PRIN 14 Immunity Flashcards
TH1 vs TH2
TH1: help activate macrophages
(role in Cell mediated Imm)
TH2: help activate naive B cells
(role in Humoral Imm)
Describe TCR Structure
a chain & b chain
both attached to a V and C region
What is the purpose of Positive Selection?
Choosing T cells that recognize peptide Ags
What is the purpose of Negative Selection?
Eliminating T cells that recognize TOO strongly to self Ag
prevent autoimmunity
What is needed to stimulate T Cells to proliferate and differentiate?
(1) Ag recognition
(2) Costimulation
(3) Cytokines
How does a CTL destroy target cells?
CTL binds DIRECTLY to target cell
Delivers Perforin & Granzyme B into the cell
Granzyme B triggers Caspases …apoptosis
What are TH17 cells?
Secrete IL-17 & IL-22
Host defense against bacterial & fungal infections
Role in tissue inflammation during autoimmunity
What is the role of T Regulatory cells?
Block activation of harmful lymphocytes specific for self Ag
Protect self from autoimmunity
Example of T cell role in Communicable Disease
People who have had TB develop memory T cells specific for TB Ags.
Therefore, when tested with SC injection … strong response
Example of T cell role in Non-communicable Disease
Obesity / Diabetes / Cancer
Islet Specific T cells in Type 2 DM secrete altered levels of cytokines. Changes occur in adipose, liver, pancreatic islets, vasculature
During the course of ones life, when does B cell production occur?
Begins before birth and continues throughout lifetime
Describe structure of Ig…
Light & Heavy Chains (Fab) with a constant (Fc) region at base.
What mechanisms contribute to the generation of Ig diversity?
(1) Combination of multiple gene segments (VDJ)
(2) Pairing of H & L Chains
(3) Junctional Diversity (addition / deletion of DNA bases)
(4) Somatic Hypermutation
What is Somatic Hyoermutation?
Which cells undergo it?
High rate of point mutations within VDJ gene DNA
Stimulated by cytokine signals via TH cells
Additional mutation occurring AFTER mature B cells are activated
Affects B cells ONLY
What is Anergy?
State of being non-functional
Unresponsive to Ag
Ag is there … but lack of cytokines mean no reactivity by B cells
Where do B cells go after they mature and leave the bone marrow?
Secondary Lymphoid Organs:
- Spleen
- Lymph Nodes
- Tonsils
- GALT & MALT
What happens during a T-Independent Ag response?
Involves Carbs / lipid Ag ..
(1) B-cell BCRs cluster via repeating carb units on microbe
(2) B Cell PRR responds to PAMP on microbe
RESULT: B cells proliferate and differentiate into Ab secreting cells (but NO memory cells)
Provide an example of surface interactions that occur during T-dependent activation of B-cells
Protein interactions between TH cell and B-cell
T-Cell CD28 binds to B-Cell B7
T-Cell CD40L binds to B-Cell CD40
What is required for Isotype class switching?
Must have the interaction between:
(1) T-Cell CD40L binds to B-Cell CD40
(2) Cytokines
What directs Isotype switching?
Cytokines
What happens if an individual has a mutation in CD40L?
T-Cell CD40L binding to B-Cell CD40
WILL NOT OCCUR
Therefore, this ppt will be stuck at IgM
RESULT: X-Linked hyper IgM syndrome
Order of Ig Production
MDGEA
What do secreted Abs do?
(1) coat infected cell, promoting NK attack
(2) Complement Activation
(3) Opsonization
(4) Neutralization
Which Ig is the greatest in the blood?
IgG
IgG Characteristics
Can cross placenta
Predominant IgG in blood
IgA Characteristics
Resistant to stomach acid
protects mucosal surfaces
secreted in milk
IgM Characteristics
FIRST Ab produced
Pentamer (so its big)
NOT CROSS PLACENTA
IgE Characteristics
Defends against parasites
causes allergies
What is PID?
Primary Immune Deficiency
- Genetically determined
- Enhanced susceptibility to infectious disease, autoimmunity and malignancy
What are current treatment options for primary immunodeficiency?
(1) Passive admin of Abs
(2) Prophylactic Abx
(3) Stem Cell transplantation
(4) Gene Therapy
What are Secondary Immune Defiencies?
ACQUIRED
(eg) HIV, Malnutrition, Medically induced immunosuppression
Gel & Coombs Classification of Hypersensitivities
(1) IgE mediated H.
(2) Ab mediated H.
(3) Immune Complex mediated H.
(4) Cell Mediated H. (time delayed)
Gel & Coombs Classification of Hypersensitivities
TYPE 1
(1) IgE mediated H.
ALLERGIES
IgE for specific Ag is produced and then sits on Mast Cells … gets activated
Wheel >2mm indicates IgE production for specified Ag
What is the new way to treat Allergic Diseases?
DRUG: Omalizumab
Anti-IgE Ab: approved in Canada for severe asthma (expensive)
Recognizes IgE and takes it out of circulation
Gel & Coombs Classification of Hypersensitivities
TYPE 2
(2) Ab mediated H.
Abs target self Ags and trigger destruction of self cells (autoimmune)
(eg) Blood Type Rejection
(eg) Hemolytic Disease of Newborn
Gel & Coombs Classification of Hypersensitivities
TYPE 3
(3) Immune Complex mediated H.
Immune Complexes form and get deposited in small vessels and in joints … cause inflammation
(eg) SLE, Serum Sickness
Is SLE considered a Primary Immune Disease?
No, SLE is not conferred by a single gene. There is myriad of variable factors that contribute to the disease.
(genetics AND environment)
Note .. Lupus is actually Types 2 & 3
Diagnosing SLE
4/7: Rash Discoid Rash Photosensitivity Oral Ulcers Arthritis Serositis Kidney dysfunction CNS involvement ... seizures Cytopenia Immunologic tests Antinucelar Abs
Gel & Coombs Classification of Hypersensitivities
TYPE 4
(4) Cell Mediated H. (time delayed)
CD4 TH cells can activate macrophages or eosinophils
CD8 CTLs cause tissue damage
often takes several days to set in
Examples of Type 4
(4) Cell Mediated H. (time delayed)
Contact Dermatitis
Mantoux Test / TB test
Type 1 DM
MS
What are the 3 signals from the Innate APC required to induce Adaptive Immunity?
(1) Ag Presentation
(2) Co-stimulation
(3) Cytokines
What is the role of cytokines?
Steer / direct / shape the quality & quantity of the immune response.
Cytokines are involved in the specific differentiation of T cells in proliferation
What states do Lymphocytes need to be in to exert effector functions?
Must be activated to offer protection from infection
Naive Adaptive Cells do NOT protect
What are the three “tempos” of immune response?
(1) RAPID
Immediate
Innate
(2) INTERMEDIATE
5-7 days
Innate & Adaptive
(most disease for vaccines)
(3) SLOW
>7 days
Adaptive
(most infections are cleared without us even knowing they were ever there…)
What are examples of pathogen virulence within the 3 tempos?
(1) RAPID
Ebola v
(2) INTERMEDIATE
Pneumococcus
Influenza
(3) SLOW
M. Tuberculosus
H. Papillomavirus
What are the 4 steps in Lymphocyte action?
Selection Activation Expansion Contraction (>95% of Ag specific immune cells die ... only a few are retaiend as memory)
How are Memory Cells stimulated?
Only need Antigen to be presented
**do not need (2) Costimulation and (3) cytokines
Vaccines prevent infections by …
Vaccines prevent infections by …
…inducing protective immune memory
What is Arepanrix (GSK)
Trade name Flu Shot (1) Antigen: influenza v. inactivated (2) Adjuvent: a-tocopherol (Vit E) Squalene
Why is a-tocopherol used?
Vit E
lipid based - keeps squalene in solution
Why is squalene used?
Main adjuvent
Causes inflammation via disruption of cell membrane
What else is a good adjuvent
Aluminum
Why use adjuvents? How do they make vaccines work?
Adjuvents work by upregulating
(2) costimulation
(3) cytokines
What does a Positive Hep C test indicate?
she been previously exposed to Hep C
OR
has a chronic HepC infection
In the Hep C pregnant woman, the rash on ther legs is caused by which type of Hypersensitivity Reaction?
Type 3: Immune Complex Mediated Hypersensitivity
Why did the doctor ask if Concepion had any joint pain?
To assess if the immune complexes were getting deposited in her joints. This occurs in about 1/3 of Hep C patients.
Hemolytic Disease of Newborn is caused by what type of Hypersensitivity Reaction?
Type 2 Ab mediated Hypersensitivity.
How does RF connect with this case?
In 1/3 of Hep C cases, IgM will be evoked to bind the Fc region of the IgG-Hep C complex. This will result in BIG ASS immune complex forming and getting deposited in small vessels.
In a male with O negative blood what Abs would be in his serum?
anti-A and Anti-B only
(he’s never encountered Rh(D) in order to produce Abs / memory against it
How do CTL’s kill?
Once in direct contact with affected cell, CTL releases Perforin & Granyme B into it … triggers Caspases … apoptosis
What is the affect of a patient having no CD40 ligand on the surface of his T cells?
Isotype / Class Switching cannot occur
What is Arthralgia?
Joint Pain
Arthralgia is an example of which Gel & Coombs Hypersensitivity?
Type 3 Hypersensitivity: Immune Complex
When immune complexes deposit on blood vessel endothelium in the skin, a rash may develop. The damage to the blood vessels at the site of IC deposition is predominantly mediated by which of the following activated cells or systems?
Neutrophils
A woman with blood type A+ is pregnant for the first time with a fetus that has B+ blood. Why DOESNT the woman destroy the fetal red cells?
Maternal antibodies to blood ABO proteins are typically IgM.
