Blood and its Composition

Zia Ur Rehman
PhD (Massey, New Zealand)
PostDoc (MUG, Austria)

Ref: Sheerwood and Guyton

CVS

• Blood

• Blood Vessels

• Heart

Veterinary Physiology-1 19 December 2020

• Blood is the
vehicle for
long
distance
mass
transport
• It is a fluid
connective
tissue
 Leukocytes

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Neutrophilia & Neutropenia
• Neutrophilia:
• Bacterial inf
• Burns
• Tissue injury
• Hypoxia
• Pregnancy
• Neutropenia:
• Bone marrow suppression
• Bacterial or Viral infections (Aids)
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 Fate of Neutrophils
• Continue Phagocytosis until
– Toxic substances from
– Hydrolytic enzymes from Lysosomes
• Accumulate in Cytoplasm and kill Phagocytes

• Neutrophils when die: release chemical substances

which further stimulate more Neutro, Mono &
Lympho to the infection site
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 Monocyte-Macrophage
system
• Reticuloendothelial sytem
• Mononuclear phagocytic system (MPS)
• Mobile Macrophage??
• Monocytes in Tissues....Macrophages
• Usually in wandering/circulate in Tissue
• A large proportion of these after being developed as
Macrophage, attached to Tissue
• Remain attached for months/years until needed/called upon
• Can easily break attachments to become circulating Macro
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 Monocyte-Macrophage
system
• Definition:
• Combo of Monocytes, Mobile Macrophages, Fixed
Tissue macrophages and a few specialized Endothelial
cells in
• Bone marrow
• Spleen
• Lymph node
• Very imp & Vital
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 Tissue Macro
Skin/Sub cut/Histiocytess
• Skin is intact.....Less chances of inf
• Broken.....More inf

• Local SC infec....
• Macrophage division....more macrophage
• Perform usual Fxs

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 Tissue Macro
Lymph Nodes
• If foriegn particles not killed in tissue
• Enter the lymph ....towards L nodes
• Foriegn particles trapped in nodes in a meshwork of sinus lined by
tissue Macro
• Lymphy flows from nods to General Circulation
– Afferent Lymphatics
– Medullary sinus
– Hilus
– Efferent lymphatics
– Venous blood
• These passage lined by Macro...which phagocytose ...prevent general
dissamination
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 Tissue Macro
Alveolar Macro in lungs
• Entry of Foriegn Particals in Lungs
• Macro in Alveolar walls
• If Foriegn particles digestable, digest and release the
particles in lymph
• If not digestable...Macro forms a Giant cell...Capsule
around particle untill slowly absorbed
• Such Capsule more often formed around:
– Tuberculosis bacili
– Silica dust particles
– Carbon particles
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 Tissue Macro in Liver
Kupffer Cells
• Entry of Foriegn Particals through GIT
• Bacteria GIT mucosa...portal Blood
• Must pass through Liver sinusoids before General
Circulation
• Liver Sinusoids lined with Kupffer cells
• Very Fine Particulate Filteration system..... None of bacteria
from GIT succeeds in passing from portal to General circ

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 Tissue Macro
Spleen & Bone Marrow
• If envading Suceeds to General Circulation
• Remaining Tissue Macrophage System
– Especially Spleen & Bone Marrow
• In both tissues Macro entrapped in reticular network
• Phagocytosis when in contact

• Spleen is same like L. Nodes... Lymph is replaced by Blood

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 Tissue Macro
Microglial Cells of Brain
• Non Neural cells of CNS
• Migratory
• Act as Phagocytes of waste products of nervous system

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 Tissue Macrophages
• Osteoclasts (bone)
• Alveolar macrophages (lung)
• Microglial cells (brain)
• Histiocytes (connective tissue)
• Kupffer cells (liver)
• Langerhans cells (LC) (skin)

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 Few Terms

• Diapedesis: Outward oassage of blood cells through

intact vesseles
• Emigration: process of crossing the intact vessel
towards infection site
• Amoebide Movements
• Chetaxis: Destruction of cells producr chemical
substance which influence movement of
WBCs...attract WBCs
– Degenerative products of inflammed tissue

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 Inflammation

• Non-specific, innate response elicited by foreign

invasion or tissue damage
• Localized protective response
• To destroy, dilute or wall of both the injurious agent
and injurious tissue
• Cause/Etiology
• Infectious agents, trauma, Chemicals, burns
• Example “Mosquito bite”
•
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 Inflammation

• Literal Meaning “To Set on Fire”

• To disinfect & clean injured tissues
• To prevent spread of infection
• To prepare for healing

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 Characteristics of
Inflammation
• Distinct Features:
– Redness (Dilation of capillaries…Inc Blood
supply)
– Swelling (Extra blood)
– Heat (Dilation of capillaries…Inc Blood supply)
– Pain (Pressure & irritation on local sensory
nerves)
– Loss of Fx
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 Characteristics of
Inflammation
• Damaged Tissue Releases:
• Histamine
• Bradykinen
• Serotonin
• PGs
• Complements
• Lymphokines etc

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 Characteristics of
Inflammation
• These released chemicals influence on:
• Vasodilation of local vessels with excessive blood
supply
• Inc permeability of capillaries, allowing Inc leakage of
fluids (Inc WBCs, Inc Phago, inc Plasma proteins)
• Often Clotting of fluid (Inc Fibrinogen) (walling off)
• Inc migration of WBCs to the area
• Swelling of tissue (localized edema)

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 Response to Inflammation
• Local
• Systemic…when infectious agents get into the blood
or TOXINS released carried throughout the body

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Response to Inflammation
• WBC Inc
• Fever
– Triggered by Toxins
– WBC released Pyrogens
– Moderate fever may contribute to defense by stimulating
phagocytosis and inhibiting microorganisms

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 Types of Inflammation
• Acute: (Sever Signs & Short Course)
• Sudden onset
• Classical signs of Inflammation
• Vascular and exudative Process Prominent
• Chronic: (To persist for a long time)
• Prolonged and persistent
• May be a continuity of acute Inflam

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 Walling off effect of Inflam
• One of the main effect of Inflammation: “Wall off”
• The injured area from remaining Healthy area
• Clotting proteins from plasma pass into interstitial fluid
• Clotting protein + Platelets make local clots to seal off
the infected region &
• Allow the repair of damage to begin
• As infected town are Quarantined & sealed

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 Infection
• Multiplication of microorganisms in body tissues
• Especially local Cellular Injury
• Invasion of microorganisms

• Infestation: invasion of complex organisms

• Typically caused by insects & worms

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27
28
 Steps of Inflammations
1 Degenerative products of inflamed tissue or
bacterial cells can be chemotactic (chemically
attracting) and diffuse through interstitial spaces to
capillaries and venules.
2 Chemotactic substances increase porosity of these
vessels and also provide for adhesion of neutrophils
to endothelium (margination).
3 Neutrophils squeeze through endothelial openings
(diapedesis).
4 Neutrophils proceed to inflammatory sites by
ameboid movement.
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 Inflammation: Neut & Macr
• Tissue Macrophages- 1st Line of Defense:
• Tissue Macrophages start phagocytic activity within minutes
• Activation by products of infection:
• 1st effect: Rapid Enlargement
• 2nd effect: Many of previous active macrophages loosing
their attachment & become mobile
• Forming the first line of defense against infection during First
hour or so

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 Neutrophil Invasion- 2nd
Line of Defense:
• Within an hour or so: Neutrophil Infiltration towards
inflamed area from blood
• Attracted by products from inflamed tissue that cause
following reaction:
• 1- Alter the inside of endothelium of capillaries…causing
Neutrophils to stick to the walls…..Margination
• 2-Cause break away the cells of Endothelium from each
other, allowing Neutros to slip away…Diapedesis
• 3-Cause Chemotaxis: Thus attracting Neutros…Area filled
with mature Neutros…instantly start activities
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 2nd Macrophage Invasion-
3rd Line of Defense:
• Invasion of Neutros & Tissue Macro Within an Hour
• Monocyte number in Circ is less
• Monocyte pool in bone marrow is also very less
• Therefore build-up of Macro in inflamed tissue area is much
SLOWER than that of Neutros…Requiring several days
• Even after reaching at Inflam site, Monocytes are still
immature cells.
• Need ~8 hrs or more to develop in size to produce large
number of Lysosomes….then acquiring capacity of Tissue
Macrophages for phagocytosis
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 2nd Macrophage Invasion-
3rd Line of Defense:
• Several days to several weeks….Dominate the phagocytic
cells @ Inflammation SITE
• Because of more production of monocytes from bone
marrow
• Importance of this Line:
• Macro r High eaters than neutro
• Key role in development of Abs:
– Activation of specific lymphocyte clone
– ILs secretion to promote growth & reproduction of Lymphocytes

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 Inc Production of Granulocyte &
Monocytes- 4th Line of Defense:

• This result from stimulation of granulocytic &

monocyte progenitors cells of bone marrow

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 Formation of PUS

• During phagocytosis Neutrophils (All), Macrophage (Many)

die because of:
• Bacterial poisons, Noxious agents they ingest
• Crowding
• Dec Oxygen etc
• After several days, a cavity is often formed in Inflamm
tissues that contains:
• Necrotic Tissue
• Dead Neutros. Dead Macros
• Tissue fluid, Debris etc
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 Formation of PUS

• This is PUS
• Dead Leucocytes in it: PUS cells
• After the suppression of Infection:
• Dead cells & Necrotic tissue in pus gradually autolyse (Self-
Digestion) over a period of days
• Products are absorbed into the surrounding tissues until
most of the evidence of tissue damage is gone

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 Leukocytes…..Eosinophils

• Eosinophils
On a stained blood film, eosinophils can be
seen to have cytoplasmic granules that are red
or reddish‐orange (eosinophilic).
These are about the same size as neutrophils.
• Acidophiles

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 Leukocytes…..
• Eosinophils
– Increased count is associated with allergies
– Eosinophilia
– Asthama
– Hay Fever
– Parasitism (internal parasite infestation)
– Cant engulf worm, attach to it, release substances
n kill it

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 Leukocytes…..Eosinophils

• Functions:
• Eosinophilia
Allergy… Eosinophil granules contain several
enzymes (e.g., histaminase) that dampen and
terminate local inflammatory reactions of
allergic origin.
• Contain Both Histamine and Anti-Histaminic
substances
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 Leukocytes…..Eosinophils
• Eosinophilia.....Allergy…
• Mast cells and Basophills released Eosino
philic chemotactic factors
• Eosinophils detoxify some of the inflammation
inducing substances like taking up and
destruction of Histamines, Serotonin &
Bradykinen
• Thus posses anti inflammatory effects
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 Leukocytes…..Eosinophils
• Parasitic infestations
• Eosinophilia…..more numerous in certain types of
parasitisms.
• The parasitic forms are opsonized (attacked by
antibodies)
• Eosinophils discharge their granular contents
onto the surface of the opsonized parasite,
inflicting lethal damage.
• Cant engulf worm, attach to it, release substances n kill it

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 Leukocytes…..Eosinophils

• Parasitic infestations
• Example of Schistosomiasis
• Common Syndrome: Hemorrhagic enteritis, anemia,
emaciation
• Killed by Eosinophils by releasing:
• Hydrolytic enzymes from granules
• O2 which is leethal
• High Larvicidal polypeptide: Major Basic Protein
(MBP) (Arginine rich protein)

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 Leukocytes…..Eosinophils

• Parasitic infestations
• Example of Trichinosis
• Enter Humans through infected meat
• Raw or Cysts in muscles tissue of pork
• When meat is cooked, Larvae killed; under
cooked...larvae live in cyst...cyst digested by
digestive juices...and larve free and become
mature in intestines

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 Leukocytes…..Eosinophils
• Stress:
• Eosinopenia…..
• Cortisol reduces the eosinophil count by:
• Enhancing eosinophil diapedesis &
• Diminishing the release of eosinophils from the bone
marrow.
• Cortisol production increases during stress, and
lowered eosinophil blood counts have been
associated with stress

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 Leukocytes…..Eosinophils

• No/Limited Role against usual (Bacterial/viral) type of

infection

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 Leukocytes…..Basophils
– Least Numerous
– Granules Stained with basic dye & appear Blue
– Nucleus often ‘S’ shaped & lobulated
– Rare in normal blood, and their distribution in blood is
usually considered to be less than 1%.
– Synthesize and Store:
• Histamine (allergy)
• Heparin (Helps in removing fat from blood after fatty meal,
immune response & anticoagulant)

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 Leukocytes…..Basophils

– Granulocytes from bone marrow…stay in transit for 1 day

– Dies in 3-4 days normally unless requires early
– Basophils are similar to the mast cells that are present in
the interstitial spaces outside the capillaries.

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 Basophils & Mast Cells
– Basophils are similar to the mast cells that are
present in the interstitial spaces outside the
capillaries.
– But True relationship is not clear, Researchers
differ
– Some Researcher: Basophil Circulating Mast Cells
– Granules of Basophils are Water Soluble But Mast
Cells NOT
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48
 Basophils & Mast Cells
– Mast Cells arise from cells of Thymus & Spleen
– May be Cells from Separate Origin BUT perform
related Fxs
– Since indicated in many Animal Species: if Large
No. of Mast cells in Circulation then Small
number of Basophils in Circulation & Vice versa

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Leukocytes….. Basophils
Functions:

• Some role in Initiate inflammation: Basophil

granules contain histamine, bradykinin,
serotonin, and lysosomal enzymes, substances
that initiate an inflammatory response.

• They seem to lack phagocytic power.

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 Leukocytes…..Basophils
• Allergy: Basophils and mast cells have receptors
on their cell membranes for immunoglobulin E
(IgE) antibodies (those associated with allergies).
• When the antibody on the cell membrane
contacts its antigen, the basophil ruptures,
releasing its granular contents, and the local
vascular and tissue reactions of allergies are
manifested.
• Rupture cause release of Histamine along with
other enzymes, Cause expedite Allergic reaction.
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 Leukocytes…..Basophils
• Basophils enhance allergic reactions, whereas
eosinophils tend to dampen them.
• There is a balance between their functions in that
inflammatory reactions proceed quickly via
basophils, and then are modified via eosinophils
so that overreaction does not occur.

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 Leukocytes…..Lymphocytes
• Morphologically as small or large.
• Small….Immature
• Large….Mature.
• Lymphocytes are involved in immune responses, and on
this basis are classified as T cells or B cells. Both T and B
cells are derived from hematopoietic stem cells
(lymphoblasts) that differentiate to form lymphocytes.
• Mononuclear, Non-granulytic, deeply staining nucleus
with dense chromatin….Pale Blue staining Cytoplasm

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Leukocytes…..Lymphocytes
…genesis
• Life of lymphocytes…100-300 days
• Lymph nodes and tonsils are lymphoid tissues
– In mammals, 1st Trimester: yolk sac
– 2nd & 3rd Trimester: liver & Spleen
– shortly before or after birth, the site of early
processing and differentiation:
– T Lymphocytes: Thymus gland
– B lymphocytes: Fetal liver, spleen, and bone marrow.

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 Leukocytes…..

• Lymphocytes
– B lymphocytes
• Humoral immunity
• Produce Abs
• Ab binds n marks
• Matures in Bone marrow or Bursa of fabricius
• Usually target Bact

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 Leukocytes….. T cells
– Produced from Stem cells which migrate to Thymus
during Late Embryogenesis
– Enormous number produced, mostly self destroyed
– About 10% cells leave Thymus to populate T cells in
Secondary Lymphoid Tissues (L.nodes, spleen, P.Patches)
• No antibodies
• Cell mediated immunity
• Mature in Thymus
• Target cells:
– Virus invaded cells……………….Cancer cells

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Leukocytes…..Lymphocyte
– T cells are
– Cell‐mediated immunity
– Formation of large numbers of lymphocytes to
destroy foreign substances (antigens).
– Three different types of T cells:
– Cytotoxic T cells (Effector cells)
– Helper T cells (Regulatory Cells)
– Memory T cells.

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 Leukocytes…..T
cells…General Aspects
– Exposure to Ags….Blastogenesis…enlarge & divide
– Some daughter cells revert to form expanded clone of
memory T cells
– For both regulatory & Effector Fx:
– Treg produce a no of substance….generally known as
Lymphokines (soluble protein mediators released by )(which
unlike Ab don't attach to Ag) but direct cell function

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 Leukocytes…..T
cells…General Aspects
– Lymphokines influence behaviours of other cells:
– Macrophages: Migration Inhibit Factors (MIF)
• Macrophage Activating Factors (MAF)
– Neutrophils (Chemotactic Fact; Leucocyte Inhibitory Factor)
– Lymphocyte (T. Lymphocyte growth factors; B Lympho GF)

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 Leukocytes…..T
cells…General Aspects
– Interleukins: group of polypeptide that carry signals b/w
cells in immune system
– IL1: monokines secreted from Macro,
– Act on T cells to enhance cell mediated immunity
– IL2: sec by T lymphoc; Inc growth of Cyto T & Suppressor T
– IL3: Sec by B Lympho & Effects B Lympho
– IL4,5 &6: sec by T lympho & act on B lympho (also called B
Lymphocyte Growth Factor)
– Monokines & Lymphokines collectively called CYTOKINES
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 Leukocytes…..Cytotoxic T
cells
– Cytotoxic T cells/Killer Cells
– T‐cell receptors bind to specific antigens
– Cytotoxic substances are released into the foreign cell
(e.g., bacteria, viruses, tissue cells) (Figure 12.5).
– Cytotoxic cells also attack cells of transplanted organs.
– Because cancer cells generate unique antigens when
they become cancerous, cytotoxic T cells recognize the
cancerous cells as foreign to the body and attack them

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Leukocytes…..Cytotoxic T
cells

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 Leukocytes…..Helper T
Cells
– Helper T cells
– Most numerous of the T cells.
– T cells activated: Assist in the activation of cytotoxic T cells
& B cells.
– Antigens ordinarily activate the cytotoxic T cells and B cells
– But activation is more intense when assisted by helper
T cells.

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 Leukocytes…..Memory T
Cells
– Memory T cells
– Long‐lived
– Respond to the same antigen when exposed at a later date.
– Memory B cells have a function similar to memory T cells
– Readily converted to effector cells by a later encounter
with the same antigen.

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 Leukocytes…..

• Repeat Slide:
• Lymphocytes
– B lymphocytes
• Humoral immunity
• i.e, Produce Abs
• Ab binds n marks
• Matures in Bone marrow or Bursa of fabricius
• Usually target Bact

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 Leukocytes…..B Cells
– First discovered in birds
– Early processing and differentiation was found to occur in
the bursa of Fabricius, from which the name was derived
(B for bursa).
No analogous organ in mammals ~Equivalent is Bone Marrow
– Activated after exposure to an antigen
– B cells activation…….proliferate…….. Start producing
Igs…ask question, what is Ig?….All cells from single clone
will produce Igs with identical Ag binding sites

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 Leukocytes…..B Cells
– B cells activation…….proliferate……..
– transform into plasma cells: Mature Ab secreting cells
– Smaller number of Memory cells.

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 Leukocytes…..B Cells
– Do not attack foreign substances directly
– Plasma cells produce large quantities of
antibodies (globulin molecules called immunoglobulins)
– Which inactivate the foreign substance
– Type of immunity is known as humoral immunity
–

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 Leukocytes…..B Cells
– Antibodies can produce inactivation by:
– causing agglutination
– Precipitation
– Diff b/w agglutination & precipitation: Size of Ags
– If Ags r soluble (small): precipitation
– If Ags are large: Agglutination (easily sediment particles)
– Neutralization (antibodies cover toxic sites)
– Lysis (rupture of the cell). Agglutination and
precipitation reactions are shown in Figure 12.6.
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19 December 2020 69
Leukocytes…..B Cells

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Leukocytes..Lymphocytes
Humoral Immunity…
Complement system
– Complement system: More common humoral method of
immunity
– Composed of a number of enzyme precursors that are
activated successively.
– From a small beginning, a large reaction occurs. Examples
of complement reactions include
– (i) opsonisation: foreign substances are covered by
antibody and become vulnerable to phagocytosis
by neutrophils and macrophages

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Leukocytes..Lymphocytes
Humoral Immunity…
Complement system
– From a small beginning, a large reaction occurs.
Examples of complement reactions include
– (i) opsonisation: foreign substances are covered by
antibody and become vulnerable to phagocytosis
by neutrophils and macrophages; and
– (ii) chemotaxis: Complement product attracts
neutrophils and macrophages into the local region of
the antigenic agent.

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Leukocytes..Lymphocytes
Humoral Immunity…
Complement system

– Lymphocytes comprise about two‐thirds of the

leukocytes in birds and in this regard are similar to
the cloven‐hoofed animals

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 Leukopenia
– Clinical condition in which very less WBCs produced from Bone
marrow
– What will happen if Dec in WBCs but there is no invasion of
pathogens???
– Leaving the body unprotected against pathogens
– Body Lives in Symbiosis with many bacteria because all
mucous membrane are constantly exposed to large no of
bacteria
– GIT/Lungs/Urethra/Reproductive tract
– Any Dec in WBCs immediately allows invasion of tissue by
bacteria already present in the body
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Leukopenia

– Within 2 days after Bone marrow stops forming

WBCs:
– Ulcer may appear in mouth & colon
– Respiratory tract disorders
– Bacteria from Ulcer then rapidly invade the
surrounding tissues and Blood

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 Leukopenia…Causes

– Aplasia of Bone Marrow:

– Aplasia (Entire Absence)
• Nuclear explosions
• Certain drugs (Chloremphenicol, Barbturates)
• Hence Leukopenia

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Leukaemia
– Progressive, Malignant Disease of blood forming
organs, Marked by:
– Distorted proliferation & Leucocytes & thr
precursors in blood & bone Marrow
– Uncontrolled production of WBCs is caused by
Cancerous mutations of a myelogenous or
lymphogenous cells
– Cause leukaemia which is Characterized by Inc no
of WBCs in circulating Blood
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Leukemia…Types
– Lymphocytic
• By cancerous production of lymphoid cells then
spreading towards other areas of body
– Myelogenous (Non Lymphocytic)
• By Cancerous production of young myelogenous cells in
bone marrow & then spreads throughout body
• Partially differentiated cells result which are called
Neutrophilic; Eosinophilic; Basophic or Monocytic
Leukemia

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Leukemia…Types
– Myelogenous
– Usually more undifferentiated the cell.....More
acute is Leukemias
– Often leading to death in few months if not Rx
– With some of more undifferentiated cells, the
process can be chronic, developing slowly over 18-
20 years
– Leukemic cells(esp undifferentiated; non functional
in providing the protection against infections)
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Leukemia…Effects on the
body
– First effect: Metastatic growth of Leukemic Cells
– Reproduction of Leukemic cells, so greatly to
invade surrounding Bones
– Increasing the tendency of fractures
– Almost all leukemis spread to all vascular regions:
spleen; liver; regardless of origin Leukemias is bone
marrow or lymph nodes
– Metastasis: Transference of a disease to the other
remote part of the body
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Leukemia…Effects on the
body
– Most important effect of Leukemia:
– Excessive use of metabolic substrates by growing
cancerous cells
– Leukemic tissues keep growing while other tissues
become deblitated
– Metabolic starvation...leads to death

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 Leukemia…Effects on the
body
– Also causes Anemia & Bleeding tendency of
thrombocytopenia
– Leukemic patients..Inc Leucocytes...Abnormal Ranges
– Cancerous cells may crowd out Proginator Cells of
RBCs & Platelets
– Resulting in Anemia & Impaired Clotting

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 Leukemia…Summary of steps

– Uncontrolled proliferation of malignant leukocytes

– Crowding of bone marrow cells
– Decreased Production of normal Hemopoitic cells

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 What differentiates Leukemia

– Cells of origin
• Myloid
• Lymphoid
– Degree of WBC differentiation
• Decresed differentiation means less function

• Acute / Chronic

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Leukemia...Clinical
Manifestation
– Increased risk of infection
– Depressed immune function
– Associated with Bone Marrow suppression

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 Terminologies....Suffix

– Cytosis: Increased
• Monocytosis .....Basocytosis
– Cythemia: Increased
• Polycythemia
– Philia: Increased
• Basophilia
– Penia: Decreased
– Dysplasia: Abnormality of
development/growth/differentiation
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89
 Immunity
• Innate (non specific)
– Neutrophils and Macrophages
1. Inflammation
2. Interferon
3. Natural killer cells
4. Complement system

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 Immunity/Immune system

• Innate (Non-specific)(Inborne/HereditaryCongenital)
– Bloodbourne (rest check from chart)
• Inflammation Acids in sweat & oil secretion
– Physical barriers
• Antimicrobial proteins (lysozyme, interferons, complement proteins)

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 Physical & Chemical
Barriers

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 Phagocytosis

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 Immunity/Immune system
• Adaptive or acquired (specific)(Doesn’t develop until after the
body is attacked by pathogens)
– 1-----Active
• Humoral………………….Cell-Mediated
– 2----Passive (transfer from a donor in which Abs were
produced to a recipient for temporary immunity)
– i.e…ready made Abs
– Patient’ immune system is not stimulated by Ags
– e.g…Fetus obtained Abs from mother from mother’
bloodstream
– Transfer by colostrum
– Or by serum
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 Immunity/Immune system

• Adaptive or acquired (specific)(Doesn’t develop until after the

body is attacked by pathogens)
– Active
• Humoral………………….Cell-Mediated
– Ags enter naturally (like flu) OR artificially (flu shot)
– Vaccination….Artificial
– Infections…….Natural
– Stimulated by Ags to produce antibodies

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 • Adaptive or acquired (specific)
– Antibody mediated (plasma cells)
– Cell mediated (T-lymphocytes)

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101
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 Lines of defenses in body
• 1st
– Physical Barriers
• 2nd
– Inflammation
• 3rd
– Humoral Immunity

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Antigens

• Any substance capable of, under appropriate

conditions, of inducing specific immune
responses and reacting with the products of
that response; i.e. with specific Abs or
specially neutralized T-lymphocytes or both
• Normally are large molecular weights
• Good Ag is that which is foreign to the body
• Ag should be able to readily stimulate immune
response
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 Antigenic determents
• Present on Ag to attach Abs
• (Epitopes) An epitope, also known
as antigenic determinant, is the part of
an antigen that is recognized by the immune system
…recurring molecular groups
– Hapten
– Bacterial
– Viral
– Blood groups

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 Antigenic determents

• Allogenic Ag: Occuring in some individuals & not all

of a species
• Blood gp Ag: present on a surface of RBCsFor your
own understanding Inactive Ag & Active Ag
• Conjugated Ag: Haptens

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 Antigenic determents

• Pollen Ag; Self Ag

• Xenogenic/heterogenic Ag: Antigenic to one spp but
not to others

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 Antibodies/Serum
Proteins/Immunoglobulins

• Substrates produced by body in response to the

presence of a foreign body (Ag)
• Protein in Nature

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Anatomy of Antibody

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 Lymphatic System
• Crucial Battleground during infection

• Involved in both specific & non-specific immunity

• Consists of: Network of vessels/ L.Nodes/ Thymus/
• Tonsils/ Appendix/ spleen/ P Patches
• Lymphatic vessels carry a fluid ‘Lymph’ collected from
tissues and returned to circulatory system via
lymphatic system

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Lymphatic System
• Crucial Battleground during infection
• Capillaries are ONLY blood vessels with walls thin
enough for substances to cross b/w blood & interstitia
fluid that bathes the body cells
• Blood leave @ arterial end of capillary bed…. Re-enter
@ venous end…that re-entry is ~99% of blood
• Remaining 1%: eventually returned by the lymphatic
blood vessels
• Lymph Compo: 90% water; 10% Plasma & Lymphocyte

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Lymphatic System
• So the lymphatic system has 2 functions:
• A) Battle ground of infection….U already know how
it restricts infection
• B) To return the tissue fluid to circulations
• Lymph drains from lymphatic capillaries into larger &
larger lymphatic vessels….It renters the circulatory
system via 2 large lymphatic vessels which fuses with
veins in shoulders… These are:
– Thoracic duct
– Right Lymphatic duct
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Lymphatic System
• How Specific & Non-Specific immune Fx??
• Lymph nodes are densely packed with Macrophages &
Lymphocytes
– Macrophages engulf in non-specific fashion
– Lymphocyte activated to mount a specific immune
response
• Thus L. System is Battleground of infection
• During infection: L. node swell coz of multiplication of
defensive lymphocytes…..often referred as ‘Swollen glands’
• Most obvious in Neck
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Immune Response-
Specific- Memmory
• When non-specific fails…Specific comes (3rd line of
defense)
• Specific system works more efficiently
• Also amplify non-specific reaction i.e inflammation &
complement reactions
• Non-specific…Always ready to fight to a variety of inf
• Specific…relatively delayed and Specific

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Immune Response-
Specific- Memmory
• Extremely specific ….. & remarkable Memory
• Can remember Ags encountered before….react them
More promptly and vigorously on subsequent
exposure
• So there are Primary & Secondary Immune response:
– Primary: slow onset; Low magnitude; Short lived; IgMs
– Secondary: Rapid; High magnitude; long lived; IgG & IgE

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Immune Response-
Specific- Memmory
• Mumps Example of Memory of Immunity
• Childhood disease….but enough to confer immunity
for the rest of individual’s life
•

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Tolerance
• Tolerance to self antigen
• Achieved by Clonal Purging … which has 2 parts
– Clonal deletion
– Clonal Anergy
• Clonal Purging … When T lymphocyte produced (10%
released while 90% killed) Only non-self-reacting T
cells released.. Immune Tolera

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Immune
Tolerance/Tolerance
• Achieved by Clonal Purging … which has 2 parts
• Clonal deletion (major mechanism)
– Self reactive cells destroyed/physical elimination
– Apoptosis of immature cells vulnerable of self reactions
– Destroy within Thymus
• Clonal Anergy (For escaped from deletion)
– Deactivated/non-functional many ways; most imp is Anerg
– T cell must receive 2 signals to turn ON…one from its
compatible Ag…2nd co-stimulatory signal found ONLY on
surface of APC
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Immune
Tolerance/Tolerance
• Dual signal never presented by self-Ags
• If a person shld become immune to own tissues, the
process of acquired immunity ’ll destroy his own body
• So T cells remained OFF in absence of Dual signal
• Anergy: Lack of energy… so called as Anergized T cells
• Survive but Inactivated

• These were 2 main ways to produce self immunity

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Tolerance

• Fortunately Immune mechanism normally recognizes

own tissues being completely distinctive from invader
• And his immune system neither from Abs nor
activated T-Lympho against his molecules
• Normal conditions immune system will not consider
his own molecules as Ags
• This is called as immune Tolerance

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Tolerance

• 3- Active suppression by T regs: by inhibiting some

lympho clones specific for body OWN throughout life
• 4- Receptor editing: on B cell surface: once Bcell
against self Ag meets self-Ag; escape destruction and
edit its receptor….Rehabilitation
• 5- Immunological Ignorance/ Ag Sequestering (side
away/ alone): Some self molecules normally hidden
from immune system because they never come in-
contact with ECF
• This is called as immune Tolerance 19 December 2020
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 Mechanism of
Tolerance…Theories
• May be determined Genetically i.e. Absence of genes to
form sensitized lymphos & Abs against person’s own tissues
• Also developed during processing of Lympho…..
• All those clones of lymphos that are specific for body’s own
tissue are self-destroyed because of their continual exposur
to the body Ag

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Failure of Tolerance

• Occasionally, the immune system fails to make the

distinction b/w self-Ag & Foreign bodies
• Unleashing the deadly powers against one or more body
tissue
• A condition, immune system fails make to recognize &
tolerate against self-Ags “Autoimmune Diseases”

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 Autoimmune Diseases
Causes…

• 1- A Dec in Ts or imbalance Ts : Th cells specific for self-Ag

• 2- Normal Self-Ags may be modified by factors such as

Drugs, Environ Chemicals, Viruses or Genetic mutation…..
– So No Longer recognized & Tolerated by immune system

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Autoimmune Diseases
Causes…
• 3- Exposure of normally unaccusable Self-Ags, sometime
induces an immune attack against these Ags
– Because the immune system usually never exposed to hidden self
Ags….. Unusual exposure caused by injury or disease
– Hashimoto’s Ds: Production of Abs against Thyroglobulin (Iodine
containing glycoprotein in thyroid gland) & destruction Thyroid
Gland Hormone secreting capacity (Hashimoto’s Thyroiditis)
– Corneal Opacity
– Cornea: clear transparent part of the eye. Corneal proteins don’t
circulate in fluid of fetus; therefore tolerance to these never
develops, when damage to cornea, some corneal proteins elicit
immune response
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Autoimmune Diseases
Causes…

• 4- Exposure of immune system to foreign Ag, structurally

identical to self-Ags may induce the production of
Abs/Activated Lympho….. Not only interact against foreign
Ag BUT also against self-Ags
– Streptococcal Bacteria, responsible for ‘Strept Throat’.
This bact Ag v similar to self-Ags of Cardiac Valves…. In which Abs
produced against Streptococcus also reactive with cardiac tissues
giving cardiac lesions associated with ‘Rheumatic Fever’

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 Autoimmune Diseases
Causes…
• 5- New Studies Hint: Bcoz Inc of more Autoimmune Ds in
females than Males… May be a legacy of Pregnancy:
• Fetal cells have access to mother’s circulation during
Delivery Trauma
• Normally these fetal cells wiped out after birth
• Sometimes these cells being ignored even for years; trigger
a gradual & more subtle but later on immunity develops
against these fetal cells and also against Body’s closely self-
Ags

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Autoimmune Diseases
Causes…

• 5- New Studies Hint: Bcoz Inc of more Autoimmune Ds in

females than Males… May be a legacy of Pregnancy:
• Systemic lupus erythematosus: Autoimmune attack against
DNA… can affect many organs….
• Most commonly Skin, Joints & Kidneys

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 Autoimmune Diseases
Examples…
• Hashimoto’s Ds
• Rheumatic Ds…. Streptococcal related
• Corneal opacity
• Addison’s Ds: Primary Adrenocortical Insufficiency
– Against adrenal cortex
• Diabetes Mellitus type I: Against Beta cells of Pancreas
• Grave’s Ds/Hyperthyroidism: Thyroid stimulating Ab/Ig is
produced whose target is TSH receptors on thyroid cells
• This Ab stimulates both secretion & growth of thyroid in a
manner similar to TSH. However there is no –ve for this Ab
so thyroid secretion & growth unchecked
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 Autoimmune Diseases
Examples…
• Multiple Sclerosis:
– T cells react against myelin (a protein that insulates axons of
neurons…. A particular form of herpes enters body & resembles
with myelins of nerves.
– So Abs produced which erroneously react with myelin & virus too
– C.F: Tingling; Numbness; visual prob;Muscle weakness; paralysis
• Myasthenia Gravis: Ms weakness which Inc with activity &
relaxedby rest…. Autoimmune is against skeletal Ms
• Pernicious Anemia: Against parietal cells of gastric mucosa
which secretes the intrinsic factor which helps in B12
digestion & making it absorbable
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 Autoimmune Diseases
Examples…

• Acute Glomerulonephritis:
• Against glomeruli, resulting from exposure to another
streptococcus
• Systemic lupus erythematosus
• Idiopathic thrombocytopenia:

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Immune Privilege
• Testis & Eyes
• When transplanted in an unrelated individual …. No immun
response
• May be because of cellular plasma memb of these tissues
cause apoptosis of approaching activated lymphocyte that
could attack tissues

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Immune Diseases
• Deficiency
– Immune system fail to respond Adequately to Ags
– Genetic (Severe Combined Immuno deficiency SCID) Both T & B
cells lacking…so death in infancy or keep it germ free
– Acquired (AIDS; Hodgken’s Ds (Lymphoma))
• Lymphoid tissue destruction
• Anti-inflammatory Agents
• Cancer therapy (Lymphocyte & cancer cells destroyed)
• Inappropriate immune response

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Immune Diseases
• Deficiency
• Inappropriate immune response
– Autoimmune
– Immune complex
• Inc Abs response damage to Body cells & Inc Ab/Ag complexes activate
complement sytem
– Allergy
• Immediate hypersensitivity
• Delayed hypersensitivity

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 Allergy &
Hypersensitivity

• Important / undesirable side effect of immunity

• Allergy is the acquisition of an inappropriate specific immune
reactivity or hypersensitivity
• Allergy/hyper to a normally harmless substances…pollen…Allergen
• Allergen (offending Ag)…may be Ag or Hapten

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Allergy &
Hypersensitivity
• Immediate
– Within 20 minutes
– B cells….elicited by Abs
– Most common allergen: pollen, bee sting, penicillin, certain food, molds, dust,
feathers, animal fur
– Unknown reasons for production of IgE
– Also involve Mast cells in both immediate n delayed
– Chemicals released: Histamine: Inc Capillary permeability & mucus production
– Slow Releasing Substance A (SRS-A): contraction of smooth muscles
– Eosinophil chemotactic factor Platelet activating factor
• Delayed

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 Some examples of
Allergy…immediate
• Symptoms vary depending on site & type of allergen& Mediators
involved
• Anaphylaxis: (Shock)….Allergen in circulation…can interact with
variety of cells i.e Basophils, mast cells
– A widespread allergic response throughout circulation & associated tissues
– Anaphylactic Shock..Severe hypotension results from widespread vasodilation
….lead to plasma fluids towards interstitial fluid (edema)…Left shift
– Respiratory failure…Asthama & suffocate
– Rx vasoconstrictors; bronchodilators; like epinephrine…Antihistamine give
partial relief
• nmbn

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 Some examples of
Allergy…immediate
• Urticaria: Nettle Rash/ dead Rash? Hires
• May be due direct exposure to chemicals
• Appearance of slightly elevated patches red marks (due to Histamine
• Local Anaphylaxis
• Vascular treatment of skin

• Hay Fever: Nasal congestion

• Allergen occur in nose….Histamine cause local intranasal vascular
dilation
• Nasal lining secretory and swollen
• Sneezing irritation local swelling

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 Some examples of
Allergy…immediate
• Asthama:
• Broncitis …SRS A causes contraction of smooth musles
• Histamine is not much involed so very less imp for Rx

• Diarrhea:
• Allergen food/ ingested

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 Allergy &
Hypersensitivity
• Delayed
– In a day or so
– T cells….cell mediated
– Poisons intoxication/ chemicals exposed to skin….cosmetics/ house hold
cleaning agents
– Usually a Hapten…which may bind skin proteins
– Allergen itself not harmfull but activates Tc, Ts & memory cells
– Tissue damage…discomfort (coz T cells secrete toxic substances & Macroph
effect Inc)
– Best relief is Anti-inflammatory applications/cortiso derivatives
• Difference in timing is due to difference in mediators involved

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