treg and cytotoxic T cells)
semi-invariant T cells (NKT, MAIT), ɣσ T cells

Question 5

What is the priming phase of adaptive immunity?

Answer 5

first time the adaptive immune system encounters an antigen

Question 6

What is the effector phase of adaptive immunity?

Answer 6

activated adaptive cells differentiate into effector cells to fight infection and eliminate pathogen

Question 7

What is the contraction phase of adaptive immunity?

Answer 7

most effector cells die following clearance of the pathogen

Question 8

What is the memory phase of adaptive immunity?

Answer 8

some long lived memory cells remain to ensure that the immune system can respond faster and stronger upon re- encountering that pathogen

Question 9

What makes adaptive immunity highly specific?

Answer 9

highly diverse antigenic receptors formed by random gene rearrangement

Question 10

What makes adaptive immunity respond slower?

Answer 10

this is because major effector functions include antibody production, cytokine secretion and cytotoxicity, some of which take days

Question 11

What is the outcome of the adaptive immune response?

Answer 11

removal/neutralisation of the pathogen and resolution of infection and memory

Question 12

What ability does memory grant the adaptive immune system?

Answer 12

the ability to respond stronger and faster on second encounter of the same pathogen

Question 13

Which lineage comprises cells of the adaptive immune system?

Answer 13

the lymphoid lineage

Question 14

What are B cells derived from and where do they mature?

Answer 14

from lymphoid progenitor

mature in bone marrow

Question 15

How many BCRs does each B cell have?

Answer 15

around 100,000 each with the same specificity

Question 16

What does BCR engagement lead to?

Answer 16

proliferation and transition into plasma cells (‘effector B cells’)

Question 17

What do plasma cells secrete?

Answer 17

soluble BCR (= antibodies) that have same specificity as surface receptor

Question 18

What is humoral immunity?

Answer 18

B cell-mediated

Question 19

What are T cells derived from and where do they mature?

Answer 19

from lymphoid progenitor in bone marrow

develop and become educated in the thymus

Question 20

What co-receptors do T cells express?

Answer 20

either CD4 (MHC class II restricted) or CD8 (MHC class I restricted)

Question 21

How do T cells recognise antigens?

Answer 21

via distinct cell surface receptors (α/β T cell receptor) with high degree of specificity
requires processing of antigen by the APC and presentation on MHC

Question 22

What happens after T cells are activated?

Answer 22

they can leave the blood and survey the periphery: accumulating where they are needed

Question 23

What is the role of CD4+ Helper T cells?

Answer 23

regulators of immune responses

Question 24

What is the role of CD8+ Cytotoxic T cells?

Answer 24

cytotoxic (perforin, granzymes)

Question 25

What is cell-mediated immunity?

Answer 25

T cell-mediated

Question 26

What determines whether a naive CD4+ T cell will become a Tfh, Th2, Th1, Th17 or iTreg?

Answer 26

the cytokines released during activation

Question 27

What does each lymphocyte carry?

Answer 27

a single and unique specificity for antigen

Question 28

What does diversity in lymphocyte specificity provide us with?

Answer 28

the greatest opportunity to fight infections throughout our lifetime - therefore it is important to remember that these cells are present (in low numbers) prior to an infection

Question 29

How does clonal expansion occur?

Answer 29

at first there are multiple lymphocytes clones with different specificities -> deletion of self-reactive clones (clonal deletion) -> clonal selection -> clonal expansion

Question 30

When it’s a one in a million chance, how does one lonely antigen-specific lymphocyte meet its perfect antigenic match?

Answer 30

‘speed dating’ in specialised areas/hubs in secondary lymphoid organs anatomical structure makes the impossible a reality

Question 31

What are the rules of lymphocyte engagement?

Answer 31

naïve lymphocytes recirculate through lymph node/spleen via blood antigens/pathogens are funnelled from the periphery into the local lymph nodes

Question 32

How do naïve lymphocytes recirculate through lymph node/spleen via blood?

Answer 32

enter lymph node via blood vessels: lymphocytes squeeze through the walls of specialised blood vessels

Question 33

How are antigens/pathogens funnelled from the periphery into the local lymph nodes?

Answer 33

``` extracellular fluid (lymph) flows from peripheral tissue and is collected by lymphatic vessels and delivered to the draining lymph node activated dendritic cells migrate to lymph node and presents antigen to T cells ```

Question 34

What are the features of antigens?

Answer 34

can be simple or complex | any substance that may be specifically bound by immunoglobulin or T cell receptor

Question 35

What is an epitope?

Answer 35

an antigenic determinant part of the antigen that is recognised each lymphocyte is specific for one epitope

Question 36

What is an immunogen?

Answer 36

substance that induces a specific immune response | all immunogens are antigens

Question 37

Which factors affect immunogenicity?

Answer 37

foreignness, high MW, chemical complexity, degradability and also genetic variation of individual, dosage of immunogen, route of administration

Question 38

Are most proteins strongly immunogenic?

Answer 38

yes and protein carriers can increase immunogenicity of other molecules

Question 39

What are haptens?

Answer 39

small organic moiety attachable to larger structure target of antibody response (contains Ab determinant) non-immunogenic

Question 40

What are carriers?

Answer 40

usually protein or polypeptide (e.g. ovalbumin) required for adaptive immune response minimum size required to cross-link surface BCRs contains T cell determinants

Question 41

In order to generate an antibody response to the hapten, what must hapten? lol

Answer 41

hapten must be covalently linked to the carrier

Question 42

How many molecules does the innate immune system recognise vs the adaptive immune system?

Answer 42

innate: ~1000 adaptive: >10^7

Question 43

How many types of receptors are there in the innate immune system vs the adaptive immune system?

Answer 43

innate: <100 types, each invariant adaptive: 2 types (Ig, TCR)

Question 44

How are receptors distributed in the innate immune system vs the adaptive immune system?

Answer 44

innate: non-clonal adaptive: clonal

Question 45

How would receptors be expressed within a population of lymphocytes before encountering an antigen?

Answer 45

single unique receptors would be expressed on each lymphocyte

Question 46

How do T cell receptors recognise antigen?

Answer 46

in the form of a complex of a foreign peptide bound to an MHC molecule

Question 47

What must happen in order for peptides to be presented?

Answer 47

must be processed

Question 48

What is required to make an effective response to the peptide antigen?

Answer 48

the CD4 and CD8 cell-surface proteins of T cells must directly contact MHC molecules

Question 49

What can immunoglobulins recognise?

Answer 49

all manner of shapes and chemical compositions because they are highly specific, discriminating between small differences in protein sequences and chemical compositions

Question 50

The majority (~90%) of B-cell receptor epitopes are what?

Answer 50

conformational (discontinuous)

Question 51

How do immunoglobulins bind to antigens?

Answer 51

bind to conformational shapes on the surfaces of antigens using a variety of non-covalent forces also influenced by steric constraints