Immune System Disorders
- 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
- need no previous contact
- Physical barriers, fever, phagocytosis, inflammation
- Acquired 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
- 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
- Immune-Mediated Tissue Injury
- hypersensitivity => "too much immunity"
- Hypersensitivity reactions (four types)
- mast cells => skin, respiratory system, intestines
- Type I: Immediate Hypersensitivity (Anaphylaxis)
- First exposure causes no noticeable reaction
- Second exposure => mast cells release histamine
- early
- 5-45 minutes
- skin, eyes, nasal cavity, lungs
- late
- 2 hours-3 days
- chemotactic factors
allergic asthma, hay fever, hives, eczema
- Type II: Ab-Dependent Cytotoxicity
- Ab attach to surface of individual cells (RBC’s, kidney cells)
- Ab attract K-cells
- Myasthenia Gravis, Graves Disease, Erythroblastosis Fetalis
- Type III: Immune-Complex-Meidated Hypersensitivity
- Immune complex => Aggregation of Ag & Ab’s
- removed from blood by liver and spleen
- Excess Ag or Ab
- Vasodilation, increased permeability, chemotaxis
- Rheumatoid Arthritis, Immune Complex Glomerulonephritis
- Type IV: Cell-Mediated, Delayed -Type Hypersensitivity
- TC cells, NK-cells, macrophage
- Tuberculosis, contact dermatitis, acute/chronic transplant rejection
Ag presentation + TH cells
TC cells, macrophage, NK cells
Lymphokines, cellular cytotoxicity
- 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
- Autoimmune Disorders
- Systemic Lupus Erythematosus
- Rheumatoid Arthritis
- Scleroderma
Immunity
Innate Acquired
Fever B-cells
Inflammation T-cells
Phagocytosis K cells
Physical Barrier NK cells
Complement Antibodies
Specific Immunity
Humoral Cell-Mediated
B-cells T-cells
Antibodies 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
IgM - produced first
IgG - main Ab in blood
IgE - Allergies
IgA - saliva, breast milk
IgD - major surface receptor on B lymphocyte
T-cell (inactive)
Ag presentation (MHC)
Ag recognition (CD4, CD8)
T-cell (active)
TC TH TS
B-cell (inactive)
B-cell (sensitized)
B-cell (activate)
Memory B-cells Plasma cells Antibodies
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
Ag presentation + TH cells
TC cells, macrophage, NK cells
Lymphokines, cellular cytotoxicity
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
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