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Basic Immunology > Lecture 4 ((3) - Week 2B) > Flashcards

Lecture 4 ((3) - Week 2B) Flashcards

1
Q

The immune system must protect us against a wide variety of pathogens

A

eg bacteria, viruses, parasites, fungi
• which pathogens an individual will encounter is not known in advance
• therefore, immune system must maximize its potential to respond to diverse challenges

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2
Q

The immune system must

A

• recognize and respond to pathogens
(failure = death from infectious disease)
• but not respond to components of our own bodies
(failure = auto-immune disease)
ie must discriminate “non-self” from “self”

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3
Q

Antigen

A

anything that binds to a specific receptor on T or B cells
• generates antibody
• can be bits of bacteria, viruses etc (foreign antigen)
• pathogens can also be bits of our own bodies (self antigen)

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4
Q

Epitope

A

the portion of the antigen that is recognized and bound by a receptor on an immune cell
• structure of antigen that’s recognized
• numerous
• antigens contain many epitopes

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5
Q

Complex antigens (eg proteins) can contain

A

multiple different epitopes, each of which can be recognized by different antibodies

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6
Q

Epitopes recognized by antibodies are

A

often shapes formed by the way proteins fold

• different antibodies “fit” different shapes

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7
Q

Cells of innate and adaptive immune systems recognize

A

non-self in different ways

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8
Q

Innate immune system

A
  • NK cells
  • monocytes/macrophages
  • dendritic cells
  • granulocytes
  • a limited number of common microbial structures can be recognized: PAMPs (toll-like receptors)
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9
Q

Adaptive immune system

A
  • T cells
  • B cells
  • can recognize MANY antigens
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10
Q

Overview of antigen recognition

A
  1. receptor binds to Ag
  2. signalling cascade initiated (to nucleus, tell cells to start division)
  3. gene transcription
  4. production of effector molecules (eg antibodies/cytokines)
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11
Q

Signalling cascade

–>

A

cell starts dividing

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12
Q

B cells

A

make antibodies

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13
Q

Antibody is also known as

A

immunoglobulin (Ig)

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14
Q

Recognition of antigen by B cells

A
  • B cells recognize antigens using the B cell receptor (BCR)
  • the BCR is an antibody molecule anchored to the B cell - transmembrane
  • antigens are recognized directly (they don’t require presentation by other cells)
  • epitopes are often conformational (shapes formed by protein folding)

• T cells recognize antigen = complex
• antibody molecules on B cell surface BIND native antigen
–shape and conformation (wrong shape = no binding = no action)

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15
Q

In mamamls, B cells develop in

A 
bone marrow
stem cell -->
pro- B cell -->
pre- B cell (start to express antibody on surface)-->
immature naive B cell -->
mature naive B cell

• naive = hasn’t seen antigen

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16
Q

Each new B cell

A

has a unique receptor

• recognizes a different antigen

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17
Q

Each B cell expresses

A

only 1 type of receptor

• recognize only 1 antigen

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18
Q

Recognition of antigen by B cells

A
  • activated B cells differentiate into plasma cells - secrete a soluble form of the receptor - antibody
  • the antibody recognizes the same antigen as the BCR

• B cell divides, loses antibody from surface –> makes a lot of antibody in solution (not on surface)

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19
Q

Activated B cells differentiate into

A

plasma cells that secrete a soluble form of the receptor (antibody)

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20
Q

Plasma cells secrete

A

a soluble form of the receptor (antibody)

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21
Q

Each antibody recognizes

A

a different antigen
• Ag = antigen
• Ab = antibody

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22
Q

Structure of a typical antibody

A 
Y shaped
Arms of the Y
• light chain on outside of each arm
• heavy chain on inside of each arm
• variable region is distal and made of a combination of shapes of 2 identical heavy (VH) and 2 identical light (VL)
• antigen binds the variable region

The stem of the Y
• constant region
• controls what the antibody does
• heavy chain = γ α μ ε δ

there are 2 types of light chain and 5 types of heavy

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23
Q

2 types of light chain

A
  • kappa κ

* lambda λ

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24
Q

5 types of heavy chain

A
  • mu μ
  • gamma γ
  • alpha α
  • epsilon ε
  • delta δ
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25
Q

Variable domains

A

contains the sequences that interact with antigen

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26
Q

Variable regions of H and L chains

A

combine to form shape that fits that of the antigen

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27
Q

Fab

A

arms of the Y
binds antigen

Papain digestion (each separately)
Pepsin digestion ( F(ab')2 both parts separated from Fc)
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28
Q

F(ab’)2
(2 = subscript)
(unsure)

A

the arms of the Y together

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29
Q

Fc

A

determines function of antibody

crystallizes

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30
Q

V domains contain

A

areas of hypervariability

• HV regions are also known as complementarity determining regions (CDRs) - 6 combine to form each antibody binding site

31
Q

HV regions

A
  • hypervariable regions
  • also known as complementarity determining regions (CDRs)
  • 6 combine to form each antibody binding site
32
Q

Antibody classes

A

determined by the constant region of the heavy chain

  • IgG = γ heavy chains
  • IgE = ε heavy chains
  • IgA = α heavy chains
  • IgD = δ heavy chains
  • IgM = μ heavy chains

all have 2 heavy and 2 light chains, but IgM has 10 heavy and 10 light chains, IgA can have 4 heavy and 4 light chains

33
Q

IgG =

A

γ heavy chains
2 heavy 2 light

4 subclasses

34
Q

IgE =

A

ε heavy chains

2 heavy 2 light

35
Q

IgA =

A

α heavy chains
2 heavy 2 light

Or another Y to get 4 heavy and 4 light

2 subclasses

36
Q

IgD =

A

δ heavy chains

2 heavy 2 light

37
Q

IgM =

A

μ heavy chains

10 heavy, 10 light

38
Q

Different classes have

A

different effector functions

39
Q

IgG has

A 
4 subclasses in humans
• IgG1
• IgG2
• IgG3
• IgG4
40
Q

IgA has

A

2 subclasses
• IgA1
• IgA2

41
Q

B cells can produce

A 
different classes of antibodies
• IgM and IgD --> 
• IgM
• IgG
• IgA
• IgE
  • IgD = recognition
  • IgE = allergies
  • ER makes protein
42
Q

B cells receptor diversity

A
  • millions of different antigens can be recognized
  • each new lymphocyte expresses only 1 type of receptor and recognizes only 1 antigen
  • lymphocytes with any given specificity are rare
  • an antigen will only activate those lymphocytes with the “right” receptor
  • these lymphocytes divide repeatedly - daughter cells express the same receptor
  • a large number of useful cells are generated (clonal expansion)
43
Q

A new lymphocyte expresses

A

only 1 type of receptor and recognizes only 1 antigen

44
Q

Lymphocytes with any given

A

specificity are rare

45
Q

An antigen will only activate those lymphocytes with

A

the “right” receptor

46
Q

Lymphocytes divide repeatedly

A

clonal expansion
• daughter cells express the same receptor
• a large number of useful cells are generated

47
Q

How is receptor diversity generated?

A
  • each developing B cell expresses a distinct receptor
  • tens of millions of receptors required - how?
  • a gene for each receptor? - no, would require tens of millions of genes
  • instead, diversity is generated by “mixing and matching” gene segments within the heavy chain and light chain loci
48
Q

Diversity is generated by

A

random “mixing and matching” of variable, diversity, and joining segments

49
Q

Diversity is generated by random “mixing and matching” of

A

variable, diversity, and joining segments

50
Q

Making an immunoglobulin heavy chain

A
  • D-J joining: DNA spliced between diversity and joining regions
  • V-DJ joining: DNA spliced out between V and DJ
  • transcription
  • RNA splicing –> chooses constant part and makes different variants

• mediated by RAG recombinase enzymes

51
Q

Somatic DNA recombination generates

A

antibody diversity

52
Q

… generates antibody diversity

A

somatic DNA recombination

53
Q

Antibody diversity

2 processes act during B cell development

A

• combinational diversity
• junctional diversity
~ 5x10^13 antibodies

54
Q

Combinational diversity

A

mixing and matching of V, (D), and J segments

• different combinations of H and L chains

55
Q

Junctional diversity

A

(CDR3)

• addition of P- and N- nucleotides at joins

56
Q

Antibody responses are dynamic

A

they evolve DURING immune response
Primary = first time see antigen
• IgM levels in serum up then down
• IgG up

Secondary = second time to see antigen
• IgG down then up

isotype switching and and affinity maturation

57
Q

Antibody responses are dynamic - they evolve during an immune response

A
  1. class (isotype) switching

2. affinity maturation

58
Q

Class switching

A
  • a given B cell starts by making IgM (and IgD) but can switch to making IgG (or IgA or IgE)
  • class switch recombination allows a given V-D-J unit to be associated with different constant regions
  • antibody specificity remains constant whilst biological effector functions are varied

IgM first, then switches primary
secondary made IgG

59
Q

Class switch recombination

A

IgM variable (VDJ) followed by constant
• activation induced cytidine deaminase (AID) = DNA chopped out
IgG made
• take out genes that make A and put in genes that make B
• different constant region

60
Q

Affinity maturation

A

improves the quality of antibodies during an immune response by increasing their affinity for antigen
(ie makes the antigen binding site a better fit for the antigen)
• changes variable regions
• affinity = strength of interaction

61
Q

Affinity maturation mechanism

A

by somatic hypermutation
• individual nucleotides in variable regions are randomly replaced with alternatives
• “tested” against antigen displayed on follicular dendritic cells (FDC) - many mutations are useless
• B cells with the best fit antibodies survive

occurs during an immune response, not during B cell development`

62
Q

Affinity maturation and class switching occur in

A

germinal centers (GC) in lymph nodes and spleen
• GC form 3-4 weeks after initial antigen exposure
• rapid initial response is followed by an improved, more effected and diversified, response
• antigen sticks on surface and presents in follicular dendritic cells

63
Q

What do antibodies do to protect us against infections?

A

five things:

  1. agglutination
  2. neutralization
  3. opsonisation
  4. complement activation
  5. antibody dependent cellular cytoxicity (ADCC)
64
Q

Agglutination

A

crosslinking by antibodies creates larger particles that are taken up more efficiently by phagocytes
• esp IgA antibody
• multivalvent antibodies and antigens

65
Q

Neutralization

A

can block attachment of pathogens to receptor on cells and block the action of bacterial toxins
• keeps shit out
• antibodies bind to pathogens so can’t fit into receptor on target cell

66
Q

Opsonization

A

FcR mediated uptake enhances pathogen clearance by macrophages and neutrophils
• FcR = receptor for Fc part of antibody
-receptor for heavy chain
• constant part of antibodies attaches to receptor on target cell so pathogens/antigens can’t get in

67
Q

Complement activation

A
  • “trained spotters”
  • proteins in blood
  • antibody binds to surface of cell enzyme splits C3 into C3a and C3b
  • C3b + C5 into C5 convertase to make MAC (membrane attack complex)
  • punches hole in cell –> lysis

• classical, alternative, lectin pathways

68
Q

Antibody dependent cellular cytoxicity (ADCC)

A

role in killing:
• virally infected cells, helminths, tumour cells
• may be utilized for therapies
• antibody bound to cell
• NK cell or macrophage comes along, recognizes, makes molecules that kill

  • viral peptides stick out of target cell surface
  • antibodies bind, constant (Fc) region sticks out
  • NK cell or macrophage hasFc receptor
  • meet up, macrophage/NK cell releases molecules to kill infected cell
69
Q

Antibody classes and subclasses have

A

different biological properties

70
Q

B cells

A

make antibodies

71
Q

Each B cell expresses

A

a single unique receptor for antigen

72
Q

Somatic recombination contributes to

A

receptor diversity during B cell development in bone marrow

73
Q

During an immune response, antibodies

A

improve and diversify - affinity maturation an isotype switching

74
Q

Antibodies have 5 main biological activities that

A

help fight infections

Basic Immunology (15 decks)

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