Lymphatic system

1. Lymphatics (lymphatic vessels) – collects protein containing interstitial fluid

2. Lymph – interstitial fluid once it enters lymph

Lymphatic capillaries

1. Distribution – everywhere except bone, teeth, CNS, and bone marrow

2. Blind ended – do not connect; interwoven between capillaries

3. Minivalves – endothelial cells loosely overlap each other

4. Filament anchors – endothelial cells to surrounding tissue; prevent collapse

5. Lacteals – in intestine receive digested fats

Lymphatic collection vessels

1. Layers – same as veins, but thinner

2. Location – superficial along veins; deeper along arteries

Lymphatic trunks

1. Lymphatic trunks – union of largest collection vessels

2. Lumbar trunk – lower body (paired)

3. Bronchomediastinal trunk – thorax (paired)

4. Subclavian trunk – arms (paired)

5. Jugular trunk – head (paired)

6. Intestinal trunk – digestive organs (single)

Lymphatic ducts

1. Lymphatic ducts – empty into junctions of internal jugular and subclavian vein

2. Right lymphatic duct – drains right arm, chest, and head

3. Thoracic duct – drains rest of body

-a. Cisterna chyli – drains both lumbar and intestinal trunks

Lymph transport

1. Respiratory pump – breathing resulting in changes in thoracic pressure

2. Skeletal muscle pump – same as with veins

3. Arterial pulsation – cause movement of lymph in adjacent vessels

4. Valves – as in veins, lymph can travel in only one direction

5. Smooth muscle – in trunks and ducts; contract rhythmically

Lymphoid cells

1. Lymphocytes – T and B cells; involved with immune reaction

2. Macrophage – phagocytes found throughout lymphatic system

3. Dendritic cells – like macrophages; associated with B cells

4. Reticular cells – connective tissue cells; make up stroma

Lymphoid tissue

1. Reticular connective tissue – loose; makes up all lymphoid organs except thymus

2. Diffuse connective tissue – above with lymphocytes; connective tissue and mucosa

3. Lymphatic follicles – more solid and spherical; organs and tissue

-a. Germinal center – center of follicles; B cells, can be dividing; and dendritic cells

Lymphatic organ

1. Fibrous capsule – found around discrete lymph organs

Lymph node

1. Number – hundreds; embedded in connective tissue

2. Location – inguinal, axillary, and cervical

3. Functions – concerned with protection

-a. Lymph filters – macrophage clean debris; dead cells, microbes

-b. Immunology – strategic lymphocyte placement to detect foreign antigen

4. Size/shape – bean shape less than one inch

5. Capsule – dense fibrous connective tissue

6. Trabeculae – extensions of the capsule; break it into sections

7. Cortex –outer part; tends to be more densely packed

-a. Lymphatic follicles – densely packed in cortex

-b. Germinal center – rapidly dividing B cells

-c. Dendritic cells – macrophage like cells encapsulate germinal center

-d. T cells – found in the remainder of the cortex

8. Medulla – inner, less dense

-a. Medullary cords – extension of the cortex

-b. Medullary sinuses – large capillaries spanned by reticular fibers; macrophages

9. Subcapsular sinuses – join up with others which cut to the medulla

10. Hilus – indented region; lymph leaves

11. Afferent lymphatic vessels – lymph comes in; more; convex side

12. Efferent lymphatic vessels – lymph leaves; hilus; lymph stagnates in node

13. Pathologies

-a. Bubo – overwhelmed by bacteria or virus; bubonic plague

-b. Secondary cancer site – metastasize from primary site; grows here

Spleen

1. Appearance – blood red organ the size of a fist

2. Location – left superior abdominal cavity; between diaphragm and stomach

3. Function

-a. Erythrocyte breakdown – macrophages; reclaim iron and globin

-b. Immunology – lymphocytes survey for foreign antigen

-c. Other functions – platelets stored; blood cleansed; fetal RBC production

4. Hilus – concave; splenic vein and artery enters, leaves

5. Capsule – fibrous connective tissue

6. Trabeculae – internal projections of capsule; partition

7. White pulp – lymphocytes cuffed around central arteries; immunological

8. Red pulp – rest of spleen; RBC and pathogen disposal

-a. Venous sinuses – large open spaces filled with blood

-b. Splenic cords – reticular connective tissue which spans the sinuses; macrophages

9. Splenectomy – when ruptured spleen must be removed; bleed to death

Thymus

1. Location – overlies the heart; deep to sternum

2. Structure – bilobed; each containing many lobules

3. Age – increases in size to adolescence then stops; decreases in size from that point

4. Function – T cell maturation

5. Thymic lobules – like flowerets of cauliflower

-a. Cortex – densely packed with T lymphocytes

-b. Medulla – contains few lymphocytes; leave through blood vessels

6. Thymocyte – epithelial derived cells

-a. Stoma – thymocytes make up the thymus

-b. Blood-thymus barrier – thymocytes surround blood vessels in cortex

-c. Thymosin – thymocytes secrete this group of hormones

Tonsils

1. Location

-a. Palatine tonsils – paired on either end of the oral cavity

-b. Lingual tonsils – paired at base of tongue

-c. Pharyngeal tonsils – single; posterior wall of nosopharynx (adenoids)

2. Function – remove food and air borne pathogens

3. Follicles – with germinal centers are prominent

4. Crypts – invaginations epithelium into tonsils; trap bacteria

Mucosa associated lymphatic tissue (MALT)

1. Tonsils – are part of this

2. Peyer’s patches – isolated collection of lymphatic follicles in intestine

3. Appendix – heavy concentration of lymphatic follicles

4. Bronchi – protection of respiratory system as well

5. Function – killing of bacteria; exposure to foreign antigen for long term immunity

INNATE BODY DEFENSES

Epidermis

1. Mechanical barrier – impermeable to water

2. Acid mantle – sweat and sebum

3. Keratin – resist against acids, bases, bacterial enzymes

Mucosa

1. Mechanical barrier – epithelium

2. Mucus – traps microbes; digestive; respiratory

3. Nasal hairs – filters, traps microbes

4. Cilia – propels debris lower respiratory

5. Gastric juices – HCl kiss gastric microbes

6. Vaginal acid mantle – vaginal mucus kills bacteria and fungi

7. Lacrimal secretions – lysozyme (enzyme) kills bacteria

8. Saliva – lysozyme also

9. Urine – acidic; inhibits bacterial growth

Phagocytes

1. Phagocytosis – cytoplasmic extensions; engulf

-a. Phagosome – vacuole containing ingested particle

-b. Lysosomes – joins up with phagosome; digestive enzymes

2. Macrophages – free one wander extracellular space

-a. Kupffer cells – fixed in lung alveoli

-b. Nitric oxide – free radical; to kill hard to kill

3. Neutrophils – also phagocytic when invaders met

-a. Defensins – protein spears; enter phagosome

-b. Bleach – free radical to kill hard to kill

4. Capsule – complex sugar covering; bacteria hard to find

5. Opsonization – coated with complement or antibodies; help find

Natural killer cells

1. Function – tumor and virus infected body cells; lymph and blood

2. Lymphocytes – large and granule

3. Nonspecific – unlike other lymphocytes

4. Mode of killing – cytolytic chemicals; membrane channels

Inflammation

1. Causes – trauma, heat, chemicals, infection

2. Purpose – prevent spread; disposal pathogen; repair

3. Five cardinal signs of inflammation

-a. Redness – hyperemia

-b. Heat – hyperemia; increase metabolism; promote healing

-c. Swelling – exudates and hyperemia

-d. Pain – pressure; toxins; chemicals

-e. Loss of function – due to too much pain

4. Vasodilation - increased blood flow to area

5. Vascular permeability – increases; blood vessels become leaky

-a. Chemical alarm – from tissue, blood, leukocytes

-b. Hyperemia – vasodilation; increased blood flow to area

-c. Exudate – fluid leaves circulation; edema

6. Phagocyte mobilization – include neutrophils then macrophages

-a. Margination – cling to endothelium

-b. Diapedesis – squeezes through endothelial cells (capillaries)

-c. Chemotaxis – inflammatory chemicals draw to site

7. Neutrophils – leukocytosis; first on scene

8. Macrophages – show up about 10 hours later; as monocytes

9. Chemicals – different sources; mediate inflammation

-a. Histamine – basophil; mast cells; vasodilation and increased permeability

-b. Prostaglandins – neutrophils; other sources; fatty acid; enhancement; pain

-c. Kinins – activated in plasma; like histamine; causes pain

Complement component

1. Complement system – 20 plasma proteins

2. Classic pathway – depends on antibody binding to pathogen

3. Alternative pathway – several of the proteins to polysaccharide of pathogen

4. Common terminal pathway – C3 cleaved to C3a and C3b

-a. Cell lysis – C3b triggers the insertion of MAC; stable hole in membrane

-b. Opsonization – C3b; increased phagocytosis

-c. Inflammation – both C3b and C5a enhance inflammation

Interferon

1. Viral infected cells – sent out from infected cell to noninfected cells

2. Neighboring cells – synthesize chemical; interferes with viral replication

3. Natural killer cells – is activated by interferon; kills host cell

Fever

1. Systemic – not localized as in inflammation

2. Pyrogens – proteins secreted by leukocyte; bacteria

3. Hypothalamus – Pyrogens cause reset of thermostat

4. Benefits – low grade, not extremely high one

-a. Microbes – iron and zinc sequestered

-b. Metabolism – speeds up defenses and repair

ADAPTIVE BODY DEFENSES

Antigens

1. Defined – molecules recognized as nonself

2. Complete antigen – large molecule like protein, nucleic acid, ect.

3. Hapten – small molecules; bind to body’s own; poison ivy

4. Immunogenicity – the ability to stimulate an immune response

5. Reactivity – ability to react with immune system

6. Antigenic determinant – binds to a particular antibody or cell; proteins no plastic

MHC proteins

1. Self antigen – body cells; immune system shouldn’t attack

2. Major Histocompatibility complex – genes that code for these proteins

3. Class I MHC – all body cells (virtually)

4. Class II MHC – cells involved in the immune response

Cells of the immune system

1. T lymphocytes – immunocompetent in thymus; antibodies; killing and mediating

2. B lymphocytes – immunocompetent in bone marrow; antibodies produced

3. Antigen presenting cells – engulf foreign protein; present it on surface

-a. Macrophages – connective tissue; lymph nodes

-b. Dendritic cells – lymph nodes

-c. B lymphocytes – lymph nodes; circulating

Humoral Immune Response

Clonal selection and differentiation of B cells

1. Cross linking –adjacent surface receptor; same antigenic determinate

2. Endocytosis – of the receptor antigen complex

3. Clonal selection – endocytosis and interaction with T cells; multiply rabidly

4. Plasma cells – most of the cells formed; antibodies generate; like surface one

5. Memory cells – not differentiated; fast response next time antigen is meet

Immunological memory

1. Primary immune response – after first exposure

-a. Lag phase – 3 to 6 days; proliferation

-b. Antibody level – rise; peak at 10 days; decline

2. Immunological memory – the result of the B cells

3. Secondary response – second encounter

-a. Lag phase – faster; 2 to 3 days

-b. Antibody level – rises much faster; remain higher much longer

Active and passive humoral immunity

1. Active – exposed to foreign antigen; produce antibody

-a. Natural – become sick; exposure to antigen

-b. Artificial – exposed to dead or weakened pathogen; vaccination

2. Passive – antibodies from an antigen exposed donor

-a. Natural – in mothers across placenta

-b. Artificial – antivenoms; antitoxins (rabies)

Immunoglobin structure

1. Monomer – a complete Immunoglobin molecule

2. Disulfide bonds – hold 4 polypeptide chains together; loops in chains

3. Heavy (H) chains – two larger chains; have a bend or hinge area

4. Light (L) chains – two smaller chains

5. Variable (V) region – at the end of each of the 4 chains

6. Constant (C) region – larger; found at other end

7. Antigen binding site – 2 per Immunoglobin; both heavy and light chains

8. Effector region – stem; determines Immunoglobin class

Antibody Classes (MADGE)

1. IgD – monomer; B cell surface; activation

2. IgM – monomer and pentamer; first released; lymph and blood

3. IgG – monomer; most plentiful; lymph and blood

4. IgA – monomer and dimmer; saliva, sweat, milk; protects mucosa and skin

5. IgE – monomer; causes mast cells and basophils to release histamine

Antibody diversity

1. Somatic recombination – reshuffling genes which code for these proteins

-a. L chain – (300V X 4J) = 1200

-b. H chain – (300V X 12D X 4J) = 14,000

2. Combination – about 17 million

3. Somatic mutation – follow reshuffling; much more; approach billion

Antibody functions

1. Complement – chief mechanism; lysis microbe, foreign cell

2. Neutralization – binds to sites; prevent binding bacteria and virus to target

3. Agglutination – invaders crosslinked; IgM

4. Precipitation – cross link soluble chemicals; come out of solution

5. Opsonization – tagged for recognition and phagocytosis

Cell Mediated Immune Response

General

1. T cell diversity – much more than B cells; types and functions

2. Function – target intercellular invader; can’t get with antibodies

3. Cell differential glycoprotein – separates T cells into 2 major types

-a. CD4 cells – helper T cells

-b. CD8 cells – cytotoxic T cells

4. T cell receptor (TCR)- variable region; specific recognition

MHC restriction

1. Thymus – where MHC restriction takes place; one or the other

2. Type I MHC – found on all body cells

-a. Cytotoxic T cells – recognizes this; destroys cell if nonself in displayed

-b. Self antigen – digested protein from normal cell

-c. Endogenous antigen – virus or cancer protein made in cell

3. Type II MHC – found only on APC and B cells

-a. Helper T cells – recognize this; mediates immunity if nonself displayed

-b. Self antigen – fragment of normal body protein

-c. Exogenous antigen – part of the invaders antigen; nonself

T cell activation

1. TCR – binds to MHC with antigen

-a. Variable region – specificity for an antigenic determinant

2. Cell differential glycoprotein – adhesion; turning on proteins

3. Activation – T cells enlarge and proliferate

4. Effector cells – mature T cells; go after a particular invader

5. Primary response – peaks in 7 days; last 7 to 30 days

6. Secondary response – faster and more intense than the primary

-a. Memory T cells – the reason for this

T cell roles

1. Helper T cells – has several functions

-a. Humoral immunity – to MHC II of B cells; stimulation to proliferate

-b. Cellular immunity – release chemicals for stimulation of cytotoxic T cells

-c. Nonspecific defenses – increase activity of macrophages; leukocyte chemotaxis

2. Cytotoxic T cells – attaches to and causes lysis of other cell

3. Suppressor T cells – releases lymphokines which suppress; prevent autoimmune

4. Delayed-type hypersensitivity T cells – type IV; cell mediated allergy

Interleukins (Cytokines)

1. Defined – chemicals released by leukocytes; mediate immune response

2. Lymphokines – those chemical released by lymphocytes

3. Monokines – chemical released by macrophages

4. Interleukin 1 – released by macrophage; stimulates T cells

5. Interleukin 2 – released by T cells; causes T cells to divide at a faster rate

Transplantation

1. Allograft – from members of the same species; typical transplant

2. Other types – less typical

-a. Autograft – such as a skin graft; from the same individual

-b. Isograft – from genetically identical individual

-c. xenograft – from a different species

3. MHC cross matching – reduce appearance of nonself

4. Immunosuppressive therapy – suppress what isn’t fooled

Pathologies of the Immune System

Immunodeficiency

1. SCID – congenital; T and B cell defective in function

-a. Plastic bubble – germ free environment

2. AIDS – devastating; epidemic

-a. HIV – the cause of AIDS

-b. Helper T cells – HIV attaches to CD4 molecules

-c. Opportunistic infections – the real killer; Pneumocystis pneumonia

3. Hodgkin’s disease – lymph node cancer; depresses lymph cell functions

Autoimmune diseases

1. Defined – when the immune system attacks its body

2. Systemic lupus erythematosus – against many self antigens; kidneys, rashes, joint

-a. Autoantibodies – against self antigens

3. Rheumatoid arthritis – immune complexes; complement lysis synovial membrane

Hypersensitivities

1. Type I (anaphylaxis) – common; half an hour; second exposure

-a. IgE – produced during initial exposure; constant end mast cells and basophils

-b. Mast cells/basophils – second exposure; degrnaulate; histamine

-c. Anaphylactic shock – system wide; blood exposure; penicillin; bee sting

-d. Treatment – epinephrine for shock; antihistamines fore rest

2. Type 11 (cytotoxic) – antibodies to cell antigens; agglutinate; lysis; transfusion

3. Type III (immune complexes) – inflammation; complement; persistent infection

4. Type IV (delayed) – cytotoxic T and DH; Hapten to MHC I; poison ivy