Madiha Zia Immunology.docx

Madiha zia Bs-3 (Biotechnology) Topic: -complement system and vaccine Subject: - immunology Teacher: - ma’am uzma

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Content: 1) Complement system i. Definitions ii. Functions of complement protein iii. Classical pathway iv. Alternative pathway 2) Vaccine i. Introduction ii. Main principle iii. Vaccine concept iv. Synthesis of vaccine v. How do vaccine work vi. Immune system response to vaccination vii. Types of vaccination viii. Properties of a good vaccination ix. Benefits of a good vaccination x. Conclusion

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COMPLEMENT SYSTEM: 1) DEFINITIONS: COMPLEMENT SYSTEM: The complement system consists of series of mechanism that ultimately protect our healthy cells from antigen and pathogenic infection. OR Complement system helps our body to protect us from pathogens and different types of toxic substance which infect us and cause damage to our body.

2) FUNCTION OF COMPLEMENT PROTEIN: 2.1) C1: C1 is a protein complex consist of: a) 6 molecules of c1q b) 2 molecules of c1r

b) 2 molecules of c1s

The constant region of certain (IgM and IgG) can bind onto the c1q molecule of c1 complex. This in turn activates c1r and c1s molecules. The c1s is a serine protease and can attract c4 complex.

2.2) C3: This is the most abundant protein of the complement system. The c4b-c2b complex act as a serine protease and cleave c3 into two subunits, there by activating it. C3 will break into c3a and c3b. C3b can bind allosterically another complement protein called c3 and prepare it for cleavage by c4b-c2b complex.

2.2.1) C3a: It binds mast cells or basophil and stimulate immune cells to release chemicals such as histamine. Histamine dilates the blood vessel and it also make capillaries much more permeable to flow it. This mean blood flow will increase in infected areas much more quickly. C3a basically increase the rate at which we can protect our body from these pathogenic infections.

2.2.2) C3b: It has 2 different function: 

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It acts as a molecule known as opsonin which carry out opsonisation. It stimulates phagocytic cell of our immune system. It binds to glycoprotein

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membrane of pathogen cells. Once it binds it carry out opsonisation and call phagocytic or macrophage which engulf the cell. It’s another function is to bind with c5b. After binding to c5b it creates conformational changes and prepare it for cleavage by c4b-c2b-complex.

2.3) C5: The c5 complement protein guides the formation of membrane attack complex(MAC).  C5 is cleaved by c4b-c2b into c5a and c5b.  C5a act as an anaphylatoxin and act as chemotaxis which mean attract immune cells such as neutrophils.  C5b serves as the formation for the membrane attack complex c5b binds to c6-7-8 complex  The c5b-6-7-8 complex stimulate many c9 molecule to bind to the membrane of pathogenic cells. This form a channel that fill the cell with fluid and lyase it.

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CLASSICAL PATHWAY: -

This pathway is initiated by antigen-antibody complexes and require heat sensitive complement components. There are 30 inactivated proteins floating around the blood that can be activated because of antigen-antibody complex formation. These proteins then create of cascade of events that ultimately destroy antigen or pathogenic agents. Complement system consist of complement protein from c1 to c9.

Explanation of classical method: -

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C1 becomes activated when it binds to the ends of antibodies.

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Once C1 is activated, it activates 2 other complement proteins, C2 and C4 by cutting them in half

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C2 is cleaved into C2a and C2b

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C4 is cleaved into C4a and C4b

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Both C2b and C4b bind together on the surface of the bacteria

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C2a and C4a diffuse away

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C2b and C4b bind together on the surface to form a C3 activation complex

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The function of the C3 activation complex is to activate C3 proteins.

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This is done by cleaving C3 into C3a and C3b

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When C3b binds to C2b and C4b it forms a new complex referred to as the C5 activation complex

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The C5 activation complex (C2b, C4b, C3b) activates C5 proteins by cleaving them into C5a and C5b

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Many C5b proteins are produced by the C5activation complex. These C5b begin to coat the surface of the bacteria.

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C5b on the surface of bacteria binds to C6

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The binding of C6 to C5b activates C6 so that it can bind to C7

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C7 binds to C8 which in turn binds to many C9’s

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Together these proteins form a circular complex called the Membrane attack complex (MAC)

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ALTERNATIVE PATHWAY: -

This pathway is triggered even in the absence of antigen-antibody complex. In this c3 spontaneously convert into c3b. When around healthy cell it can convert onto healthy cell membrane and can be inactivated.

Explanation of alternative method:     

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In this case c3b will attach another factor that is B still they are inactive form. Now they will attach to factor D which will make them activate. This process need water to hydrolyse c3b C3b can recruit c5. C5 start the process of MAC

vaccine: introduction: It was introduced by Edward in 1798. He used cowpox virus to immune people against smallpox. In this we used killed or attenuated pathogens, toxin. They are inoculated inside our body. They stimulate our immune system. The response which is produced is known as primary immune response. Memory cells are produced against them. These memory cells are long lasting. When naturally they attack us memory cells shows immediate response and kill them.

Main principle: The main principle of vaccination is production of memory cells inside the body.

vaccine concept: Expose a human to a foreign protein associated with a disease-causing microbe (dead microbes, live but weekend microbes, altered toxin). The immune system responds and eventually makes antibodies and memory cells for that specific protein and disease.

synthesis of vaccine:   

We modify pathogens in a way that its virulence decreases such type of pathogens are known as attenuated pathogens. We can even kill pathogens through heat, uv radiation or gamma radiations. Some pathogens release toxin which damage our body cells. We remove such components but their antigenic property is retained.

how do vaccine work: To know about working we should know about immune system how it works when foreign microbes invade us. The immune system triggers a series of responses in attempt to identify and remove them from bodies. The response shown by bodies are: 1)Coughing 2) Sneezing 3) Inflammation 4) Fever We experience which work to trap, determine the body like bacteria. These innate and triggers the second line of defence called adaptive immunity. Special cells called B-

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cells and T-cells are recruited to fight microbes and record information them creating a memory how invaders look like and how best to fight them. This know how become handy if the same antigens invade the body again but despite this risk is involved it takes time to learn how to fight with antigens and build defence against them and even then, if the body is to weak or young to fight back then it might face very serious risk if pathogens is particularly serious. If we prepare body’s immune response ready in it before someone got ill. This is where vaccines come in. Using the same experience body uses to defend itself. Scientist use vaccine to trigger the bodies i.e. adaptive immune system without exposing human to the frosting disease. This in result many vaccines which each work uniquely separated into different types.

Immune system response to vaccination: Proteins from microbes is injected into body

Macrophages circulate through body and ingest some of the foreign protein, helper T-cells by presenting protein coat.

Helper t-cells recognize protein coat and alert T and B cells by producing cytokines

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B-cells make antibodies that neutralize microbes with that protein coat.

Killer T-cells develop to kill microbe or human cells infected with microbes with protein coat

Memory B-cells remain to provide immunity.

Memory T-cells remain to provide immunity.

Types of vaccination: There are 5 types of vaccines: 1) 2) 3) 4) 5)

Live or attenuated (e.g.: - oral polio vaccine) Killed vaccine (e.g.: - typhoid vaccine) Toxoids (e.g.: - tetanus toxoid) Conjugated or Prepared antibodies (e.g.: - anti-tetanus serum) Second generation vaccine (e.g.: - hepatises B vaccine)

LIVE OR ATTENUATED VACCINE: They are made from pathogens itself but a much weaker version. In this a virulent pathogenic organism are treated to become attenuated and avirulent but antigenic. They have lost their capacity to induce fall-blown disease but retain their immunogenicity. They show both type of immune response i.e. humoral and cellular mode. They are less stable. They can revert.

KILLED VACCINE: In this whole organism is taken but dead. It is either treated with heat or uv radiation. It does not develop disease but trigger the immune system. Teaching the immune system to recognize, attack and make profile of it.

SUBUNIT VACCINE: They are made from only one part of pathogens called antigens. The ingredient which triggers the immune response by even further isolating specific components of antigen like protein or polysaccharides. These vaccines can prompt specific response.

CONJUGATED OR PREPARED VACCINE: We take the antigen and attach it with other type of macromolecule (i.e. peptide chain or sugar). The immune response shown by them is humoral mediated. They are partially stable. They cannot revert.

DNA VACCINE: In this we isolate the vary gene that make specific antigens in the body need to trigger it immune response. When they are injected into the human body those genes instructs the cell in the body to make the antigens this causes a stronger immune response and prepares the body for any further reflex and because the vaccine includes specific genetic material it does not contain any other material from rest of pathogens that could develop into the disease and harm the patient. It shows both type of immune response that are humoral and cellular mode. It very stable. It does not revert.

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PROPERTIES OF A GOOD VACCINE: Following properties should be in a good vaccine:     

Ability to elicit the appropriate immune response for a particular pathogen Long term protection Safety Stability Inexpensive

BENEFITS OF VACCINE: Vaccines have following benefits: -

 Save 33 thousand lives.  Prevents 14 million infection.  Save $10 billion in medical cost.

CONCLUSION: If these vaccines become success we might be able to build more effective treatment for pathogens which use to come just like Edward amazing discovery spread on modern medicines all those decades ago continue in the development of vaccine might allow us to treat the disease like HIV, malaria, or Ebola one day.

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