Immunology module 2

Immune system

a network of cells, tissues and organs that work together to protect the body from infection

What are the functions of Immune system?

1. Protect the body from pathogens

• Intracellular (e.g. viruses and some bacteria and parasites)

• Extracellular (e.g. most bacteria, fungi and parasites)

2. Eliminate modified or altered self

3. Defend the body against the growth of tumor cells

4. Homeostasis

Intracellular

viruses and some bacteria and parasites

Extracellular

most bacteria, fungi and parasites

Stem cells (bone marrow)

source of lymphocytes

Primary or Central Lymphatic Organs (Thymus, Bursa analogue)

site of antigen, independent proliferation and differentiation to T- and B lymphocytes

Secondary peripheral lymphatic organs

(lymphocyte proliferation and exposure to antigens)

Effector Cells

(T and B lymphocytes involved in immune responses)

Other cells

(Macrophages, Dendritic antigen-presenting cells, eosinophils, memory cells)

Lymphoid organs are classified on the basis of their roles which includes:

• generating lymphocytes

• regulating production of lymphocytes

• providing an environment for trapping foreign antigens

Lymphoid Organs

processing of foreign antigens and maximizing the opportunity for processed antigens to encounter and interact with antigen sensitive cells

In primary lymphoid organs, organs that regulate the maturation of lymphocytes or sites of antigen-independent lymphocyte proliferation. (True or false)

True

In primary lymphoid organs, all develop early in fetal life. True or false

True

As animal develop, newly produced, immature lymphocytes migrate from the bone marrow to the primary lymphoid organs. True or false

True

Take note that these are sites where lymphocytes encounter antigens, thus, they do not enlarge in response to antigenic stimulation. True or false

False

Sources of lymphocytes

• Yolk sac

• Fetal liver

• Bone marrow

Sites of lymphocyte development

• Thymus

• Bursa

• Peyer’s patches

• Bone marrow

Sites where lymphocytes respond to antigens

• tonsils

• spleen

• lymph nodes

• Peyer’s patches

• Bone marrow

Thymus

• Located in the thoracic cavity in front and below the heart

• It also extends up to the neck as far as the thyroid gland in horses, cattle, sheep, pigs and chickens

• The size varies but relative size being greatest in the newborn and absolute size being greatest in puberty

• Very small and difficult to find in adult animals

• Consists of lobules of loosely packed epithelial cells

A round layered bodies found within the medulla in which it may contain immunoglobulin A in cattle; had cytoplasmic keratinization in some species

Thymic or Hassall’s Corpuscles

What is the function of thymus

Takes in immature T cells and puts out mature (immunocompetent) T cells

T cells that enter the thymus undergoes a two-stage selection process particularly in the __________

thymic medulla

thymocytes with receptors that bind self-antigens that could cause autoimmunity are killed by ________

apoptosis

Thymic hormones

• Thymosins

• Thymopoietins

• Thymic humoral factor

• Thymulin– a zinc-containing peptide; can partially restore T-cell function

• Thymostimulins

Thymulin

a zinc-containing peptide; can partially restore T-cell function

essential mineral for the development of T cells

Zinc

• A round sac located just above the cloaca

• It reaches its greatest size in the chick at 1-2 weeks after hatching and then shrinks as the birds ages

• Most prominent cells include lymphocytes, macrophages and plasma cells

Bursa of Fabricius

What is the function of Bursa of Fabricius

A maturation and differentiation site for the cells of the antibody-forming system (B cells)

• Lymphoid organs located in the walls of the small intestine

• In ruminants, pigs, horses, dogs and humans 80%-90% are found in the ileum

• Consist of densely packed lymphoid follicles and contain only B cells

• Maximal size and maturity are before birth at a time when they are shielded from foreign antigens

• In rabbits and rodents PPs are located in random intervals in the ileum and jejunum

Peyer’s Patches

What is the function of Peyer’s patches

• Ileal PPs in sheep resembles that in avian bursa

• Sites of rapid B cell proliferation although 95% undergo apoptosis

• Thus, ileal PPs in lambs are primary lymphoid organs

There are also the accumulations of lymphoid tissue in the lamina propria of the intestinal wall called _____

M cells

Where is the site of hematopoiesis, B cell maturation and selection?

Bone marrow

What is the function of Bone marrow

equivalent to the Bursa of Fabricius in birds or PPs in pigs

Bone marrow is ______ in the young while _____ in adult

Red: Yellow

In Secondary Lymphoid Organs, Arise early in fetal life and persist in adults. True or false

False

In Secondary Lymphoid Organs, They enlarge in response to antigenic stimulation. True or false

True

In Secondary Lymphoid Organs, Contain dendritic cells that trap and process antigens and lymphocytes that mediate the immune responses. True or false

True

• They are round or bean-shaped filters on lymphatic vessels to trap antigens carried in lymph

• Depression on the convex side of the node is called the hilum which is the site of entry and exit of blood vessels and nerves

• Consist of reticular network filled with lymphocytes, macrophages and dendritic cells

Lymph Nodes

Depression on the convex side of the node is called the _____ which is the site of entry and exit of blood vessels and nerves

hilum

Lymph Nodes Divided into two regions

cortex (outer cortical) and medulla (inner)

Peripheral cortex

B cells predominate in the cortex where they are arranged in nodules

Paracortex

T cells and dendritic cells or antigen presenting cells predominate

Central Medulla

reticulum cells, dendritic cells, macrophages, B cells and plasma cells arranged in cellular cords

Spleen

• Filters blood and removes both antigenic particles and aged blood cells

• stores red cells and platelets and undertakes red cell production in fetus

• filters antigen from the blood (blood-borne invaders)

• many aged erythrocytes are broken down and destroyed by macrophages in this organ

Red pulp

where red cells are stored; for antigen trapping

White pulp

where the immune response occurs; rich in lymphocytes

30-40ml blood are stored in the spleen. However, about _____ of all blood platelets of the body are stored in the spleen to meet physiological demands in cases of emergency

30%

Bone marrow

largest mass of secondary lymphoid tissue in an adult

Have the capacity to differentiate and form populations of progenitor cells which are committed to the main marrow cell lines

myeloid progenitor cells and lymphoid progenitor cells

Myeloid Lineage

• Neutrophils

• Eosinophils

• Basophils

• Monocytes

• Mast cells

• Megakaryocytes (platelets)

• Erythrocytes

When microbial invaders gain access to body tissues, they must be promptly attacked and destroyed. They may be killed either by antimicrobial peptides or complement but many are eaten and killed by cells. The uptake of microbes by cells is called __________

phagocytosis

When microbial invaders gain access to body tissues, they must be promptly attacked and destroyed. They may be killed either by antimicrobial peptides or complement but many are eaten and killed by cells. The uptake of microbes by cells is called phagocytosis. These defensive cells of the body are found in the blood and are called ________

Leukocytes

cytoplasm is filled with granules; have characteristic lobulated, irregular nuclei “polymorphonuclear”

Granulocytes

take up basic dye such as hematoxylin

Basophils

take up acidic dye such as eosin

Eosinophils

take up neither basic nor acidic dyes

Neutrophils

• Major cell blood leukocyte; act as first line of defense; mobilize rapidly and eating and killing invading microorganisms

• Formed in the bone marrow, migrate to bloodstream, move into the tissues in about 12 hours

• Dies at an average of 5 days after leaving the bone marrow

• Constitutes about 60-70% of the blood leukocytes in most carnivores and humans and only about 50% in horse and 20-30% in ruminants

Neutrophils

During bacterial infection, the numbers of circulating neutrophils may increase _____ as they are released from the bone marrow and the sequestered pool

10-fold

Once on the site of microbial invasion and inflammation, neutrophils capture and destroy foreign particles through ________

phagocytosis

Destruction of ingested bacterium occurs through generation of potent oxidants causing ________ or through release of lytic enzymes and antimicrobial peptides from intracellular granules

respiratory burst

• Second population of cells that serve as “backup system”

• Speed of response is slower than neutrophils but has greater antimicrobial abilities

Removal of dead and dying cells

Macrophages

__________ are immature macrophages that forms about 5% of the total white blood cell population

Monocytes

• Motile phagocytic cells

• Express receptors for IgE

• Effective in destroying infectious agent that stimulate IgE production (e.g. helminth parasites)

• Abundant in sites of immediate hypersensitivity and inflammation

• Growth and differentiation are stimulated by Th cytokine IL-5

Eosinophils

• Non-phagocytic granulocytes

• Circulating counterparts of tissue mast cells

• High affinity for IgE

• Granules contain chemical mediators for immediate hypersensitivity

• Effector cells of IgE

Basophils

• cells responsible for mounting acquired immune response

• two major types are: T cells and B cells

• small, round cells (7-15 µm diameter) and contains a large, round nucleus that stains intensely and evenly with hematoxylin

• mainly found in lymphoid organs, in blood and scatter under mucosal surfaces

• they must be able to recognize and respond to a large number of very diverse foreign antigens

• they have cell surface receptor that are specific for antigen

Lymphocytes

T Lymphocytes

• leave the thymus and accumulate in the paracortex of lymph nodes, periarteriolar lymphoid sheaths of the spleen and in peyer’s patches
•account for 40% -80% of the lymphocytes in blood

T helper cells (CD4)

• commander in chief of the immune system

• can respond to a foreign antigen only when the antigen is presented in association with an appropriate MHC molecule

• can identify the enemy in conjunction with MHC class II

• rush to the spleen and lymph nodes where they stimulate the production of other cells to fight infection by cytokine release

• stimulate macrophages to be effective in destroying pathogens

for viral or bacterial attack

Th1

for parasitic infection

Th2

Cytotoxic T cells (CD8)

• Kill other cells that are perceived as foreign or abnormal (virus infected cells, tumor cells or foreign grafts) – intracellular pathogens

• Recognize endogenous peptides with MHC class I

• Kill their target by releasing a protein perforin inducing apoptosis

Regulatory T cells (CD8)

•Down regulation of the immune response

•Stop the activities of B cells and other T cells

•Calling off the attack after the infection has been conquered

Delayed hypersensitivity T cells

• Associated with certain allergic reactions and with the rejection of transplanted tissues or organs

• Important against cancer

• originate in bone marrow but mature within peyer’s patches or bone marrow before migrating to the secondary lymphoid organs

• found in the cortex of lymphoid nodes, follicles withing peyer’s patches and spleen and marginal zone of the white pulp of spleen

• account for 10%-50% of blood lymphocytes

• produces antibodies

B Lymphocytes

Career choices of B cells

• Plasma cells

• Memory B cells