Adaptive Immune System Flashcards

1
Q

Antibodies

A

protein molecules that can bind to an specific antigen - specificity

  • Y-shaped
  • produced by B cells
  • (4) chains
  • multivalent (several sites of attachment)
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2
Q

(4) chains - Antibodies

A

> IDENTICAL (light chains identical & heavy the same)

(2) light (short)
(2) heavy (long)
- joined by disulfide bonds

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3
Q

Antibodies > Chains

- Variable Region

A

binding site for antigens

like active site of enzyme binding substrate

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4
Q

Protein Domain

A

part of protein with specific function

part of protein sequence & tertiary structure >

function independently

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5
Q

Hinge regions - Antibody

A

^^ Flexibility -> better binding

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6
Q

Variable Region of Antibody

A

forms binding site for antigen

different antibodies specific for different antigens will have DIFFERENT variable regions

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7
Q

Protease -significance in Antibodies

A

used to cut antibody into fragments

- can produce fragments by digestion

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8
Q

Structure of Antibodies

- FRAGMENTS (3)

A
  1. Fc
  2. Fab
  3. Ig
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9
Q

Antibody Structure

  • Fragments

Fc

A

crystallized easily

  • communicates between antigen-binding site & Immune system
    “bridge”
  • Fc RECEPTORS = FcR
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10
Q

Fc receptors

  • found on what cells?
A

receptors that recognize Fc portion of antibodies

  • Mast Cells (IgE)
  • Macrophages
  • Dendritic Cells
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11
Q

Antibody Structure

  • Fragments

Fab

A
  • BINDS TO ANTIBODY

Fab > ab > antibody

may have 2 Fab regions joined at hinge region

- Fab2 = antibody without Fc portion

  • constant region

- variable region

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12
Q

complementarity-determining region (CDR)

A

cause of variability

  • mostly from 3 loops
  • variability (sequence of aa’s) affects specificity
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13
Q

Heavy Chain > Constant Regions

A

aa sequence portion determines class of Ab

determines mechanism of destroying antigen _(effector function) -_ heavy chain

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14
Q

Heavy Chain > Constant Regions

- Classes of Antibodies

A

IgM

IgG

  • IgG1
  • IgG2
  • IgG3
  • IgG4

IgA

IgD

IgE

(A, M, E, G = type of heavy chain constant region)

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15
Q

Classes of Antibody

- constant region of heavy chain & Effector functions

A

2 Ab’s with SAME variable region (specific for same antigen)

BUT

from different AB type > DIFFERENT EFFECTOR FUNCTIONS

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16
Q

Effector Functions of Different Classes of Antibodies

A

differ

peanut allergy example

allergic > IgE antibodies (inflammatory) for peanut antigens

non-allergic > IgA Ab (anti-inflam) for peanut antigens

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17
Q

Antibodies - function (5)

A

1) Neutralize
2) Opsonization
3) Compliment Activation (classical)
4) ADCC (Ab-dependant cell-mediated cytotoxicity)
5) Activation of Mast cells & basophils
- allergies
- helminth clearance

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18
Q

Functions of Antibodies -> NEUTRALIZE

- explain

A

important in preventing toxins from exerting effect

> Ab binding - prevents virus/toxin binding

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19
Q

Importance of Immune System differentiating between a free antibody & an antigen-bound antibody?

A

to allow ImmS to decide to initiate Immune Response or not ->

in absence of antigen -> NO response

OTHERWISE in constant state of inflammation /immune response in absence of allergen

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20
Q

(2) ways Immune System detects presence of antigen

A

B__inding of Antigen can cause:

1) Conformational change of Ab due to antigen binding
2) Aggregation of Ab

21
Q

Complement Activation

  • IgM vs. IgG/IgE
A

IgM - pentamer

  • 1 binds antigen > conformational change > exposure of hidden sites on Fc > binds C1 of complement > Classical Pathway

IgG- monomer

  • need multiple Ab binding to same antigen in close proximity to activate complement
    i. e. 100,00 IgG binding to same RBC
  • IgE similar mechanism
22
Q

IgG vs. IgE

A

IgG - many bind to same antigen closely

  • aggregation > binds complement

IgE - binds to antigen > aggregate on antigen

  • can bind to Fc receptors on mast cells & basophils
  • leads to aggregation of Fc Receptor -> g_ranulation of mast cells_
23
Q

Agglutination/precipitation

  • due to?
  • causes?
  • use?
A

due to multivalent nature of antibodies

> leads to creation of antigen-antibody complexes

used to identify antigens in solution (via precipitation)

24
Q

Antigen-Antibody Complex - clinical significance

A

get stuck in kidney glomerulus or joints

activates complements there

can lead to glomerulonephritis & arthritis

25
Q

Antibody-Antigen Complex

  • size
A

influenced by quantity of antigen & antibody

Antibody Excess zone

26
Q

PSGN

Post-streptococcal glomerulonephritis

A

kidney disease mostly affects children 5 to 12 years & patients older than 60

group A streptococcus > strep / skin infection ⇒ clears

1-6 wks later ⇒ symptoms of VOLUME overload

  • ^ BP, Hematuria-blood in pee) caused by fluid retention
  • antibody excess zone
    • compliment activation but INefficient opsonization
27
Q

Multivalence of Antibodies

A

refers to multiple sites on Ab for binding of antigen

28
Q

Crossing Placenta

A

IgG antibodies can cross placenta (except IgG2)

IgM cannot

29
Q

Fetal Anemia

A
30
Q

Antibody Excess Zone

A
31
Q

Monomeric, Dimeric, other?

  1. IgA
  2. IgM
  3. IgG
  4. IgE
A
  1. Dimeric & monomeric
  2. Pentameric
  3. Monomeric
  4. Monomeric
32
Q

Antigen Binding sites in Antibody

A

IDENTICAL

33
Q

IgM

A

1st produced in immune response

LOW affinity for antigen

efficient @ activating compliment

34
Q

IgE

A

activate mast cells by binding to FcReceptors

- allergies, parasitic infections

35
Q

IgG

A

IgG1, IgG2, IgG3, IgG4

  • greater ↑ affinity for antigen
  • ​OPSONINS
  • can cross placenta (except IgG2)

IgG4 - counteracts effects of other antibodies
IgG1,2,3 = activate complement

36
Q

igA

A

most abundant in mucosa

v important role in anti-inflammatory response

do NOT activate macrophages, DC or complement

37
Q

Clonal Selection Theory of Antibody Production

A

explains functions of lymphocytes in response to specific antigens invading body

Resting B-cells must be activated by antigen binding to secrete antibodies (“selected by antigen”)

  • divide & form clones of B-cells
  • secrete antibodies of same class & specificity as BCR
38
Q

Plasma cells

A

differentiated B cells that secrete antibodies

39
Q

Diversity in Antibodies produced by (5) mechanisms

A

BEFORE antigen presence:

1) Combinational Diversity
2) Junctional Diversity

AFTER antigen presence

3) Class-Switch Recombination (CSR)
4) Somatic Hypermutation
5) Alternative Splicing of Heavy chain RNA

40
Q

BEFORE antigen presence:

1) CombinationalDiversity

A

RAG protein randomly rearranges gene segments via recombination signal sequence (RSS)

Successful recombination (VDJ/VJ) prevents recombination of other chromosome = Allelic Exclusion

41
Q

BEFORE antigen presence:

2) Junctional Diversity

A

creates MORE diversity than Combinational Diversity

by TdT (terminal deoxinucleotide transferase)

  • inserts extra nucleic acids @ junction regions

Proper VJ/VDJ joined to constant chain via looping out

  • Kappa/Lambda of light chain OR
  • constant M region of heavy chain
42
Q

AFTER antigen presence

5) Alternative Splicing of Heavy chain RNA

A

normal process in eukaryotes

switches between membrane-bound BCr & secreted antibody

exons included/excluded from mRNA

different AA sequence > different function

ALL BCr = monomeric (even IgM)

43
Q

AFTER antigen presence

3) Class-Switch Recombination

A

CD4+ T-cell activates B-cell via BCr to generate different class of antibody

AID enzyme produced by activated B-cell

  • loops out IgM constant region & connects variable region to different constant region to produce different Antibody class
44
Q

AFTER antigen presence

4) Somatic Hypermutation

A

AID enzyme & CD4+ T cells

important for affinity maturation

@ variable region of light/heavy chains

> cloning process - AID inserts random mutations

B cell only survives if ^ affinity increased

45
Q

Allelic Exclusion

A

important part of Combinational Diversity

required for monospecificity

Successful VDJ (or VJ) recombination of 1 will prevent recombination of other chromosome

(i.e. will excludethe other)

46
Q

Monoclonal antibodies

A

antibodies from clone of 1 type of B cells

→ Identical antibodies for same epitope

47
Q

Polyclonal antibodies

A

Secreted from clones of different B cells

Bind to same antigenbut different epitope

48
Q

Mono vs. Polyclonal antibodies

pros. vs. cons

A

MONOCLONAL

  • more consistent
  • allow for discrimination b/w similar antigens

POLYCLONAL

  • cheaper
  • more robust detection of antigens (stronger signal)