1. Overview on Immunology and Introduction to Innate Immunity

2. Over view What are the main types of white blood cells?
Name the two main types of immunity?
What are the main distinctions between these two categories?
What cells are involved in which aspects of the immune system?

3. Lymphocytes
Many types; important in both humoral and cell-mediated immunity
B-cells produce antibodies (APC cell)
T- cells
Cytotoxic T cells
Helper T cells
Memory cells

4. Lymphocytes Natural Killer cells
Large granular lymphocytes (not B or T)
Kills tumor cells
Kills cells infected with certain viruses (intracellular pathogens)

5. Monocytes/Macrophage
Phagocytosis and killing of microorganisms
Activation of T cells and initiation of immune response
Monocyte is a young macrophage in blood
There are tissue-specific macrophages
APC cells

6. Dendritic Cells Phagocytosis and killing of microorganisms
Function as antigen presenting cells (APC)
In the blood and tissues – mature and migrate to the lymph nodes

7. Neutrophil Granulocyte Polymorphonuclear Phagocytosis
Cytoplasmic granules
Polymorphonuclear
Phagocytosis
Short life span (hours)
Very important at “clearing” bacterial infections
Innate Immunity

8. Eosinophils Kills Ab-coated parasites through degranulation
Involved in allergic inflammation
A granulocyte
Double Lobed nucleus
Orange granules contain toxic compounds

9. Basophils Might be “blood Mast cells’ A cell-killing cells
Blue granules contain toxic and inflammatory compounds
Important in allergic reactions

10. Antigen-presenting cells (APC)
Highly specialized
Process antigen and display peptide fragments on cell surface
Involved in T-cell activation
Macrophages, dendritic cells and B-cells

11. Over view What are the main types of white blood cells?
Name the two main types of immunity?
What are the main distinctions between these two categories?
What cells are involved in which aspects of the immune system?

12. Immune system divisions
Innate immunity
First line of defense
Adaptive (acquired) immunity
Takes time to develop
Humoral immunity (antibody–mediated specific immunity)
Cell-mediated immunity (The aspect of the adaptive immune response where antigen-specific T cell have a main role)
Active immunity
Passive or maternal immunity
Injection of Immunoglobulin
Absorption of maternal antibodies

13. Innate vs. adaptive immunity
Innate immunity
First line of defense (present in all individuals at all times)
Immediate (0 – 4 hours)
Non-specific
Does not generate lasting protective immunity
Adaptive immune response (late: > 96 hours)
Is initiated if innate immune response is not adequate (> 4 days)
Antigen-specific immunity
Generates lasting protective immunity (e.g. Antibodies, memory T-cells)

14. Over view What are the main types of white blood cells?
Name the two main types of immunity?
What are the main distinctions between these two categories?
What white blood cells are involved in which aspects of the immune system?

15. Immune system cells Adaptive immunity Lymphocyte Memory cells
Innate immunity
Granulocytes (i.e. neutrophils)
Macrophages
Dendritic cells
Natural killer (NK) cells
Adaptive immunity
Lymphocyte
B cells
T cells
Cytotoxic T cells (CTLs)
Helper T cells (Th)
Memory cells

16. Innate immune system The first line of defense:
Penetration of the epithelial surface of the body by microorganism (e.g. bacteria)
Engulfment of microorganism by macrophages, neutrophils, and dendritic cells
Release of cytokines and chemokines
Inflammation
(Immunology animation: Janeway)

17. Killing by granulocytes
Macrophages and neutrophils recognize pathogen by means of cell-surface receptors
Example: mannose receptor, CD14 receptor, scavenger receptors, glucan receptor etc.
Binding of MØ/neutrophils with pathogen leads to phagocytosis
Bound pathogen is surrounded by phagocyte membrane
Internalized (phagosome)
Killing of pathogen (Phagolysosome*)
Oxidative burst (synthesis of hydrogen peroxide (H2O2)or free oxygen radicals)
Acidification
Antimicrobial peptides (e.g. defensins)
* Phagolysosome = lysosome +phagosome

18. Phagocytosis Mannose receptor Scavenger receptor LPS receptor (CD14)
Lipid mediators
Cytokines
Mannose receptor
Lysosome
Phagosome
Scavenger
receptor
LPS receptor (CD14)
Bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of inflammation
Phagolysosome
The macrophage expresses receptors for many bacterial constituents
Macrophages engulf and digest bacteria to which they bind

19. Phagocytosis (Immunology animation: Janeway) Immune response (IV)
Immune response (IV)
9.1 - Phagocytosis

20. Humoral immune response
V region; At binding
Cell-surface immunoglobulin receptors (BCR) detect extracellular pathogens
Once activated, secrete immunoglobulins as soluble antibodies
Antibodies
Variable region (2 identical antigen-binding sites)
Constant region (determines how antibody disposes of the pathogen once it is bound)
Fc region

21. Cell killing – NK cells
NK cells do not require prior immunization or activation
They attach to ‘target’ cells (ADCC)
Cytotoxic granules are released onto surface of cell
Effector proteins penetrate cell membrane and induce programmed cell death

22. Bacteria trigger macrophages to release cytokines and chemokines
Inflammation
Cytokines
Chemokines
Inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain
Fluids
Proteins
Bacteria trigger macrophages to release cytokines and chemokines
Vasodilation and increased vascular premeability cause redness, heat, and swelling

23. Cytokines Adaptive immune system
Low molecular weight, soluble proteins that are produced in response to an antigen and function as chemical messengers for regulating the innate and adaptive immune system
Innate immune system
Macrophages and Dendritic cells
Tumor necrosis factor-alpha (TNF-)
Interleukin-1 (IL-1)
Interleukin-12 (IL-12)
Adaptive immune system
T-lymphocytes
Interleukin-2 (IL-2)
Interleukin-4 (IL-4)