1. Lecture 1 review

2. Self vs. Non-Self Recognize self Recognize the absence of self
Recognize non-self
Pattern recognition receptors
Somatically generated receptors

3. The innate vs. adaptive immune systems (5)
First response time
Immediate activation of effectors; minutes to hours
Activation only requires a single signals
Response by actual activated cell
Long response times; Days-weeks
Multiple permissive signals required
Stimulated cell can undergo clonal proliferation. Amplified immune responses.
Response to repeat stimuli
Quick, but identical to primary response
Much more rapid than primary responses. Generation of robust “memory”
Major components
Physical barriers
Phagocytes
Granulocytes
Pattern recognition molecules
T and B cells
Antigen-specific receptors
Antibodies

4. DIVERSITY OF RECEPTORS
OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS

5. Antigen – collection of ligands
recognized by cells of both the
innate and adaptive immune
systems
Epitope – smallest individually
identifiable part of an antigen
that is bound by a receptor

6. Innate Pattern Recognition Receptors
How innate immune cells distinguish between microbes and self-cells?
How do they “know” if something is “dangerous” or not? (i.e. food, commensal organisms in the mouth and gut)
Use sets of highly conserved receptors that recognize patters of molecules shared by microbes – Pathogen-Associated Molecular Patterns (PAMPS)

7. Hematopoietic
Lineages

8. Cytokines of Innate Immunity
Interleukins – produced and act on leukocytes
Chemokines – direct cell movement
TNF, IL-1 - active vessels and recruit Neutrophils
IL-1 – Fever
IL-6 – Acute phase response

10. Inflammation and local response
Activated innate cells trigger the process of inflammation:
Dolor (pain)
Calor (heat)
Rubor (redness)
Tumor (swelling)
Functio laesa (Loss of function; Immobility)

11. Inflammation and local response
Release of vasodiolators = increased blood flow (rubor) and heat (calor)
Altered permeability (edema) = leakage of plasma proteins containing complement components, CRP, MLB, clotting factors
Leads to production of inflammatory cytokines (IL-1, TNF by macrophages) that trigger a whole range of effects designed to Recruit other cells to the site

12. Local vs. systemic responses by innate immune system
Local inflammatory response can be mild, short-lived
May not even involve adaptive immune response
If infection is not contained, leads to systemic response, with more extensive consequences

13. Natural Killer Cell
Recognition

14. Big picture: local innate immune responses

15. Big picture: local innate immune responses

17. Big picture: innate cell initiation of adaptive immune responses

18. Adaptive Immune System 1 E1542 Biomedical Science Tower
Immunology - Lecture 2
Adaptive Immune System 1
Heth R. Turnquist, PhD
E1542 Biomedical Science Tower
200 Lothrop Street

19. Molecules of the Adaptive Immunity - 6

20. Adaptive Immune System
The adaptive immune system uses a broad range of molecules to function.
Some of the molecules used by the adaptive immune system are also used by the innate immune system.
Other molecules are specific to the adaptive immune system.
B cell receptor (antibodies)
T cell receptor
i.e. Ag – receptors
CD (Cluster of differentiation Molecules) – CD3, CD4, CD8, etc

21. Immunoglobulins Synthesized by B lymphocytes (B cells)
Synthesized and secreted by plasma cells – terminally differentiated B cells
Antibody is an immunoglobulin molecule with specificity for an epitope of an antigen.
Antibodies facilitate cells and molecules in the immune system to identify and interact with antigens.
Soluble antibodies are components of humoral (soluble) immune responses.

22. Immunoglobulin (Ig)
Basic structure:
-4 polypeptide chains
2 Heavy Chains
2 Light Chains
-Called Ig Monomer
Variable domains on HC
And LC form epitope
Binding domain
Epitope = part of Ag
Fc - Region

23. Ig Monomers
Contain 2 identical light chains and two identical heavy chains
Binding site for each monomer is identical
Diversity generated by different pairings of heavy and light chains

24. Properties and Biological Activities of Immunoglobulin Isotypes
Property/Function
IgG
IgA
IgM
IgE
IgD
Heavy chain g a m e d
Highest concentration in serum √
Activates complement
Crosses placenta
Present on B cell membrane
Binds to receptors on phagocytes
Involved in mucosal immunity
Mast cell degranulation
IgM
IgD
IgG
IgA
IgE

25. Ig and Complement Cascade (1)
Interaction of antibody with antigen
activates the classical complement pathway.
Ag binding to epitope on Ag = change in Ab Fc region = C1q,r,s binding
C1 components activate cascade culminating in MAC formation and cell lysis

26. Ig and Complement Cascade (2)
Interaction of antibody with antigen
activates the classical complement pathway.
Ag binding to epitope on Ag = change in Ab Fc region = C1q,r,s binding
C1 components activate cascade culminating in MAC formation and cell lysis

27. Major Histocompatibility Complex (MHC)
Tightly linked cluster of genes in all mammals
Called Human Leukocyte Antigen (HLA) complex
Gene products (3 classes) play a role in
Intercellular recognition
Discrimination between self and nonself
Important in cellular and humoral immunity
Acts as antigen presenting structures
The particular set of MHC molecules expressed by an individual influences the repertoire of Ag to which individual T cells can respond
May have a role in susceptibility to disease and in development of immunity
On Chromosome 6

28. MHC Class I, II, and III
Located on Chrom 6; Human Leukocyte Antigen

29. MHC Class I, II, and III
Located on Chrom 6; Human Leukocyte Antigen

30. 2 Types of MHC
MHC class I – expressed
on all nucleated cells
MHC class II – expressed
on APCs

31. T Cell Receptor (TCR)
T cells – each T cell expresses a unique, epitope specific cell surface receptor
Heterodimers of two polypeptide chain
Lack the capacity to initiate signaling to the nucleus capacity and rely on CD3 to transmit signals
Unlike Ab – can not bind soluble Antigens. See peptides in context of MHC

32. Two subsets of T cells interact differently with MHC:
CD4+ T cells only interact with peptides bound to MHC class II
CD8+ T cells only interact with peptides bound to MHC class I

33. Cells and Organs - 7

34. Lymphocytes All originate from bone marrow
Named after place of “education”
Thymus-derived cells = T cells (CD3+ TCR+)
CD4+ T cells
CD8+ T cells
Bone-marrow-derived cells = B cells (BCR+ CD19+)
B cells – BCR+ cells
Plasma cells – terminally differentiated B cells producing Ig and no longer displaying it on surface
Natural Killer Cells (CD3- BCR- CD56+)
Granular appearance due to perforin and granzyme
Develop in BM – no education in Thymus

35. CD4+ T cells
Comprise two thirds of all T cells
Recognize antigen in complex with Class II MHC molecules
Provide helper function

36. CD8+ T cells
Comprise one third of all T cells
Recognize antigen in complex with Class I MHC molecules
Potent cytotoxic functions
“Cytotoxic T cells”

37. B cells
Mature in the bone marrow
Express membrane bound antibody (Ig) on surface
Recognize soluble antigen

38. When Ab on the surface of
a B cells binds antigen for the first time, the B cell begins to divide rapidly to become a
Plasma cell – secretes antibody;
Small amount of membrane Ab;
life span of a few days Or
Memory cell – identical membrane antibody as on parent B cell, longer life span

39. Natural Killer (NK) and
Natural killer T (NKT) cells
bridge the innate and adaptive
Immune systems.
NK Cells
Granular lymphocytes
No expression of TCRs
No expression of BCRs
Express receptors for:
1. Stress molecules (KARs)
2. MHC class I molecules (KIRS)
NK T cells
Express low levels of TCRs with limited repertoires

40. Lymphoid tissues and organs - Primary Lymphoid organs
Primary Lymphoid organs – Place where T and B cells learn to see self from non-self
Thymus: Bilobed organ where“prothymoctyes” from bone marrow turn into T cells
Where T cells aqcuire CD4, CD8, TCR
Self reactive cells removed

41. Thymic Education of T cells

42. Lymphoid tissues and organs - Primary Lymphoid organs
Bone Marrow: lymphocytic lineages that become B cells stay and undergo differentiation here
If early IgM on surface recognizes “self” they undergo apoptotic death

43. Lymphoid tissues and organs – Secondary Lymphoid tissue and organs
Lymphatic circulatory system
Cardiovascular system is responsible for circulating the soluble and cellular components of the immune system
Collection/filtration in the spleen

44. Lymphoid tissues and organs – Secondary Lymphoid tissue and organs
Lymphatics – Extensive capillary network that drains the tissues and collects lymph
Lymph = watery clear fluid that contains leukocytes and cells debris
Drainage system to remove cellular debris and microbes from the body’s tissues to the lymph nodes

45. Lymphoid tissues and organs – Secondary Lymphoid tissue and organs
Spleen – Largest lymphoid organ
Clears particulate from blood
Concentration of Ag and microbes
Lots of T cells and B cells (making antibody) Lots of Macrophages – dead cell removal

46. Lymphoid tissues and organs – Secondary Lymphoid tissue and organs
Lymph nodes – places of leukocyte accumulation and lymph filtration

47. Lymphoid tissues and organs – Secondary Lymphoid tissue and organs
Mucosa associated lymphoid tissues (MALT)

48. Lymphoid Organs and Tissues
Primary Lymphoid Organs
Secondary Lymphoid Organs and Tissues
Thymus
Bone Marrow
Spleen
Lymph nodes
Mucosa-associated lymphoid tissues (MALT)
Tonsils
Appendix
Peyers’s patches