immune system Flashcards
The function of the immune system is to…
- prevent infections
- eradicate established infections
- detect and eliminate tumours as well as tolerate self
Congenital (primary) immune deficiencies
e.g. patients who completely lack key cells and molecules of the immune system
Acquired (secondary) immune deficiencies
e.g. HIV infection that leads to the eradication of key immune cells
The immune system is integrated with other systems…
gastrointestinal, cardiovascular, respiratory, nervous, endocrine, skin
Molecules of the immune system can act in a … matter
Autocrine
paracrine, or
endocrine (when secreted)
The cells and molecules of the immune system access most organ systems in the body by travelling via:
blood vessels
lymphatic vessels
Immune cells originate from…
bone marrow stem cells
central sites
often used to refer to lymphoid tissues or lymphoid organs
Primary lymphoid organs:
bone marrow, thymus
Secondary lymphoid organs:
spleen, lymph nodes, mucosal & cutaneous associated lymphoid tissues
Peripheral sites
all other tissues and systems
skin, liver, gut, heart, brain, CNS, muscle, lungs etc
Innate
Neutrophil
Basophil
Eosinophil
Monocyte
Adaptive
Lymphocyte
Hallmarks of the Innate Immune System
Speed - Early, rapid
Duration - short-lived
Repetitive - responds the same way each time a microbe is encountered
Interactive - with other cells of the innate immune system and with cells of the adaptive immune system
Non-reactive to the host
Lymphocytes
express receptors that specifically recognise a wider variety of molecules produced by microbes as well as noninfectious substances
lymphocytes expand and differentiate into…
Effector cells
Memory cells
how does innate immune system tell the difference between self and non-self?
Different Microbes express different “patterns”
Our own cells do not express these microbial patterns
Epithelial, Endothelial and Resident Immune Cells express receptors on their surface that allow them to sense danger
Phagocytes
neutrophils & macrophages
scavengers that ingest microbes
Exocytes
eosinophils, mast cells, basophils
release active mediators from granules
Tissue Resident Mast Cells
- reside in peripheral tissues exposed to the environment
- have receptors on their surface that allow them to sense danger - 1st responders
- perform antibacterial functions
- degranulate the contents of their cytoplasm - granules contain histamine & other soluble factors increases vascular permeability & promotes inflammation
What are Cytokines
Proteins that are produced & secreted by many different cell types
* modulate inflammatory and immune reactions
* are a principal mediator of communication between cells
Cytokines can target cells in an
- autocrine manner (acting on the cell that produced the cytokine)
- paracrine manner (acting on neighbouring cells)
- endocrine manner (acting on distant cells or systemically)
When danger is detected a few things happen:
- Release of histamine & inflammatory cytokines
- Dilated blood vessels allow for more blood flow to the area (redness) and fluid to come in (swelling)
- Induces the expression of adhesion molecules on endothelial cells lining the blood vessels which attracts innate immune cells
Chemokines
- Set up in a gradient: more chemokines closer to source
- Helps neutrophils know where to move
Chemotaxis
Chase bacteria and consume by phagocytosis
Leukocyte rolling
- Cytokines released at site
- Stimulate endothelial cells that line blood vessels to express surface proteins (selectins)
- Selectins bind to carbohydrates in the membrane of the leukocytes
- Leukocytes can roll along these in search for a point where they can pass through - causes them to stick to wall of blood vessel
- Squeeze between endothelial cells without breaking the cell wall (only occurs in veins)
- Crawl out of blood vessel into adjacent connective tissue
Phagocytosis and Antigen Capture
- Binding of the microbe to the cell is followed by extension of the phagocyte plasma membrane around the particle.
- The membrane then closes up and pinches off, and the microbe is internalised in a membrane-bound vesicle, called a phagosome.
- The phagosomes fuse with lysosomes to form phagolysosomes.
- Enzymes & toxic substances in phagosome kills microbes
Enzymes & toxic substances that kill microbes
Nitric Oxide (NO)
Reactive oxygen species (ROS)
Too much inflammation may be “Bad”
septic shock
chronic inflammation can lead to severe diseases
arthritis, cancer, Inflammatory Bowel Disease (IBD), diabetes
Many autoimmune diseases are linked to the genes responsible for:
- T cell activation
- Maintaining immunological tolerance
Environmental Factors of Autoimmune disease
- Often preceded by an infection
- Many autoimmune diseases are more common in women
- Local trauma leading to an inflammatory reaction may release previously hidden antigens that our immune system responds to
Autoimmune disease may be
organ specific or systemic
Multiple Sclerosis (MS)
- multifocal demyelinating disease
- progressive neurodegeneration caused by an autoimmune response to self-antigens in a genetically susceptible individuals
Some MS symptoms
Motor control issues
Fatigue
Heat sensitivity
Other neurological symptoms
Incontinence and constipation
Neuropsychological symptoms
Tumour growth
- Patients with tumours that have been infiltrated by lymphocytes have a better prognosis
- Enlarged tumour-draining lymph nodes = better prognosis
- Immunodeficient patients have a higher susceptibility to tumour growth
Promising new cancer therapies that target the immune system
- Bone marrow transplantation
- Re-engineered T cells: Chimeric Antigen Receptor (CAR) T cells
- Antibodies
Thymus
- Generative (or primary) lymphoid organ
- T cells learn how to be “good” T cells (i.e. a cell that doesn’t “attack” self-cells)
humoral immunity
B lymphocytes secrete antibodies that eliminate extracellular microbes.
cell-mediated immunity
different types of T lymphocytes:
* help phagocytes to destroy ingested microbes and
* kill infected cells
Helper T cells
- “help” other cells of the immune response
- different types w/ specialised functions
- Some helper T cells suppress or regulate the immune response rather than activate the immune response (regulatory T cells)
Cytotoxic T Lymphocytes (CTLs)
- kill their target cells in a highly specific way
- get “help” from helper T cells
- CTLs play a key role in:
viral infections
anti-tumour immunity
Immunological Tolerance
a system for determining which lymphocyte clones will be allowed to survive
* 2 types (central & peripheral)
Central Immunological Tolerance
occurs in the primary lymphoid tissues
bone marrow (for B cells)
thymus (for T cells)
Peripheral Immunological Tolerance
mediated primarily by regulatory cells
What is the most likely consequence if the immune system does not tolerate self correctly?
Slowing of the reaction of the innate immune system to infection
Why might an immunodeficient individual be more susceptible to cancer?
Because the immune system destroys cancer cells
Which of the following has been shown to be an effective treatment for multiple sclerosis?
Preventing T cells from adhering to blood vessel walls
