Humoral Adaptive Immunity Flashcards
The main defence cells in adaptive immunity are?
Lymphocytes
B lymphocytes in humoral adaptive immunity
T lymphocytes in cell-mediated adaptive immunity
Where is primary and secondary lymphoid tissue? What occurs in each?
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
What occurs in the lymph node?
- 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)
What occurs in the spleen?
- Filters blood
- B & T lymphocytes meet blood-borne pathogens
- pathogen is in blood (systemic infection)
- intravenous injection
What occurs in mucosa-associated lymphoid tissue?
- B & T cells meet pathogens in mucosal areas
- includes gastrointestinal, respiratory and reproductive tracts
- adaptive responses in these areas = mucosal immunity
How are antibodies produced?
- 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
What is the structure of an antibody?
2 identical light chains (kappa or lambda)
2 identical heavy chains
- Variable region = ends of light and heavy chains
- Constant region = remaining region
How do antibodies form?
- 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
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?
- 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)
What happens to a B cell whose variable region binds to an antigen?
The B cell is activated and undergoes clonal expansion to produce a pool of identical antibody secreting Plasma cells
Will antibodies made against the measles virus be effective against influenza?
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
What is an antigen?
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
Why is it so hard to find a compatible organ transplant?
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
How does an antibody protect us?
- Neutralization
- Opsonization
- Complement activation
Antibody function is defined by?
What the constant region binds to
i.e. determines how to eliminate the pathogen
What happens when an antibody uses neutralization?
Antibody stops the antigen from binding to anything
- Coats the pathogen’s surface (variable region binds to epitopes)
- Gold standard for anti-virals
What happens when an antibody uses Opsonization?
Opsonization promotes phagocytosis
- Variable region binds to epitopes (coats pathogen)
- Constant region binds to Fc Receptor (FcR) on phagocyte
What happens when antibodies activate complement proteins?
- Variable region binds to eptiope on antigen (coats pathogen)
- Constant region binds to complement protein
- Activates Complement protein
- Complement-mediated phagocytosis or lysis
How do the 5 classes (isotypes) of Ig/antibodies differ?
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
What is the function of IgG?
(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
What is the function of IgM?
(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
What is the function of IgA?
(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
What is the Function of IgD?
(1 hinge)
- Remains bound to B cell surface (not secreted)
- Naive B cells express IgD and IgM
Function: Binds to antigens on pathogens
What is the function of IgE?
(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
The antibodies most important to eliminate extracellular bacteria and viruses are?
IgG
IgA
IgM - less effective than other 2
Naive B cells circulate in blood and enter secondary lymphoid tissue via?
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
What happens when a naive B cell encounters an antigen it can bind to?
B cell is activated, undergoes clonal expansion and differentiates into a plasma cell which will secrete antibodies
What are the differences between a B cell being activated by a pathogen only and pathogen+T cell?
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
What is isotype switching regulated by?
Cytokines secreted by T cell
How can a B cell already activated by a pathogen undergo isotype switching if this changes the antibody?
- 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
What are properties of a memory B cell?
- 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
What is the difference between short-lived plasma cells and long lived plasma cells?
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
How does a vaccine create an adaptive immune response?
- 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
What is the influenza vaccine made of?
Mostly hemagglutinin (H) antigens - Sometimes Neuraminidase (N) antigens are included
What are the differences between primary and secondary response?
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)
If an individual without T cells undergoes a secondary response, what will happen?
- No memory B cells will be produced
- Only IgM will be secreted
- Antibody concentration will not strengthen with subsequent exposures (primary response every time)
What is wrong if an infant (10 months) with a series of bacterial chest infections has high levels of IgM, no IgG or IgA?
- 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
What is agammaglobulinemia?
- No IgM, IgG or IgA = lack B cells and antibodies
- Can be treated with IV gamma globulin
