The immune System

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Immunity

Non-Specific immunity (General)

·         Primary Immunity

·         Protects generally, all pathogens

-       Barriers; skin & mucosal layer

-       Chemical barriers: lysozyme, enzymes in tears, HCL in stomach (low PH).

Specific immunity

·         Target specific pathogens

·         Target Not whole organisms but Antigen

 

Primary immune system

The response is initiated by APC

?          APC (Antigen Presenting Cells): A type of phagocyte that continually work their way through tissues, especially in the skin & mucosa.

When APC encounter foreign cells (those that don’t show the MHC on their surface) identify a cell as “self” [Note: every individual has a unique MHC]

APC engulfs foreign cell to destroy it then presents antigens on the APC’s own surface

?          Antigen: specific surface proteins on outer surface

 

When APC encounters T-lymphocyte (T-helper cells; T regulatory cells) it passes on info about the new antigen to those cells sensitizing them to that specific antigen.

 

T-helper cells then proliferate to form a plasma clone which circulates in the blood.

 

Sensitized T-helper cells then go on to encounter 2 other immune cell type:

§  T-killer cells

§  B-lymphocytes

then sensitized to the antigen & both types go on to proliferate & form plasma clones as well.

 

·         T-killer cells (cell-mediated)

directly contacting pathogen cells with that antigen & destroying them.

 

·         B-lymphocytes (humoral)

-         Produce specialized proteins (gamma globulins) called antibodies that are built to match the antigen.

-         They are released into blood & circulate but when they encounter pathogen with that specific antigen will destroy it by mechanisms including

®      pathogen membrane lysis

®      agglutination,

®      precipitation,

®      opsonization

-          (increasing susceptibility to phagocytosis etc. & complement activation

 

Primary immune response

Typically takes 7-10 days from first exposure to antigen to production of adequate level of T-lymphocytes & antibodies in blood to effectively control a pathogen.

 

The pathogen start to colonize your body so that often we can get sick  then if we are unsuccessful at controlling the pathogen well enough it can lead to significant tissue damage or even death but if we begin to gain control over the pathogen we eventually recover. 

 

Secondary immune response

Typically take 2-3days

At the same time as we establish plasma clones in the primary response, we also produce & additional set of clonal populations that are initially dormant and move to the lymph system (lymph nodes). These populations are referred to as the memory clones. 

?          Dormant: having normal physical functions suspended or slowed down for a period, in or as if in a deep sleep.

On subsequent exposure (months to years to decades later) to that same pathogen with the same antigens we are able to activate the memory clones to form new plasma clones & we can quite quickly (2-3 days) reach a high enough level in the blood to control the pathogen.

This is referred to as a secondary immune response

 

it is usually adequate to completely control the pathogen so that we do not get sick or develop only very mild symptoms.

This immunological memory can last decades or even the rest of your lifespan.

 

Immune system: Components

Immunoglobulins/antibodies - Produced by B-lymphocytes.

 

(1)   IgE antibodies

®      Allergens antibody. 

®      Bind to basophil (in blood) or mast cells (in tissue).

®      Trigger release of histamines, leukotrienes, other mediators of inflammation.

 

(2)   IgM antibodies

®      ABO antibodies; the earliest to be produced.

®      Involved in blood incompatibility reactions ® very effective at Activating complement proteins.

?          ABO incompatibility reaction: RBC inside your circulatory system break down. Blood clotting occur throughout your body, shutting off blood supply to vital organs or causing a stroke.

?          Complement: a complex protein network of plasma

?          Complement activation: rapid clearance of bacteria by immune cells, and direct bacterial killing via large pore-forming complex.

 

(3)   IgG antibodies

®      Most abundantly produced

®      Primary & secondary immune response; destroy bacterial, viral pathogens

®      Activate complement proteins.

®      Natural passive immunity provided to newborns as they can pass via placenta.

 

(4)   IgA antibodies

®      High levels in mucus membranes (gut lining), tears, saliva.

®      Found in early form of breast milk (colostrum), so they contribute to a newborn’s Natural Passive Immunity.

 

(5)   IgD Antibodies

®      Bound to B-lymphocytes

®      Activate other B-lymphocytes.

 

Complement proteins

-          Produced by the liver & circulate as inactive form in blood.

-          Activated by IgG & IgM antibodies.

-          Enhance the effects of antibodies

-          Lysis: breaks membrane of pathogen

-          Chemotaxis: attract phagocytes to the pathogen for phagocytosis.

-          Stimulate inflammatory reaction.

 

Summary

Primary immune response

Pathogen ® macrophage (APC) ® T helper cell – clone ® T killer cell or B lymphocytes – clone, memory cells ® 7-10 days

 

Secondary immune response

Pathogen ® clonal population (T helper cell) ® clonal population (B&T) + memory cells (all 3 cells) ® 2-3 days

·         T lymphocytes

·         Helper T cell

·         T killer cells: Cell-Mediated Response directly encounter pathogen by detecting its antigenic surface destroys the cell directly.

·         B lymphocytes

·         Humoral response – indirect response.

·         Begins to produce antibodies (gamma globulin proteins) released into blood & antibodies binds to antigenic surface & destroy them.

 

Types of Immunity.

 

1.    Natural Active Immunity.

Natural: No technology

Active: primary immune response to establish

1)       Plasma clones

2)       Immunological memory E.g. when we encounter new diseases or some common diseases like colds

 

2.    Natural Passive Immunity: 

Natural: No technology

Passive:

-    No primary response as we receive antibodies

-    no memory created (temporary protection)

·   Transfer antibodies to individual to provide temporary protection – lasting only as the antibodies last - often a few months to a year. E.g. mom & baby.

-         Baby gets antibodies via placenta & breast milk.

-         Breast milk contains antibodies & proteins that will stimulate immune system to develop rapidly & completely.

 

3.    Artificial Active Immunity (Vaccine)

Artificial – Technology

Active:  Primary response leads to

1)    Plasma clones

2)    Immunological memory

 

Vaccines come in form of

1)    killed pathogen: can cause a disease, but immune system is synthetized.

2)    Live attenuated (weakened) pathogens Sample: weakened pathogen, provides stronger immune response, ↑ number of clones & longer memory last. 

3)    Recombinant DNA vaccines: there is no pathogen present just purified antigen protein from pathogen.

-         Produced by isolating gene for pathogens antigen ® inserting into laboratory culture - yeast. This culture produces antigen which can then be purified for use as a vaccine.

-         This provide adequate effects for establishing immunological memory w/o exposing individual to pathogen so there is no significant risk & as an industrial process it should lead to much pure & less costly vaccines)

·         No vaccine is risk free; someone will show an adverse reaction to vaccine. But the benefits of vaccine are very high, & risk is relatively very low.

 

4.    Artificial Passive Immunity

Artificial: technology

Passive:

-   No primary response as we receive antibodies

-   no memory created (temporary protection)

·   Not usually common – except in extreme cases where pathogen presents with extreme risk, & something must be done right away.

·         Antibodies are injected to get rid of antigens –

-         Rabies

virus that can infect any mammal & in all human infection

it is fatal & painful

if you are infected, ASAP given vaccine containing antibodies to viral antigens (antibodies are obtained from other animals). –The hope is the antibodies will immediately destroy virus before it can establish. 

-         Clostridium tetani bacteria Common in the environment.

We vaccinate against tetanus

But if significant wound contaminated with soil then get tetanus booster but also you may be given antibodies not to the bacterium but rather to the toxins produced by the bacterium – i.e. antitoxins  - before they get to interfere with your neural control over such basic functions as breathing.

Antitoxins to counteract snake & spider venoms or Clostridium botulinum toxins.

 

Anti-inflammatory drug:

·         Antihistamines: histamines are chemical mediator that cause allergy reactions

-          Do not block/alter release of histamine

-          Binds to receptors sites for histamine on target cells. Aka blocks histamine receptors.

-          Histamine is still released, but organs that typically do not response b/c receptor is blocked.

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