Humoral Adaptive Immunity Flashcards

1
Q

The main defence cells in adaptive immunity are?

A

Lymphocytes
B lymphocytes in humoral adaptive immunity
T lymphocytes in cell-mediated adaptive immunity

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2
Q

Where is primary and secondary lymphoid tissue? What occurs in each?

A

Primary: B & T lymphocytes develop
- Bone Marrow (B & T)
- Thymus (T)
Secondary: B & T lymphocytes meet and respond to pathogens
- Lymph nodes
- Spleen
- Mucosa (gut) and associated lymphoid tissue

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3
Q

What occurs in the lymph node?

A
  • Filters lymph
  • B & T lymphocytes meet lymph-borne pathogens
  • Pathogen in infected peripheral tissue is transported via lymph to lymph node
  • Intradermal or subcutaneous injection
  • lymph enters tissue to supply nutrients and remove waste (pathogen)
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4
Q

What occurs in the spleen?

A
  • Filters blood
  • B & T lymphocytes meet blood-borne pathogens
  • pathogen is in blood (systemic infection)
  • intravenous injection
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5
Q

What occurs in mucosa-associated lymphoid tissue?

A
  • B & T cells meet pathogens in mucosal areas
  • includes gastrointestinal, respiratory and reproductive tracts
  • adaptive responses in these areas = mucosal immunity
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6
Q

How are antibodies produced?

A
  • B cells express immunoglobulin (Ig) molecules on surface
  • Ig binds to pathogen activating B cell
  • B cell differentiates to a plasma cell
  • plasma cell sheds surface Ig molecules = antibodies
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7
Q

What is the structure of an antibody?

A

2 identical light chains (kappa or lambda)
2 identical heavy chains
- Variable region = ends of light and heavy chains
- Constant region = remaining region

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8
Q

How do antibodies form?

A
  • When B cells develop heavy and light chain genes join together by random gene recombination
  • 10^11 - 10^15 possible combinations
  • Each B cell expressed many identical copies of its own unique Ig molecule
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9
Q

On an antibody, what part of the antigen does the variable region bind to? What is the part of the variable region binding to the antigen called?

A
  • The part of the antigen bound by the antibody is called the epitope
  • The part of the variable region bound to the epitope = FAB region (antibody binding fragment)
    ^SUB-MOLECULAR BINDING^
    (very precise, based on structural fit)
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10
Q

What happens to a B cell whose variable region binds to an antigen?

A

The B cell is activated and undergoes clonal expansion to produce a pool of identical antibody secreting Plasma cells

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11
Q

Will antibodies made against the measles virus be effective against influenza?

A

NO, antibodies only have the specificity for the epitope on the antigen on the bacteria it binds to

NOTE: Some auto-immune diseases are due to self-antigen recognition as a pathogen

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12
Q

What is an antigen?

A

Any molecule that stimulates antibody production

  • Antigens can be “self”molecules (not only pathogens)
  • This is the basis for blood transfusion compatibility
  • If blood type does not match the body will recognize the blood cells as foreign molecules and attack
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13
Q

Why is it so hard to find a compatible organ transplant?

A

Tissue type is based on Human Leukocyte Antigens (HLA)

  • There is a vast # of HLA combinations
  • Its very unlikely for any 2 people have identical tissue types (except identical twins)
  • So organ transplantation requires immunosuppression therapy to avoid graft rejection
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14
Q

How does an antibody protect us?

A
  • Neutralization
  • Opsonization
  • Complement activation
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15
Q

Antibody function is defined by?

A

What the constant region binds to

i.e. determines how to eliminate the pathogen

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16
Q

What happens when an antibody uses neutralization?

A

Antibody stops the antigen from binding to anything

  • Coats the pathogen’s surface (variable region binds to epitopes)
  • Gold standard for anti-virals
17
Q

What happens when an antibody uses Opsonization?

A

Opsonization promotes phagocytosis

  • Variable region binds to epitopes (coats pathogen)
  • Constant region binds to Fc Receptor (FcR) on phagocyte
18
Q

What happens when antibodies activate complement proteins?

A
  • Variable region binds to eptiope on antigen (coats pathogen)
  • Constant region binds to complement protein
  • Activates Complement protein
  • Complement-mediated phagocytosis or lysis
19
Q

How do the 5 classes (isotypes) of Ig/antibodies differ?

A

The 5 isotypes are based on differences in constant region of the heavy chain (constant region determines function)

  • Length
  • Carbohydrates
  • Location of hinges
  • Each has a different function
20
Q

What is the function of IgG?

A

(2 hinges)
- Most abundant antibody in blood(plasma) and gives passive immunity to newborns (only antibody which can cross the placenta)
- More effective than IgM
- Hinges give more flexibility and better binding affinity
Function: Complement activation, neutralization,opsonization

21
Q

What is the function of IgM?

A
(No hinge) 
- First antibody produced after exposure to pathogen (always produced in an immune response)
- First antibody produced by a newborn 
- Expressed by naive B cells
	Function: Complement activation
22
Q

What is the function of IgA?

A

(1 hinge)
- Most abundant antibody in secretions (tears, mucus)
- Provides passive immunity to newborns (from breast milk)
- more effective than IgM
Function: Neutralization and complement activation

23
Q

What is the Function of IgD?

A

(1 hinge)
- Remains bound to B cell surface (not secreted)
- Naive B cells express IgD and IgM
Function: Binds to antigens on pathogens

24
Q

What is the function of IgE?

A

(No hinge)
- Instrumental in anti-parasitic humoral immunity
- Involved in allergic reactions and anaphylaxis
- Increased serum IgE levels help diagnose these conditions
Function: Activates mast cells

25
Q

The antibodies most important to eliminate extracellular bacteria and viruses are?

A

IgG
IgA
IgM - less effective than other 2

26
Q

Naive B cells circulate in blood and enter secondary lymphoid tissue via?

A

T cell area

NOTE: if B cell does not find a pathogen its variable region can bind to it goes back into circulation, after 7-10 days it self-destructs

27
Q

What happens when a naive B cell encounters an antigen it can bind to?

A

B cell is activated, undergoes clonal expansion and differentiates into a plasma cell which will secrete antibodies

28
Q

What are the differences between a B cell being activated by a pathogen only and pathogen+T cell?

A
Pathogen only:
- Only produces IgM antibodies
- No memory produced
Pathogen + T cell:
- Ab production takes more time due to isotype switching, but more effective Ab's are produced to kill pathogen
- Produces memory B cells
29
Q

What is isotype switching regulated by?

A

Cytokines secreted by T cell

30
Q

How can a B cell already activated by a pathogen undergo isotype switching if this changes the antibody?

A
  • Variable region of the Ab does not change,therefore epitope:FaB binding remains the same
  • Isotypes are defined by the constant region on the heavy chain, so this is the only part that changes, which leaves the variable region unaffected
31
Q

What are properties of a memory B cell?

A
  • Always develop during the first exposure to a pathogen
  • Remember the pathogen
  • Mount a more effective and faster immune response when reinfected with the identical pathogen
  • Memory B cells last for years
32
Q

What is the difference between short-lived plasma cells and long lived plasma cells?

A
Short-lived:
- Activated by antigen only
- Survives for days in secondary lymphoid tissue
- secretes IgM only
Long-lived:
- activated by antigen and T cell
- Survives for months to years 
- Lives in bone marrow
- constitutively secrete antibodies
33
Q

How does a vaccine create an adaptive immune response?

A
  • A vaccination allows first exposure to a pathogen in a form that cannot cause disease (innocuous)
  • Pathogenic antigens or killed/weakened whole pathogens are injected to stimulate the production of memory B cells
  • Individual mounts a memory response with re-exposure to same pathogen creating a more rapid and protective immune response
34
Q

What is the influenza vaccine made of?

A
Mostly hemagglutinin (H) antigens
- Sometimes Neuraminidase (N) antigens are included
35
Q

What are the differences between primary and secondary response?

A

Primary response:

  • Clonal expansion and isotype switching take time to complete (7-10 days)
  • IgM antibodies first, IgG (IgA, IgE) later (memory cells produced)

Secondary response:

  • Isotypes are already switched and some memory cells are circulating (1-3 days) (new memory cells are still produced, but the already existing ones make the response much quicker)
  • Rapid increase in IgG (IgA, IgE)
  • Antibodies secreted by memory B cells (Memory response)
36
Q

If an individual without T cells undergoes a secondary response, what will happen?

A
  • No memory B cells will be produced
  • Only IgM will be secreted
  • Antibody concentration will not strengthen with subsequent exposures (primary response every time)
37
Q

What is wrong if an infant (10 months) with a series of bacterial chest infections has high levels of IgM, no IgG or IgA?

A
  • Problem with T cells (no isotype switching) = Hyper-IgM syndrome
  • B cells can produce a primary response with IgM Abs
  • no memory can be produced, no secondary response will occur
  • Can be treated with IV gamma globulin
    • purified IgG pooled from 1000+ donors
38
Q

What is agammaglobulinemia?

A
  • No IgM, IgG or IgA = lack B cells and antibodies

- Can be treated with IV gamma globulin