1. Adaptive Immune System
Eric Scott
BIO422
10/19/15

2. Objectives
Describe the roles of various types of lymphoctyes in an adaptive immune response.
Define antigen and antibody
Distinguish the response to intracellular pathogens from the response to extracellular pathogens

3. “Jobs” of the Immune System
Recognize that invaders are present
Recognize that these are different than self
Recruit more cells/factors to fight invaders
Kill the invaders
Block any toxins produced by the invaders
Learn from past encounters to increase future effectiveness

4. Overview of Host Response to Pathogens

5. Time Course of an Immune Response

6. Levels of the Immune Response

7. Levels of the Immune Response

8. Adaptive Responses Are Specific to Individual Molecules
Antigen: the molecule recognized by the response
Each cell can only recognize one antigen

9. Two Branches of Adaptive Response
Cellular immunity
Main cells are T cells
Used against intracellular pathogens
Humoral immunity
B cells and antibodies
Used against extracellular microbes and toxins

10. Cellular Immune Response
T cell Mediated Immunity
Cellular Immune Response

11. How do T cells recognize antigen?
T cell receptor
Recognizes small parts of proteins “presented” on MHC molecules
MHC is present on antigen presenting cells

12. Starts with phagocytes recognizing antigen

13. Antigen is processed and displayed: MHCI

14. Antigen is processed and displayed: MHCII

15. Initial recognition by pAPCs
Professional antigen presenting cells
Dendritic cells, macrophages, and B cell
Offer activating signals to T cells—primes for activity

16. Types of T cells Cytotoxic T cells: CD8+ T cells
Recognize antigens on MHCI
Releases granules to kills target cells
Helper T cells: CD4+ T cells
Recognize antigens on MHCII
Secrete cytokines to activate other cells
Two types: Th1 and Th2

17. Cytotoxic T cells (Tc)

18. Helper T cells (Th) Th1 Cells: activate phagocytes
Th2 Cells: activate B cells

19. Concept Question Cytotoxic T cells are important for defense from…
Bacteria only
Intracellular pathogens
Viruses only
Fungus only
Extracellular pathogens

20. Concept Question What do helper T cells recognize?
Exogenous peptides on MHCI
Carbohydrates on bacteria cells
Exogenous peptides on MHCII
Endogenous peptides on MHCII
Endogenous peptides on MHCI

21. Humoral Immune Response
B cell Mediated Immunity
Humoral Immune Response

22. B cells Produce Antibodies
Defense from extracellular pathogens and toxins
Recognize antigen in native form

23. Activation of B cells B cell receptor (BCR) recognizes antigen
Th2 cells help activation
B cell differentiates to plasma cell
Produces antibodies

24. Antibody Structure Immunoglobulins (Ig) Functions
Neutralize pathogens and toxins
Lead to phagocytosis
Activation of complement

25. Types of antibodies

26. Types of Antibodies Functional Activity IgM IgD IgG IgA IgE
Neutralization +  ++
Phagocytosis
+++
Natural killer cell killing
Mast cell activation
Complement activation
Location
BCR &
Serum
BCR (minor)
Serum & tissue
Mucus & tissue
Mast cells

27. Immunological Memory

28. Timing of Adaptive Response

29. Immunological Memory

30. Secondary Immune Response

31. Memory Responses
Small populations of B and T cells retained from first exposure
Survive for a long time
Begin faster than first response
Stronger than first response

32. Immune System Summary

33. Adaptive Immune System

34. Adaptive immunity T B T B T B B B T T T B T T Immune response microbesMB MB Y
Memory B cells MB MB T Y B Y T Y Y Y T B PC B Y B Y PC Y T T B PC T T B Y T
B cells
PCs
Germinal Centers
Immune response
T cells Y
antibodies
To begin with, T cells, B cells and in many ways plasmacytoid dendritic cells (pDCs) are apart of the adaptive immune system. Upon stimulation by foreign microbes in the environment, B cells are activated and move into follicles called germinal centers. Within the germinal centers B cells receive T cell help clonally expand and may differentiate into either memory B Cells or plasma cells. Plasma cells that produce antibodies that bind the foreign antigen resulting in its elimination from the host. In addition effector T cells role is to eliminate invading microbes. pDCs produce proinflammatory cytokines to help eliminate microbes. Together these three cell types help rid the body of harmful antigens.
Type I IFN Y Y
E-T
E-T Y Y
E-T Y Y
pDC Y Y
Eliminates microbes
Eliminates microbes

35. Adaptive immunity T B T T = B B B B T T T B T T autoimmune response
Dying cells
Self antigen Y MB MB Y
autoreactive Memory B cells MB MB T B Y Y T Y Y Y T = B Y B Y PC PC B Y
autoreactive PCs PC T T B T T B Y T
B cells Y
Germinal Centers
autoimmune response
T cells Y Y
autoAbs Y Y Y
To begin with, T cells, B cells and for the most part pDCs are apart of the adaptive immune systems. With the help of T cells, B cells are activated and differentiate into plasma cells that produce antibodies. In addition effector T cells role is to eliminate invading microbes. pDCs produce proinflammatory cytokines to help eliminate microbes. Together these three cell types help rid the body of harmful antigens. However in the case of autoimmunity, these three cell types have a devastating effect.
Type I IFN
E-T
E-T Y Y
E-T Y Y Y
pDC Y
Self antigen immune complexes
Tissue damage/organ failure
Activate autoreactive T cells

36. Autoimmunity
Autoimmune responses are incited by specific self-antigens that are expressed on normal host tissues
Autoimmune diseases may be organ-specific and have aberrant immune antibody responses directed against antigen(s) associated only within target organs being damaged.
Type I diabetes mellitus is an example of organ-specific autoimmunity where CD4+ T cells and CD8+ T cells destroy pancreatic beta cells in genetically predisposed individuals
Autoimmune diseases can be classified as systemic (non-organ specific) and have antibody directed against an antigen not associated with any particular target organ.
Systemic Lupus Erythematosus (SLE) is an example of systemic autoimmunity

37. Systemic Lupus Erythematosus (SLE)
SLE is a chronic autoimmune disease characterized by the production of auto-Abs to intracellular proteins and nucleic acids.
It is the prototype of the systemic autoimmune diseases characterized by multi-organ involvement.
The prevalence of SLE in the United States range as high as 1.5 million with an incidence ranging from 1.8 to 7.6 cases per 100,000 persons per year in the United States (Rus V. 2001).
SLE affects women more often than men, at a ratio of about 10:1, with minority women being affected three times more often than caucasians (Rus V. 2001).
Renal involvement is a principal cause of morbidity and mortality in SLE, but the underlying immunopathological mechanisms of nephritis are still largely unknown
Read slide