SECONDARY OR PERIPHERAL LYMPHOID ORGANS

As stated earlier, the lymphocytes mature, proliferate, and differentiate in the primary or central lymphoid
organs. These lymphocytes migrate therefrom via circulation to the secondary or peripheral lymphoid organs.
Here they bind appropriate antigens and undergo further antigen-dependent differentiation.
Once in the secondary lymphoid organs, the lymphocytes do not remain there but move from one lymphoid
organ to another through the blood and lymphatic’s. The passage of lymphocytes facilitates the induction of an
immune response. These organs include the Lymph nodes, the spleen and mucosa-associated lymphoid tissue
(MALT).

1. LYMPH NODES
- Kidney shaped organs > 1cm
- During immune response, swell in size
- Fluid enters through afferent vessel
- Fluid leaves via efferent vessel
- Lymph perculates through all lymphocytes before leaving the node
- there are many afferent vessels but one efferent vessel
- Rich blood supply lets lymphocytes into the lymph nodes via the high endolthelial venues
- T-cell zone: parafollicular cortex
- B-cell zone: lymphoid follicle- mostly on the periphery of the lymph node
- During immune response, there is a massive proliferation of B cells, which leads to the formation of a
germinal centre
- Specific chemokines target their respective lymphocytes to their specific areas, e.g. T-cells to the
parafollicular cortex
- The lymph entering lymph nodes may also contain cells such as dendritic cells and macrophages

2. Spleen
- Filter for antigens in the blood
- Large organ in the abdomen
- Separated into white pulp: lymphoid cells around blood vessels, full of lymphocytes and red pulp: contains
old damaged RBC
- Any diseases involving RBC, i.e. sickle-cell, often results in an enlargement of the spleen
- T cell area: peri-arteriolar lymphatic sheath (PALS)
- B cell area is located further away from blood vessels
- Individuals who do not have a spleen are highly susceptible to infections with encapsulated bacteria.
3. Mucosal-Associated Lymphoid Tissue (MALT):

 The mucous membranes lining the alimentary, respiratory, and genitourinary systems have a very large
combined surface area (about 400 m2 ), which is
 The surface is constantly exposed to numerous antigens and is the major site of entry for most pathogens.
 These membranes lining surfaces possess a group of organized lymphoid tissues which defend it from
pathogens and antigens.
 The group of organized lymphoid tissues is known collectively as mucosal-associated lymphoid tissue
(MALT).
 There are several types of MALT; the most studied one is the gut-associated lymphoid tissue (GALT)
which includes tonsils, Peyer’s patch, appendix, and loosely organised clusters of lymphoid cells in the
lamina propria of intestinal villi.
 Mucosal-associated lymphoid, tissue (MALT) is functionally very significant in immune system of the body
because of the presence of large number of antibody-producing plasma cells in it.

i. Tonsils:
 There are three groups of tonsil present at three different locations: palatine, lingual, and pharyngeal
(adenoids).
 Palatine group of tonsil occur at the sides of the back of the mouth; lingual in the basal region of the
tongue; and pharyngeal (adenoids) in the roof of the nasopharynx (Fig. 42.5).
 All the tonsil groups are nodule-like and consist of a meshwork of reticular cells and fibres interspersed
with lymphocytes, macrophages, granulocytes, and mast cells.
 The B-lymphocytes are organised into follicles and germinal centres.
 The germinal centres are surrounded by regions showing T-lymphocyte activity.
 The tonsils protect against antigens that enter through the nausal and oral epithelial routes.
 ii. Peyer’s Patch:
 Peyer’s patches occur in the sub-mucosal layer present beneath the lamina propria lying under the
epithelial layer of intestinal villi.
 Each Peyer’s patch is a nodule of 30-40 lymphoid follicles.
 Like lymphoid follicles in other sites, those that compose Peyer’s patches can develop into secondary
follicles with germinal centres (Fig. 42.6).

iii. Lamina Propria:

 Lamina propria occurs under the epithelial layer of intestinal villi (Fig. 42.6).
 It is populated with large number of plasma cells, macrophages, activated T helper cells (activated TH
cells) in loose clusters.
 More than 15,000 lymphoid follicles have been, reported within the lamina propria of a healthy child.
 CLINICAL APPLICATIONS OF IMMUNITY

1) Vaccinations
based on primary vs secondary response
primary
 persons initial exposure to an antigen
 lag of several days before antibodies begin being produced
 peak production in ~10 days
secondary
 reexposure to same pathogen triggers memory cell response
 memory cells can persist for 20 years or more
 much quicker response
 much stronger response
2) Monoclonal Antibodies
 specific B cell (with desired antibodies) is fused to cancer cell
 rapid production of large numbers of the same antibody
3) Organ Transplants and Rejections
 same principle as blood transfusions
 usually need immunosuppressive drug therapy

TOLERANCE
 Tolerance can be defined as:
1. Immunological tolerance is the failure to mount an immune response to an antigen.
2. an active physiological process producing immunological unresponsiveness to an otherwise
immunogenic substance
 Tolerance is of two types:
a) Natural or "self" tolerance. This is the failure (a good thing) to attack the body's own proteins and
other antigens. If the immune system should respond to "self", an autoimmune disease may result.
b) Induced tolerance. This is tolerance to external antigens. Examples:
o deliberately manipulating the immune system to protect us from unpleasant, even dangerous,
allergic reactions to such things as food (e.g. peanuts), insect stings, grass pollen (hay fever).
o deliberately manipulating the immune system to enable transplanted organs (e.g., kidney, heart,
liver) to survive in their new host; that is, to avoid graft rejection.
o Preventing the immune system from mounting an inflammatory attack against the vast numbers
of harmless (even beneficial) bacteria living in the intestine.

 Immunological tolerance is not simply a failure to recognize an antigen; it is an active response to a

particular epitope and is just as specific as an immune response.
 Both B cells and T cells can be made tolerant, but it is more important to tolerize T cells than B cells
because B cells cannot make antibodies to most antigens without the help of T cells.

DISORDERS OF IMMUNE SYSTEM

 Most immune disorders can be categorized as:

1. autoimmune diseases
2. hypersensitivities
3. immunodeficiencies

AUTOIMMUNITY & AUTOIMMUNE DISEASE

Autoimmunity can be defined as:

1) Adaptive immune responses with specificity for self ‘antigens’ (autoantigens)

2) Failure of the immune system to “tolerate” self tissues may result in pathological processes known as
autoimmune diseases.
Mechanisms of Autoimmunity
Adaptive immune reactions against self-tissue use the same mechanisms as immune reactions against
pathogens and environmental antigens.
Autoimmune diseases involve breaking T-Cell tolerance
Because self-tissue is always present, autoimmune diseases are chronic conditions
Effects any organ/ organ system
Causes of autoimmunity
Several theories have been proposed to explain autoimmune responses, or the termination of self-tolerance:
a. An excess of self-reactive helper T (Th)-cell activity induced, for example, by altered forms of self-antigen or
with antigen that cross-reacts with self-antigen, which might be produced by a coupling of chemicals or drugs
(e.g., hydralazine) or viruses to self-antigen: the modified chemical (drug)-host or viral-host antigens would
then trigger a self-reactive Th-effect and elicit autoantibody production.
b. A bypass of the lack of requisite self-reactive Th-cell activity or bypass of the need for such Th-cell activity
via polyclonal B-cell activation with materials such as bacterial lipopolysaccharide, Epstein-Barr virus, or
purified protein derivative (PPD) of tuberculin.
c. A deficiency of suppressor T (Ts) cells designed to down-regulate the immune response to self-antigen.
d. Release of sequestered antigen (e.g., from lens of the eye, sperm) not ordinarily available for recognition by
the immune system: release might occur via such means as trauma or infection.
e. There is clearly a role for genetic factors in autoimmune disease. Most autoimmune diseases appear to be
HLA associated with DR2, DR3, DR4, and DR5.
f. Autoimmune diseases tend to occur at a higher frequency in females than in males. The incidence of SLE in
women is six to nine times more common in females.

Classification of autoimmune diseases

Autoimmune diseases are classified according to the location of the autoimmune attack. Based on this criterion,
autoimmune diseases are distinguished into systemic or organ-specific.
Systemic: Affects Many Organs
Systemic autoimmune diseases are those where the autoantigens are found in almost any type of cell in the
body, for example the DNA - protein complexes. Consequently, the pathological damage involves many
different organs and tissues. Typical systemic autoimmune diseases are rheumatoid arthritis, systemic lupus
erythematosus, scleroderma, and dermatomyositis.
Organ-specific: Affects One Main Organ
Organ-specific autoimmune diseases are those where a particular organ or tissue is preferentially targeted by
the patient's immune system. For example, the thyroid gland in patients with Graves disease, the beta cells of
the endocrine pancreas in patients with type 1 diabetes, or the skin in patients with vitiligo
Examples of organ autoimmune diseases
• Addison’s disease – this disease results from damage to the outer layer of the adrenal gland (the adrenal
cortex), of which autoimmunity is the most common cause. As a result of this damage the adrenal gland does
not produce enough steroid hormones (primary adrenal insufficiency), resulting in symptoms which include
fatigue, muscle weakness, and a loss of appetite. This can be fatal if not recognised and treated, but treatment is
relatively simple.
• Grave’s disease – affecting the thyroid, Grave’s disease is one of the most common causes of
hyperthyroidism. It results from the production of antibodies that mimic Thyroid Stimulating Hormone, which
produces a false signal causing the thyroid gland to produce excessive thyroid hormone. Symptoms including
insomnia, tremor, and hyperactivity.
• Type 1 diabetes – diabetes mellitus type 1 is a consequence of the autoimmune destruction of cells in the
pancreas which produce insulin. Insulin is essential to control blood sugar levels and if left uncontrolled the
disease can lead to serious complications, such as damage to the nerves, heart disease, and problems with the
retina. Without adequate treatment type 1 diabetes would be fatal.
Examples of systemic autoimmune diseases
• Rheumatoid arthritis – a chronic condition that causes painful stiffness and swelling in the joints.
Rheumatoid arthritis is a result of the immune system attacking tissues in the joint lining, eventually leading to
damage of the joint itself. Rheu-matoid arthritis can also effect inflammation around other organs, such as the
heart and lungs. It differs from osteoar-thritis, which is generally caused by mechanical stresses on the joint.
• Multiple sclerosis – a chronic condition that can cause signif-icant disability, multiple sclerosis is a disease in
which the electrically insulating layers of the nerves are destroyed, thus affecting signalling between the brain
and other parts of the body.
• Lupus – systemic lupus erythematosus is a complex condition affecting many parts of the body, including
the skin, joints, heart, lungs and nervous system. It occurs as a result of a widespread systemic autoimmune
reaction and results in symptoms including fatigue, joint pain, and rashes.
• Scleroderma – in scleroderma the immune system attacks the connective tissue under the skin, resulting in a
thickening of these tissues. In more severe forms it can affect blood circu-lation and internal organs.