Lymphatic System and Immunity
:
Overview (lymphatic system)
- lymph
- lymphatic vessels
- lymphoid tissues/organs
- specialized cells (lymphocytes)
- Organization
- Functions
- Production, maintenance and distribution of lymphocytes
- Return of fluid and solutes from tissues to blood
- Distribution of hormones, nutrients and wastes
- Lymphatic Vessels
- carry lymph from peripheral tissues to blood (capillaries)
- one-way network of vessels
- recycle fluid
- Lymphatic capillaries (terminal lymphatics)
- beginning of lymph system
- lined by endothelial cells (NO basement membrane)
- endothelial cells overlap => fluid can go in but can’t come out
- differ from blood capillaries:
- originate as blind pockets
- larger in diameter
- thinner walls
- flattened/irregular outline
- Valves => prevent backflow
- Major lymph collecting vessels
- Thoracic duct
- drain below diapragm and left side of body above diaphragm
- empty into left subclavian vein
- Right lymphatic duct
- drain right side of body above diaphragm
- empty into right subclavian vein
- Lymphocytes
(Innate) (Acquired)
Non-Specific Immunity Specific Immunity
Physical Phagocytes Fever Inflammation Complement Lymphocytes
Barriers
T-cells B-cells NK cells
- Types of Lymphocytes
- T-cells
- thymus-dependent lymphocytes
- 80% of circulating lymphocytes
- Cytotoxic T-cells, Helper T-cells, Suppressor T-cells
- B-cells
- Bone-marrow derived
- 10-15% of circulating lymphocytes
- Plasma cells, Memory cells
c. NK cells and K cells
- Lifespan and Circulation
- constantly moving
- ration of B-cells/T-cells is constantly changing
- Lymphoid Tissue
- C.T. dominated by lymphocytes
- GALT (gut associate lymphoid tissue), tonsils, appendix
- Lymphoid Organs
- Lymph Nodes
- small, oval lymphoid organs
- filter/purify lymph before it reaches venous system
- early warning of infection
- transport system for metastatic cancer cells
- Thymus
- cortex and medulla
- maturation of T-cells
- secretion of thymosin
- Spleen
- filter blood
- phagocytosis of blood components
- iron storage
- initiation of immune response
- red pulp (RBC’s) and white pulp (lymphoid tissue)
- Immunity
- Innate (non-specific) and Acquired (specific)
Immunity
Innate Acquired
Fever B-cells
Inflammation T-cells
Phagocytosis K cells
Physical Barrier NK cells
Complement Antibodies
- Innate Immunity (Non-specific Immunity)
- Physical barriers
- Fever
- Inflammation
- Complement
- phagocytes
- Microphage
- neutrophils and eosinophils
- target foreign compounds and pathogens coated with Ab’s
- Macrophage
- Respond to pathogens
- Fixed
- Free
- Surveillance
- NK cells
- monitor tissues
- recognize and destroy abnormal cells (Ag) and cancer cells
- versatile
- respond rapidly
- Acquired Immunity (Specific Immunity)
- learned response
- process of recognition, learning, memory & self-discrimination
- Fundamentals of Specific Immunity
- Lymphocytes => cells that mediate immunity
WBC’s (35% of WBC population)
T-lymphocytes, B-lymphocytes, third population
cells
Specific Immunity
Humoral Cell-Mediated
B-cells T-cells
Antibodies Cell-cell combat
B-cells
Antibodies
T-cells
Cell-Cell combat
BONE MARROW
Lymphoid Stem Cells
THYMUS
Lymphoid Stem Cells NK-cells B-cells
T-cells
Cell-mediated Surveillance Ab-mediated
immunity immunity
- T lymphocytes
- cells produced in marrow, specialized in thymus
- surface studded with T-receptors
- able to recognize antigens
- T-cells attack pathogens themselves
- self-tolerance
- B lymphocytes
- produce antibodies
- made in marrow, mature in marrow
- surface studded with antibody the B-cell produces
- react to a specific antigen
- Antibodies
- Y-shaped protein molecules
IgM - produced first
IgG - main Ab in blood
IgE - Allergies
IgA - saliva, breast milk
IgD - major surface receptor on B lymphocytes
- Third population cells (null cells)
- cell killing
- K- cells
- NK- cells
D. The Immune Response
- T-cells & Cell-Mediated Immunity
a) TH => helper T-cells
- stimulate response of both T-cells & B-cells
- activate B-cells to make Ab’s
- AIDS
- Ts => suppressor T-cells
- inhibit T-cell & B-cell activity
- moderate immune response
- Tc => cytotoxic T-cells
- responsible for cell-mediated immunity
- direct physical/chemical attack of Ag
- T-cell Activation
- Ag presentation
- Ag recognition by T-cells
- CD8 => Tc and Ts
- CD4 => TH
- T-cell Activation
T-cell (inactive)
Ag presentation (MHC)
Ag recognition (CD4, CD8)
T-cell (active)
TC TH TS
- B-cells & Ab-mediated immunity
- B-cell Activation
- B-cell sensitization
- B-cell activation
- TH cells, Memory B-cells & Plasma cells
B-cell (inactive)
B-cell (sensitized)
B-cell (activate)
Memory B-cells Plasma cells Antibodies
- Overview
Ag
TC cells Specific Defenses Ab’s
Activation TH cells Activation
of T-cells of B-cells
TS cells
Produce memory Produce memory B-cells
TC cells & TC cells & plasma cells
IV. Therapeutic Applications of Immunity
- Immunization
- Immunization => preventive techniques of artificially inducing an immune response
- stimulate the immune system without exposing the body to an infection
- killed, attenuated or killed vaccine
- rabies
- Use of Antisera
- active immunity => immunity induced by vaccination
- passive immunity => protection imparted in the form of ready-made antibodies from outside the body
- Natural passive
- Artificial passive
- antiserum
- erythroblastosis fetalis
V. Tissue Transplantation
- cell surface protein "fingerprint" => chromosome 6 => MHC
- ABO, age, response/tolerance to immunosuppression drugs, further diseases, previous transfusion/transplant
- Tissue vary in immunogenicity
Least Most
Liver Kidney Heart Pancreas Skin Bone Marrow
TH cells come into contact with graft tissues
Activation & TH cells move TH cells interact
Proliferation to graft site with B-cell
of TC cells
Release lymphokines Ab production
Focused attack Monocyte/macrophage Ab attach to MHC
on tissues to graft site of graft tissue
Graft tissue Graft tissue Graft tissue
attacked attacked attacked
- Acute rejection
- Chronic rejection
- Improving graft survival
- Immune Deficiency Syndromes
- Primary Immune Deficiencies
- B-cell, T-cell, combined B & T-cell, defects in phagocytosis/cytotoxicity and complement components
- often determined genetically
- B-cell deficiencies
- recurrent/overwhelming infections by viruses that are normally neutralized by Ab’s or by bacteria that can resist phagocytosis unless attacked by an Ab.
- Rubella, staphylococcus, influenza
- Isolated IgA defieciency
- T-cell Deficiencies
- result in chronic or recurrent infections with viruses, yeast & fungi
- DiGeorge Syndrome
- SCID (Severe Combined Immunodeficiency Disease)
- disorder of both T-cell and Ab production & function
- autosomal recessive or X-linked diseases
- common stem cell disorder
- opportunistic infections
- bone marrow transplant
- Secondary Immune Deficiencies
- Thymus
- atrophy after puberty
- decreased capacity to mount a T-cell mediated immune response with increasing age
- increase in self-reactive Ab’s
- Diet
- Primary Disorder
- tumor, extensive burns, diabetes mellitus
- Medical Treatment
- immunosuppressant therapy, anaesthesia, chemotherapy and radiation therapy
- Stress
- interaction between neuroendocrine and immune
- corticosteroids
- IL-2
- AIDS (Acquired Immune Deficiency Syndrome)
- HIV-1 (Human immunodefieciency virus)
gp120 bind to TH cells at CD4
Viral core protein & RNA brought into TH cells
RNA codes for viral DNA Reverse
Transcriptase
Viral DNA merges with host DNA
New Virus Synthesis AZT
Virus Shedding
Repetition of infection sequence
- Pathogenesis
- latent period => HIV present but inactive (may not really exist)
- progression
- Infection
- Acute phase (30-50%)
- Seroconversion
- Chronic phase
- Crisis phase
3) Treatment
- AZT
- AIDS cocktail
- Vaccine
- Impact of TH cells
Decrease in TH cells
Impaired Impaired Impaired
Ab production inflammatory cellular
response immunity
Increased rate & Tumor Growth
severity of infection
