Ch. 22 – The Lymphatic System and Immunity

Above: macrophage (gray), T lymphocyte (pink), and bacteria (orange)

The lymphatic system General functions: • • •

It acts with other organ systems to help provide immunity (= the ability to prevent and fight disease) It returns “lost” plasma (= interstitial fluid) to the blood It transports dietary lipids from the digestive tract to the blood (more in Ch. 24)

Components: • • • •

Lymph = interstitial fluid that gets absorbed and transported by… Lymphatic vessels (lymphatics) = low pressure tubes that ultimately return lymph to the blood Lymphoid tissues and organs Lymphocytes and supporting cells Fig. 22-1, p. 783

1

Lymphatic capillaries

• Are different than typical blood capillaries, in part because they: – – – –

Have larger diameters Have thinner walls Are more permeable Are composed of loosely bound, overlapping endothelial cells… • Which act as one-way valves for entry

Fig. 22-2, p. 784

Lymphatic vessels

• Are a.k.a. lymphatics • Are similar in structure to veins, but they have even thinner walls • The larger ones have valves to prevent the backflow of lymph Fig. 22-3, p. 785

2

Lymphatic trunks and ducts •

Lymphatic vessels merge to form lymphatic trunks, which drain into either the… – Thoracic duct – which empties into the left subclavian vein, or the… – Right lymphatic duct – which empties into the right subclavian vein

Fig. 22-4, p. 786

Types of lymphocytes Total in the body: ~ 1 trillion = 1 kg = 2.2 pounds!

Fig. 22-5, p. 787

3

Lymphocyte production

Fig. 22-6, p. 789

Lymphocytes – NK and T cells • NK cells (natural killer cells) – Are responsible for “immune surveillance” – Function: nonspecifically attack foreign, virus-infected, and cancerous cells

• T cells (thymus-dependent cells) – Are responsible for cell-mediated immunity – The main types of T cells include: • Cytotoxic T cells (TC cells) – Function: specifically attack foreign, virusinfected, and cancerous cells

• Helper T cells (TH cells) – Function: stimulate T and B cells; coordinate cell- and antibody-mediated immunity

• Suppressor T cells (TS cells) – Function: inhibit T and B cells Fig. 22-6, p. 789

4

Lymphocytes – B cells • B cells (bone marrow-derived cells) – Are responsible for antibodymediated (humoral) immunity • Function: when stimulated, they differentiate into plasma cells which secrete specific antibodies (immunoglobulins)

– Effects of antibodies include: • • • • •

Neutralizing toxins Agglutinating and precipitating antigens Activating complement proteins Attracting phagocytes Opsonizing antigens (making them easier to hang onto) to enhance phagocytosis • Promoting inflammation…

Fig. 22-6, p. 789

– By stimulating basophils and mast cells

• Interfering with bacterial/viral adhesion to body surfaces

= connective tissues (CTs) dominated by lymphocytes •

•

Lymphoid tissues

No external fibrous CT capsule is present (as opposed to lymphoid organs – see the next slide) If the lymphocytes are densely packed, it’s called a lymphoid nodule

Examples: • MALT (mucosaassociated lymphoid tissue)

Fig. 22-7, p. 791

– E.g. aggregated lymphoid nodules (Peyer’s patches) in the digestive tract

•

Tonsils = large lymphoid nodules in the walls of the pharynx – E.g. the palatine tonsils (2), pharyngeal tonsil (1, a.k.a. the adenoid), and lingual tonsils (2)

5

Lymphoid organs • Have an external fibrous CT capsule separating the organ from other tissues (as opposed to lymphoid tissues – see the previous slide) • Include the: – Lymph nodes – Thymus – Spleen Fig. 22-1, p. 783

Functions: •

1. They filter (purify) lymph before its return to the bloodstream

Lymph nodes

– They remove > 99% of the antigens in the lymph – Antigen presentation is performed by macrophages and dendritic cells (which are examples of antigenpresenting cells, or APCs) • This is the 1st step in the activation of an immune response • Reminder: antigens = substances that trigger an immune response

•

2. They serve as an “early warning system”, monitoring the condition of peripheral tissues via the interstitial fluid/lymph

•

3. They are strategically located in the axillae, groin, neck, and torso

Fig. 22-8, p. 792

6

The thymus • • • •

Is where lymphoid stem cells mature (differentiate) into T cells Is located in the mediastinum above the heart Reaches its maximum relative size (% of body weight) in the first 1–2 years of life Reaches its maximum absolute size just before puberty – It gradually involutes (deteriorates into CT and shrinks) from then on

Fig. 22-9a, p. 793

Fig. 22-9, p. 793

The thymus • Is filled with lymphocytes that are surrounded by thymic epithelial cells (TECs), which… – Maintain the blood-thymus barrier – Secrete thymic hormones (thymosins) that promote the division and maturation of T cells

7

The spleen

•

Note the non-intuitive orientation here!

Is the largest lymphoid organ

Fig. 22-10, p. 795

• Functions:

The spleen

– Its macrophages remove (via phagocytosis) abnormal or worn out blood cells – It stores iron (recycled from RBCs) – It initiates immune responses (via APCs) to antigens that are present in the blood • The spleen is sort of like a lymph node for the blood!

Fig. 22-10c, p. 795

8

Body defenses

• Function: provide resistance (= the ability to maintain immunity; i.e., the ability to fight infection, illness, and disease) • The main types of body defenses: – 1. Innate (nonspecific) defenses – provide nonspecific resistance to disease; a.k.a. innate (nonspecific) immunity • They provide general protection against a wide range of pathogens • The response is the same regardless of the type of invader • They are present at birth

– 2. Adaptive (specific) defenses – provide specific resistance to disease; a.k.a. adaptive (specific) immunity or the immune response • They provide specific protection against a particular pathogen • An immune response is specific to the particular antigen(s) associated with a particular pathogen • They require functioning specific lymphocytes (T and B cells) and exposure to the pathogen

Innate (nonspecific) defenses • 1. Physical barriers = epithelium and its accessory structures and secretions, which keep hazardous organisms and materials outside the body • 2. Phagocytes consume debris, foreign objects, and pathogens in peripheral tissues • 3. Immune surveillance (by NK cells) destroys abnormal (foreign, bacterial, virus-infected, and cancerous) cells in peripheral tissues • 4. Interferons cause the production of anti-viral proteins • 5. The complement system = circulating proteins that enhance the action of antibodies • 6. Inflammation = a localized tissue response to limit the spread of an injury/damage and/or infection • 7. Fever = a higher-than-normal body temperature that accelerates tissue metabolism and the activity of defenses

9

1. Physical barriers (and their accessory structures and secretions)

• Epithelial coverings – – – –

Are often thick and/or keratinized, and sometimes hairy Are held together by desmosomes or tight junctions Have a dense, fibrous basement membrane Have an acidic pH in the skin, stomach, and vagina • This inhibits pathogen growth, but is OK for “friendly” resident bacteria

– Tears and saliva are antimicrobial and may contain antibodies

• Mucous membranes and cilia – Mucus traps pathogens, and can be swept away by cilia for removal

• Tears, saliva, and urine – wash away pathogens

Fig. 22-11, p. 797

• •

Microphages include neutrophils and eosinophils Macrophages (most are derived from monocytes from the blood) include:

2. Phagocytes

– Fixed macrophages – permanently reside in specific tissues • E.g. microglia in the CNS, Kupffer cells in the liver

– Free (wandering) macrophages – travel throughout various tissues

•

Phagocyte movement and phagocytosis – Emigration (diapedesis) – they exit the bloodstream through the capillary walls – Chemotaxis – they are attracted to (or repelled by) chemical signals released by other body cells and pathogens – Adhesion – surface membrane receptors allow the attachment to a target – Phagocytosis is followed by the fusion of the vesicle that contains the target with a lysosome or peroxisome for digestion/destruction

Fig. 22-11, p. 797

10

3. Immune surveillance

Fig. 22-12, p. 781

•

Is carried out by NK cells, which… – Recognize a variety of abnormal antigens on bacteria, cancerous cells (tumorspecific antigens), and virus-infected cells – When activated, release perforins, which cause the abnormal cell’s membrane to rupture (lyse)

Fig. 22-11, p. 797

4. Interferons

• Are examples of cytokines (chemical messenger proteins released by tissue cells that can act locally or system-wide as hormones) • Are released by: – Activated lymphocytes – Macrophages – Virus-infected cells

• Main effects of interferons: – They cause the production of antiviral proteins that interfere with viral reproduction in nearby cells, slowing the spread of infection – They stimulate NK cells and macrophages

Fig. 22-11, p. 797

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• •

5. The complement system = a group of over 30 special plasma proteins that complement the action of antibodies Is involved in both specific (the classical pathway) and nonspecific (the alternative pathway) defenses (see the next slide for a figure that depicts these pathways): – The classical pathway (which is faster, and specific): • C1 binds to antibodies that are already bound to the invader’s membrane antigens • A cascade is initiated, and eventually C3b forms and attaches to the invader

– The alternative (properdin) pathway (which is slower, and nonspecific): • Factors P (properdin), B and D interact directly with the invader’s membrane • C3b forms and attaches to the invader

•

Some effects of activated and bound complement (C3b): – Membrane attack complexes (MACs) are formed, causing lysis (similar to how perforins work) – Inflammation is stimulated (due to ↑ histamine release) – Phagocytes are attracted (chemotaxis) – Phagocytosis is enhanced (opsonization)

Fig. 22-11, p. 797

(antibodies are NOT involved)

Complement activation (antibodies are involved)

Fig. 22-14, p. 800

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Fig. 22-15, p. 801

6. Inflammation • • • •

= a localized tissue response to injury/damage Examples of damaging stimuli: impact, abrasion, chemical irritation, infection by pathogens, extreme temperatures Signs and symptoms: swelling (edema), redness, heat, pain Overall effects: – It temporarily repairs the damage – It “walls off” the damaged area to prevent or slow the spread and additional entry of pathogens – It activates nonspecific and specific defenses to kill pathogens – It initiates permanent tissue repair (regeneration)

Fig. 22-11, p. 797

7. Fever • = a regulated elevation of body temperature above 37.2°C (99°F) • Pyrogen = a circulating protein that can cause a fever – Stimuli that either act as pyrogens themselves or stimulate macrophages to release pyrogens include: • Pathogens, bacterial toxins, and antibody-antigen complexes

• The benefits of a fever (as long as it’s “mild”): – It leads to an overall increase in metabolic rate, so there is increased activity of WBCs and other body defenses – It inhibits some viruses and bacteria

Fig. 22-11, p. 797

13

Adaptive (specific) defenses • Adaptive defenses = specific defenses = specific resistance = adaptive immunity = the immune response • Are provided by the activities of T cells and B cells • Some properties of adaptive immunity: – 1. Specificity – the response is targeted to an antigen of a specific molecular size and shape – 2. Versatility – millions of different lymphocyte populations exist, each sensitive to a specific antigen – 3. Memory – activated lymphocytes divide to produce many clones: • Some clones are active cells that respond to a specific antigen immediately • Other clones are memory cells = inactive reserve cells that recognize the same specific antigen if exposed to it at a later date

– 4. Tolerance – normally, self-antigens do not stimulate an immune response

Forms of immunity

(“get sick”)

(vaccine) Fig. 22-16, p. 803

14

An overview of the immune response • 1. Cell-mediated (cellular) immunity – Is directed against specific cellular and intracellular pathogens, such as… • Abnormal cells (e.g. cancerous cells) • Foreign cells (e.g. bacteria, protozoa, and tissue graft cells) • Pathogen-containing cells (e.g. virus-infected cells)

– Is carried out by… • TC cells that directly attack target (“bad”) cells • TH cells that secrete cytokines, stimulating:

– Macrophages and NK cells to attack target (“bad”) cells – The division and maturation of other T cells – The activation of B cells (see below)

• 2. Antibody-mediated (humoral) immunity – Is directed against specific antigens (both free and on the surface of pathogens) that are found in body fluids – Is carried out by antibodies that attack these antigens • Activated B cells differentiate into plasma cells, which then secrete antibodies

An overview of the immune response

Fig. 22-17, p. 805

15

T cells and antigen presentation

• T cells need to be exposed to an antigen in order to be activated

– This most often occurs due to an antigen being presented on the surface of a cell’s membrane in combination with a MHC (major histocompatibility complex) protein

• There are 2 types of MHC proteins: – Class I MHC proteins are found on all nucleated cells • Antigens bound to Class I MHC proteins stimulate TC cells (quickly, and in larger numbers) and TS cells (slowly, and in smaller numbers) [both of which have CD8 markers]; the message = “I’m abnormal—kill me!”

– Class II MHC proteins are found on APCs (e.g. macrophages and dendritic cells) and lymphocytes only • They are present on an APC only when it has engulfed and is processing an antigen • Antigens bound to Class II MHC proteins stimulate TH cells [which have CD4 markers]; the message = “This antigen is dangerous—help me get rid of whatever it came from!”

• The first binding of a T cell to an antigen-MHC complex (on a stimulating/presenting cell) prepares the T cell for activation – Costimulation (= the binding of a T cell to the stimulating/presenting cell at a 2nd site, OR additional chemical stimulation from the stimulating/presenting cell or other activated lymphocytes) is needed for complete activation

Class I MHC antigen presentation

(which can be any nucleated cell) Fig. 22-18a, p. 807

16

Class II MHC antigen presentation (remember, only APCs and lymphocytes can express Class II MHCs)

Fig. 22-18b, p. 807

TC (cytotoxic T) cell activation

Fig. 22-19, p. 808

17

Fig. 22-20, p. 809

TH (helper T) cell activation • Some effects of cytokines secreted by TH cells:

– 1. ↑ Memory TH cell production and TC cell maturation – 2. Attract macrophages and ↑ their activity – 3. Attract TC cells and ↑ their activity – 4. Activate B cells, and ↑ their division, maturation (into plasma cells), and antibody production; see Fig. 22-22

A summary of the pathways of T cell activation These processes can take a few days…

(found on any nucleated cell)

In which case, they will immediately respond!

(found on APCs and lymphocytes only)

In which case, they will immediately respond!

Fig. 22-21, p. 810

18

B cell sensitization and activation Up to 100 million antibodies per plasma cell per hour!

Fig. 22-22, p. 811

Antibody structure and function

Fig. 22-23, p. 812

19

The classes and effects of antibodies (immunoglobulins)

• There are 5 classes (*denotes the biggest players):

– *IgG – make up 80% of all antibodies; they are versatile and effective; they can cross the placenta – IgE – are found on basophils/mast cells – IgD – are found on B cells – *IgM – are secreted first (soonest) following antigen exposure; they are potent agglutinators – IgA – are found in secretions (e.g. mucus, tears, and saliva)

• Effects (repeated from earlier in the Ch. 22 notes): – – – – –

Neutralize toxins Agglutinate and precipitate antigens Activate complement proteins Attract phagocytes Opsonize antigens (making them easier to hang onto) to enhance phagocytosis – Promote inflammation… • By stimulating basophils and mast cells

– Interfere with bacterial/viral adhesion to body surfaces Table 22-1, p. 813

Primary and secondary responses by B/plasma cells to antigen exposure • • •

A primary response will occur upon the initial (first) exposure to a specific antigen Thanks to memory cells, a secondary response will occur upon subsequent exposure to the same specific antigen as before There is a dropoff in antibody titer (= level of antibodies in the blood plasma) with time because: – Plasma cells are short lived (they have a very high metabolic rate) – Suppressor T cells eventually inhibit antibody production by plasma cells

Fig. 22-24, p. 814

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A summary of the immune response

Fig. 22-26, p. 816

The time course of an immune response to a bacterial infection

Fig. 22-25, p. 815

21

Defenses against bacteria and viruses

Fig. 22-27, p. 817

A summary table of the cells that participate in tissue defenses

Table 22-2, p. 815

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