1. Ms. S. Scott Human Health and Physiology J205
Topic 11.1 – Defense Infectious Against Disease
Ms. S. Scott
Human Health and Physiology
J205
Higher Level

2. Assessment Statements
 Describe the process of blood clotting
 Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity
 Define active and passive immunity
 Explain antibody production
 Describe the production of monoclonal antibodies and their use in diagnosis and treatment
 Explain the principle of vaccination
 Discuss the benefits and dangers of vaccination
11.1

3. Clotting is triggered very rapidly following tissue injury and limit spread of invading pathogens into the blood stream.
Clotting System:
      Platelets : Circulate with the erythrocytes and the leukocytes in the plasma
Process: Release of clotting factors from damaged tissue cells or from platelets
Semi-solid liquid formed to prevent entry of pathogens
The body has an internal mechanism to slow bleeding and begin healing.
Bleeding stops because blood has the ability to form a clot.    .
Blood clotting is made possible by plasma proteins and platelets.
11.1.1

4. Overall Reaction of Blood Clotting
Clotting Factors
Activator
In the last reaction Fibrogen, a soluble plasma protein is altered by the removal of sections of peptide that have many negative charges.
Polypeptide bind to others, forming long protein fibers called fibrin.
Fibrin forms a mesh across wounds
Through clotting system, thrombin formed from prothrombin.  Thrombin acts on soluble fibrinogen in tissue fluid plasma to produce insoluble strands of fibrin and fibrnopeptides.  The insoluble fibrin strands crisscross one another forming a clot which serves as a barrier to the spread of infection.  This mechanism is referred as “walling off” reaction.  The fibrnopeptides act inflammatory mediators inducing increased vascular permeability and neutrophil chemotaxis.
Fibrinolytic System:
            Fibrinolytic system removes clot. The end product of this pathway is the enzyme plasmin, which is formed from plasminogen.  Plasmin breaks down fibrin clots into degradation products that are chemotactic for neutrophils.  Plasmin also contributes to the inflammatory response activating the classical complement pathway. 
Fibrin + RBC = Clot
11.1.1

5. Process 1: Blood Clotting
When we cut ourselves, we cut small blood vessels.
When this happens, our body forms a clot.
A clot stops us from losing blood and from a foreign pathogen from entering into our body.
Blood clotting is made possible by a number of plasma proteins and cell fragments called platelets.
11.1.1

6. Process 1: Blood Clotting
A wound triggers a cascade of events by which a blood clot is formed.
First platelets collect at the site of the wound.
Platelets are small disc shaped cell fragments
Platelets do not contain a nucleus
Blood clotting is made possible by a number of plasma proteins and cell fragments called platelets.
11.1.1

7. Process 2: Blood Clotting
Blood clotting is made possible by a number of plasma proteins and cell fragments called platelets.
Platelets build up at wound and seal off small breaks in blood vessels
11.1.1

8. Process 3: Blood Clotting
Blood clotting is made possible by a number of plasma proteins and cell fragments called platelets.
11.1.1

9. Process 4: Blood Clotting
Fibrin proteins form a mesh of fibres which traps red blood cells. These dry and become a scab which closes the wound.
Blood clotting is made possible by a number of plasma proteins and cell fragments called platelets.
11.1.1

10. Fibrin + RBC = Clot
Blood cells are caught in the mesh and soon form a semi-solid clot.
Exposed to air, semi-clot forms a protective scab, remains until wound has healed
11.1.1

11. 11.1.2 Challenge and Response
When the body is challenged by a foreign pathogen it will respond with both a non-specific and specific immune reaction
The body is capable of recognizing invaders as they do not possess the molecular markers that designated all body cells as 'self' (MHC class I)
Non-specific immune cells (macrophages) present the foreign antigens to lymphocytes as examples of 'non-self' (on MHC class II)
These lymphocytes can then respond with the production of antibodies to destroy the foreign invaders
11.1.2

12. Lymphocytes Recognize Self
Cells are identified by specific molecules lodged in the outer surface of the cell (plasma) membrane.
These molecules are called glycoproteins ( a molecule that contains a carbohydrate and a protein)
Glycoproteins that identify cells are known as the Major Histocompatability Complex (MHC)
There are genes on our 6th chromosome that code for our MHC. Thus, our MHC is genetically determined.
Each of us as a unique MHC on our cells membrane.
11.1.2

13. Clonal Selection
The majority of B cell clones will differentiate into antibody-producing plasma cells, a minority will become memory B cells (BM cells)
Because the adaptive immune response is dependent on clonal expansion to create sufficiently large amounts of antibodies, there is a delay between initial exposure and the production of antibodies.
When a B cell does divide and differentiate into antibody-secreting plasma cells, a small proportion of clones will differentiate into memory cells
Each B lymphocyte has a specific antibody on its surface that is capable of recognizing a specific antigen
11.1.2

14. Polyclonal Selection
Because the adaptive immune response is dependent on clonal expansion to create sufficiently large amounts of antibodies, there is a delay between initial exposure and the production of antibodies.
When a B cell does divide and differentiate into antibody-secreting plasma cells, a small proportion of clones will differentiate into memory cells
Because pathogens may contain several antigenic determinants, several B cell clones may become activated (polyclonal activation)
11.1.2

15. Infection and Immune Response
Memory cells remain in the body for years (or even a lifetime)
If a second infection with the same antigen occurs, the memory cells react faster and more vigorously than the initial immune response, such that the symptoms of the infection do not normally appear
Because the individual no longer presents with the symptoms of infection upon exposure, the individual is thus said to be immune
11.1.2

16. Types of Immunity
Passive immunity is due to the acquisition of antibodies from the mother via the placenta and milk. Also antibodies can be received by injections.
11.1.3

17. Types of Immunity
Active immunity is due to the production of antibodies by the organism, after the body’s defense have been exposed to antigens.
11.1.3

18. Types of Immunity
Active Immunity – -- develops when a person is exposed to microorganisms or foreign substances and the person’s immune system responds.
Passive Immunity –
- is acquired when antibodies are transferred from one person to another.
- The recipients do not make the antibodies themselves
11.1.3

19. Types of Immunity
11.1.3

20. Definitions of Immunity
Types of Immunity
Definitions of Immunity
Active
Production of antibodies by organism itself after the body defense mechanism have been stimulated by an antigen
Passive
Acquisition of antibodies from another organism in which active immunity has been stimulated
Artificial
The antibodies are produced elsewhere and injected
Natural
Your body produces its own antibodies
11.1.3

21. Review Active & Passive Immunity
Is this active or passive immunity?
Antigen enters body….the body produces antibodies to neutralize antigen.
NATURALLY ACQUIRED --- ACTIVE IMMUNITY

22. Review Active & Passive Immunity
Is this active or passive immunity?
Antibodies passes from mother to fetus during pregnancy
NATURALLY ACQUIRED --- PASSIVE IMMUNITY

23. Review Active & Passive Immunity
Is this active or passive immunity?
Weakened or dead fragments of a microbe are injected into the body….the body produces antibodies to neutralize microbe
Artificially ACQUIRED --- Active IMMUNITY

24. Review Active & Passive Immunity
Is this active or passive immunity?
Antibodies in a serum (i.e. antivenom used to treat snake bites) are introduced to the body……
Artificially ACQUIRED --- PASSIVE IMMUNITY

25. Antibody Production: The Primary Response
Step 1: Antigen Presentation
Macrophages take in antigen by endocytosis
Antigen
Macrophage
The macrophage processes the antigen and attaches it to a membrane protein called a MHC protein
The MHC protein is moved to the cell surface membrane by exocytosis so that the antigen is displayed on its surface.
MHC protein
11.1.4

26. Antibody Production: The Primary Response
Step 2: Activation of Helper T-cell
Helper T-cells have receptors on their cell surface membranes which can bind to antigens presented by macrophages.
receptor
Helper T-cell
Helper T-cell binds to macrophage presenting the antigen
Macrophage sends a signal to activate the helper T-cell
11.1.4

27. Antibody Production: The Primary Response
Step 3: Activation of B-lymphocytes
B-cells have antibodies in their cell surface membranes
Inactive B-cell
Antibody
Antigens bind to the antibodies in the surface membranes of B-cells
Antigen
11.1.4

28. Antibody Production: The Primary Response
An activated helper T-cell with receptors for the same antigen binds to the B-cell
SIGNAL
The helper T-cell sends a signal to the B-cell, activating the B-cell.
11.1.4

29. Antibody Production: The Primary Response
The activated B-cell starts to divide by mitosis to form a clone of plasma cells.
Plasma cells are activated B-cells with a very extensive network of rough endoplasmic reticulum.
Plasma cells synthesis large amounts of antibody, which they excrete by exocytosis.
11.1.4

30. Antibody Production: Summary
Antigen
Macrophage
Antigen
Activate
B-cell
Helper
T-cell
Activate
Clone
Antibody Production:
Summary
Memory
Cell
Antibodies
Plasma Cell
11.1.4

31. Monoclonal Antibody Production
Antibody produced by a single clone (type) of B lymphocytes
It consists of a population of identical antibody molecules.
A monoclonal antibody has many uses in medicine because:
They are stable molecules
They can be used over a long period of time
11.1.5

32. Monoclonal Antibody Production
Antigens that correspond to desired antibody are injected into an animal (usually a mouse)
B-cells are produce by the above animal and the antibodies produced by B-cells are removed.
They are made from genetic engineering using mouse cells.
11.1.5

33. Monoclonal Antibody Production
Tumour cells are obtained. These cells grow and divide endlessy.
B-Cells from above animals are fused with tumour cells, producing a cell called a hybridoma.
These hybridoma divide endlessly and produce a lot of the desire antibodies.
The hybridoma cells are culture & the antibodies they produce are purified and extracted
11.1.5

34. Monoclonal Antibody Production
Monoclonal antibodies are prepared by fusing immortal myeloma cells with the spleen cells, B cells, derived from a mouse that has been immunized with the intended antigen to produce monoclonal antibody-producing cells, hybridomas. Hybridomas have the characteristics of the two different types of cells, and are able to both produce antibodies and reproduce infinitely.
11.1.5

35. 11.1.5

36. Uses of Monoclonal Antibodies
Determine/ diagnose pregnancy
Pregnant women produce a urine with high concentration of human chorionic gonadotrophin (HCG)
Monoclonial antibodies that bond with HCG have been engineered to also carry color granules.
Thus a change in color in a pregnancy test confirms pregnancy.
11.1.5

37. Uses of Monoclonal Antibodies
Treatment of Disease
Cancer cells carry specific tumour-associated antigens (TAA) on the cell (plasma) membrane
Monoclonial antibodies to TAA have been produced….
These antibodies as carry drugs to kill the cancer cell
11.1.5

38. Principles of Vaccination
A weakened pathogen is injected into the body to generate an immune response and produce memory B cells.
Vaccines don’t prevent infections, but on subsequent exposure to the pathogen the secondary immune response is faster.
11.1.6

39. Vaccination and the Immune System
V= Vaccination I=Infection
Sometimes two or more vaccinations are needed to stimulate the production of enough antibodies to fight off a disease.
There are many diseases in which the primary infection stage can do considerable damage to the body. Some of these are serious enough to be fatal.
Vaccination (immunization) uses modified pathogens (Antigen) which have significantly reduced pathogenicity.
The pathogen organism in some vaccines is dead and in others is weakened (attenuated).
These vaccines carry the pathogen antigen (epitope) and therefore stimulate clonal selection and the development of immunological memory but without developing the disease symptoms or signs
11.1.6

40. Vaccination and the Immune System
V= Vaccination I=Infection
The first vaccination causes little antibody production and the production of some memory cells.
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41. Vaccination and the Immune System
V= Vaccination I=Infection
The second vaccination, called a booster shot causes a response from the memory cells & therefore a faster & greater production of antibodies.
11.1.6

42. Benefits and Dangers of Vaccination
Elimination of disease
Neurotoxic side effects due to mercury-based preservatives
Decreased spread of epidemics
Overload of immune system
Cost-effective preventative medicine
Anecdotal evidence of autism associated with MMR
Decrease in symptoms associated with disease
Allergic reactions and autoimmune responses
11.1.7