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WBCs + WBC DISORDERS, Watch lecture for receptor presentation - Coggle…
WBCs + WBC DISORDERS
Neutrophils
T\(\frac{1}{2}\) = 6-8hrs
Rate of production = 5-10x10\(^{10}\) per day
Structure
Multi-lobed nucleus
Cytoplasmic granules
Digestive enzymes
Cytotoxic
Produce ROS
Most common WBC in peripheral blood
Recruited by IL-8
No neutrophils
Overwhelming infection
Chronic granulomatous disease
Genetic disease
X-linked in 65% cases
Dysfunctional neutrophils
Mutated NADPH oxidase
Less protein produced
Critical to create ROS - kill invading microorganisms
Granuloma formation in tissues
Symptoms
Recurrent infections
Pneumonia
Abscess of skin, tissues, organs
White blood cells
Leukocytes
Described based on
Appearance under microscope + flow cytometry
Function
Development
Where they function
Suspended in plasma in blood
Blood is 7-8% body weight
Females - 5 litres
Men - 5.5 litres
Heavy cells settle to bottom of blood
RBCs packed at bottom
Haematocrit
Used to measure RBC number
Men - 45%
Women - 42%
Buffy coat
WBCs + platelets
After time blood clots
Remove clot to leave serum (clotted plasma)
Immune system
Made up of components that protect against pathogens + cancers
Key function is to recognise + discriminate 'self' and 'non-self'
WBC's important part of immune system
Monocytes
Eosinophils
Basophils
Lymphocytes
Neutrophils
Phagocytes
Monocytes in blood
Differentiate when move to tissue
Macrophages
APC
DCs
APC
Microglial cells
Basophils
Neutrophils
Eosinophils
Phagocytosis
Pathogen interacts with phagocyte receptors
Phagocyte pathogen envelops into phagosome
Lysosome enzymes released and pathogen digested
Pathogen proteins presented to T Cells on MHC
Lymphocytes
B cells
Pathogen neutralisation
Phagocytosis
Complement activation
Activated by antigens
Differentiate to plasma cells
Secrete Ab
T helper cells
Macrophage activation
T and B cell activation
Inflammation
Cytotoxic T cells
Elimination of infected/malignant cells
Regulatory T cells
Suppress immune system
Natural killer cells
Elimination of infected/malignant cells
Origin of immune cells
Haematopoietic stem cells
Myeloid lineage
DCs
Monocytes
Macrophages
Neutrophils
Basophils
Platelets
Eosinophils
Erthrocytes
Lymphoid lineage
NK cells
T cells
B cells
DCs
Colony stimulating factors determine type of cell that matures
All produced in bone marrow
Inner spongy tissue
Highly regulated/organised organ
Site of haematopoiesis + fat deposition
%fat increases with age - eventually >50%
T cells mature in thymus
Differentiation mediated by cell interactions
Cell - cell
Cell - cytokine
Distinguishing cells
Morphological features limited
Clusters of differentiation (CD) markers used to distinguish
Different cells at different stages of development express different CD markers
400 CD markers
Nomenclature
By number
CD1, CD2 etc..
CD3 is T cell receptor
Mature WBCs circulate in blood
Transported to site of damage/invasion via bloodstream
Basophils
Structure
Large cytoplasmic granules
Often obscure nucleus
Stain deep blue/purple
IgE surface receptor
Receptor
Uncommon WBC in blood
<0.2%
Do not phagocytose
Release variety of mediators
Allergic response
Mostly found in blood stream
Unlike mast cells
Infectious mononucleosis
Symptoms
Fever
Pharyngitis
Lymphadenopathy
Inflammation of lymph nodes
Significant fatigue
Caused by
EBV
Frequent in young adults
'Kissing disease'
Spread by saliva
Incubation period
4-8 weeks
Mode of infection
Infects epithelial cells of pharynx
Infects B cells
Through CD21
Replicates inside B cells
B cells become proliferative
T cell response initiated
Lymphocytosis
Raise in total lymphocytes >50%
1 more item...
Pharyngitis
2 categories of immunity
Innate
Neutrophils
Monocytes
Macrophages
NK cells
Eosinophils
Complement
Adaptive
Lymphocytes
Time after infection
0-12 hours
Innate response
12 hours - days, weeks
Adaptive
Immunological memory
1st infection generates memory
2nd infection produces quicker + more potent response
Mechanism of vaccine
Lymphocytes
Structure
Smallest WBC
~10\(\mu\)M
Few cytoplasmic granules
Stain pale blue
Nucleus is proportionally large
Fills most of cell
Stains dark blue
Natural killer (NK) cells
Innate
~10% blood lymphocytes
Visually similar to T and B cells
Recognise + destroy
Cancer cells
Virus-infected cells
Signalling
Target does not display "I am self" signal
NK cell instructed to kill
Lose effectiveness over lifetime
More susceptible to cancer in old age
Association with obesity
Mode of cytotoxic killing
Cytoplasmic granules secrete
Perforin
Creates pores in target cell membrane
Granzyme B
Gains access to cell via perforin pores
Inside cell activates caspase cascade
Apoptosis
T cells
Adaptive
DiGeorge syndrome
Absence of thymus
No T cells
B cells
Adaptive
XLA
Immunodeficiency - no B cells
No antibodies
Flow cytometry
Large cells scatter light more
Data presented on a scatter graph of forward scatter (\(x\)) against side scatter (\(y\))
Granulocytes scatter light sideways
Eosinophils
2-5% of all blood cells
Allergic reaction
Parasitic infection
Parasites bind complement protein
Eosinophils activated
Granules contain enzymes for killing parasites
Produce ROS by respiratory burst
Granule proteins create hole in parasite membrane
Activated by IL-5
WBC disorders
Leukocytosis/leukophilia
High levels
Due to
Infection
Cancer
Allergy
Inflammatory disease
Leukopenia
Low levels
Due to
Bone marrow conditions
Primary/secondary
Drugs/treatments
Infections e.g. HIV
Malnutrition
Autoimmunity e.g. lupus/SLE
Phagocytes
2 lineages
Mononuclear agranulocytic
Monocytes/macrophages
20\(\mu\)M diameter
Important APCs
Cytoplasm is agranular
Largest WBC
U/kidney shaped nucleus
Stains dark blue/purple
Abundant light blue cytoplasm
Monocytes arise from bone marrow
1-5% circulating WBCs
After ~24 hours migrate to tissue
Differentiate to M\(\phi\)
Macrophages are more efficient phagocytes than monocytes
Secrete wide range of cytokines
Regulation of inflammation + adaptive immunity
Functions
Antimicrobial action
Bone resorption
Wound healing - growth factors
Ag/Ab uptake
Phagocytosis
Antigen presentation
2 types of macrophage
M1
Proinflammatory
M2
Anti-inflammatory, wound healing
Can be tumour promoting
Polymorphonuclear granulocytes (PMN)
Neutrophils
Eosinophils
Basophils
Liver disease
Hepatic M\(\phi\)
Presentation of MAA adducts
Proinflammatory
Profibrogenic
Aldehydes
Microbicidal activity
Anti-inflammatory
IL-1Ra
IL-10
TGF-\(\beta\)
Phagocytosis
Links to anti-inflam.
Tissue repair/regeneration
Tissue factors
Matrix metalloproteinases (MMPs)
Calcium dependent
Tissue inhibitors of metalloproteinases (TIMPs)
Liver fibrosis
Links to tissue repair
Inflammatory function
Il-1
Il-12
IL-23
TNF-\(\alpha\)
Chemokines
Watch lecture for receptor presentation