Specific Acquired Immunity Flashcards
2 kinds of cells dividing up work of adaptive immune response
phagocytes - eat things up that trigger PRRs with PAMPS and DAMPs –> antigen presentation and induction of adaptive immune response
lymphocytes - specialized for recognizing foreignness & enhancing phagocytosis
epitope
Epitopes are regions on an antigen that can be recognized by an antibody or by T cell receptors. Epitopes are also called antigenic determinants.
2 kinds adaptive immunity
B cell –> release antibodies to protect extracellular = humoral
T cell –> survey surfaces of body’s cells looking for ones w/ damage or parasites = cell-mediated
MHC class 1
Antigens synthesized within the cell. Cell antigens of antigens from cell infections. Recognized by CD8+ killer T cells. Expressed on all cells except RBCs.
MHC class 2
antigens are products of phagocytosis. Recognized by CD4+ helper T cells. Expressed on monocytes / macrophages, dendritic cells, B cells, and epithelial cells of the thymus.
cytokine to make hsc –> lymphoid progenitor
IL-7
lymphoid progenitor goes to make
NK cells
dendritic cell
b cell progenitor
t cell progenitor
b cell progenitor goes to
mature b cell which makes plasma cells and memory b cells
t cell progenitor goes to
cd 8+
cd 4+
cd 8+ t cell goes to
effector cd8+
memory cd8+
cd 4+ t cell goes to
memory cd 4+ Th1 Th2 Th17 Th reg Th FH
cytokine to make Th1 CD4
IL-12
cytokine to make Th2 CD4
IL-4 (IL-10?)
cytokine to make Th17 CD4
IL-6, IL-23
cytokine to make T FH CD4
IL-6, IL-21
cytokine to make Treg CD4
IL-2, TGFbeta
B and T cells both being production
in the bone marrow
B cells are released from the bone marrow as mature cells, while T cells must pass through the thymus to become mature cells.
Mature B cells and T cells can be in the
blood or resident in the lymph nodes and spleen
can travel from one lymph node to another and to and from the spleen
Major lymphoid organs and tissues
Primary:
Thymus, bone marrow
Secondary:
Tonsils/adenoids, lymph nodes, spleen, lymph nodules, peyer’s patch, urogenital lymphoid tissue
Where do T cells recognize epitopes?
Starting in lymphoid tissue
After T cell activated, where do they go
proliferates and daughters travel throughout body until they reach place where antigen invaded
What happens when T cells get to infection site
Restimulated by local APCs and release short-range lymphokines that attract and activate monocytes and macrophages
All T cells express
CD3 and have TCRs created through DNA rearrangement
αβ T cells
In αβ T cells the TCR is made up of the variable αβ peptides coupled with the CD3 complex.
These αβ T cells only function by binding to MHC I or MHC II molecules.
They make up all of the CD4+ and CD8+ T cell populations and represent 90-95% of all of the blood T cells in humans.
γδ T cells
In γδ T cells the TCR is made up of the variable γδ peptides coupled with the CD3 complex.
Some of these T cells can function by binding directly without the use of a MHC complex.
They protect mucosal surfaces of the body.
Most intraepithelial lymphocytes are CD8+ γδ T cells. Circulating γδ T cells are “double-negative” (CD4- CD8-) T cells.
2 main classes of T cells
Helpers and killers
5 specialized subsets of helper T cells
Th1 helper Th17 Th2 T follicular helpers T regulatory
Th1
recognize antigen and make a lymphokine that attracts thousands of macrophages, the heavy-duty phagocytes, to the area where antigen has been recognized.
Th17
are similar to Th1 in that their main role is to cause focused
inflammation, although they are more powerful than Th1. They have been implicated in many serious forms of autoimmunity
Th2
stimulate macrophages to become ‘alternatively activated,’ able to function in walling-off pathogens and promoting healing, a process that usually takes place after the pathogen-killing Th1 response. They are very important in parasite immunity.
T fh
stimulated by antigen and migrate from T cell areas of lymph nodes into the B cell follicles, where they help B cells get activated and make the IgM, IgG, IgE and IgA antibody subclasses.
T reg
make cytokines that suppress the activation and function of Th1,
Th17, and Th2 cells, so they keep the immune response in check. They are part of the Th family.
CTL
destroy any body cell they identify as bearing a
foreign or abnormal antigen on its surface.
CD8
Activation of αβ T cells
Signal 1 - TCR recognition of HLA bound antigen (CD4 to MHC II or CD8 to MHC I)
Signal 2 - CD80/86 on APC to CD28 on T cell (if no CD 80/86 assume autoimmune)
Other signals
Cytokine signals (to tell what to differentiate into)
APC –> Th0: IL-12
Th1
APC –> Th0: IL-6, IL-23
Th17
APC –> Th0: IL-10
Th2 (IL-4?)
APC –> Th0: IL-10, TGF-b
Treg
Activated killer T cell
If activated, a clone of the CD8+ T cells gets expanded and the daughters circulate in large numbers throughout the body. When one of the daughters of a stimulated CD8+ T cell binds a cell showing the its “activation” peptide, the T cell delivers a lethal hit to that cell by signaling the target cell to commit suicide through apoptosis. The target cell’s nucleus disintegrates and the cell dies.
Killing by killer t cells
Kill by FAS – FAS ligand interaction. T cells expressing the FAS ligand bind to FAS, a protein on a target cell to induce caspase activation and apoptosis.
Kill by secreting toxic agents as well. TNF, a cytokine, can also induce apoptosis. Perforin is a pore-forming protein. Granzymes also induce apoptosis.
Functions of the thymus
Maturation/selection of T cells
Positive and negative selection t cells
Positive selection – T cells must recognize MHC class I or MHC class II molecules in order to be stimulated to mature (self-restricted).
Negative selection – T cells that recognize self-antigens bound to MHC class II on the thymus epithelial cells are driven to apoptosis (tolerant to self-antigens).
CD3
all T cells
CD4
Helper T Cells
CD8
Cytotoxic T cells
CD16, CD56
on NK Cells
CD16 - Low affinity receptor for Fc region of IgG
CD56 - Adhesion molecule
CD19, CD21
B cells
CD19 - signal transduction (Coreceptor CD21)
CD21 - Receptor for complement (C3d and EBV)
CD28
T cells
Receptor for costimulatory B7 (CD80/96 of APCs)
CD40
Signal transduction between T cells and APCs and T cells and B cells
On B cells (CD40L on T cells)
what markers indicate B cells
19,21
what markers mean NK cells
16,56
What markers distinguish t cells
4, 8
CD3 on all T cells
B cell receptor made of
Signal through Ig Alpha and Beta
CD79A and CD79B
most abundant antibody in blood.
IgG
IgG and complement
Two adjacent IgG molecules, binding an antigen such as a bacterium, cooperate to activate complement, a system of proteins that enhances inflammation and pathogen destruction.
Class of ab that passes through placenta
IgG
IgM
a large polymeric immunoglobulin. It’s even better at activating complement than is IgG and is the first antibody type to appear in the blood after exposure to a new antigen. It is replaced by IgG in a week or two.
IgD
main form of antibody inserted into B cell membranes as their antigen receptor, which seems to be its only biological role.
most important antibody in secretions
IgA
Ab designed to attach to mast cells in tissues
IgE
IgE and allergies
mast cell to make prostaglandins, leukotrienes, and cytokines, and release its granules which contain powerful mediators of inflammation like histamine.
Ab function in disease
First time - mucous membrane - IgA (maybe IgE)
Secreted and local immunity from IgA
Antigen then maybe to local lymph nodes or spleen –> IgM then IgG
Ab important for combatting what
extracellular pathogens like bacteria Staph, strep and hemophilus
neutralizing toxins, block spread of virus in blood (once in cell, need killer t cells)
X-linked agammaglobulinemia
absence of B lymphocytes
CD40 ligan deficiency
Failure of immunoglobulin class switching B cells can't get T cell help (can't use AID to class switch)
Activation-induced cytidine deaminase deficiency
Failure of immunoglobulin class switching
Common variable immunodeficiency
failure to produce Ab against particular antigens
Omenn syndrome
VDJ recombination failure
Cannot produce BCRs or TCRs
X-linked severe combined immunodeficiency
failure to produce mature T lymphocytes
Digeorge
failure of thymus to develop correctly
hemophagocytic lymphohistiocytosis
failure of CD8+ t cells and NK cells to produce and/or release lytic granules
IPEx
failure of peripheral tolerance due to defective regulatory T cells
