Immunology 2 W2 Flashcards
immune response of 1st contact of innante immunity
good (+)
immune response of 2nd contact of innante immunity
the same
good (+)
immune response of 1st contact of adaptiveimmunity
good (+)
immune response of 2nd contact of adaptive immunity
greater (+++)
what is a neutrophil granulocyte
moat common lwukocyte in bloood, enriched in acute inflamed tissue
short life span of 5 days
multiplw segmented nucleus
lots of granula
what are macrophages
long life span of years
type of white blood cell that are part of the innate immune response and are responsible for detecting, engulfing, and destroying pathogens, dead cells, and cellular debris through a process called phagocytosis
in tissues and organs
used to fight against bacteria, viruses andn protozoa
TH1 and TH2 differntiation
An antigen presenting cell identifies and presents toxins or an infection to a TH0
The TH0 decides what to do with it
If there is IL-2, IFN-Y and TNF-a cytokines present then it will become TH1
If there is IL-4, IL-5, IL-6, IL-10 and IL-13 cytokines then it will become TH2
TH1 cytokine: Interferon-y
-A cytokine
-Provides protection against diseases by acting directly on target cells or through activation of the host immune system
-Can educate immune cells to recognise and destroy pathogens
-Has an anti-viral function
TH1 cytokine : TNF
Tumour necrosis factor
Helps elimination of interest cellular bacteria
Helps maturation and migration of dendritic cells
Created by inflammatory cells
TH2 cytokine : IL-4
Is a marker cytokine
For the activation and growth of B cells
Essential for IgE and TH2 development
TH2 cytokine : IL-5
Help B cell differentiation and IgA synthesis
TH2 cytokine : IL-10
Is a regulatory cytokine
Is an inhibitor of macrophage function?
Mechanisms of T cell mediated cytotoxicity
If a cytotoxic cell binds with an infected T cell through the FAS receptors then it will undergo clean apoptosis when the FAS is activated
If a cytotoxic cell binds with an infected T cell and perforin granzyme is released I have the enzymes make holes and the cell bursts which is messy.
FAS = kill itself - cleanee
Granzyme = bursts - messy
Five classes of antibody
IgM
IgA - saliva,breast milke
IgD - always stuck to B cells
IgG - most in blood
IgE - allergic reactions
Antibody structure
A Y shape
Has a light chain and a heavy chain X2
An anti-binding site which interacts with the antigen
Has an FC region which is only heavy
Has a tail
The top end of the Y is the variable region
And the bottom end of the Y is the conserved region
It has disulphide bonds between the light and heavy chains as well as between heavy and heavy
What is the variable region made of?
V gene segment
Diversity gene segment (D)
Joining gene segment (J)
How many segments does each chain have?
Times together the V, D and J gene segments
Where did immunoglobin get most of their diversity?
Heavy chain and light chain get most of their diversity from the number of V gene segments
Heavy chain gets some diversity from D gene segments
Heavy chain and light chain get a mild amount of diversity from J
Where do T cell receptors get most of their diversity?
A and B chains get most of their diversity from the V gene segments and J gene segments
D. Gene segments do not contribute
VDJ recombination
Variable-diversity-joining rearrangement
Is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation?
Results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors found in B cells and T cells
The process is a defining feature of the adaptive immune system
V(45) D(23) J(6)
-123456789- -123456789- -123456789-
The D-J join
-12346789- -12345656-
The V-DJ join
- 123656-
Transcription
-123656-
RNA processing
-365-
This contains one of each gene segment (VDJ) to make the variable region of an antibody
Antibodies changing structures (3)
Affinity maturation - somatic mutations in the variable region (top of the Y)
- Increases affinity of antigen recognition
- No change on effector functions
Switch from membrane to secreted form - Cleve off membrane and released into the blood
- No change in antigen recognition
- Change from Bcell receptor function to effector function
Isotope switching - change isotope
- No change in antigen recognition
- Each isotope serves a different set of effector functions
What actually are immunoglobins
proteins produced by B cells in response to the presence of antigens.
identifying, binding to, and neutralizing pathogens or harmful molecules.
Immunoglobulins have a Y-shaped structure consisting of: Two heavy chains and two light chains held together by disulfide bonds.
Variable regions are specific to a particular antigen. This is where antigen binding occurs.
Constant regions determine the class or type of immunoglobulin.
There are five types and each target a specific antigen type
D,E and G all use a single Y chain
A Uses a double Y chain called a dimer
M is a combination of five Y chains called a pentamer
IgA
Two types
Not typically in the blood, but in saliva and milk
Innate
Fight Pathogens
IgD
Monomer
Role in B cell activation
Found on the surface of mature B cells
Least well-known
Role in activation of mast cells to attack invading microbes
IgE
Monomer
Respond to allergens and worms
Involved in Allergic reaction and asthma
Bound to mast cells and basophils
IgG
Monomer
Long term immunity
Blood
70% of entire IG pool in the body
Target pathogens
Bind to antigens on one end and the other two phagocytic cells which absorb and destroy it
Smallest so can migrate into fissures
It is the only one that can diffuse through the placenta
IgM
Pentameter
Early immune response and complement activation
Blood
First antibody produced in infections
B. Cell development
- HCSs - bone marrow
- CLP - bone marrow
- Pro - bone marrow - heavy chain rearrangement by VDJ recombination
- Pre - bone marrow - light chain rearrangement by VDJ recombination
- Immature - bone marrow - functional IgM expressed
- Mature - peripheral blood+2ndary lymphoid organs - express IgM+IgD, naive(not yet encountered antigen)
- Activate+dfferentiate - 2ndary lymphoid organs - plasma or memory
Allergic reaction first exposure
Mast cells have IgE receptors
IgE antibodies bind to the receptors
This takes time
Allergic reaction, repeat exposure
This is faster
The allergen binds to the IgE
This activates mast cells
They degranulate and histamine is released
Act on surrounding tissues and dilates blood vessels to slow the blood flow
Immune cells are attracted into tissue
Makes blood vessels leaky
Allows antibodies to enter tissues
Infection is removed
Once removed mast cells produce anti-inflammatory mediators which stop further immune cells entering the tissues and this promotes the rebuild of tissues
Mast cells then regulate for the future
Mast cell versus basophil
Mast:
- Have a round nucleus
- Have CD34 surface marker
- Secreted from bone marrow when immature
- Granule composition is versed with serine proteases, histamines, lysosomal enzymes and cytokines
- Can eliminate bacteria and parasites and can interact with dendritic cells and B/T cells
Basophil:
- Do you not have round nucleus
- Have CD34 surface markers
- type of white blood cell released into the blood in response to an allergen
- Already mature when released
-
Mast cells have different effects depending on their location : gastrointestinal tract
- Increased fluid secretion
- Increased peristalsis
- Leading to the expulsion of gastrointestinal tract contents (diarrhoea, and vomiting)
Mast cells have different effects depending on their location : gastrointestinal tract
- Increase fluid secretion
- Increased peristalsis
- Leading to the expulsion of gastrointestinal tract contents (diarrhoea, and vomiting)
Mast cells have different effects depending on their location : airways
- decreased diameter
- Increased mucus secretion
- Leading to congestion and blockage of airways (wheezing, coughing, phlegm), swelling and mucus secretion in nasal passages
Mast cells have different effects depending on their location : blood vessels
- Increased blood flow
- Increased permeability
- Leading to an increased fluid in tissues, causing increased flow of lymph to lymph nodes, increased cells and proteins in tissues and increased effector response in tissues
More information on mast cells
-Reside under connective tissue
- Found in connective tissues and respiratory epithelium
- Don’t circulate in the bloodstream
- Born from bone marrow
- They are immature when in the blood
- move into tissues and become mature
- Contain granules
Anaphylactic shock
- Blood pressure becomes solo that there isn’t adequate blood supply to the organs
- Swelling to upper airway further reduced oxygen
- Body tries to compensate for the low blood pressure by increasing heart rate
- Isn’t enough to compensate for the loss of oxygen to the brain and the heart
- Become unconscious and going into cardiac arrest
- EpiPen can easily reverse the symptoms
- Adrenaline relaxes the airways and constricts blood vessels and increases heart rate which can all increase blood pressure for oxygen supply
- Antihistamines and corticosteroids may be given to further reduced symptoms after life-saving measures
Mast cell activation disorders
Some cells have DNA mutations causing them to be more reactive known or unknown triggers
This can be inherited or acquired
Type 4 hypersensitivity
- also called delayed type hypersensitivity
- An example is contact dermatitis and drug related allergies
- Has a delayed reaction of 24 to 48 hours after exposure
- TCell mediated not antibody
- APC take up antigen and present it to T cell
- Requires primed antigens specific T cell CD4+ or CD8+
- need T cells that react towards an allergen
Example of an allergen - touching poison ivy
- You touch poison ivy - causes localised inflammatory response and releases toxins
- Cells in the epithelial layer take up the toxins, react and produce cytokines and chemotkines
- Attract cells from the plasma: basophil, monocytes and memory T cells and they migrate into the tissue
- Antigen is being presented to the memory cell after migration.
- Memory cells become activated.
- Activated mast cells
- Histamine released.
Site of receptor and its effect : receptor H1
Smooth muscles = Bronco construction and contraction of the GIT
Endothelium = vasodilation and increased permeability of capillaries -> oedema
Sensory endings = pain and itch
Site of receptor and its effect : receptor H2
Smooth muscles of blood vessels only enlarged doses
Vasodilation
Site of receptor and its effect : receptor H4
Immune active cells as eosinophils
Chemotaxis
What should antihistamines actually be called?
They are blocking the receptors from interacting with histamine so they should be called histamine receptor antagonist
Reduction of the effect of release histamine
- Physiologic antagonist.
- epinephrine has smooth muscle actions opposite to histamine but by acting on different types of receptors it is used in conditions of massive releases of histamine - Histamine release inhibitors.
- Reduce immunologic release of histamine from mast cells - Histamine receptor antagonist/antihistamines.
Generations of histamine H1 antagonist
1st
- Sedating because it’s lipophilic and can cross the blood brain barrier
- affect the CNS
2nd
- As poorly penetrates the blood brain barrier
- Does not affect the CNS
