Immune and Adaptive Immune System I : Antigen Recognition Flashcards
Immunity: two systems
1) Innate immunity / nonspecific resistance
2) adaptive immunity / specific immunity
Define Innate immunity
Response to pathogens same each time the body is exposed
Define Adaptive immunity
Response to pathogens improves each time the pathogen is encountered.
Characteristics: Specificity and memory
What is Specificity ?
Adaptive immunity: recognize a particular substance eg specific virus or bacteria
Memory
Links to what system?
Adaptive immune system: “remembers” previous encounters with a particular substance.
Future responses are faster, stronger, and longer-lasting
If pathogen is destroyed before any symptoms develop, the person is said to be ______.
immune
Innate Immunity
- Rapid and non specific
Consists of
Physical Barriers
Chemical Mediators
Leukocytes (WBC)
Inflammatory Response - Enhances adaptive immune response
List the Physical Barriers;
Skin
Epidermal Keratinized cells
Sweat and secretions – lower pH
Mouth / oral cavity
Salivary glands – lysozyme
Stomach/GI tract
Low pH
Mucosal epithelia
GI tract
Respiratory tract
Ears
Nose
Traps and removes
Tears, saliva, and urine wash these substances from body surfaces
Pathogens cannot cause a disease if they cannot get into the body
What are Chemical Mediators?
Promote the immune system
Chemical mediators - examples and how they work;
Complement
> 20 Proteins in plasma
Normally inactive
Once activated - series of reactions - each complement protein activates the next.
Chemical mediators - step by step process
Contribute to adaptive and innate systems
Innate: “alternate pathway” of complement activation
Bind to the cell membrane of the pathogen labelling it for phagocytosis (OPSONIZATION)
Act as chemotactic agents to attract phagocytic cells to the site of inflammation
Form damaging pores in the plasma membrane of the pathogen
Cells swell and lyse (rupture)
3 pathways - Chemical mediators
Wha is the most importnant?
- alternate pathway (Innate)
Other examples of chemical mediators;
- Cytokines
- Interferons (IFNs)
Cytokines;
is signaling molecule that allows cells to communicate with each other over short distances.
Cytokines are secreted into the intercellular space, and the action of the cytokine induces the receiving cell to change its physiology.
A chemokine is a soluble chemical mediator similar to cytokines except that its function is to attract cells (chemotaxis) from
longer distances.
Interferons
are proteins that protect the body against viral infections. When a
virus infects a cell, the infected cell produces viral nucleic acids and proteins, which are
assembled into new viruses. The new viruses are then released to infect other cells. Because
infected cells usually stop their normal functions or die during viral replication, viral
infections are clearly harmful to the body
Fortunately, viruses often stimulate infected cells to produce interferons, which do not protect the cell that produces them.
Instead, interferon bind to the surface of neighboring cells > stimulate those cells to produce antiviral proteins. In this way interferon is like a “Save yourself!” signal from an infected cell to its neighbors.
These antiviral proteins inhibit viral reproduction by preventing the production of
new viral nucleic acids and proteins.
Some interferons play a role in activating immune cells, such as macrophages and natural
killer cells (see “White Blood Cells” in this section).
Concise definition cytokines
Small signalling molecules released from cells to trigger immune response
Egs Interleukins + chemokines + interferons
Concise definition Interferons (IFNs)
Viruses:
Induce cells to produce viral nucleic acids and proteins
Cells infected with viruses secrete interferons
Travel to adjacent cells and induce them to make antiviral proteins
Prevents production of new viral nucleic acids and proteins
Inhibit viral reproduction in these surrounding cells
Some IFNs also activate other immune cells (macrophages and NK cells)
Chemical mediators;
Histamine
Prostaglandins
Leukotrienes
Variously;
vasodilation,
increasing vascular permeability
stimulating phagocytosis
Promote inflammation
Innate Immunity: White Blood cells
[Production + release + type of cell]
> Produced in red bone marrow / lymphatic tissue
> Chemicals released from pathogens or damaged tissues attract WBC
Leave blood and enter tissue
> Phagocytic cells
Neutrophils normally first
Release signals that increase inflammatory response
Recruits and activates other immune cells
Pus- dead neutrophils
Macrophages (monocytes that leave blood)
Larger - later stages of an infection
cleaning up dead neutrophils and other cellular debris
Innate immunity - inflammatory cells
Inflammatory cells
Basophils
Mobile cells
Mast cells
Non mobile cells in connective tissue
Eosinophils
Allergic response
When activated: release histamine and leukotrienes
Inflammatory response
Natural Killer cells
NK cells recognize classes of cells, eg tumour cells / virus-infected cells
Kill their target cells
releasing chemicals that damage cell membranes –> causes the cells to lyse
Inflammatory Response
Hallmark of the innate immune
Tissue injury (eg bacterial infection causing damage)
Mast cells/ basophils degranulate
What does the inflammatory response release > chemical mediators???
Stimulates releases or activation of chemical mediators
- Histamines
- Prostaglandins
- Leukotrienes
- Complement
Process which happpens in the inflammatory respone
Vasodilation (particularly histamine / prostaglandin)
Dilation of local capillaries
Increased blood flow (brings WBC / phagocytes)
Heat / redness
Characteristics of inflammatory response;
1) Increased vascular permeability (histamine)
leakage of fluid into tissue > swelling /oedema
Allows complement to enter tissue
enhances inflammatory response / attracts more phagocytes
Clotting factors enter (fibringogen- fibrin) –
Wall off/ first step in wound repair
2) Recruitment of phagocytes (Leukotrienes / complement)
Phagocytes leave blood and enter tissue
Neutrophils
Followed by macrophages
3) Cycle continues until the pathogens are destroyed
4) Phagocytes remove microorganisms and dead tissue
damaged tissues are repaired.
Is the inflammatory response; local + systemic
Local:
Redness, heat, swelling, pain
Systemic:
More widespread
More neutrophils
Pyrogens > fever – hypothalamus
In severe cases: Sepsis - decreased blood volume can cause shock and death
Adaptive immune response
Specificity and Memory
Antigens:
substances that stimulate adaptive immune responses
Foreign (bacteria, viruses, pollen, food)
Self (tumour)
Adaptive Immunity
Antibody Mediated / Humoral Immunity
Protein generated by plasma cells
differentiated B cell
Cell-mediated
T cells
Helper T cells (Th)
Cytotoxic T cells
Lymphocyte: Origins
Where do they originate?
= from stem cells in Red Bone Marrow
>B cells mature in in bone marrow
>T cells mature in thymus
Clones: Small no’s of identical B cells or T cells
form during embryonic development (and after)
Type any info about clones
Each clone derived from a single, unique B or T cell
Respond only to a particular antigen
> large variety of clones
> Antigen receptors on surface
- B-cell receptors
- T-cell receptors
> Each receptor binds with only a specific >antigen
Each lymphocyte clone have identical antigen receptors on their
Clones against self antigens normally eliminated
Adaptive immune response - step by step
1) Antigen recognition by lymphocytes
Activates
2) Lymphocyte receptors and antigens combine
B cell and T cell receptors
3) Proliferation of lymphocytes recognising that antigen
Antigens?
[bound to which molecule]
May be part of larger molecules
Eg after phagocytosis and b/d by macrophages
Bound to major histocompatibility complex molecules (MHC) on cell surface
Recognition: MHC molecules
[classes]
Antigens presented by MHC receptors
MHC class I molecules
All other cells with nuclei
MHC class II molecules
APC – macrophages, dendritic cells lymphocytes (B and T cells)
Combined MHC and antigen can then bind to the antigen receptor on a B cell or T cell
Co-stimulation
Cytokines
Surface proteins
Recap - innate immune system
> Non-specific
Physical barriers
Chemical Mediators
Leukocytes (WBC)
Inflammatory Response
> Hallmark: Inflammatory Response
Tissue injury –>
Vasodilation
Increased vascular permeability
Recruitment of phagocytes
Local or systemic
Recap - Adaptive immune system
> Specific: Specificity and Memory
Antibody mediated
Cell mediated
> Lymphocytes need to recognise be activated by antigen
After pathogen phagocytosed antigen presented on surface of a cell (eg macrophage) by MHC molecule
> Lymphocyte clones proliferate
What is not affected by antibodies?
Viruses
Lymphocyte proliferation
> Helper T cells
MHC class II molecule
Macrophages release IL (helps to stimulate helper T cells)
Helper T cells
CD4 molecule
> Helps T cell receptor and MHC II molecule bind
After presentation: Helper T cells secretes IL2 stimulates them to bind
Helper T cells: ‘help’ B cells and other T cells to be activated
Lymphocyte proliferation - can daughter cells divide again?
Yes, if presented with antigen
Lymphocyte Proliferation - BC
Phagocytoses same antigen as Helper T cell
Presented on surface of B cell by MHC class II molecule
T-cell receptor binds to MHC class II / antigen complex
Aided/co-stimulated by CD4 molecule
Co-stimulated by ILs (TH cell)
Stimulate B cell to divide
These can go onto divide
Some will differentiate into Plasma cells
Produce Antibodies
Antibody (Humoral) Immunity - Antibodies
Bind to antigens: destroyed
Extracellular antigens
Antibody (Humoral) Immunity - Proteins
Y-shaped molecules
consisting of four polypeptide chains: two identical heavy chains and two identical light chains
Variable region (top)
Antigen binding site
Constant regions
Immunoglobulins (Ig)
IgG, IgM, IgA, IgE, IgD
Antibody Production - primary response
First exposure to antigen
B cell undergoes several divisions
Forms plasma cells and memory B cells
Plasma cells produce antibodies
Normally takes 3–14 days
Normally develops disease symptoms
pathogen has had time to cause tissue damage
After antigen destroyed antibodies degrade and plasma cells die
IgM
Antibody Production - secondary response
Previously exposed to antigen
Memory B cells quickly divide to form plasma cells
Quickly produce antibody
Makes more memory cells
Quicker to produce antibodies
More plasma cells/antibodies
Memory cells persist for long time
IgG
What are the effects of antibodies?
Extracellular Pathogens
a) Inactivate antigen: antibody binds to an antigen or when many antigens are bound together
b) Activates Complement Cascade: Antigen binds to antibody. Antibody can then activate complement proteins > inflammation, attracts WBC and lyses cells
c) Initiates release of inflammatory mediators: Antibody binds to mast cell /basophil. Triggers degranulation
d) Facilitate Phagocytosis: Antibody binds to antigen. Macrophages attaches to Fc of the antibody and phagocytoses both the antibody and the antigen
e) Antibody dependent cellular activity : Activates cytotoxic cell responses. Cytotoxic cells release chemicals that destroy the antibody-bound antigen
Antibodies (Immunoglobulins)
1) IgG
secondary immune responses
Some maternal IgGs cross the placental membrane
2) IgA
external secretions
saliva, tears, intestinal and bronchial mucus, breast milk
3) IgE
target gut parasites and are associated with allergic responses
4) IgM
primary immune responses
5) IgD
Cell mediated Immunity
> Cytotoxic T cells
- Intracellular effects
pathogens, allergic reactions, tumours
- Essential Viral infections
- Antibodies can’t cross into cell
- Destroys infected/affected cell
Proliferation Cytotoxic T cells - e.g. of virus
Viruses infect cells
Some viral proteins are broken down and become processed antigens
Combined with MHC class I molecules
displayed on the surface of the infected
Proliferation Cytotoxic T cells - activation
T-cell receptors binding with the MHC class I/antigen with the MHC class I/antigen complex
Proliferation Cytotoxic T cells
- co stimulation
surface molecule CD8
Helper cells: co-stimulation with eg IL2
Stimulates T cell to divide
Cell mediated Immunity
> Series of divisions
> Additional cytotoxic T cells
Immediate response
> memory T cells
Secondary response
long-lasting immunity
Cell mediated Immunity - Cytotoxic T cell Function
Release cytokines
Attract innate immune cells
Macrophages
Phagocytosis of antigen/cell
inflammatory response
Activate additional cytotoxic T cells
Cell mediated Immunity - Directly kill virus infected cells
Viral antigens on surface
T cells bind to the antigens on the surfaces and cause the cells to lyse or under go apoptosis
Cytotoxic T Cells Cytotoxic T (TC) cells _______ + _______
cells that display MHC-I-antigen complexes
attack + destroy
Flow chart: Acquired ADAPTIVE immunity
ACTIVE
Level 1
Active immunity = immunity is provided by individual’s own immune system
Level 2
Natural = antigens are introduced through natural exposure
Artifficial = Antigens are deliberately introduced in a vaccine
low chart: Acquired ADAPTIVE immunity
PASSIVE
1) Passive immunity = immunity is transferred from another person or an animal
2) Natural = antibodies from the mother are transferred to the child across the placenta or in milk
Artificial = antibodies produced by another person or an animal injected
Allergic response
Immune response to a non-pathogenic antigen
Allergen is an antigen that is typically not harmful to the body
Sensitive individuals : inappropriate immune response
Sensitivity / hypersensitivity to the antigen
Immediate hypersensitivity reactions are mediated by antibodies
Sensitisation and Re-exposure Phase
What is the Sensitization phase
equivalent to the primary immune response
Allergic response
Antibodies Produced
IgE and IgG
IgE antibodies: immediately bound to mast cells and basophils.
Memory T and memory B cells formed
Allergic response - Re-exposure
- Allergen binds to IgE already present on mast cells
- triggers immediate release of histamine, cytokines, other mediators
- —> cause allergic symptoms
- strong and rapid response
What happens to an Aging Immune system?
> Little effect on the lymphatic system
remove fluid from tissues,
absorb lipids from the digestive tract
remove defective red blood cells
Aging immune system - severe effect?
Severe impact on the immune system =
thymus replaced with adipose tissue
lose the ability to produce mature T cells
May lose functionality
Antigen exposure leads to fewer helper t cells
Less stimulation of B and cytotoxic T cells
Aging immune system - responses?
Antibody and cell mediated responses decrease
Primary and secondary antibody responses decrease
Aging immune system - responses?
Antibody and cell mediated responses decrease
Primary and secondary antibody responses decrease
