mbio 1220 the adaptive immune response, lecture 13

the adaptive immune response

• a specific defensive response to invasion by a foreign object

• this can be acquired naturally or artificially

• natural adaptive immunity: an organism or toxin enters the body and promotes an immune response (getting dirty)

  • way you exposed determines which you have

• artificial adaptive immunity: results form an immunization wit a vaccine (0 natural)

• both types are specific and have a memory component

natural adaptive immunity:

• an organism or toxin enters the body and promotes an immune response (getting dirty)

• artificial adaptive immunity:

• results form an immunization wit a vaccine (0 natural)

specifc

• the immune response protects against one disease

• does not protect against other diseases

• the only exception is when two diseases are very closely related

  • ex. small pox and cow pox

memory component

• results in a much stronger response upon re0exposure

• long term immunity: possibly for life

the immune system

adaptive immunity involves two general repsonses

1. antibody mediated response

2. cell mediated response

antibody mediated response

• also referred to as the humoral response

• mediated by small molecules called antibodies or immunoglobulin (Ig)

• antibodies specifically bind to an inactive foreign particles (make anti-bodies)

  • foreign particles can be cells, toxins, pollen, etc.

• neutralize them → “bear hug”

cell mediated response

• not mediated by small molecules

• triggers the activation of specific cells called lymphocytes

• these lymphocytes recognize and destroy abnormal or infected host cells

• they attack bigger targets such as tumor

• regulated carefully! otherwise kill yourself

• lose something valuable but saving the institution

antigen

• a foreign particle that enters the body

• the antigen can be broken into smaller parts call epitopes → small part that you target (foreign part)

• the epitope is the particular portion of the antigen that is recognized by the antibody

• bacterium, virus, peanut, etc.

• many ways to learn a bad guy via an antigen

• the ones that are most immunogenetic

antibodies

• proteins produced in response to the antigen

• antibodies bind to the antigen in a very specific manner

  • like lock and key

• monoclonal, polyclonal

• made by us (protein)

• epitope on one bad guy

antibodies (Ab) =

Immunoglobulins (Ig)

antibodies are made of 4 parts

• 2 identical heavy chains and 2 identical light chains which are held together by covalent bonds

• each antibody has 2 identical antigen binding sites (Fab)

  • Fab is specific for one epitope

• each antibody also has a constant fragment (Fc)

  • Fc binds complement proteins, and phagocytes

five classes of antibodies

1. immunoglobulin G (IgG)

2. immunoglobulin M (IgM)

3. immunoglobulin A (IgA)

4. immunoglobulin D (IgD)

5. immunoglobulin E (IgE)

immunoglobulin G (IgG)

• most common

• found in blood: can also enter tissues in regions of inflammation

• can cross the placenta and confer passive immunity to a fetus

  • use these until you can make your own

• IgG binds to antigens very tightly

• monomers → 2 binding sites (good and strongly)

• 2 antigens are identical to each other

• look for against HIV virus

immunoglobulin M (IgM)

• a pentamer:

  • consists of 5 antibody units

• does not move into tissues as freely as IgG

  • it remains in blood

• often found attached to the surface of B cells

• this is the first type of antibody produced upon infection

  • first time, all the time, only lasts so long (then IgG)

• IgM is very good at aggregating antigens

• huge so it doesn’t leave the blood

• FAB stays consistent, only bottom changes

immunoglobulin A (IgA)

• this is found as a dimer (two antibodies stuck together) → bind to 4 antigens that are all identical

• IgA is found in bodily secretions

  • saliva, mucous, tears, and milk

• functions to protect mucosal surfaces

• IgA protects the gastrointestinal tract of newborns

• passed via breast milk → exposed to infants

“this is what goes on in there”

immunoglobulin D (IgD)

• unknown function

• located on the surface of B cells

• poor efficacy but good idea

• it acts as a receptor on itself

• in the plasma membrane

• monomer

• B cell produces antibodies

• B cell will only ever produce one type of FAB

• “advertisement”

immunoglobulin E (IgE)

• found on the surface of certain immune cells

• (tissue) mast cells and basophils (his inside)

• when it binds to antigens the cell released histamine

• this attracts complement and phagocytes to the area

• histamine is responsible for allergy symptoms

• peanut → bind to particle of peanuts → cell de-granulates → his is released and causes vasodilation

• against allergies

• FC IgG receptor for FC (foot) for IgE

what is the functions of an antibody?

1. agglutination

2. neutralization

3. complement activation

4. opsonization

1. agglutination

• antigens become stuck together

• this reduces the number of infectious units to be dealt with

• internalize with phagocyte and gets destroyed

“paper towel super absorbent”

2. neutralization

• the antibody binds to and inactivates toxin bacteria and viruses

• neutralize behaviour

3. complement activation

• the antibody binds to the bacteria: this acts as a starting point for the complement pathway (MAC attack)

• one way to hit the first domino

• set of protein, 30 of them off

4. opsonization

• this flags down phagocytic cells to destroy the antigen

• captures

• exact same way as complement protein

cells of the adaptive immune system

1. lymphocytes

   • b lymphocytes

   • t lymphocytes

2. antigen presenting cells

b lymphocytes

• also referred to as B cells

• antibody producing cells

• involved in the humoral or antibody mediated response

• produced in the bone marrow by stem cells (trained in bone marrow)

• they need to have a trust source

• only do it when we need it

• when an antibody sticks to something, you made, trust it and take it seriously and respond

• don’t turn immune system unless we are sure (otherwise might cause auto-immunity)

t lymphocytes

• also referred to as T cells

• these are produced in the bone marrow but mature in the thymus gland

• help anti-body immunity

• there are two types of T cells

  • Helper T cells (T_H cells)

    • these help B and T_c cells prepare for an immune response

    • they are a part of humoral and cell mediated immunity

    • important for immune system

  • cytotoxic T cells (T_c cells)

    • these cells lyse foreign and abnormal host cells (infected or cancerous)

    • they are a part of the cell mediated immune response → why we can’t take drugs against viral infections

    • receive training → this healthy don’t kill, this not healthy, kill it

antigen presenting cells (APC)

• macrophages, B cells, and dendritic cells

• the stages of an antigen presenting cell:

  • the foreign material such as a bacterial cell is engulfed by the APC

  • the antigen is processed and presented to the T helper cells of the immune system along with self antigens

    • self antigens: these are part of the major histocompatibility complex (MHC)

    • this is a check to prevent the destruction of our own cells by mistake

  • T helper cells become activated against the foreign material

the stages in antibody production

1. the antigen enters the body

   • the antigen will be phagocytized and digested by a B cell

   • small fragments of the antigen will be presented on the surface of the B cell along with MHC

2. a T helper cell will bind to the antigen presenting B cell after recognizing the antigen bound to the MHC protein

3. the T helper cell will then deliver cytokines that stimulate B cell to undergo clonal expansion

   • the B cell multiplies to produce more identical B cells that will then fight off the specific antigen

4. clonal expansion

   • B cells divide and differentiate becoming either

     a. plasma cells:

     • antibody producing cells

     • these cells have a short lifespan and produce many antibodies

     b. memory cells :

     • these cells live for a very long time (20-30 years)

     • these cells circulate in the blood and propagate at very low level

     • when the memory cell encounters an antigen it will quickly change, multiplying and becoming an antibody producing plasma cell

     • booster constantly refreshes memory pool

1. primary response

• this is the response the first time the body encounters the antigen

• the antigen stimulates the production of low levels of antibody

• this is a slow process taking 5-7 days (because you are learning)

• IgM is made first followed by IgG (blood) and IgA (mucous membrane)

• the major income: memory is built for the antigen (very very high level of antibodies)

• through a vaccine or due to exposure

2. secondary response

• this is the response that occurs during every subsequent encounter with the antigen

• high levels of antibody are produced

• this is a quick response taking only 1-2 days

• as a result of this response the infection is quickly overcome

• memory cells are replenished

cell mediated immune response

• this is response is activated by invading cells or abnormal host cells

• involves antigen presenting cells (APCs), T helper cells and cytotoxic T cells

• cytotoxic T cells are responsible for destroying abnormal cells in the body

the stages of the cell mediated immune response include

1. Recognition of abnormal host cells:

   • cells infected with virus or bacteria

     • ex. cells infected with Mycobacterium tuberculosis

   • cancer cells

   • foreign cells

     • ex. blood transfusions or bone marrow transplant

2. endogenous antigen is processed and displayed on cell surface:

   • presented on the surface of the antigen presenting cell together with the MHC I self antigen

   • different type of MCH then used during the Ab mediated responses

3. perforins:

   • these are released from the cytotoxic T cell

   • they poke holes in the membrane of the abnormal cell

active immunization

1. active immunization

   • the body goes through the complete process to generate specific antibody or cytotoxic T cells

   • it can be natural or artificial

   • a. natural

     • when the antigen is encounter from the environment (primary response)

     • exposed naturally in your life

     • active

   • b. artificial

     • when the antigen is injected as a vaccine

     • take vaccine full of virus and poke it in you

     • we force exposure to get an outcome

     • active

   “active: eating pizza”

2. passive immunization

• given ready made antibody: does not result in lasting immunity

• can be neither natural or artificial

• get just the product

  a. natural

  • ex. from mother to infant

    • IgG is transferred from mother to fetus via placenta

    • IgA is transferred from mother to child via milk

  b. artificial

  • pre-made antibody is injected

  • very fast acting for life-threatening situations

  • ex. snake venom

    • no anti-toxin antibody can be given (no memory)

  • ex. anti-rabbis shot → passive

    • then give vaccine → active has memory