Blood & body defences

Haematopoiesis

Formation of the cellular components of blood.

Occurs during embryonic development & throughout adulthood to produce & replenish the blood system

Haematology

Study of blood & associated disorders

Blood

composed of blood cells & plasma

Average volume: males - 5-6L, females - 4-5L

roughly 8% of the body weight

38° (~one degree higher then body temp)

Plasma

55% of whole blood

pH 7.35-7.45

7% proteins (main: albumin,) 91.5% water, other solutes 1.5%

Formed element

Buffy coat - leukocytes (WBCs) & platelets (<1% of whole blood)

Erythrocytes (RBCs) - 45% of whole blood

Functions of blood

transportation - oxygen, hormones & nutrients to cells & tissues; removal of waste products (CO₂); transport of ummunoglobulins

regulation - maintains body temp (distribution of what to and away from tissues); control the speed of blood flow; maintain correct pH and water % of cells

protection - carries immune cells, antibodies, etc.; prevents blood loss (platelets & clotting factors); WBC for fighting infection

Abnormal blood parameters reflect organ dysfunction

liver function - ALT & AST levels are indicative of inflamed or injured liver cells

Cardiac markers - troponins released from damaged or dying heart muscle cells after MI

Cardiovascular function - lipid and cholesterol levels. increased levels can increase risk of heart disease

Renal function - creatinine - high levels indicate kidney disease

Haemoglobin

Globin - amino acids

Heme - Iron & Bilirubin (bile)

1/3 weight of RBC

ABO blood groups

Type A - has A antigen, produces Anti-B antibodies

AB - has both antigens, no antibodies

B - has B antigen, anti-a antibodies

O - no antigens, both antibodies

Rhesus (Rh) Blood group

Rhesus antigens are transmembrane proteins at the surface of RBCs

the protein responsible is known as D antigen, or RhD antigen

~ 15% of population has no RhD Antigens and are ‘Rh negative’

Antibodies are only generated after exposure to RhD (I.e. pregnancy)

Rh- can only receive Rh- blood

Rh+ can receive Rh+ or Rh- blood

Haemostatis

3 keys steps to stop blood less when a blood vessel is damaged:

1 - blood vessel damage results in spasm, reduced blood flow, and release of clotting factors

2 - Vasoconstriction limits blood flow, plateletters form a sticky plug & stick to exposed blood vessel

3 - fibrin strands adhere to the plug and form an insoluble clot. RBC are trapped in fibrin threads

3 lines of defence against pathogens

1 - Barriers (anatomical, chemical, biological, mechanical)

2 - Innate immunity

3 - Adaptive ummunity

Barriers

Physical - skin, epithelial cells, mucus

Chemical - lysozyme (tears & saliva) acid (stomach, vagina) and antimicrobial peptides

Biological - commensal microorganisms (produce antimicrobial bacteriocins); lung alveolar macrophages

Mechanical - cilia lining respiratory tract, cough reflex, vomiting & defecation, urinary tract flushing

Innante immune response

• proteins (complement, interferon (IFN)

• cellular (phagocytes, natural killer (NK) cells)

• Inflammation

Components of lymphatic systen

lymph, lymphatic vessels, & lymphatic tissues

Functions of lymphatic system

Drains excess interstitial fluid

Absorbs/transports dietary lipids & fat-soluble vitamins from GIT to blood

Transports antigen to lymph nodes

Transports lymphocytes in and out of lymph nodes

Sequence of flow

Blood capillaries (blood) —> interstitial spaces (interstitial fluid) —> lymphatic capillaries (lymph) —> lymphatic vessels (lymph) —> lymphatic ducts (lymph) —> Junction of the internal jugular & subclavian veins (blood)

Complement system

consists of ~30 plamsa proteins

present in plasma & interstitial tissues

activates pathogens

enhances phagocytosis (via opsonization)

inflammation

lysis of microbe

Cells of Innate Immune response

mast cell - stimulated by complement to secrete histamine

neutrophil - major phagocytic cell

eosinophil

basophil

macrophage - major phagocytic cell

dendritic cell

NK cell (natural killer)

processes of phagocytosis

chemotaxis - movement of phagocytes to the site of damage due to chemical stimulus

adherence - attachment of phagocyte to microbe

ingestion - formation of phagolysosome

digestion - use of lysosome to degrade microbial material

killing - elimination of microbe

opsonisation

opsonins are used to tag foreign pathogens for phagocytosis

opsonins:

• antibody (IgG)

• complement (e.g. C3b)

• antibody + complement (degree of binding is further enhanced, phagocytosis more effective)

antibodies physically block binding sites so pathogens can’t latch onto tissues. they mark the cell for death by phagocyte

Dendritic cells

‘professional antigen presenting cells’

take up foreign material and ride the lymphatic vessels, activating specific lymphocytes in lymph nodes.

Neutrophils

major phagocytic cell entering infected tissues from the blood.

only last a few hours

most common WBC - ~50-70%

pus is mostly ‘spent’ neutrophils

monocytes

comprise 3-10% of wbc

leave the blood, enter tissues & turn into macrophages

Live longer than neutrophils & ingest larger particles

found in sinuses, within spleen, liver, lymph nodes, & bone marrow

remove microorganisms and debris from blood and lymph

Eosinophils

Rare, 2-4% of WBC.

important in controlling parasitic infections - secrete chemicals that kill/inhibit worms

involved in damage to airways seen in asthma

Basophils/Mast cells

Basophils: blood cells which leave circulation and promote inflammation at infection sites.

rare, 0.5-1% of WBC

Mast cells: non-motile cells found in CT.

involved in inflammation & tissue healing, and allergy

release large amounts of histamine when allergen is contacted, causing vasodilation

Natural Killer (NK) cells

special type of lymphocyte - kills cells not expressing as special immune-related molecules called MHC on their surface.

MHC are used to signal the immune system when a cell is infected

can kill distressed, cancerous, or virus-infected cells

they release granules containing toxic substances - perforin which creates perforations in the cell membranes in order to allow granzymes to enter the cell and cause apoptosis

Acute inflammation

Inflammtion is the body’s natural response to harmful stimuli

part of our innant immune response and initial vascular response

localized response to stimulus (infection, damaged cells, trauma, irritation, allergy)

response continues as long as the threat exists

gives no direct protection against future attacks from the same agent

alerts the adaptive immune system & contributes to its activation

acute inflammation characteristics

increased blood flow

leakiness of capillaries (bringing fluid, nutrients, proteins, phagocytes into the tissue to fight infection or trauma)

cardinal signs of inflammation - redness, swelling, heat, pain, sometimes loss of function

allows dendritic cells to take pathogen(-derivied) material to lymph nodes to initiate adaptive immune response

purpose of inflammatory response

contain/isolate offending agents & limit their effects

neutralize & dispose of pathogens & cellular debris

prepare the body to promote healing and repair

stimulate & enhance the adaptive immune response

B lymphocytes

humoral immunity

become plasma (effector) cells after differentiation and activation (by cytokines from T cells) and produce antibodies

T lymphocytes

many different subsets. 2 major subsets:

• CD4 T cells - helper cells that help B cells make high affinity antibodies; help & regulate the responses of other cells (B, T, and dendritic cells)

• CD8 T cells - cytotoxic lymphocytes or killer T cells. Can kill cells infected with intra cellular pathogens (viruses/bacteria)

produced in marrow, mature in thymus

can only recognize antigen with MHC

Clonal deletion

lymphocytes that recognize self antigens as dangerous are deleted

clonal selection

the receptors on B cells are randomized through somatic recombination (randomizing bits of DNA) so that they can have the best chance to identify every pathogen. Once activated, B cells clone themselves quickly with the same receptors to fight the pathogen.

Adaptive immune response

Lymphocytes - B & T cells

B cells produces antibodies (2000/s for 4-5 days)

has ‘memory’ (B&T cells that are left over become memory cells) so it can fight specific pathogen easily in future

MHC

Major Histocompatibility complex

proteins found on the surface of cells to help immune system distinguish between self & foreign antigens

allows T cells to determine if cells are healthy or infected

can have foreign peptide fragments attached for T cells to recognise and respond

MHC1 is on all nucleated cells

MHC2 is on professional antigen presenting cells (macrophages, dendritic cells, B cells)

antigen

a substance that can evoke an immune response

often proteins (but can be nucleic acids, lipoproteins, etc.)

Epitopes

B cell epitope - the part of a native antigen recognized by an antibody or B cell receptor

T cell epitope - antigenic peptide + MHC

Antibody / immunoglobulin (Ig) structure

Y-shaped with two heavy chains and two light chains

Variable (V) segments are at the antigen binding site

Immunoglobulin classes

IgG - most abundant; effective against virus & bacteria; enhances phagocytosis, neutralizes toxins and tiggeres complement activation; can cross placenta to fetus

IgA - found in sweat, tears, mucus, saliva, breast milk, GI secretions; provides localised protection of mucus membranes

IgM - found in lymph & blood. activates complement, lyses microbes. acts as antigen receptors on B cells.

IgD - found on B cells, involved in activation of b cells

IgE - binds to mast cells & basophils via Fc receptors; protection against worms; allergy and hypersensitivity reactions