Immunology Flashcards
Immunology
The study of the mechanisms that human and other animals use to defend their bodies from invasion by other organisms
Pathogen and examples
An organisms with the potential to cause disease
Examples: Bacteria, fungi, viruses, unicellular protozoa, worms
What are the 4 hallmarks of the immune system?
Specificity: The ability to distinguish between closely related substances
Diversity: The capacity to specifically recognize and astoundingly large number of different molecules
Memory:The ability to recall previous exposure to a foreign substance and respond more rapidly and more effectively
Tolerance:The ability to avoid responding to the host’s own cells and tissues
Antigen
Any foreign material which can evoke an immune response
Can be a molecule, particle or portion of a larger molecule or even a chemical structure
Antibody/immunoglobulin
Proteins produced by animals which bind specifically to a foreign chemical structure or antigen
Antibody= the protein that binds to a specific Ag
Anti-covid antigen antibody
Immunoglobulin= the protein as a whole
Immunoglobulin A, IgG, etc.
Innate response
Reacts quickly
Within minutes to hours
First line of defense
Always will be the same
More primitive (found in insects, worms, starfish, as well as higher animals)
Adaptive immune response
Slower initially
Found only in fish and higher animals
(Adapts to give a better response over time)
Faster and better response at the next encounter
Has specificity, diversity, memory and tolerance
What immune response has specificity, diversity, memory and tolerance?
Adaptive immune response
Erythrocytes/RBC
Not much role in immunity
No nucleus
Transport oxygen to the tissues
Leukocytes/WBC
Cells of both the innate and adaptive immune response
Neutrophils (type of leukocytes/WBC)
Obvious polymorphic nucleus
major phagocytic cells of microbes
50-70% of human blood leukocytes
Eosinophils
Granules, nucleus, type of cell, role
Many red-staining granules
Polymorphic nucleus
Rare in blood
Phagocytic cells
Plays a major role in defense against worm and parasites
Basophils
Dark blue/purple staining granules
Polymorphic nucleus
Very rare
Not phagocytic cells
Produce histamine (help to induce inflammation)
Function in anti-parasite defense and allergic responses
Mast cells
Found in tissues
Have dark blue/purple staining granules
Produce histamine
Role in inflammation, anti-parasite responses and allergic responses
Monocytes
Have a large beaned-shape
2-12% of blood leukocytes
Phagocytic cells
Develop into tissue macrophages
Macrophages
Antigen presenting cells (APC)
(Present Ag peptides to T Lymphocytes)
Phagocytic cells
Produce cytokines that induce inflammation
Dendritic cells
Star-shaped with many long projections
Collect Ag in tissues and carry them to the sites of the immune response
(Lymph nodes; spleen)
Major APC
Produces cytokines
Lymphocytes
20-40% of blood leukocytes
Usually have a small, thin rim of cytoplasm around the nucleus
Most are in the G0 phase of cell cycle
Waiting to be activated by Ag
Includes B cells and T cells
But all look very similar
B cells
Have a B cell receptor (immunoglobin as integral membrane receptor on their plasma membrane)
Produce antibodies
Differentiate into plasma cells (antibody factories)
What are the two major types of T cells? What do they do?
Both have t cell receptors (Integral membrane receptors on their plasma membrane that recognizies antigen peptides)
Cytotoxic T cells (CTLS): have the CD8 receptor on their plasma membrane, can recognize and kill virus infected cells and cancer cells and important in organ rejection and autoimmune disease
Helper T cells (TH): have the CD4 receptor on their plasma membrane, control the immune response, produce cytokines, help B cells produce antibodies, help cytotoxic T cells to become killers
What are the primary lymphoid organs?
Sites where leukocytes are produced
Bone marrow: hematopoietic tissues for producing all blood cells except T cells
Thymus: hematopoietic organ that produces T cells
What are secondary lymphoid organs?
sites where antigen presenting cells (macrophages and DC) come together with lymphocytes to produce the immune response
Spleen: filters the blood
Lymph nodes: Found in the lymphatics
Filter the lymphatics
What is the lymphatics?
System of lymphatic vessels that collect fluid from the tissues
Fluid is called Lymph
Returns the lymph fluid to the blood circulatory system
In the innate immune response, the barriers are the first line of defense. What are the Barries?
Physical barriers
(Skin, intestinal epithelium, etc.,
Tears, saliva, urine, intestinal secretions)
Chemical barriers
(pH of the stomach and skin inhibits microbe growth, lysozyme in years and intestinal secretions)
Phagocytes
Macrophages, monocytes and neutrophils
Ingest and destroy microbes
The complement system
Serum proteins that bind to microbes. When they bind they can enhance phagocytosis and they form pores in the microbial membranes to kill microbes
Natural killer cells
A type of lymphocytes that can kill some virus infected cells directly
They secrete interferons
(Cytokines that tell other cells to block viral replication and activate immune cells)
And the inflammatory response is activated in response to:
Tissue damage (cuts, abrasions, torn muscles)
Activated immune cells (innate and adaptive cells)
Cytokines
Histamines from mast cells
Inflammation is characterized by 4 hallmark responses
Redness: Increased blood flow to the area
Swelling: Leaking of fluids from the blood into the tissuesm allows complement and antibodies to get into the tissue, allows leukocytes into the tissues
Heat: Blood vessel dilation
Pain: Swelling pressure on nerve endings
What happens when the innate response activates the adaptive response?
- Inflammation activates cells
Macrophages and DC pick antigens in the tissue
2.Macrophages and DC carry antigens to the draining lymph nodes
3.Macrophages and DC present Ag to T cells
Activate the immune response - B cells pick up soluble Ag on their B cell receptor (BCR)
Activated B cell becomes a Plasma Cell to Secrete Antibodies
Immunoglobulin structure
2 identical light chains
Disulfide bonds hold light chains to the heavy chains
Disulfide bonds hold the 2 heavy chains together
Ag binding site formed from end of the Heavy and Light chains
The two antigen binding sites are identical
What are the 2 differnet types of light chains?
Kappa and Lambda
What are the 5 heavy chains?
Mu=IgM
Gamma=IgG
Alpha=IgA
Delta= IgD
Epsilon= IgE
How many Ig domains does a light chain have?
2
Vl= varies between different Abs
Cl= same between all Kappas or Lambdas
How many domains do heavy chains have?
One variable domain (varies between different abs)
3 or 4 constant domains (Mu and epsilon have 4 and gamma, alpha, and delta have 3)
What are the secreted immunoglobulins
IgM, IgG, IgD, IgA, IgE
What are naiive B cells?
B cells that have never seen Ag before
What is a J chain?
Helps in forming of polymers
IgM
Pentameric (has 5 monomers)
Monomers held together by disulfide bonds
Has J chain
Has 10 binding sites
But only 5 can usually bind at a time
First Ig type produced by naive B cells
First Ig type produced in a first immune response
IgG
Most abundant Ig in internal blood fluids
(Blood, interstitial fluid, lymph)
4 subclasses
(Differ by slight AA sequences of CH domains
and differ in function)
Monomer in blood
Protects the internal body
IgD
Rare in blood
Monomeric
Almost exclusively as a B cell receptor on Naive B cells (Is not secreted)
Helped in activation of Naive B cells
IgA
Major Ig in external secretions
(Milk, saliva, tears, sweat, GI secretions, etc.)
Protects the mucosal surfaces
Monomeric in blood
In external secretions it is dimeric with J chain
Transported across the epithelium by transcellular transport
IgE
Extremely rare in blood
Monomeric
Immediately binds to high affinity receptors on Mast cells and basophils
Arms mast cells with allergen specific IgE
(Binding allergen causes Mast cell to release histamine)
B cell receptor is the same Ig that the cell secrete except it:
Is integral membrane protein in the plasma membrane of the B cell
Has a transmembrane domain
Has a very short cytosolic domain
The cytosolic tail of a B receptor is too short to transmit a signal
BCR must associate with ____ to transmit a signal
IgA/IgB
Antibody functions
Neutralization: Block binding of microtubules, viruses or toxins to cells
Agglutination: Clumping of bacteria/viruses with Ab, enhances phagocytosis, prevents infection of cells
Activate complement: Leads to killing of microbes
How to create enough different Ig binding sites?
Have multiple gene segments for the variable region
Then randomly match the segments together
Variable region gene recombination for a light chain
Cell randomly picks one V segment and attaches it to a randomly picked J segment
Deleted the sequences between
Now chosen V and J segments are next to each other
This creates a function VL region gene
Then creating a functional mRNA after making a functional VL region gene
Then the messenger RNA is made from this modified gene
Has only the chosen VJ rearranged variable region put onto the Kappa Constant Region
Variable region gene recombination for a heavy chain
Except has 65 variable, 27 diversity, and 6 joining gene segments
Randomly add on D segment to one J segment and then to one V segment
Creates a VDJ functional VH region gene
How do we get more diversity of Ig genes?
Junctional imprecision: The joining of the V to J and V to D to J segments is not always straightforward
Slight variation in joining gives more diversity
Also enzymes add and delete nucleotides before joining together to add more diversity
Somatic hypermutation: When a B cell is activated, it can actually allow mutations in the V regions of the Heavy and Light chains
Then adds more variability to variable regions
Multi V region segments
Random Recombination**
How to make IgM, IgG, IgA that bind to the same antigen?
Put VDJ segment on C Mu segment= IgM
Put VDJ segment onto C Delta segment= IgD
But if the T cells tell the B cell to make IgG3 to the same antigen
Put VDJ segment onto C gamme 3 segment= IgG3
Also, same VDJ is used for BCR and secreted IG
What can T cells not bind to? What can they bind to?
Direct to antigen. Can only response to peptide fragments of the antigen. They must have the peptide presented to them by Antigen presenting cells (APCs)
What are the 3 Antigen Presenting Cells?
Dendritic cells (Bring Ag from the site of infection)
Macrophages (bring Ag from the site of infection)
B cells (to activate T cells to give the B cells help_
What are major hiscompatibility proteins? what are 2 examples?
They are cell surface proteins that can bind to antigen peptides found on antigen presenting cells. Genes are in the HLA complex region of the chromosome.
Class I MHC proteins
Class II MHC proteins
What are Class I MHC proteins?
HLA-A, HLA-B, HLA-C
Present antigen peptides to CTLS
Bind antigens from inside the infected cells (proteins from viruses, intracellular bacteria)
What are Class II MHC proteins?
HLA-DP, HLA-DQ, HLA-DR
Present antigen to TH cells
Bind antigen from outside the cell (free bacteria from viruses, toxins, other proteins)
Processing Ag for MHC class I
- Viral protein labeled with ubiquitin
- Viral protein destroyed by the proteasome
- Viral peptides transported into the RER
- New MHC Class I being made in the RER
- Viral peptide loaded onto new MHC Class I
- MHC Class I with viral peptide moved to plasma membrane
CTL T-Cell receptor recognizes viral Ag peptide on MHC Class I. TCR “recognizes” (binds) to:
Some of the MHc and the antigen peptide
Processing Ag for MHC Class II
1.Outside Ag brought into APC by: Phagocytosis, pinocytosis, receptor mediated endocytosis
and attached to the BCR (For B cells)
2.Vesicle fuses with lysosomes
3.New MHC Class II from RER in vesicle
4.Vesicle fuses with endosome containing Ag peptide
5.MHC Class II with Ag peptide moves to plasma membrane
T-cell receptors
Has an alpha and beta chain
Each has a constant and variable region
TCR antigen bidning site is made from the variable region of the alpha and beta chains
T-cell receptor diversity is due to
- Multiple V region gene segements
- V region gene recombination
- Junctional imprecision
Activation of T-Cells Signal 1
TCR cytosolic tail too short for intracellular signaling
Requires CD3
4 polypeptides in 3 dimers
CD3 gamma/epsilon
CD3 epsilon/delta
CD3 zeta/zeta
Role of CD3 polypeptides
Cytosolic tails of the CD3 polypeptides have ITAMs
ITAMs are sites where kinases phosphorylate tyrosines
Creates binding sites for proteins with SH2 domains
This links to the TCR-CD3 to intracellular signaling pathways
Co Receptors
2 and what do they do 2 reasons
Helper T cells require CD4
(Receptor with 4-Ig-Like domains binds to MHC class II)
CTLs require CD8
(Receptor dimer with 2-Ig-like domains binds to MHC Class I)
Both CD4 and CD8:
Strengthen binding to MHC (along with the TCR)
Play a role in intracellular signaling
Activation of T Cells- Signal 2
TCR binding to MHC + Ag
With CD3 and CD4/8 signaling
CD80/86 on APC binds to CD38 on T cell
Activates T cell to help produce interleukin-2
Full IL-2 gene activation requires signals from TCR-CD3 and CD28
IL-2 autocrine signal induces T cell to start proliferation
Clonal selection vs clonal expansion
Clonal selection: Antigen binding to BCR or TCR “selects” lymphocytes with the best binding receptor
Clonal expansion: That “chosen” B or T cell is activated. Then proliferates to amplify r expand the number of responding cells
TH1 Cells
Secrete:
Interferon= antiviral
And tumor necrosis factor (TNF)= induces inflammation
Induce the inflammatory response
Activate macrophages to become better killer
Activate CD8 + CTLs to become killers
By IL-2 from TH1 cells
Induce cell-mediated immunity
Major response to intracellular viruses
TH2 cells
Secrete interleukin-4
Helps B cells to produce IgG and IgE
Helps B cells to differentiate into plasma cells
Induce B cell antibody response
(once called the humoral response)
Major response to:
Extracellular bacteria and viruses
Parasites and worms (via IgE)
And also the allergic responses
Secreted toxins from bacteria
Regulatory T cells (Treg)
Can suppress other T cells to prevent their response
Down-regulate a specific immune response
4 other specific types of T cells
Produce specific TH cells for specific responses
Activation of CTLs
Naive CTLs cannot kill
Must be activated by APC presenting Ag peptides to the CTL TCR
Then must get IL-2 from the TH cell
CTL then differentiates into a killer cell
CTL produces killing granules (vesicles) in their cytosol
Leaves the lymph node or spleen to go looking for infected cells
Killer CTLs
Encounter an infected target cell
Infected target cell has MHC class I + virus Ag on plasma membrane
CTls TCR binds to the target’s MHC Class I + Ag along with CD8
Activates CTL to focus killing granules toward the target cell
Killing granules are released directly at the target cell membranes
Killing of the target cell
CTL granules contain:
______ and ______.
Perforin:
Pore forming proteins
Insert into the membrane
Polymerize to form a pore
Granzymes:
Proteases
Enter target cell through perforin pore
Cleave procaspases
Activate caspase induce apoptosis
