Chapter 5: Blood Physiology

(II): Defense systems &

Immunity

○ Overview
○ Leukocyte types
○ Leukopoiesis
○ Immune system

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 Overview

○ Leukocytes present an irregular morphology.

○ Lower in number than erythrocytes
○ They are not blood specific. 2% are in blood and the rest in lymph,
spleen, cerebrospinal fluid, and other tissues
○ Leukocytes form part of the immune system

○ In blood, five different types of leukocytes:

● Neutrophils
● Eosinophils Granulocytes
● Basophils
● Monocytes !3
● Lymphocytes Agranulocytes
○ In order to protect the organism, leukocytes carry a
number of tasks:

● Neutrophils and monocytes are phagocytes

● Basophils and eosinphils release substances
● Lymphocytes generate antibodies and specific
immunity

○ Leukocytes cross capillary walls (migration,

extravasation or diapedesis) towards the infected
area, following a trail of substances (chemotaxis)

○ Leukocytosis: High level of white blood cells.

Normal reactionof the organism in case of infection
○ Leukopenia: Low leukocyte level. Abnormal
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Leukocyte extravasation

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Chemotaxis

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Video: Neutrófilos
○ Overview
○ Leukocyte types
○ Leukopoiesis
○ Immune system

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Types of leukocytes

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 Neutrophils
○ 55-75 % of total leukocytes
○ Neutrophils protect the body through phagocytosis
○ Neutrophils can phagocyte in the blood flow or in body
tissues

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 Eosinophils
○ 2-3 % of leukocytes
○ Mostly in tissues and red bone
barrow
○ Eosinophils release the content
of their granules/vesicles
○ They present chemotaxis
towards histamine
○ Present in allergic reactions
and in parasitic processes

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 Basophils
○ The fewest among leukocytes (0.5-1%)
○ They content heparin, histamine, and protelytic
enzimes
○ In alergic reaction
○ Functions are not well known:
○ They release their content producing an increase
of capillar permeability, vasodilation, and
chemotaxis of eosinophils

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 Monocytes
○ 3-7 % of blood leukocytes (much abundant in tissues, 400-
fold)
○ Large cells (10-18 µm)
○ In body tissues monocytes differenciate into macrophages

○ Macrophages are larger (around 80

µm)

○ Macrophage morphology varies

among the tissues. In fact, they
receive different names in
accordance with the tissue they live
in:
● Histiocytes in connective tissue
● Kuppfer cells, in the liver
● Alveolar macrophages in lungs
● Microglia in the nervous system !12
○ Macrophages are defending the body through
phagocytosis
○ There are macrophages in every tissue of the body
○ Macrophages have other functions:

● They participate in the generation of fever and

inflammation

● Important role in adaptive immunity

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 Lymphocytes
○ In charge of the specific defense of the body
○ Three different types of lymphocytes:
● B cells, differenciate into plasma cells and generate
antibodies
● T cells, mediate the cellular adaptive immunity
● NK cells (natural killer)

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Functions of lymphocytes:
○ B cells main function is to evolve into plasma cells
and release antibodies (immunoglobulins)

○ In order to produce antibodies, B cells are stimulated

by T helper cells through hormones known as
interleukins (IL)

○ Immunoglobulins are glucoproteins present in plasma

and other fluids of mammals
○ 5 types of immunoglobulins: IgM, IgG, IgD,
IgA e IgE
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○ T cells carry different functions:
● Defense against intracellular bacteria and viruses
● Immune response versus foreign tissues and tumor
cells
● Increase the response ot other T cells and B cells

○ Two types of T cells:

● Cytotoxic T cell: they kill directly to their targets

● T helper cell: enhance the response of other
components of the immune system

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○ Overview
○ Leukocyte types
○ Leukopoiesis
○ Immune system

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○ During fetal live, leukopoiesis occurs in liver, splen,
and bone marrow. In the adult, it happens just in the
red bone marrow

○ From pluripotent hematopietic stem cells, all the

different blood cell lines are generated

○ Lymphoid stem cell generates lymphocytes,

whereas myeloid stem cells forms granulocytes and
monocytes

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○ Overview
○ Leukocyte types
○ Leukopoiesis
○ Immune system

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○ Immune system: structures and processes that
protect the organism against disease, identifying and
killing pathogens

○ Immune system is constantly activated

○ There are two possible mechanisms of immunity:

○ Innate immunity (non-specific)

○ Adaptive imunity (specific)

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 Diferences
Innate Immunity Adaptive Immunity

Non specific response Specific response

Exposure od the pathogen drives to Delay between exposure and

maximum response maximum response

No immunological memory Immunological memory

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 1. Innate Immunity
○ First line of defense: external barriers
• Skin
• Mucous membranes
• Hairs and cilia
• Mucus
• Coughs and sneezes
• Gastric juice
• Tears
• Saliva
• Urine
• Vaginal secretions
• Vomiting
• Defecation
• Transpiration !23
Second line of defense: internal defenses

○ Humoral Innate Immunity

○ Antimicrobial substances (interferons,
complemetn system…)
○ Inflammation
○ Fever

○ Cellular Innate Immunity

○ Phagocytes
○ Neutrophils
○ Monocytes/Macrophages
○ NK cells
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 Cellular Innate Immunity
○ NK cells
○ 5-10% of lymphocytes
○ They attack any cell without CMH-I
○ When it binds to the target cells, NK releases
granzims or perforins
○ Granzims: induces apoptosis
○ Perforins: punch the cell membrane

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○ Phagocytes
○ Neutrophils and macrophages
○ During infection they migrate to affected area via
chemotaxis
○ Monocytes differenciate into macrophages
○ Phases:
○ Chemotaxis
○ Adherence
○ Ingestion
○ Digestion
○ Killing

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 2. Adaptive Immunity
○Specificity and memory

○Antigens: Any substance (own or foreign) that might be

recognized by the adaptive immune system

○Antigens are usually proteins that are part of bacteria,

viruses, and other micoorganisms

○Non-microbial antigens: pollen, egg yolk, proteins in

transplanted tissues, or proteins in transfused red blood cells

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Antigen processing by antigen-
presenting cells (APCs)

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 Apaptive immunity steps

a) Antigen recognition In peripheral lymph tissue

such node glandsand
b) Lymphocyte activation spleen

c) Elimination of the antigen

In infection site
d) Return to homeostasis

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○ Cellular adaptive immunity
○ T cytotoxic lymphocytes
○ Effective against:
○ Intracellular pathogens
○ Tumor cells
○ Foreign tissues (trasplants)

○ Humoral adaptive immunity

○ B cells, plasma cells
○ Antibodies
○ Effective against:
○ Antigens
○ Extracellular pathogens
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 Cellular adaptive immunity
○ With the arrival of the antigen-MHC complex, T cells switch on
○ T-cell receptors bind to specific antigen-MHC complexes
○ CD4 and CD8 surface proteins help maintaining the union
(coreceptors)
○ T cells needs also costimulation from IL-2 to get active
○ Once T cells are active, they proliferate and differenciate (in
secondary lymph organs, such as spleen, nodes)
○ When T cells differenciate they become:

○ Helper T cells; CD4. They release cytokines (IL-2). Helps

in humoral anc cellular immunity
○ Cytotoxic T cells, CD8
○ Memory T cells (both helper and cytotoxic)
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Activation, Proliferation and Differentiation of T cells

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○ Cytotoxic T cells migrate towards their target cells
○ They bind the target cells
○ Mechanims is similar to
NK cells, but specific
○ Granzims
○ Perforins

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 Humoral adaptive immunity
○ Ag bind the B-cell receptor

○ B-cells can process the antigen

○ They form a Ag-CMH-II complex which binds to a T helper

cell

○ T-helper releases costimulators (IL-2).

○ Activation, proliferation, differentiation

○ Avtivated B cell differenciates into plasma cells (that release

antibodies) and B memory cells
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○ Antibodies travel towards the infected area
Activation, Proliferation and Differentiation of B cells

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 Antibodies

○ Able to bind antigens

○ The structure matches the antigen that formed it
○ Immunoglobulins (Ig)
○ Formed by polypeptid chains
○ Typess: G, A, M, E, D

○ Actions:
○ Neutralizing antigen
○ Immobilizing bacteria
○ Agglutinating and precipitating antigen
○ Activating complement
○ Enhancing Phagocytosis
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Immunological memory

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Passive immunity.
Naturally adquired passive immunity : Maternal-filial. IgG cross
the placenta towards the fetus blood. Breastmilk is also rich in Ig

Artificially adquired passive immunity: Transfusion of serum

rich in Igs

Active immunity.

Naturally adquired active immunity: as we are expose to

pathogens we create memory B and T cells

Artificially adquired activeimmunity: Through vaccination. An

antigen is inoculated and the immune system genereates specific
immunity (attenuated viruses or fragments of bacteria) !39