Blood and Immune

Understand and describe the functions of blood

Transport
o Oxygen from lungs to cells
o Carbon dioxide back to lung
o Carry nutrients to cells from gastrointestinal tract
Nutrients diffuse from blood into interstitial fluid and into cells
*Reverse this process for waste products
o Remove heat
o Remove waste products to lung, kidney, skin
o Hormones
o Drugs, vaccines
o Interstitial fluid
Bathes body cells
Constantly renewed by blood
Regulation
o Maintain body homeostasis
Carry substances that regulate temperature
Variable flow in skin (vasodilation, vasoconstriction)
Coolant properties of water
pH by buffers
Convert strong acid/base into weak ones
Salinity, osmorality
Dissolved ions
Dissolved proteins
o Transport hormones from endocrine glands and other body cells
Control body function
Negative feedback
Relatively constant blood volume and osmotic pressure
Protection
o White blood cells (WBC)
o Carry proteins
Antibody molecules
Immune system molecules
o Platelets
Cellular fragments
Clotting system
Seal circulation leaks with fibrinogen (interacting proteins)
Prevent excessive loss from cardiovascular system

Understand and describe the physical characteristics of blood
Blood
o 8% of body
o Denser and more viscous than water
o Alkaline pH
o Liquid connective tissue
o ECM is blood plasma
Understand and describe the components of blood
Centrifuge
o Red blood cells (RBC) sink (more dense)
o Plasma forms layer at top
o Bluffy coat between RBC and plasma
WBC and platelets
Haematocrit
o Percentage of total blood volume occupied by RBC
o Testosterone
1.Stimulate erythropoietin synthesis
2.Stimulate RBC production
o Anaemia
Lower than normal RBC number
Low haematocrit
o Polycythemia
Abnormally high RBC percentage
Body
o *These are proportions
o *Blood is about 8% body weight
o 70Kg man has 5L
o New born has 300mL
o Circulation time is 1 minute

*Hematopoesis
o Process by which formed elements of blood develop
Occurs initially in yolk sac then liver, spleen, thymus, lymph node;
finally red bone marrow
*Most formed elements last for a short time
o Replaced continuously
o Negative feedback regulation
*WBC number varies in response to pathogen/ foreign antigen
*Red bone marrow
o Highly vascularised connective tissue
o Space between trabeculae of spongy bone tissue
o Most in axial skeleton
o Pluripotent stem cells (hemocytoblast)
Red bone marrow cells that derive from mesenchyme
*Formed element does not divide once they leave red bone marrow
o Except lymphocytes
Understand and describe the structure and function of erythrocytes and haemoglobin
Biconcave discs (flattened spheres): good shape to squeeze through capillaries
8 micrometre diameter
*10 angstrom= 1nm
Lack nucleus, DNA, internal organelles
o Not undergo cell division
Originate from reticulocytes
o Which derive from bone marrow
Carries oxygen from lung to tissue
Each cell contain 280 million haemoglobin molecules
Haemoglobin
o Each molecule binds to 4 O
2
molecules
o Alpha-helical protein
o 4 iron containing haem group
Each bind to 1 O
2

Red colour due to iron
o 2 alpha polypeptide (141 aa)
o 2 beta polypeptide (146 aa)
150mg/ml
*Adult haemoglobin is different from embryo

Describe the structure and function of the plasma proteins; serum albumin and
immunoglobulin or antibody
Serum albumin
o 585 aa
o Single chain
o Main protein of blood plasma
o 35mg/ml
o Carrier for insoluble molecules
Lipids
Some hormones
Synthetic drugs
o Mostly alpha helices
Immunoglobulin
o 20mg/ml in blood serum
o Heavy chain= 434 aa
o Light chain= 214 aa
o Only beta sheath
o Recognises antigens (foreign molecules)
Surfaces of bacteria or virus particle
o IgG is the predominant class
12 immunoglobulin domains
Binds and recognises specific antigens
Mainly beta strands
No alpha helices
Differ only in binding site region
B lymphocytes (B cells) make Ig with same antigen binding specificity
Membrane bound Ig have same specificity
o *Epitope of antigen bind to antibody

Understand and describe the structure and function of white blood cells

Contain DNA, nucleus, internal organelles
Monocytes and macrophages
o Monocytes
Produced in red bone marrow
Circulate blood for 6 days
Migrates through capillary walls and come into tissue
Develop into macrophages
o Macrophages
Recognise more obvious features of infections
Ingest, destroy infecting material
Report infection to centralised immune memory system
Future reference
To make molecular tags (antibodies) for more difficult to
recognise infections
B lymphocytes
o Make antibody molecules
T helper
o Detective in immune system
o Process, store information for infection
o Respond rapidly to infection that has occurred before
o Instruct others cells to take action
Cytotoxic T lymphocytes
o Kill target cells
Infection permanently changes composition (B, T cell ) of lymph node
Understand and describe the structure and function of the lymphatic system
Lymphatic system consist of lymph node + spleen + lymphatic tubes
Some components of blood leaves capillaries
o 1.Enter tissue
o 2.Transported back to blood stream via lymphatic system
Most immune system associated with lymphatic system
Lymph circulation allow immune system cells and molecules to circulate throughout
the body
o Circulate by muscles e.g. breathing
o *Immobilised people have low circulation
Lymph contains B cells, T cells, macrophages
Plasma cells in lymph nodes
Most T cells reside in the lymph node ad spleen
*Lymph node is a mosaic of B,T lymphocyte clones
Understand and describe how macrophages, B/T lymphocytes and immunoglobulins
function to protect against infection
First infection
o Inflammatory response
Localised swelling at infection
Tissue damage
Mast cells with histamine granules
o Breakdown
o Release histamine
Attracts: neutrophils, RBC, macrophages
*Phagocytosis I ineffective as bacteria are not
tagged with antibodies and is not specific
Local openings of capillary walls
Antibody in lymph fluid accumulate at infection site
Binds to bacteria
More macrophages arrive at infection site
Pathogen recognised by toll receptor (ineffective as it is not
specific)
Engulf and destroy bacteria
Bacteria is recognised as they are tagged with antibody
molecules
Macrophages and B cells that digest bacteria
Carry pieces of processed antigens on MHC-II on cell surface
o Helper T cell activation
Antigen presenting macrophages in lymph from infection site pass
through lymph nodes
Finds specific T cell
T cell is stimulated
Processed antigen is copied by T-cell receptor
Clonal expansion
Produces T cell clones with same specificity
Assist B cells to produce more antibody molecules
Stimulate formation of cells which destroy other cells
Foreign cells
Cells containing virus
Now there is a much larger number of helper T cells specific to
pathogen
System develop memory
Future infection stimulate response more rapidly
o B cell activation
B cells presenting antigen
Finds specific helper T cell in lymph node
T cell triggers B cell to differenciate into activated B cell clones which
produce large amount of antibodies
o B cell clonal expansion
Delayed
Much more effective
7-14 days after initial infection
Swollen lymph nodes dues to B cell clones producing huge amounts of
antibodies
More T cell clones in lymph nodes to stimulate development of more B
cells
All bacteria is tagged with antibodies to be destroyed by macrophages
and B cells
Macrophage recognise constant region
Bind to FC region
No more infection!
Antibody genesis is dangerous
Correct antibodies must be made
Or self destruction
o Memory update
Specific T cell, B cell clones remain
Ready to respond to future infections
Increased levels of specific antibodies in blood stream
Second and later infections
o Same pathogen reinfects body so immune response is more rapid and effective
o There is already elevated levels of antibodies in blood
Initial recognition is more likely
Remove infection before it spreads
o Clones of B cells, T cells
Memory alert occur more rapidly
Amplication happens much quicker
Understand AIDS epidemic
HIV (human immunodeficiency virus) causes AIDS (acquired immunodeficiency
syndrome)
o Fatal
o Incurable
o No vaccine
o Drugs
Side effects
Not eradicate virus
HIV
o Lentivirus (slow virus)
o No symptoms until 5-10 years after infection
o Transmitted via body fluids (blood semen, and milk)
o It has many different strains (difficult to make vaccine)
o GP120 is covered by carbohydrates that are very variable
Limit spread
o Education
Promote safe sex (condom)
Overcome political discrimination and social prejudice about sexual
and drug issues
o HIV testing
o Distribute drugs to slow progression of disease
HAART
Treatment to reduce mother to child transmission
AZT is first AIDS drug
Binds into active site of reverse transcriptase
Understand and describe the form and functions of HIV
Retrovirus
o RNA virus
o RNA
Converted to DNA
Incorporated into genome of infected cell during viral replication cycle
by integrase
100nm diameter
Surrounded by lipid bilayer membrane containing surface proteins
2 copies of 9749 RNA genome
9 genes in open reading frame
o encode 15 proteins; done by proteolysis
Surface protein gp120, gp41
o Virus surface has closely packed glycoprotein molecules with 3 copies each of
gp120 and gp41
o Made by proteolysis of env gene product
o gp120 binds to CD4
o CD4-gp120 complex binds to other cell surface molecule
o gp41 allows fuse membrane of virus with cell membrane
Releases capsid
Make cDNA
Viral integrase integrates to chromosomal DNA (provirus)
Not detected by immune system
Reverse transcriptase
o Make RNA DNA hybrid
o RNA part is replaced with DNA to make cDNA
o DNA is incorporated into host cell genome by integrase
Proteinase
o Small 99 amino acid proteins
o Dimers
o Cleaves polyproteins
Combination of reverse transcriptase and proteinase inhibitors are current AIDS
therapy
Understand and describe how HIV causes AIDS by attacking the immune system
Infection
o Normal antiviral immune response
o Antibodies against viral surface proteins
o Tag virus particles for destruction by macrophages
o Cell-mediated response removes hidden viruses by eliminating cell advertising
pieces of virus proteins on MHC-II molecule surfaces
o Some HIV DNA incorporated into host DNA which does not produce proteins
to alert immune system
Immune system cannot find DNA
o Infected T helper cells activated, the incorporated HIV DNA is transcribed
o HIV particles produced when immune response occurs
o New T cells and macrophages are produced but infection eventually dominates
o With not T helpers, body is not protected from infection
HIV destroy CD4 immune system cells
o T helper
o Macrophages
Stop immune response development