Lymphocytes Flashcards
There is immune ___ and immune ____.
Protection
Pathology
Most pathogens enter the body through ___ ____ of the digestive, respiratory, and reproductive tract. It is a thin and ____ layer epithelium. ___ ____ are encapsulated lymph nodes in the gut that drain the gut lymph.
Mucosal surfaces
Permeable
Peyer’s patches
Lymphocytes are ___ and ___. They are part of the ____ immune system.
T cells
B cells
Adaptive
B cells have receptors on their surface called ____ (Ig) and recognizes pathogens
Antibodies
CD4+ helper T cell have receptors on their surface that recognize ____ presented by MHC class II from an antigen presenting cell or infected cell. They produce factors that help ___ cells and ___ __ cells.
Peptide
B
CD8+ T
CD8+ cytotoxic T cell ___ infected cells. They have receptors on their surface that recognize ____ presented by MHC class I.
Kill
Peptide
B lymphocytes mature in the ___ ___. They reside in ___ ___, ____, and blood. Each B cell expresses a unique __ ___ receptor (BCR) which is the ____ receptor.
Bone marrow
Lymph nodes
Spleen
B cell
Antigen
During infection, only B cells with the antigen-specific BCR clonally expand and secrete _____, which is critical for protection. After clearance, some B cells are long lived and have ___.
Antibody
Memory
An ____ is a secreted BCR by an activated B cell. Two identical ___ chains and two identical ___ chains. The ends of the chains combine to form a ___ ___. This region (fab fragment) is the antibody ____ site. The ___ region is constant with no variation and binds FcR on innate cells.
Antibody
Heavy (H)
Light (L)
Variable (V) region
Binding
Fc
An ____ is anything that stimulates an adaptive immune response and binds BCR
antigen
___ ___: lymphocytes that express a self-reactive antigen receptor (BCR or TCR) are deleted during development
Central tolerance
VDJ recombination occurs in immature B and T cells to generate a unique ___ or ___. Each cell ____ expresses a unique receptor allowing for limitless recognition. This is unique is each person.
BCR
TCR
randomly
Central tolerance ____ most potentially harmful lymphocytes but is imperfect causing _____.
Deletes
Autoimmunity
B cells mature in the bone marrow. ___ ___ occurs in the bone marrow where immature B cells bound to self are removed. ____ of mature B cells to the lymphoid organs and become activated by foreign antigens.
Negative selection
Migration
Activated B cells give rise to ___ cells and ____ cells.
Plasma
Memory
_____ diseases can be due to the failure to delete all self-reactive lymphocytes
Autoimmune
Diagram of B cell development:
____ B cell is mature and circulates in the blood and secondary lymphoid organs (____ ____ and ____) and have never encounter antigen. They are not activated.
Naive
Lymph nodes
Spleen
Clonal selection theory:
1. Each lymphocyte bears a unique ___ or ___
2. Interaction between ___ and receptor is specific and required for lymphocyte activation and differentiation
3. All daughter cells from a single lymphocyte express the same ___ ___.
4. After clearance, most lymphocytes die but a few persist and form ____ that lasts for years
BCR or TCR
antigen
Antigen receptor
Memory
A small number of genes can become millions of different receptors through ____ ____. Random joining of gene segments ____ (heavy) or ___ (light) creates a unique variable region. Heavy and light chains combine with a ____ region.
VDJ recombination
V-D-J
VJ
Constant
Antibody isotypes:
IgM, IgG, IgA, IgE, IgD
Ig class is determined by change in ___ ___ (isotope switching) in B cells during immune response
Constant region
____ is the first antibody secreted after primary infection. It activates classical complement pathway. Weak opsonin meaning receptors can’t bind Fc
IgM
____ is the most abundant in serum after secondary response. Most abundant in plasma. Crosses placenta. Two antigen binding sites .
IgG
____ is a dimer. Found on Mucosal surfaces. Secreted into milk. Trans-endocytose epithelial cells
IgA
____ binds to FcR on mast cells. Causes release of inflammatory mediators after crosslinking. Defense of parasites. Mediator of allergy.
IgE
____ has no known function. Co-expressed with IgM on naive mature B cells
IgD
Diagram of antibody isotype locations:
All naive B cells express ___ and ___ on the cell surface. During an immune response, help from ____ T cells instruct activated and antigen-specific B cells to switch ____ regions.
IgM
IgD
CD4
Constant
Antibody functions:
Neutralization of pathogen
Antibody functions:
Antibody dependent cell cytotoxicity (ADCC)
Antibody functions:
Opsonization
Antibody function:
Inflammation
Antibody functions:
Activation of the classical complement pathway
____ ___: follicles in lymph nodes during an immune response. They have different zones. ____ zone is proliferating cells (centroblasts) undergo somatic hyper mutation. ____ zone is hypermutated resting B cells (centrocytes) and follicular dendritic cells. ____ zone is mutated B cells and Tfh cells. Stimulation by Tfh plasma or memory cell transformation.
Germinal center
Dark
Light
Mantle
____ ____ is the process of generating higher affinity antibodies by mutation of the V region and selection during an immune response
Somatic hypermutation
Somatic hyperpermutation does not affect the DNA, therefore it is restricted to B lymphocytes and there is no transfer to ____. Somatic hypermutation does not occur in T cells but it does require ____ help.
Offspring
CD4
Somatic hypermutation occurs in ____ ___.
Germinal centers
Kinetics of the antibody response to SARS-CoV-2:
____ help is required for isotope switching and somatic hypermutation
CD4
Diagram of T dependent and T independent B cell responses:
Activated helper T cell expresses ____ and secretes cytokines. B cells are activated by ____ engagement and cytokines. This leads to B cell ____ and ___.
CD40L
CD40
Proliferation
Differentiation
Roles that antibodies play in the clinic:
1. ____ testing: evidence of antibodies indicate prior exposure to an infection
2. ____: anti-CD20 treats leukemia and lymphoma. Anti-TNF treats autoimmune diseases. Anti-IL-6 treat cytokine release syndrome
3. ____
Diagnostic
Immunotherapy
Vaccinations
Primary exposure has both quantitative and qualitative effects on antigen specific B cells:
Primary exposure has both quantitative and qualitative effects on antigen specific B cells:
Primary exposure has both quantitative and qualitative effects on antigen specific B cells:
Antibody isotypes in serum throughout human development:
Review
T lymphocytes mature in the ___. They reside in ___ ___ and ___ and blood. Each T cell expresses a unique ____ but it is not excreted like BCRs.
Thymus
Lymph nodes
Spleen
TCR
Two major subsets of T lymphocytes:
CD4 Helper T cells
CD8 cytotoxic T cells
____ is generated by VDJ recombination during T cell development. It is on the surface with ___ complex.
TCR
CD3
TCR recognizes peptide ___ ____.
MHC complexes
Picture of TCR:
The major histocompatibility Complex (MHC) is ____, encoded by multiple genes and it is ____ meaning genes can have various alleles.
Polygenic
Polymorphic
Human versus pathogen MHC:
MHC binds peptides for presentation to __ ___.
T cells
Human MHC molecules are called Human ____ ____ (HLA). They are the most ___ gene family in humans.
Leukocyte Antigen
Polymorphic
MHC (HLA) proteins are the major determinants of graft ____. This is why you need a match for donors, looking for similar HLA genes. These genes are ____.
Rejection
Inherited
____ tells a T cell whether a cell is self versus non-self.
MHC
MHC presents both ___ and ___ peptides. MHC is only on the cell surface if it has ___ in its binding groove.
Self
Foreign
Peptide
T cell development:
Rule of 8:
2 x 4 = 8
1 x 8 = 8
MHC II is recognized by CD4
MHC I is recognized by CD8
T cell development:
T cell maturation establishes ___ ____. There needs to be a balance of recognition strength to be able to recognize own ____ but too strong will result in _____ T cells an autoimmunity
Self tolerance
Cells
Self-reactive
The affinity model of T cell selection:
If TCR is not rearranged properly during VDJ recombination, the cell dies by programmed ___.
Apoptosis
_____ syndrome is a deficiency in CD4+Foxp3+ regulatory T cells. it is X linked. Absence in transcription factor Foxp3 required for regulatory T cells. These cells are critical to develope tolerance to self antigens. Patients die within 1 to 2 years.
IPEX
Immunize early in life because as we age, the ___ reduces in size and output. We must then heavily rely on immune memory for protection in later years
Thymus
MHC class I is expressed by all nucleated cells. Any cell can get infected, and ____ T cells bind and kill infected cells. Both self and foreign peptides can be presented. MHC I loads peptides synthesized from ___ the cell
CD8
Inside
MHC class II is only expressed by ___ ___ cells like macrophages, dendritic cells, and B cells. It presents peptides from proteins that have been ___ ___ from extracellular space. The antigen presenting cell helps instruct the type of helper cells that ____ T cells become
Antigen presenting
Taken up
CD4
How are adaptive immune responses initiated?
____ cells in tissues take up antigen and migrate via the lymphatics to the draining lymph nodes.
Dendritic
Dendritic cells are critical for the ___ of the immune response by ____ naive T cells in the draining lymph nodes.
Initiation
Priming
Dendritic cells upregulate ____ and costimulatory molecules ___ and migrate to lymph nodes to activate T cells.
MHC
B7
Infection causes ___ to bind pattern recognition receptors. PAMPS induce expression of ____ on antigen presenting cells. B7 binds ___ on naive T cells. CD28 signaling promotes T cell ____.
PAMPs
B7
CD28
Activation
The innate immune system converts ____ (infection) signals into activation signals for the adaptive immune system
Danger
TCR signaling and costimulation are both required for T cell ____.
Signal 1: _____, naive T cells need to bind peptide:MHC
Signal 2: ____, naive T cell also needs CD28 signaling to proliferate
Activation
Specificity
Context
Activated T cells express a high affinity IL-2 receptor alpha (____).
CD25
____ promotes T cell proliferation, T cell survival, expand only those T cells that have encountered antigen, CD4 production of IL-2 helps CD8 cells, activated T cells also produce IL-2 so they can act in both an Autocrine and Paracrine manner
IL-2
IL-2 diagram:
Activated CD8 T cells differentiate into ___ T cells. They produce ____, protect against cancer. They produce ____ to induce apoptosis. They produce ___ to poke holes in the membrane of target cells.
Effector
IFN-gamma
Granzymes
Perforin
CD8 T cells are regulated by co inhibitory receptors ___ and ___
PD-1
CTLA-4
CD4 helper T cells can differentiate into different subsets depending on signals from the ___ response.
Innate
CD4 T cells are essential for inducing CD8 T cell ___ and better B cell ___.
Memory
Responses
Vaccine examples:
Isotype class switching is changes in the ____ region of the antibody. The isotype that results is dependent on the type of ___ that stimulated an immune response
Constant
Antigen
Does isotype class switching alter the specificity of the antibody?
No
Class switching does effect how the antibody ____, not what antigen it reacts to
Functions
Tfh cell stands for:
T follicular helper cell
Somatic hypermutation does not occur in ____, only B cells
T cells
Review:
Generally, we don’t need __ ___ for viral clearance. We do need __ ___ for viral clearance. The diagram below all occurs in the germinal center.
B cells
T cells
Positive selection of T cell:
Can it see self?
Alternative selection of T cells:
Is it binding MHC I or MHC II? Making it CD8 or CD4
Negative selection of T cells:
Is the binding too strong to self? If yes, it gets deleted
Activation of T cells requires 3 signals:
MHC-TCR
B7-CD28
Cytokines: IL-12, IL-1, IL-6
Clinicians administer IL-12 for:
Autoimmune disease. IL-12 will increase the number of T regulatory cells and therefore decrease the number of problematic T cells
CD8 T cells use the same mechanisms as ___ ___ cells. They also produce ____
Natural killer
IFN-gamma
