Adaptive Immunity Flashcards
what do antigens react with
- antibody molecules and antigen receptors on lymphocytes
Epitope
portion or fragment of antibodies made of 5-15 amino acids that reacts with antibodies and lymphocyte receptors
where is the MHC located
On the APC
MHC function
allows the T lymphocyte to recognize epitopes of the antigens and disciminate self from non self.
does the TCR recognize any epitope
No, only the one bound to the MHC
3 examples of APC
- Dendritic cells
- Macrophages
- B lymphocytes
2 functions of APC
- capture and process antigens and present them to T lymphocytes
- Produce signals required for the differentiation and proliferation of T lymphocytes
Antibodody function
remove extracellular microorganisms and toxins
What do B cells require for maturation
bone marrow stromal cells and their cytokines
what do CD4 lymphocytes express on their surface
CD4 molecules and TCRs
most effecient APC for activation of T lymphocytes
Dendritic cells
while other APCs can, they are less efficient
how is T cell diversity achieved
VDJ recombination with junctional diversity. with D in the Beta chain
T cell developmental stages - 5
- released from the BM as progenitor cells
- aim is to build the receptor
- interacts with self antigens and differentiates into either CD4 OR CD8
- released from the thymus, express alpha or beta. cd3 complex with co receptors = NAIVE mature T cell
- T cells circulate in the blood and go to secondary lympoid tissues to bind APC
TCR vs antibody recognition
For TCRs, they specifically recognize peptide epitopes presented by MHC molecules. For antibodies, they recognize a wider range of epitopes (often on the surface of the whole antigen, this can be sugars, carbohydrates etc).
Implication of TCR recognition
Bc it recognizes a short sequence, it is sensitive to any changes in the AA
Why is T cell co stimulation important - 3 -RAN
- Needed for survival/proliferation
- To induce differentiation
- Cell-cell cooperation
what is tolerance in T cells
It is a process which prevents T cells from reacting to body’s own cells. Initially occurs in the thymus (central) or in the immune periphery (peripheral)
T regs
- help maintain immune balance
- have autoreactive T cell receptors
- inhibit other cells with autoreactive T cell receptors in the immune periphery
- use special molecules, like CTLA-4 and PD-1, to “shut down” or inhibit the activity of other T cells
Th1
- Stimulated by IL-12 (from dendritic cells or macrophages).
- Produce IFN-γ, which helps activate macrophages and is important for fighting intracellular pathogens (e.g., viruses, some bacteria).
- More involved in cell-mediated immunity
Th2
- Stimulated by IL-4 (often from other T cells or mast cells).
- Produce IL-4, IL-5, and IL-13, which help activate B cells for antibody production and promote responses against extracellular pathogens (e.g., parasites).
- More involved in humoral immunity
CD4+ cells become - 3
- follicular
- effector/ helper
- regulatory/suppressor
CD8+ cells become
cytotoxic
Intracellular pathogens
live inside cells… viruses and bact (hiv/tb)
Extracellular pathogens
parasites (worms) some bact like streptococuss
Th1 deficiency and overactivity
def- myobact infect
over- crohns and RA
Th2 dysregulation
leads to allergic disease (asthma or atopic dermatitis) and responds to helminth worms schistosoma
Parasites and allergens
both trigger the same immune response
Th17 deficiency and overactivity
def- mucocutaneous infections from yeast candida albicans
over- autoimmune disease
candida albicans
fungus (yeast) that naturally exists in small amounts in the human body, particularly in the mouth, gut, and vaginal area. Under normal conditions, it doesn’t cause problems, but when the immune system is weakened or the balance of microorganisms is disrupted (e.g., due to antibiotics), Candida albicans can overgrow and cause infections.
Tfh mutation and overactivity
- mutation of gene encoding CD40L leads to hyper IgM syndrome and overactivity leads to autoimmune disease
Immunoglobins fxn
IgM – First antibody made, strong in early infection
IgG – Most abundant, long-term immunity, crosses placenta
IgA – Found in mucosal areas (gut, lungs, saliva, breast milk)
IgE – Involved in allergies and parasite defense
IgD – Role in B cell activation (least understood)
Hyper IgM syndrome
as M is the intial one activated, there always has to be a switch depending on what you are affected with at the time and this is bc M fully enough to fight off infections
T regs
- boosting activity help with transplant rejection and autoimmune diseases
- Reducing activity helps in cancer immune therapy and chronic infections
- Prevents graft rejection and graft-versus-host disease (GVHD).
CD8 cells activation
by IL-2 cells from the Th1 cells and micgrate to the secondary lymphoid tissue. Then they will produce the cytokines: TNFa, TNFb, and IFNy
CD8 T cells clinical relevance
immune deffense against viruses, intacellular parasites e.g Listeria monocytogens
How cytotoxicity works
- Granule exocytosis which mediates the release of perforins and lytic granules
- Expression of the Fas ligand which activates the caspase pathway leading to cell death
- Also recruits effector cells such as macrophages
functions of the IS
- Transfer the MHC-peptide complex to lymphocyes
- Regulates lymphocyte activation
- Directs the secretion of cytokines and lytic granules
consequences of failed IS
- T cell gets half a signal and this could result in T cell apoptosis or anergy
- Anergy is when the T cell is non reactive or non regulatory and no longer stimulates a proper immune response
Do B cells require an MHC
NO
positive selection
whether the cell binds to MHC
negative selection
whether the cell binds to self antigen
Are Tregs solely in the immune periphery
No, a small subset can also be found in the thymus
What is a B cell
a specialized lymphocyte that expresses a BCR on its surface and produces antibodies upon activation
Gene splicing
The rearrangement of genes for gene diversity (UNIQUE SPECIFICITY)
Antibody structure - YAT VC
- Y shaped monor with two heavy chains and two light chains connected by disulphide or non covalent bonds
- Additional S-S bond folds individual glycoprotein chains into disticnt globular domans
- The hinge region is flexible and allows for the binding of numeroud antigens that are various distances apart
- Variable Fab region has the first 110 amino acids and binds proteins, lipoproteinsa=, etc
- Constant region Fc defines isotypes and binds to other cells to mediate Fc effector functions
what is IgA associated with
secretory protein (sIgA)
Mechanisms of B cells following antigen exposure
- Neutralization of microbes and toxins
Opsonization and phagocytosis
ADCC
complement activation
2. Lysis of microbes
Inflammation caused by neutrophils
Phagocytosis of microbes opsonized by complement fragments 3b
Development of B cells - 5
- mature in the BM with the help of stromal cells and cytokines
- Pro B cells - heavy chain rearrangement
- Pre B cells - light chain rearrangement
- Immature B cells - express IgM. Undergoes selection to ensure tolerance
- Mature B cells - express IgM and IgD. Circulate in the blood and lymph
Do B cells have positive and negative selection
no
they just eliminate cells that bind to self antigens
Activation of naive B cells
- B cells bind directly to antigens using their BCR
- The antigen is presented to the MHC-II by the B cell
- The Th cell recognizes the antigen (binds to cytokine receptor on B cell) and produces cytokines which activate the B cell
- The B cell is proliferated and differentiates into antibody producing plasma cells
- It also differentiates into memory B cells
T cell Independant antigen structure
- large carbohydrates and lipid molecules with repeating subunits
TI-1
can serve as TLR
TI-2
activate B cells by simultaneously crosslinking multiple BCRs
Resulting molecules of TI antigens
- natural antibodies are og IgM isotype
- no memory B cells
How B cells deal with exogenous antigens
- free viruses, bacteria, protozoa, yeats, toxins
- they get engulfed by the B cell through enodcytosis. The lysosome reacts with the proteosome and degraded into peptides by a series of proteases
Cytokine function in B cells - PEES
- Promote differentiation of B lymphocytes to plasma cells
- Enables plasma cells to produce antibodies
- E enable B lymphocytes to proliferate
- Stimulate B lymphocytes to synthesize and produce antibodies
what does clonal expansion entail
- It has to do with the B cells proliferating and basically expanding, BUT the antigen doesnt just bind to any BCR but it binds to the one that fits/matches
when B cells differentiate, what do they undergo
Infinity maturation through somatic hypermutation
How long does it take for the naiive B cell to be activated
4-5 days
A subsequent exposure to the same antigen results in - 3
- Antibodies are produced rapidly
- Produced in large amounts
- Produced for a longer period of time
Primary response to antigen vs Secondary
5-10 days vs 1-3 days
Vaccination
Many B cells migrate to the bone marrow and produce antibodies for months or years after the antigen has been eliminated
and this is so there is a quicker response to an infection? = YES THIS IS LONG TERM IMMUNITY
