antigen antigen antigen antigenantigen.pptx

antigen antigen antigen antigen

1. ANTIGEN Dr. P riyanka pandey JR1

2. ANTIGEN Antigen is defined as- - Any substance -Capable of provoking lymphoid system -To respond with an immune reaction -Specifically against stimulating substance -not at other related substances

3. DEFINITIONS Epitope or antigenic determinant -smallest unit of antigen -responsible for antigenicity -also known as antigenic determinant -capable of sensitising an immunocyte and reacting with its complementary site on the specific antibody or TCR(T Cell receptors)

4. DEFINITION Epitome may be sequential or conformational Sequential or linear epitome -single linear segment of primary sequence - recognised by T cells -Conformational epitope -formed during peptide chain folding -formed from distant residues - recognised by B cells

5. Epitopes

6. Paratope Area on the antibody corresponding to an epitope Epitopes and paratopes determine specificity Bacteria and viruses carry different epitope, presenting an antigenic mosaic Similar epitopes on different antigens leads to antigenic cross reaction

7. Antigenic cross reaction Cross reaction of antibodies with common or closely related antigens may be clinically important in some disease status Certain Streptococcal M protein antigens G roup A Streptococcal carbohydrate antigen N –acetyl-BETA-D-glucosamine C ross react with cardiac myosin and several other proteins ( tropomyosin , vimentin ) found in heart muscle and heart valve tissue

8. In this model ,antibodies developed during acute Streptococcal pharyngitis subsequently bind to these cross –reactive epitopes in heart tissues, A ctivating the complement cascade and resulting in immunologically mediated damage to cardiac muscle and adjacent tissues and development of acute rheumatic fever (ARF)

9. A similar mechanism is operated in pathogenesis of post streptococcal glomerulonephritis Antibodies elicited against various non-m protein antigens of “ nephritogenic ” group A streptococci ( e.g , cytoplasmic endostreptosin , extracellular “nephritis strain-associated protein [NSAP], Streptococcal pyrogenic exotoxin B[ speB ]) may react with renal tissues to produce glomerular injury

10. Various structural components of Streptococcal pyogenes exhibit antigenic cross reaction with different tissues of human body Antigenic relationships demonstrated between:- Capsular hyaluronic acid and human synovial fluid 2) Cell wall proteins and myocardium

11. 3) Group A carbohydrates and cardiac valves 4) Cytoplasmic membrane antigens and vascular intima 5) Peptidoglycans and skin antigens These antigenic cross reactions may account for manifestation of rheumatic fever, streptococcal disease and tissue damage being of an immunological nature

12. Adjuvant Substances that enhance the immunogenicity of an antigen - stimulates antigen by helping it gain entry into the antigen –presenting cell -helps to enhance immune response against the antigen by maintaining a sustained release of antigen and by producing a depot (where antigen is stored) effect - maximising immune response before body clears the antigen

13. EXAMPLES OF ADJUVANTS Freund’s incomplete adjuvant: - Aluminium hydroxide or phosphate and protein antigens incorporated in water phase of a water-in-oil emulsion -Delay release of antigen from site of Injetion and prolong the antigenic stimulus

14. EXAMPLES OF ADJUVANTS Freund’s complete adjuvant: - A suspension of killed tubercle bacilli added to incomplete adjuvant - increases both humoral and cell - mediated immune response -adjuvant effect of tubercle bacilli due to presence of water-soluble peptide MDP ( muramyl dipeptide)

15. EXAMPLES OF ADJUVANTS Freund’s complete adjuvant: - Bordetella pertusis which has,in addition lymphocytosis –promoting factor for diphtheria and tetanus toxoid in triple vaccine -mineral salts aluminium hydroxide , aluminium phosphate and calcium phosphate are adjuvants commonly used with human vaccines

16. DETERMINANTS OF ANTIGENICITY Foreigness :-Non-self antigens elicit immune response Size:- large molecules are highly antigenic Chemical nature:- -Antigens are protein and polysaccharides -Lipids and nucleic acids are less antigens . Susceptibility to tissue enzymes:- - phagocytosis and intracellular enzymes breaks antigen into immunogenic fragments

17. Bacterial antigenic structures

18. DETERMINANTS OF ANTIGENICITY Susceptibility to tissue enzymes Substances not susceptible to tissue enzymes are not antigenic Antigens introduced into body degraded by host into fragments of appropriate size containing antigenic determinants Other factors Dose, route and time of administration Excess dose: Immunological tolerance Intravenous route elicits more response

19. Examples of common antigen

20. TYPES OF SPECIFICITY OF ANTIGENS Basis of specificity: Stereochemistry and spatial configuration Types of specificity Species specificity - Tissues of all individuals in a species contain species- specific antigens - used in tracing evolutionary relationship between species -forensic application in identification of species from blood and seminal fluid

21. Antigenic specificity Isospecificity Isoantigens : present only in some members of same species Blood group — Human erythrocyte antigen Histocompatibility antigen (cellular determinants specific to each individual of a species — Transplantation

22. ANTIGENIC SPECIFICITY Autospecificity : Self antigens—no immune response Sequestered antigen—non-self (e.g., lens proteins) Organ specificity: Different species share same antigen (brain) Neuroparalytic complications following antirabies vaccine from sheep brain (no longer used)

23. Heterogenetic specificity Heterophile antigen-same or closely related antigens may occur in different biological species , classes or kingdoms Forssman antigen—humans, animals, birds, plants and bacteria ,absent in rabbit Heterophile antigen used in diagnostic tests Weil–Felix reaction in typhus fever –test between OX-19,OX-2 and ,OX-K which are proteus antigens

24. Heterophile antigen used in diagnostic Weil–Felix reaction in typhus fever – These proteus antigen share rickettsial antigen They cross react with rickettsial antibodies Paul– Bunnell test in infectious mononucleosis (caused by EBV) Cold agglutinin test in primary atypical pneumonia(positive in mycoplasma)

25. BIOLOGICAL CLASSES OF ANTIGEN T cell-dependent (TD) antigens T-B interaction and cytokines provide stimulus for B cell activation T cell-independent (TI) antigens Directly stimulate B cells to produce antibody Type I antigen: Endotoxin,LPS -Directly mitogenic for B cell Type II antigen: B cells activated by cytokines

26. Comparison between T cell dependent and T cell – independent antigens

27. HAPTEN (PARTIAL ANTIGEN) Immunogenic when combined with a carrier protein (induces antibody production) but reacts specifically with antibodies Complex haptens Polyvalent Precipitate with specific antibodies Simple haptens Univalent Inhibit precipitation with specific antibody

28. SUPERANTIGENS Antigens that evoke an excessive immune response Do not get processed by an antigen-presenting cell (APC). Attach directly to the MHCα1 domain and β variable chain of TCR Two types of superantigens Endogenous: Intracellular (e.g., virus) Exogenous: Extracellular (e.g., bacteria)

29. Superantigen

30. SUPERANTIGENS Microbial superantigens are medium-sized proteins (MW 22-29 KDa ) characterised by high resistance to proteases. Characteristics of superantigens -potent CD4+T cell activators -initiate release of cytokines (IL-2) , massive proliferation of T lymphocytes.

31. ACTIONS OF SUPERANTIGENS Superantigen binds to class II MHC antigens expressed on antigen –presenting cells (APCs) outside the peptide-binding groove Sequentially bind T cell receptor (TCR) via variable region of TCR Beta–chain High levels of IL-2 released causing symptoms of fever, nausea,vomiting,diarrhea and malaise

32. ACTIONS OF SUPERANTIGENS Excessive IL-2 leads endothelial damage due to IL-1 and inflammatory chemokines IL-8, Platelet-activating factor (PAF) causing intravascular coagulation, shock, multiple organ /system failure

33. Human diseases associated with microbial superantigens

34. Determinants recognised by innate immune system The receptors of adaptive immune system recognise discrete determinants Demonstrated a high degree of specificity Enabling this system to recognise and react to a particular pathogen Component of innate immune system recognise unique molecular pattern

35. Which are shared by many related pathogens but not with their host Hence immunity has property of pattern recognition The broad molecular patterns are called pathogen associated ,molecular patterns (PAMPs) The receptors for PAMPs are called Pattern recognition receptors (PRRs)

36. PRRs divided into three classes: Toll like receptors (TLRs): transmembrane receptors present on macrophages and dendritic cells 13 different TLRs recognise pathogens and enhance phagocytosis Leads to inflammation at the site

37. Scavenger receptors : CD-36,CD-68,SRB-1 Can bind to bacterial cell wall componentsa LPS,peptidoglycans , infected,injured or apoptotic cells and modified lipoproteins Mannose receptors:receptors on the surface of phagocytes bind mannose rich glycan short carbohydrate chains with mannose as the terminal sugar,found in microbial glycoprotein ,glycolipids , rare in those of human

38. Major Histocompatibility Complex Tissues and organs grafted from one individual to another member of the same species (allografts) recognised as foreign and rejected Gorer in 1930s on the antigens responsible for allograft rejection in inbred mice that led to discovery of major histocompatibility complex (MHC) Histocompatibility antigens are cell surface antigens that induce an immune response leading to rejection of allografts

39. Gorer identified two blood group antigen system in mice Antigen-1 : common to all strains Antigen-2 : found only in some strains and appeared to be responsible for allograft rejection This was called H-2 antigen (major histocompatibility antigen for mice )

40. MHC Classes of proteins Class I proteins : determine histocompatibility ,acceptance and rejection of allografts Class II proteins: regulate the immune response Class III proteins: Include some components of complement system and few others The name Histocompatibility complex arose because its discovery was based on transplantation experiments

41. Mechanism of presentation of antigens by MHC class II complex

42. MHC restriction T cell can accept the processed antigen only if it is presented by a macrophage carrying on its surface the self-MHC antigens : This is known as MHC restriction Cytotoxic T cells can recognise class I MHC antigens on the target cells Helper T cells can accept antigens presented by macrophages/dendritic cells only when they bear the same class II MHC molecules on the surface

43. Human leucocyte antigen complex The HLA complex of genes is located on the short arm of chromosome 6 Consist of three separate clusters of genes class I – comprising A,B and C loci Class II –D region consisting of DR,DQ and DP loci Class III – Complement region containing genes for compliment component C2 and C4 of classical pathway

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