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Samenvatting Immunology and Disease
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Contains all lectures given during the course Immunology and disease.
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Immunology and DiseaseLecture 1 – introduction
Studying the immune system: Natural role
Protection
• Protection from infection
• Protection from re-infection
• Homeostasis
Pathology
• Pathological events accompanying infections
• Immune deficiencies
• Inappropriate immune responses (autoimmunity, allergy)
Studying the immune system: applied
• Diagnosis of disease
• Prevention of disease → increase immunity with vaccination
• Immunotherapy → decrease immunity
Methods to control or prevent autoimmunity, allergy and transplant rejection
Studying the immune system: methodology development
Diagnosis
• Techniques to diagnose and monitor disease
→ immunohistochemistry (IHC), Enzyme linked immunosorbent assay (ELISA), flow
cytometry
Immunotherapy
• Modulation of immunological effector functions to treat disease
→ Biologicals, ‘engineered’ antibodies
Refresher immunology course
Main goals of immunity
• Defend the body against invading pathogens
• Remove ‘worn-out’ cells
• Destroy abnormal/mutant cells within the body → control of cancer
Pathogens can be extracellular and intracellular. Also eg. in the gut skin or blood.
There is also a difference in size of pathogens: virus/parasite.
The challenge of immunity: there is a universe of microorganisms (different structures, life-
forms and size. The threat:
• Bacteria and viruses grow exponentially → the body must respond in time once an
infection occurs
• Rapid evolution of microorganisms → adaptable system necessary
• The immune system must accomplish this without destroying the body itself
(discrimination self/non-self)
,A balanced immune system:
Ineffective immunity is life threatening: Severe combined immunodeficiency syndrome
(SCID):
• Genetic disorder
• Absence of functional T cells
• Patients very prone to infections
AIDS
• Acquired immune deficiency syndrome
• Caused by HIV that targets cells (CD4+ cells) and slowly undermines immune function
• Patients become susceptible to a variety of viral, bacterial and fungal infections
Hyperactive immunity
• Asthma/allergies: uncontrolled / allergic reaction to innocent substances
• Autimmunity: detrimental immune reaction to self tissues as a result of unbalanced
immune regulation (rheumatoid arthritis, type-1 diabetes etc).
Effective immunity: a complicated and delicate balance
Requirements for effective immunity:
• Barriers for prevention
• Recognition:
• Detection and identification of the foreign substance
• Communication and organization
• Coordination to mount the most optimal immune response
• Effector mechanisms
• To destruct or suppress the invading pathogen (without harming self-tissues)
,Organization of the immune system:
Allows:
• Prevention (barriers)
• Fast response (innate immunity)
• Extracellular (humoral immunity) and
intracellular (cellular immunity) microbes
• Adaption (adaptive immunity)
• Specificity (innate and adaptive)
= protection
Physical and chemical barriers prevent infection: three major interfaced between body and
external environment: skin, respiratory tract and gastrointestinal tract. Continuous epithelia
protect against entry of microbes
Innate immunity is the first line of defense, when this barrier is broken → innate immune
system:
• Initial and rapid response against invasion by a variety of pathogens
• The response is rapid (hours) but has limited specificity
• Main components:
- Humoral- Complement system, cytokines
- Cellular- Phagocytes and Natural killer cells
Innate immune system: elimination of danger (phagocytosis, lysus) + observation of danger
(inflammation, activation of adaptive immune system)
, Components of innate immunity: complement system
- Humoral part of innate immunity
- Important for the defense against extracellular pathogens
- Collection of circulating and membrane-associated proteins
- Many of these are proteolytic enzymes enzymatic cascade
- Complement system can be activated by one of three pathways: alternative
pathway, classical pathway and lectin pathway
Complement activation serves three important functions
1. Inflammation: recruitment and activation of neutrophils (C3a and C5a)
2. Lysis of microbes (membrane attack complex)
3. Opsonization of microbes (C3b)
Cells of the innate immune system:
natural killer cells (NK):
- are lymphocytes
- respond to intracellular microbes
- Kill these cells directly
- Respond to IL-12 from macrophages
- Produce IFN-γ
- IFN-γ activates macrophages to kill phagocytosed microbes
- do not attack normal cells because of inhibitory receptors
- Inhibitory receptors recognize MHC-I which is present on all nucleated cells
- In infected cells MHC-I expression is reduced → inhibitory receptors are not
engaged →cell is killed
Granulocytes-monocytes
- Granulocytes: neutrophil aka polymorphonuclear cell, eosinophil, basophil
- Monocyte → circulation
- Macrophage → tissue
- Phagocytes: any cell that ingests microorganisms, cells, or other substances
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