Download Physiology of the Blood III. White Blood Cells and the Immune

Physiology of the Blood III.
White Blood Cells and the
Immune System 1.
Prof. Szabolcs Kéri
University of Szeged, Faculty of Medicine,
Department of Physiology
2016
„ENEMY” IN IMMUNOLOGY:
1. VIRUS, BACTERIA, FUNGI, PARASITES
2. STRANGER CELLS and MOLECULES (transplantation,
allergic reactions)
3. SELF CELLS (autoimmunity, tumor cells)
4. DANGER SIGNALS (e.g., after tissue injury)
Enemy in general – e.g., differentiation of bacteria from self
cells
Enemy specifically – recognition of one particular bacterium or
its subtype (e.g., E. Coli)
Basic concepts in immunology
PATHOGEN MOLECULAR PATTERN: general markers eliciting a nonspecific immune reaction
ANTIGEN: large molecules that elicit a specific immune response
Epitop: small part of the antigen that directly binds with the antibody
ANTIBODY: immunoglobulin that specifically reacts to the antigen
Specific immune response: only for a particular antigen
Aspecific immune response: similar for many antigens (e.g.
phagocytosis)
Active immunization: administration of antigens (e.g. a killed virus) to
elicit an immune response (e.g. production of specific antibodies)
Passive immunization: administration of readily made antibodies
HA – hemagglutinin
NA - neuraminidase
Science, 12. Sept. 2014
E. COLI
180 O antigen
70 K antigen
54 H antigen
1. WHITE BLOOD CELL
2. CYTOKINES
-
- Mainly produced by white blood cells
- Communication, activation, and
differentiation of white blood cells
Phagocytosis
Presentation of antigens
Immunoglobulin production
Killing cells (tumor, virus infected)
Fight against worms
3. SPECIFIC PLASMA PROTEINS AND LIPID DERIVATES
COMPLEMENT system
Acute phase proteins
Arachidonic acid derivate (prostaglandins, leukotrienes)
- Facilitating the destruction of pathogens
- Communication and activation of immune cells
- Microcirculation (dilatation, increased permeability), inflammation
The white blood cells (leukocytes)
• Number: 6000-8000/μL
• Occurrence: bone marrow, circulation, lymphoid
system, organs
Quantitative changes: leukocytosis (↑), leukopenia (↓)
• Types:
1. Granulocytes (neutrophil, eosinophil, basophil)
2. Lymphocytes
3. Monocytes-macrophages
Types of leukocytes
NEUTROPHIL
- 50-70%
- diameter: 10-12 μm
- nucleus: segmented (multiple lobes)
- granules: small, pale
- life: hours in blood, days in specific tissues
- target: bacteria, fungi – phagocytosis
EOSINOPHIL
- 2-4%
- diameter: 10-12 μm
- nucleus: two lobes
- granules: pink with hematoxylin-eosin staining
- life: 1-2 weeks (only few hours spent in the circulation)
- target: large parasites (e.g. worms), allergic reaction
BASOPHIL
- < 1%
- diameter: 12-15 μm
- nucleus: two or three lobes
- granules: strong basophil (blue-purple) staining
- life: few hours-days
- histamine release during inflammation and allergy - anaphylaxis
LYMPHOCYTE
- 20-40%
- diameter: 7-8 μm
- nucleus: non-central, round
- life: week-years
- B cell: production of antibodies (plasma cell) – humoral immunity
- T cell: destroying cells infected by viruses and tumor cells (killers) – cellular
immunity
- NK (Natural Killer) cell: large lymphocyte, non-specific cellular immunity
T cell: Thymus derived
Forms rosette with red blood cells
B cell: Bursa Fabricii in birds
Peyer’s plaques in humans?
In adult humans the primary site of genesis and development is the
bone marrow
Secondary sites of further maturation: the lymphatic system
(nodes and vessels)
Tonsil
(pharynx)
Tonsil (nasal)
Thymus
Lymphatic
vessels/nodes
Spleen
Appendix
Bone marrow
Peyer’s
plaque
Lymphatic
vessels/nodes
MONOCYTE
- 4-8%
- diameter: 15-20 μm
- nucleus: bean-shaped
- phagosoma in the cytoplasm
- life: few hours-days in circulation, diapedesis to tissues – macrophag
(without activation months-years in tissues)
- phagocytosis (infectious agent, tissue debris) - presentation of antigens
Tissue macrophages (reticuloendothelial system):
Dendritic cells (skin, mucosa epithelium) – main antigen presenter
Kupffer-cells (liver) – extraction of old erythrocytes
Microglia (brain)
Histiocyte (many organs)
Mastocyte (mast cell) – similar to basophils (allergic reaction, innate immunity,
wound healing) [resident cell in tissues, but different from macrophages]
Osteoclast (bone)
QUALITATIVE BLOOD TEST: percentage of specific leukocytes
(big)
May-Grünwald-Giemsa staining
Flow-cytometry: separation based on cell surface proteins
Young neutrophils in the circulation
Jugend (metamyelocyte)
Stab
Mature
Increased genesis in bone marrow (e.g. infection) → young, immature
variants run out to peripheral circulation – LEFT-SHIFTED PATTERN
Interim summary 1: Types of
leukocytes
• Granulocyte, lymphocyte, monocyte
• Neutrophil and monocyte-macrophages:
general phagocytosis
• Eosinophil, basophil: worms, allergy
• Lymphocyte: specific immune response –
antigen-antibody reaction, cytotoxicity
• Qualitative blood sample, young forms
Types of immune responses
I. Natural (innate) immunity
- first contact with the infectious agent
- no memory
- mechanism: phagocytosis, complement proteins (stimulation of
phagocytosis [opsonization], chemotaxis, cytolysis)
II. Adaptive (acquired) immunity
- based on the recognition of the antigen
- cell-based (cytolysis) and humoral immunity (production of antibodies)
- memory (vaccinations)
Communication and regulation of leukocytes: CYTOKINES
Inflammation response: Arachidonic acid-derivates
Natural immunity
Pathogen-associated molecular pattern (PAMP) (e.g., polysaccharide of
bacteria, viral RNA): signing groups of microorganisms but not specific ones
Pattern recognition receptors (PRR):
Detection of PAMP
Toll-like receptors
NOD-receptors [within the cells, viruses]
CELLS:
MACROPHAGES – DENDRITIC CELLS
GRANULOCYTES
NK cells (virus)
Attachment to endothelial cells → „rolling”, diapedesis (stepping out to
tissue between two endothelial cells) → migration in tissues
Rolling
Attachment
Diapedesis
Leukocyte membrane proteins:
- S-Le (syalil-Lewis protein)
- Integrins
Endothelial membrane proteins:
- E-selectins
- ICAM (Intercellular Adhesion Molecule)
Phagocytosis
The role of phagosomes and first-line factors
General:
- proteolytic enzymes
- lysosim (digestion of cell wall sugar of bacteria)
- lactoferrin (binding iron)
- free-radicals (e.g. superoxid anion, hydroxyl radical)
- cathelicidin peptides (stimulated by vitamin D, protection against bacteria
and viruses)
- beta defensins (epithelial surface, inhibition of colonization)
Eosinophils:
MBP (major basic protein)
ECP (eosinophil cationic protein, ribonuclease 3)
Basophils:
Heparin (inhibition of blood coagulation)
Histamine (vasodilatation, increased permeability of vessels, allergy)
Beyond phagocytosis:
1. Platelets detect bacteria
2. Neutrophils release DNA
3. DNA forms a mesh around bacteria
NET (Neutrophil Extracellular Trap)
Leslie M. Science 2010;328:562.
Interim summary 2: Natural
immunity
• Specific antigen-antibody reaction is not
included
• PAMP-PRR interaction
• Macrophages, granulocytes, NK-cells
• Attachment, migration, phagocytosis,
cytolysis (complement, NK-cell), DNAmesh (ENT)