محاضرة 4- مناعة نظري

antigen

1. DEFINITION.

2. CHEMICAL NATURE OF ANTIGEN

3. TYPES OF ANTIGEN.

4. HAPTENS.

5. SUPER ANTIGEN.

6. DETERMINANTS OF ANTIGENICITY.

7. ADJUVANTS.

 توبة حلقية - 8. EPITOPES.

9. USES.

10. ANTIGEN DETECTION METHOD

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ANTIGENS

Definition:- Any substance when introduced into the body stimulate the production of antibody and react with the specific antibody and antigen receptors present on lymphocytes are called antigen.

Immunogens: - Are the molecules which induce an immune response.

المستمنع ( مثير المناعة ) : جزيئة تحفز الاستجابة المناعية مثل ( اللقاحات ومولدات الضد باشكالها )

All antigens are immunogens, but all immunogens are not antigen.

  1.  كل مولد ضد =  مستمنع
  2.  ليس كل مستنمنع = مولد الضد
  • كل داعشي ( مولد ضد ) = سني (مستمنع )
  • ليس كل سني (مستمنع ) = داعشي ( مولد ضد )

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CHEMICAL NATURE OF ANTIGEN

  • Most naturally occurring antigens are proteins, polysaccharides followed by lipids and nucleic acids.
  • All proteins are not antigenic in nature.
المكونات الكيميائية لمولدات الضد هي
  1. proteins - لكن هذا ليس معنه ان كل البروتينات في الطبيعة هي مولدات ضد
  2. polysaccharides - عديد السكاريد ( هو أحد أنواع السكريات المعقدة )
  3. lipids
  4. nucleic acids 
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TYPES OF ANTIGEN

1. Based on the ability to carry immunogenicity and immunological reaction:
a) Complete antigen.
b) Hapten.

 2. Based on origin:
I. a) Microbial antigen. 
b)Tissue antigen.

عامل خارجي ( خارج الخلية - بكتريا ممرضة ) - II. a) Exogenous
عامل داخلي ( الجهاز المناعي الذاتي - مهاجمة نسيج من الجسم) - b) Endogenous

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3. Based on immune response:

a) T-cell dependent antigen.
b) T-cell independent antigen(TI)

Other antigens:

Super antigens.
Histocompatibility antigens or transplantation antigens.👉
Tumor antigens👉.
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a) Complex antigen or complete antigen:

A complete antigen is able to induce antibody formation and produce a specific and observable reaction with the antibody produced.

It has mainly 2 properties:

a) Immunogenicity
ويُفهم من استجابة المناعة: رد مناعة الجسم على دخيل يهدده - b) Immunological reaction




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HAPTENS

These are low molecular weight substance that is not immunogenic by itself, but can react with antibody produced by it.


ملاحظة : لا يمكن اعتبار الـ haptens كــ immunogenic لانه
1- وزنه الجزيئي صغير جدا
2- يفشل في تنشيط الخلايا التائية المساعدة
3- احادي التكافئ وبالتالي لا ينشط الخلايا البائية
4- يمكن اعتبار الشيء كـ immunogenic فقط عندما تنشط الخلايا T المساعدة + خلايا B

Haptens are not immunogenic because,
✓ Failure of hapten to activate helper T cells.
✓ Haptens are univalent, hence cannot activate B-cells.
✓ low molecular weight

احادي التكافئ - univalent : هو أيون يتكون من ذرة أو أكثر من عنصر واحد ولهذا السبب له وزن جزيئي منخفض ( هو بحجم الذرة شتريد يكون وزنه )
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How hapten can become immunogen?

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Types of haptens

1. Complex hapten - One that can participate in precipitation reaction and are usually polyvalent in nature.

2. Simple hapten - Hapten which do not participate in precipitation reaction is called as simple hapten.

ما الفرق بين الهبتاين المعقد والبسيط
1- المعقد : يشارك في تفاعل الترسيب + متعدد التكافئ ( مكون من ذرات عدة )
2- البسيط : لا ياشرك في تفاعل الترسيب + مكون من ذرة او اكثر

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ADJUVANTS

Adjuvants are the substance that when mixed with an antigen and injected with it, boost the immunogenicity of the antigen. Adjuvants increase both strength and duration of immune response.








 على سبيل المثال- E.g
👈 Aluminium potassium sulphate(alum)
 👈 Freund's water-in-oil

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Functions of adjuvant

i. Boost immune response when antigen has low immunogenecity and when small amount of antigen is available

ii. enhance co-stimulatoty signals

iii. Prolong retention of immunogen

iv. Increase the effective size of the immunogen

v. Increase local inflammation by stimulating local influx of macrophages or immune cells to injected sites

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2) Based on origin:

I. Microbial antigen:
These are structural antigens.
e.g., Flagellar H-antigen, Fimbrilar antigen.

Tissue antigen:
e.g, Blood group antigen, Transplantation antigen.



عامل خارجي ( خارج الخلية - بكتريا ممرضة ) - II Exogenous antigen:
Antigen which are present outside the cell.

 عامل داخلي ( داخل الخلية - الجهاز المناعي الذاتي ) - Endogenous antigen:
Antigen of self immune system.

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3. Based on immune response.

a) T cell dependent antigen (TD).

b) T cell independent antigen (TI).
TI type I →
TI type II →

1- TD : يعتمد على خلايا مساعدة
2- - TI : لا يعتمد على خلايا مساعدة - مباشرة ( لا اعتمد الشاي في الصباح )
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a) T-cell dependent antigen(TD):

Antigen that require help of T cell to activate B cell for antibody production is called T dependent antigen.

e.g. Erythrocytes, serum proteins.
✓ Induce immunoglobulin isotypes - IgM, IgG, IgA, and IgE.
✓ Show immunological memory.
✓ Require preliminary processing.
✓ Rapidly metabolized in the body.



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b) T cell independent antigen (TI):

Antigen directly stimulates antibody production without the
help of T-cell are called TI antigen.
e.g. ▲ Pneumococcal capsular polysaccharides.
Flagellar protein - flagellin ▲       .
There are 2 subtypes:

i) TI type I:
👈 These are antigens of microbial origin.
👈 Can activate both mature and immature B cell.
eg. Lipopolysaccharides.
  • الشاي اصله هنا ميكروبي 
  • حيث ينشط الخلايا البائية الناضجة وغير الناضجة ( الشباب يشربوه والشياب )
  • مثل دهن + سكر متعدد = Lipopolysaccharides

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ii) TI type II: These are polysaccharides that can activate only mature B cell.

Consisting of limited number of epitopes.💧
Antibody response is usually limited to IgM and IgG,.💧
Do not show immunological memory.💧
These are metabolized slowly and remain in the body for long💧 periods.

الشاي الثاني 
  • يشنط الناضجين فقط ( كبار العمر 
  • وهو متعدد السكاريد ( سكر بدون دهن - لان مو زين الدهن على الناضجين )
  • الشاي الثاني ( الناضج ) عددحلقاتهم محدودة بهذا الزمن
  • الاجسام المضادة بالشاي الثاني محدودة ومجة ( IgM and IgG - لان بدون دهن ههه
  • المثيل الغذائي لكبار السن الناضجين بطيء ويبقى في الجسم اطول فترة - يحتسي الشاي ليبدو ناضج
  • لا يتعرف على الذاكرة المناعية لانه نضج وخرف

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Superantigens are the antigens which polyclonally activate a large fraction or number of the T cells (up to 25%).

سبور مان انتيجين : ينشط اجزاء كبيرة من من الخلايا التائية ( اكثر من 25%)

E.g. a) Staphylococcal enterotoxins (food poisoning).
b) Streptococcal pyogenic exotoxins.
c) Mouse mammary tumor virus.

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Histocompatibility antigen or Transplantation antigen:

Antigen that participate in graft rejection are called transplantation or histocompatibility antigen.
e.g. Blood group antigen are important in transplantation.

Tumor Antigens:
Tumor antigens are antigen that are present in malignant cells but are absent in corresponding normal cells of the host.

تامر حسني يوجد بالرب من الخلايا الملائكية , ويغيب في الغلايا السليمة

e.g. 1. Alpha fetoprotein in hepatomas.
2.Carcinoembryonic antigen found in colonic cancer

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Determinants of antigenicity or immunogenecity:

a. Size.
b. Chemical structures.
c. Foreignness.
d. Susceptibility to tissue enzyme.
e. Antigenic specificity.
f. Species specificity.
g. Isospecifity.
h. Autospecificity.
 خوصية غيرية ( غير متجانسة ) - i. Heterophile specificity

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a) Size:
A substance or molecule should have optimum size to induce immunogen (10,000 D). Smaller molecules may either be weakly or non immunogens.

E.g. 💧Heamocyanin - large molecule and highly immunogen.
Haptens low molecular weight molecule and are non💧 immunogenic.

Heamocyanin هو ابروتين وظيفته هي نقل الأوكسجين عبر الدم
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b)Chemical structure:

Proteins are highly immunogenic followed by polysaccharide, lipids and nucleic acid.

Note: Gelatin is not immunogenic because of increased tyrosin content.
جلاتين المخدة غير مناعي لان ملء بالتايروزين

c) Foreignness:
Antigens which are foreign to the individual (non self) induce an immune response. Self antigen are usually not immunogenic because they do not come in contact with immune system during com the developmental stage. Breakdown of this mechanism will result in autoimmune disease.
Self antigen E.g. Eye lens antigen.

امراض المناعة الذاتية : هي مجموعة أمراض تحدث نتيجة فشل الجهاز المناعي لجسم الكائن الحي بالتعرف على الأعضاء والأجزاء الداخلية الخاصة به، حيث لا يستطيع معرفة البصمة الوراثية الخاصة بخلايا الجسم فيتعامل معها كأنها غريبة عنه ويبدأ بمهاجمتها باستخدام خلايا المناعة والأجسام المناعية.
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d) Susceptibility to tissue enzymes:
Substances which can be metabolised and are susceptible to the action of tissue enzymes behave as a good antigen.

Substance that are not susceptible to tissue enzyme are not immunogenic.

  • المواد التي تتحسس من انزيمات الانسجة - تحفز المناعة
  • المواد التي لا تتحسس من انزيمات الانسجة - لا تحفز المناعة

e.g. Polystyrene latex.
Substance that cannot be metabolised in the body

e) Anitigenic specificity:
Depends on position of antigenic determinant group in the antigen molecule.

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f) Species specificity:
These antigens are present in all members or individual of a species.
Species specific antigen has got phylogenetic relationship used to trace evolutionary relationship and in forensic application for the identification of species of blood and seminal fluid.

الطب الشرعي forensic :هو تخصص طبي فرعي يركز على تحديد سبب الوفاة من خلال فحص الجثة

نوعية الخصوصية
خصوصية الفلوجة ( تطور الارهاب ونشوئه ) 
خصوصية الطب الشرعية النوعية
تحديد السائل المنوي
خصوصية انواع الدم
g) Isospecificity:
It depends on isoantigen present on some but not all the members of species. They are genetically determined.
e.g. Blood group antigen, transplantation antigen, HLA antigen.

هلا بحيدر
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h) Autospecificity:
Self antigen are usually non antigenic but there are exception - Lens protein and sperm. These are not recognized as self antigen because they do not come in contact with immune system, therefore it is not recognised. when these are released into tissue following injury antibodies are produced against them resulting in autoimmune disease.

i) Heterophile specificity:
Same or closely related antigen present in different tissues of more than one species are known as heterophile antigen.

Eg 1.Forssman antigen- absent in rabbit.
2. Antigen used in Wel- Felix reaction.
3. Antigen used in Paul-Bunnel reaction.

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J) Organ specificity:
Organ specific antigens are confined to a particular organ. Some organs like Brain, kidney and lens protein of one species share specificity with that of another species.

E.g. Brain specific antigen are shared by man and sheep.

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EPITOPES (ANTIGENIC DETERMINANT)
Immunologically active region of an immunogen that binds to antigen-specific membrane receptors on lymphocytes or secreted antibodies.

Structure:
Size: Very small, consisting of four or five aminoacid or monosaccharides residues.

Conformation:
💧 Linear
💧 Non linear.

💧 Site Internal(with in antigen) 
💧 external(on the antigen)

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Uses:
💧 Laboratory diagnosis of infectious disease by antigen detection.

💧 Diagnosis of non infectious diseases. e.g. Autoimmune disease.
💧 In epidemiology of infectious diseases.
💧 Detection of enzyme or hormone (hCG)
💧 Used in vaccine preparation.

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Antigen detection methods:

1.Enzyme Immuno Assay for detecting antigen in
a) Bacterial antigens:
✓ Capsular antigen of Streptococcus pneumoniae.
✓Haemophilus influenzae type b.

b) In virology:
✓ Rota virus in stoel filtrates.
Respiratory syncytial virus in case of lower respiratory tract
specimen.

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c) In Parasitology:
✓E. histolytica dispar
✓Giardia lamblia
✓ Cryptosporidium parvum.

d) In Mycology:
✓Histoplasma and Cryptococcus antigen test.

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2. Immunofluorescence technique.
3.Agglutination test.
4. Immunodiffusion test.
5.Complement fixation test

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REFERENCES :

1. Review of Medical Microbiology and Immunology by Warren Levinson, 10th edition.

2. Text Book of Microbiology by Ananthanarayan and Paniker, 7th edition.

3. Immunology, International edition by Ivan Roitt, David B Roth, Jonathan Brastaff, David Male, 7th edition.

4. Immunology by Kuby, 6th edition.

5. Encylopedia of immunology.

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