Adaptive & Innate Immunity

1. Adaptive & Innate Immunity

2. The Immune Response and Immunity • Immune response • Innate (non-specific) • Adaptive (specific): • Primary: when encountering the microorganism for the first time. • Secondary: in recurrent infections (memory)

3. Acquisition of Immunity • Natural: - active - passive • Artificial: - active - passive

4. Naturally Acquired Immunity • Active: • Acquired through contact with microorganisms (infection). • Provides long term protection. • Passive: • Antibodies pass from motherto fetus across placenta or in breast milk (IgG) • Provides immediate short term protection (few months)

5. Artificially Acquired Immunity • Active: • Antigens introduced through vaccination. • Provides long term protection. • Passive: • Induced by the transfer of antibodies • Referred to as: Immune serum globulins(ISG), immune globulins (IG) or gamma globulins • Provides immediate short term protection

8. Soluble mediators of the immune system: • Immunoglobulins • Cytokines • Interferons • Complement

9. Immunoglobulins Immunoglobulins (Ig): • Are gammaglobulins(proteins) of defined specificity for different epitopes that make up antigens. • They are produced by plasma cells (differentiated B cells)

10. N epitopes

11. Immunoglobulins are divided into five classes: • Three major classes ( IgG, IgM, IgA). • Two minor classes (IgD and IgE).

12. N Basic Structure of Immunoglobulin: • The immunoglobulin molecule consists of four polypeptides chains: two heavy (H) and two light( L) chains fastened together by disulfide bonds.

14. Heavy chains consist of two different domains (constant, and variable). • Light chains also have two different domains (constant, and variable). • A light chain variable domain and a heavy chain variable domain together form a pocket that constitutes the antigen-binding region (Fab). • The flexibility of Ig is associated with the presence of hinge region.

15. Heavy chainsare designated by using of Greek letters (μ, γ, α, δ, and Є), and the immunoglobulins produced are IgM, IgG, IgA, IgD, and IgE, respectively. • The lightchain consists of two kappa(κ) or two lambda(λ) chains.

16. Immunoglobulins Isotypes: • IgG • IgG accounts for approximately 75-85% of the total serum Ig • It is the most abundant antibody produced during secondaryhumoral immune response. • Have monovalent affinity. • It is the only class that can cross the placenta.

17. IgGstructure: • n

18. IgM: • Found either as a B cell boundmonomeror as a secretedpentamer. • Present on B lymphocyte surfaces. • Normally secreted as a J-chain containing pentamer with molecular mass of 900 KD. • Form ~ 5-8 % of normal serum immunoglobulin.

19. Dominates in early primaryimmune response. • Anti-A and Anti-B blood groups. • Complement fixation. • Multivalentavidity (10 antigens).

20. IgM Structure: • n

21. IgA: • It accounts for 10-16% of serum Igs. • Most abundant in saliva, tears, intestinal mucus, bronchial secretions, milk, prostatic fluid(body fluids & secretions). Called secretory IgA • The predominant Ig produced in Peyer’s patches (illume submucosa), tonsils and other submucosallymphoid tissue.

22. It has two subclass: in • IgA1: Monomerin the serum. • IgA2: Dimerwhen secreted (secretory IgA). • IgA1: IgA2 ratio in blood is 5:1

24. IgD • Has a Molecular weight of 180 KD. • Present on B-cell surface.

25. IgE: • Form less than 1% of total serum Igs. • A unique high affinity Fc receptor on mast cell and basophils. (bounded) • Great role in allergy, through cross linking and release of histamine from mast cells and basophils. • play a role in helminthsinfection.

28. Summary • There are 5 isotypes of immunoglobulins. • IgG is the most abundant in serum, the most important in secondary infections and the only one that can cross the placenta. • IgM is the most important in the primary exposure and in complement fixation.

29. The secretory IgA is most important in immunity in body secretions, submucosaand lumens. • IgDis bounded to the surface of B cells. • IgE is bounded to the mast cells and basophils and is the most important in allergic reactions and helminthsinfestation.

30. Primary & Secondary Antibody Response • Primary Response • Following the first exposure to an antigen, there is a slow rise in IgM followed by a slow rise in IgG • Secondary Response • Following exposure to previously encountered antigen, there is a rapid rise in IgG and slow or no rise in IgM

32. Molecules of Cellular Interaction: Cytokines:are low-molecular weight soluble protein messengers that are involved in : • Cellular interaction; inflammatory response in innate and adaptive immunity. • Cellular growth, differentiation, and repair mechanism.

33. Cytokines are produced by a wide variety of immune and non-immune somatic cells. • Cytokines produced by lymphocytes are known as lymphokines.

34. N • N

35. Cytokines and Immune cells interaction: N

36. Interferons (IFNs): are low molecular weight soluble proteins. • Activated by presence of intracellular pathogens such as viruses ,bacteria, and parasites or tumor cells. • Released by lymphocytes and other somatic Non-immune cells. • Major Action: - Anti-Viral infection. - Fight Tumors.

37. N N

38. Complement system: • Complement system: series of soluble enzymes and proteins (C1,C2…….C9) that function in both innate and adaptive immune response against pathogens. • Complement activation can be initiated via: • Alternative pathway. • Classical pathway • Mannan-binding lectin pathway.

39. Alternative pathway: • Activation of the alternate pathway started from C3 in the presence of the microbe, and continue tell activation of membrane attack complex (MAC)

42. Classical pathway of Complement: • Starts by antigen - antibody interaction which enables C1 binding and continue tell MAC activation.

44. Mannan-binding lectin pathway • Lectinsare proteins that bind to carbohydrates. • Mannan is polymer of the sugar mannose. • This pathway is activated by binding of mannan-binding lectin (MBL) to certain microbes, and continue tell MAC formation.

45. N

46. The Complement Anaphylatoxins: • The small fragments (C3a, C4a, C5a) generated in the alternative and the MBL pathway act as anaphylotoxins. • They attract and activate some cells (neutrophils, phagocytes and mast cells) to the site of infectionto produce an inflammatory reaction.

47. Mechanism of Inflammation: N