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63 Cards in this Set

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Positive TCR Selection

Found in cortex thymus. Double negative thymocytes (CD3-,CD4-,CD8-). Progenitor cells develop into positive selection. Self MHCI and self MHCII binding with moderate affinity gets survival. Differentiate into CD8 or CD4

Negative TCR Selection

Found in cortico-medullary thymus. T cells dialogue with dendritic cells. High affinity self peptides and MHCI/MHCII destroyed. Remove self reactive T cells.

Location of TCR development


Thymus Cortex

Epithelial cells create thymic stroma composed of macrophages and thymocytes

Thymus Medulla

Epithelial cells. Dendritic cells self reactive screening. Macrophages remove dead lymphocytes and Hassall's corpuscle site of cell destruction.

TCR structure and location

Heterodimer of alpha and beta chain variable region. Membrane bound. CD3 [epsilon,delta][gamma,epsilon][zeta,zeta]

CD4 structure

T cell co-receptor. Four domains D1,D2,D3,D4. Found on helper T cell. Contact MHCII at beta2


T cell co-receptor. Alpha and beta domain. Found on cytotoxic T cell. Contact MHCI at alpha3.

Variable domain TCR response

Multiple gene segment, somatic recombination, junctional diversity (P/N nucleotide division), RSS recombination. No class switching or hypermutaiton.

Variable domain TCR

Alpha chain on chromosome 14 (V+J)

Beta chain on chromosome 7 (V+D)


autoimmune regulator is a transcription factor turns on peripheral genes in thymus

Naive T cell stimulation

TCR signal and B7 co-stimulation from APC. Lack of stimulation lead to anergy

Naive T cell loaction

Recirculating of T cell in SLT. Enter lymphatic drainage via HEV, requires homing.

Homing naive T cell

Cell adhesion molecules and chemokines CCL19+CCL21 produced by stromal and dendritic cells. Glycan and selectin slows movement

Naive T cell adhesion

L selectin binds to GlyCAM slows lymphocyte rolling. Activated LFA binds to ICAM. Anchor T cell leads to diapedesis

Naive T cell adhesion molecules

link dendritic cell to t cell. ICAM-LFA, ICAM3-DC-Sign


secondary signal for activation by APC. Ligates with T cell CD28. Stimulates T cell differentiation and proliferation


Cytotoxic T lymphoctye Associated Antigen. Present on activated T cell that has high affinity for B7. Delivers inhibitory signal limits cell proliferation


Monoclonal antibody against CTLA4 blocks B7-CTLA4 ligation. T cell remain active enhance immune system

Dendritic cell

APC originating in bone marrow myeloid stem cell. Located in all peripheral tissues. Phagocytize antigen and migrate to lymph node.

Mature dendritic cell characterisitcs

Stop phagocytosis, develop finger like extensions to increase surface area. Expression of MHC with co receptors

Dendritic cell co-receptors and ligands

Receptors (ligand): B7(CD28 Tcell), CCR7(CCL21 SLT), DC-SIGN(ICAM3 Tcell). ICAM1/2(LFA T cell)

IL-2 function

Stimulate T cell proliferation and differentiation to effector. Produced by activated T cell. Autocrine signalling.

IL-2 receptor naive vs active t cell

Naive t cell has gamma and beta chain for low affinity IL-2 and active has gamma, beta, and alpha chain for high affinity.

Transcription Factor TH1


Cytokine Exposure TH1

IL-12 from DC/macrophages and INF-gamma from NK cells

Cytokine Profile TH1

INF-gamma (positive feedback but inhibits TH2 and TH17) and CD40L.

Immune Role of TH1

Activate macrophages and kill resident bacteria. Cell mediated IR

Cytokine Exposure TH2

IL-4 from eosinophils, basophils, mast, or NK

Transcription Factor TH2


Cytokine Profile TH2

IL-4 (positive feedback but inhibits TH17), IL-5, IL-13, CD40L, IL-10 and TGF-beta (both inhibit TH1 and macrophages)

Immune Role TH2

IgE production, recruit eosiniphils, mast cells, basophils, protect mucosa parasites. Humoral immunity bias due to Ab dominated

Cytokine Exposure TH17

IL-6, IL-23, TGF-beta (all from DC)

Transcription Factor TH17


Cytokine Profile TH17


Immune Role TH17

IL-17 triggers tissue to produce:

IL-6 (Inflammation), CXCL8,12 (recruit neutrophil), G-CSF and GM-CSF (stimulate neutrophil release from bone marrow). Protects against extracellular bacteria and fungi.

Cytokine Exposure TFH


Transcription Factor TFH



CXCR ligates with CXCL13 produced by stromal cells in B cell follicle. Causes migration from T cell area to B cell area. ICOS binds to ICOSL of DC

Cytokine Profile TFH

IFN-gamma induces IgG1/IgG3, IL-4 induces IgE, and CD40L to signal CD40 on B cell

Immune Role TFH

Stimulate B cell for:

somatic hypermutation, affinity maturation, class switching. Bias towards humoral immunity Ab dominated

Origin Natural Treg

immature thymocyte within thymus. High TCR affinity for self peptide but not enough to be deleted. 10-15% CD4 cells

Transcription Factor Natural Treg


Receptors on Natural Treg

CD4, CD25, CD62L (L-selectin), CTLA4 (monopolizes APC B7 to lead to T cell anergy).

Cytokine Profile Natural Treg

IL-10 and TGF-beta inhibit T cell proliferation

Immune Role Natural Treg

Prevent autoimmune response and curtail normal protective immune response

Origin Induced Treg

Naive CD4 T cell in periphery in absence of infection. DC produce lots of TGF-beta. Some IL-6, IL-12, and IFN-gamma

Transcription Factor Induced Treg


Receptors on Induced Treg

CD25 and CD4

Cytokine Profile Induced Treg

IL-10 and TGF-beta inhibit cell proliferation. TGF-beta positive feedback.

Immune Role Induced Treg

suppress immune response, inflammation

Why regulate macrophages

Prevent local tissue damage, toxic microbiological agent releaced

Cytokines that inhibit macrophages

TGF-beta and IL-10. Treg and TH2 produces them


inflamed nodules made of macrophages. Form around non-degradable foreign bodies or around chronic intracellular infection. Central core giant macrophages. Outer ring is TH

Naive B cell activation

cross-linking of BCR to multiple antigen epitopes and co-receptors

Thymus dependent antigens

Require TFH and TH2 to activate B cell. Cognate interaction significant

Cognate interaction of T/B cell

B cell recognizes surface epitope and T cell recognizes intracellular protein

Thymus independent antigen

Activate naive B cell without T cell influence. High density of repetitive epitopes like polysaccharides. (capsule) Produces mostly IgM without class switching. Fetus to age 5. Found in peritoneum and pleural cavity


substance that cause differentiation of B cell regardless of specificity. Polyclonal activation. High dose of LPS via TLR-4

T cell synapse

Contact point between T cell and DC

Transcription factors activated during T-DC synapse

NFAT:nuclear factor of activated T cell

NFKB:nuclear factor kappa B

AP-1:Fos/Jun protein

Protein tyrosine kinase

enzyme that phosphorylates tyrosine. FYN associated with CD3, Lck associated with CD4 and CD8, ZAP70 cytoplasmic protein


immunoreceptor tyrosine based activation motif. Present in cytoplasmic tail of CD3 (gamma, delta, epsilon, zeta) binds ZAP70