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POM 4: Immunity and Infection > 7: Lymphocytes > Flashcards

7: Lymphocytes Flashcards

Adaptive immunity, immune memory, antigen receptor diversity, T cells, MHC, B cells, antibody function

1
Q

Adaptive immunity

A

response of vertebrate immune system to a specific antigen that typically generates immunological memory

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2
Q

Cells involved in adaptive immunity

A

B cells
Antibodies
T cells
Natural killer T cell (also in innate immunity)

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3
Q

An adaptive immune response (AIR) is initiated when

A

a pathogen overwhelms innate defence mechanisms
pathogen replicates, antigen accumulates = sensor cells become activated to trigger AIR
Expansion of antigen-specific lymphocytes that target pathogen specifically, formation of memory cells providing long-lasting specific immunity

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4
Q

Role of adaptive immune system

A
  • Improves efficacy of innate immune system
  • Focuses a response on site of infection and organism responsible
  • has memory
  • needs time to develop
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5
Q

What major event occurs in peripheral lymphoid tissues to initiate adaptive immune responsse?

A

B or T lymphocytes encounter antigens for which receptors have specific reactivity

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6
Q

Antigen

A

molecules recognised by highly specialised lymphocyte receptors, which act to induce an adaptive immune response

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7
Q

2 hallmarks of adaptive immune response

A
  • Creates immunological memory; long-lasting protection
  • Highly specific : recognises non-self antigens
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8
Q

Issue with Specificity

A

antigen diversity - large number of lymphocyte receptors that can recognise array of antigens needed
10^15 different antibody/BCR molecules can be generated each coded by one gene = this isnt possible so immunoglobulin gene rearrangement occurs

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9
Q

Immunoglobulin gene rearrangement

A

Each BCR receptor chain encoded by separate multigene families on different chromosomes
During B cell maturation, gene segments rearranged and brought together

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10
Q

How is diversity generated overall?

A

Germline diversity
Combinatorial diversity
Junctional diversity
Heavy + light chain diversity

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11
Q

Germline diversity

A

Each gene segment consists of different base sequence

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12
Q

Combinatorial diversity

A

formation of different combinations of V, J and D segments from each cluster

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13
Q

Junctional diversity

A

addition/removal of random bases to form a viable junction between selected V, D and J segments

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14
Q

Heavy+light chain diversity

A

same heavy chain can be combined with different versions of a light chain (and vice versa)- many different combinations of heavy and light chain V regions that pair to form antigen-binding site in immunoglobulin molecule

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15
Q

Issues with the process of gene rearrangement

A

with many different receptors generated randomly during lifetime, possibility of self-reactive antibodies –> autoimmunity

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16
Q

Immunological memory

A

quicker response, producing antibodies

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17
Q

T cell response

A

Cell-mediated response

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18
Q

B cell response

A

Humoral/antibody response

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19
Q

Lymph node interactions of B cells

A

stay outside lymph node
- respond directly to antigens drained into the lymph node

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20
Q

Lymph node interactions of T cells

A

Interior to lymph node

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21
Q

3 Types of T cells

A

Antigen binds to receptor - cell proliferates and differentiates into :
Cytotoxic T cells
Helper T cells
Regulatory T cells

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22
Q

Cytotoxic T cells

A

kill infected cells or other intracellular pathogens bearing the antigen

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23
Q

Helper T cells

A

provide signals (specific cytokines) that activate other cell functions e.g B cell antibody production / macrophage killing engulfed pathogens

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24
Q

Regulatory T cells

A

suppress other lymphocyte activity
help limit possible damage of immune response

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25
Q

What molecule on T cell surface helps distinguish T helper and T killer cells

A

CD4 - helper
CD8- killer

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26
Q

Types of Th cells

A

Tfh
Th1
Th17
Th2
Treg (Th0)

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27
Q

Tfh cells

A

pro-antibody
B-cell support
Produce : IL-21

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28
Q

Th1 cells

A

pro-inflammatory
boost cellular immune response-
produce interleukins that promote B cell class switching
involved in macrophages and inflammation
Produce: Interferon Gamma, Tumour Necrosis Factor, IL-12

29
Q

Th17 cells

A

pro-inflammatory
control bacterial and fungal infection, neutrophils
Produce: IL-17, IL-23, IL-6

30
Q

Th2 cells

A

pro-allergic
involved in allergies and worms (parasites)
Boost multicellular response
Produce: IL-4,IL-5, IL-13

31
Q

Treg (Th0) cells

A

anti-inflammatory
limit immune response /supress T cell response
Produce: IL-10, TGFbeta

32
Q

By what pathway do T helper cells activate B cells

A

thymus dependent pathway
- release of cytokines cause B cell proliferation and differentiation (clonal selection + expansion) into plasma and memory B cells

33
Q

How do CD8 T cells kill pathogens?

A

Release perforins and granzymes

34
Q

How do CTLs initiate programmed cell death?

A

Cytotoxic T cells (CTL) kill targets by apoptosis (characterised by fragmentation of nuclear DNA)
CTL store perforin, granzymes, granulysin in cytotoxic granules- released after target recognition
Perforin molecules polymerise, form pores

35
Q

Two ways T cells recognise foreign antigens

A

Interactions between MHC and T-cell receptors

36
Q

Epitope / antigenic determinant

A

region recognised by T cell antigen receptor
- antigen broken down into peptide fragments
-epitope peptide binds to self molecule and MHC molecule
-T cell receptor binds to complex of MHC molecule and epitope peptide

37
Q

Epitope is formed by

A

combination of MHC-II and part of antigenic protein

38
Q

MHC stands for

A

Major Histocompatility Complex

39
Q

Role of MHC

A

Recognises self and non-self
APC takes in foreign peptides and forms MHC, which allows for T cell selection

40
Q

What is the difference between MHC-I and MHC-II

A

MHC-1 : all nucleated cells, single variable alpha chain and common B-microglobulin

MHC-2 : only on “professional” antigen presenting cells e.g Dendritic cells, macrophages, B lymphocytes
has 2 chains, alpha and beta

41
Q

Describe the structure of MHC class I molecules

A

Consist of two polypeptide chains
An alpha chain noncovalently associated with smaller chain, B2-microglobulin

Complete MHCI has 4 domains, 3 formed from MHC-encoded alpha chain, one from B2-microglobulin

Folded a1 and a2 domains form walls of cleft on surface of molecule = peptide-binding cleft/groove

MHC molecules are highly polymorphic - major differences in allelic forms located in cleft= influences peptide binding

42
Q

Describe the structure of MHC-II molecules

A

consists of a noncovalent complex of two chains, a and b both of which span membrane

peptide-binding cleft is formed by two domains from different chains, a1 and B1 domains

sites of major polymorphism in MHCII molecules located in peptide-binding cleft

43
Q

How does MHCI interact with T cell receptors

A

Intracellular pathogen/antigen presented on MHCI binds to CD8 T cells in cytosol

CD8 cytotoxic T cell responsible for pathogen surveillance and cytolysis of somatic cells

44
Q

How does MHCII interact with T cell receptors

A

Extracellular pathogen/antigen presented on MHCII binds to CD4 T cells in endosomes

CD4 cells differentiate into several subsets of effector T cells that have different immune functions

45
Q

Process of MHCI recognition

A
  1. Virus infects cell
  2. Viral proteins synthesized in cytosol
  3. Peptide fragments of viral proteins bound by MHCI in ER
  4. Bound peptides transported by MHCI to cell surface
  5. Cytotoxic T cells recognise complex of viral peptide with MHCI and kills infected cell
46
Q

How is MHC expressed

A

co-dominant expression

each person can have up to 6 of each gene if completely heterozygous
more than 17,000 MHC variants

47
Q

Two properties of MHC making it difficult for pathogens to evade immune response

A

MHC is polygenic - several different MHCI and MHCII genes, so every person has a set of MHC molecules with different ranges of peptide-binding specificities

MHC is highly polymorphic - multiple variants/alleles of each gene within whole population

48
Q

B cell antigen receptors

A

BCR - surface bound antibody
- encodes antibody the cell will make

49
Q

BCR region of B cell

A

unique binding site which binds to antigenic determinant / epitope of antigen

Made before cell ever encounters antigen
Present in 1000s of identical copies on B cell surface

50
Q

Two pathways by which antibody production by B cells is achieved

A

Thymus-dependent pathway
Thymus-independent pathway

51
Q

Thymus dependent pathway

A
  • membrane bound BCR recognises (thymus dependent) antigen
  • receptor-bound antigen is internalised and degraded into peptides
    -peptides associate with “self” molecules (MHC-2) and is expressed at cell surface
  • Complex recognised by matched CD4 T helper cell
  • B cell activated (class switched, mature plasma/memory cell)
52
Q

Thymus independent pathway

A

-some microbial antigens (thymus-independent antigens) activate B cells, in absence of helper T cells
-second signal triggered from direct recognition of common microbial constituent (LPS) = activating TLR signalling in B cell
-only IgM ; no memory produced

53
Q

Thymus-independent antigens

A

highly repetitive molecules
can cross-link the BCR on B cells
e.g polysaccharides of bacterial cell walls

54
Q

What happens once B cells undergo clonal selection

A

clonal expansion

55
Q

Describe what is meant by clonal expansion of lymphocytes

A

1.foreign antigen interacts with receptor on mature naive lymphocyte, cell activated and divides
2. undergoes clonal expansion
3. antigen specificity maintained as cloned cells proliferate and differentiate into effector cells

56
Q

5 types of antibodies produced by B cells

A

IgM
IgG
IgA
IgE
IgD

57
Q

What is antibody type and function defined by

A

structure of its heavy chain

58
Q

IgG

A

\//
||
Highest opsonisation and neutralisation acrivities
Classified into four subclasses - IgG1/2/3/4
lymphatic system

59
Q

IgM

A

(5 Y star structure)
produced first upon antigen invasion, increase transiently
lymphatic system

60
Q

IgA

A

(Two or 3 star Y structure)
expressed in mucosal tissues
forms dimers after secretion
small intestine, mouth, oesophagus

61
Q

IgD

A

\//
||
unknown function
lymphatic system

62
Q

IgE

A

\//
||
||
Involved in allergy
lymphatic system

63
Q

Fab region of antibody

A

antibody region - varies between antibody types

64
Q

Fc region of antibody

A

constant region

65
Q

Describe the structure of the IgG antibody

A

Two heavy chains and two light chains
two heavy chains linked by disulphide bonds, each heavy chain linked to light chain by disulphide bond
Two identical antigen-binding sites
Two types of light chains, lambda and kappa, found in antibodies (never one of each)

66
Q

3 core functions of antibodies

A

Neutralisation
Opsonisation
Complement activation

67
Q

Neutralisation

A

antibodies bind to viruses/bacterial toxins and block access to cell they might infect or destroy

68
Q

Opsonisation

A

antibodies coat bacterium to better enable phagocytic cells e.g macrophage/neutrophil to ingest and destroy it (Fc receptor on phagocytic cell binds to C receptor)

69
Q

Complement activ

A

antibodies coat bacterial cell; C regions form platform that more efficiently activate complement proteins (covalent deposition on bacterial surface)–> complement proteins on bacterium can be recognised by complement receptors on phagocytes; stimulates phagocytes to ingest and destroy the bacterium

POM 4: Immunity and Infection (9 decks)

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