Lymphocytes Flashcards
What is Innate immunity?
Receptors that recognize pathogens are germline encoded
What is the reponse like in Innate immunity?
Reponse to pathogens is fast & nonspecific
Is there memory in Innate immunity?
No memory
What does Innate immunity consist of?
- Neutrophils
- Macrophages
- Dendrictic cells
- Natural killer cells (lymphoid origin)
- Complement
What is Adaptive immunity?
Receptors that recognize pathogens V(D)J recombination during lymphocyte development
What is the response like in Adaptive immunity?
Response is slow on first exposure, but memory response is faster & more robust
What does Adaptive immunity consist of?
- T cells
- B cells
- Circulating Ab
What is MHC?
Major histocompatibility complex
What is MHC encoded by?
Human leukocyte Ag (HLA) genes
What does MHC do?
Present Ag fragments to T cells & bind TCR
What are the HLA genes of MHC I?
HLA-A, HLA-B, HLA-C
What does MHC I bind to?
TCR & CD8
Where is MHC I expressed?
On all nucleated cells
Not expressed on RBC
Where are MHC I Ag’s loaded?
RER w/ mostly intracellular peptides
What does MHC I mediate?
Viral immunity
What does MHC I pair w/?
ß2-microglobulin (aids in transport to cell surface)
What are the HLA genes of MHC II?
HLA-DR, HLA-DP, HLA-DQ
What does MHC II bind to?
TCR & CD4
Where is MHC II expressed?
Only on Ag-presenting cells (APCs)
When are the MHC II Ag’s loaded?
Following release of invariant chain in an acidified endosome
What dz is HLA-A3 assoc w/?
Hemochromatosis
What dz is HLA-B27 assoc w/?
- Psoriasis
- Ankylosing spondylitis
- Inflammatory bowel dz
- Reiter’s synd
What dz are HLA-DQ2/DQ8 assoc w/?
Celiac dz
What dz is HLA-DR2 assoc w/?
- Multiple sclerosis
- Hay fever
- SLE
- Goodpasture’s
What dz is HLA-DR3 assoc w/?
DM I & Grave’s dz
What dz is HLA-DR4 assoc w/?
Rheumatoid arthritis & DM I
What dz is HLA-DR5 assoc w/?
Pernicious anemia→ B12 def
Hashiomoto’s thyroiditis
What do Natural Killer cells do?
Use Perforin & granzymes to induce apoptosis of virally infected cells & tumor cells
NK cells are the only lymphocyte member of the ____ ____ ____.
Innate immune system
What is NK cell activity enhanced by?
- IL-2
- IL-12
- IFN-ß
- IFN-alpha
When are NK cells induced?
To kill when exposed to a nonsepcific activation signal on target cell &/or to an absence of class I MHC on target cell surface
What are the B cell functions?
Make Ab
What does Ab do?
- Opsonize bacteria
- Neutralize viruses (IgG)
- Activate complement (IgG, IgM)
- Sensitize mast cells (IgE)
What does IgE respond to?
Allergy
Type I hypersensitivity
What does IgG respond to?
Cytotoxic (type II) & Immune complex (type III) hypersensitivity
What are B cells involved in?
Hyperacute & humorally mediated acute & chronic organ rejection
What are the functions of CD4+ T cells?
Help B cells make Ab & produce cytokines to activate other cells of immune system
What is the function of CD8+ T cells?
Kill virus-infected cells directly
What are T cells involved in?
Delayed cell-med hypersensitivity (type IV)
Acute & chronic cellular organ rejection
Where does Positive selection happen?
Thymic cortex
What is Positive selection?
T cells expressing TCRs capable of binding surface self MHC molecules survive
Where does Negative selection happen?
Thymic medulla
What is Negative selection?
T cells expressing TCRs w/ high affinity for self Ag’s undergo apoptosis
What causes T & B cell activation?
Antigen-presenting cells (APCs)
What are the APCs?
- Dendrite cell
- Macrophage
- B cell
What is the only APC that can activate naive T cell?
Dendrite cell
How many signals are required for T & B cell activation& B cell class switching?
Two signals
What is the 1st step of Naive T cell activation?
Foreign body is phagocytosed by dendritic cell
What is the 2nd step of naive T cell activation?
Foreign Ag is presented on MHC II & recognized by TCR on Th cell. Ag is presented on MHC to Tc (cytotoxic) cells (signal 1)
What is the 3rd step in naive T cell activation?
“Costimulatory signal” is given by interaction of B7 & CD28 (signal 2)
What is the 4th step in naive T cell activation?
Th cell activates & produces cytokines. Tc cell activates & is able to recognize & kill virus-infected cell
What is the 1st step of B cell activation & class switching?
Helper T cell activation same as naive T cell activation
What is the 2nd step of B cell activation & class switching?
B cell receptor-med endocytosis; foreign Ag is presented on MHC II & recognized by TCR on Th cell (signal 1)
What is the 3rd step of B cell activation & class switching?
CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2)
What is the 4th step of B cell activation & class switching?
Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates & undergoes class switching, affinity maturation & Ab production
What do Th1 cells secrete?
IFN-gamma
What do Th2 cells activate?
Macrophages
What are Th1 cells inhibited by?
IL-4 & IL-10 (from Th2 cell)
What do Th2 cells secrete?
IL-4, IL-5, IL-10, IL-13
What do Th2 cells recruit?
Eosinophils for parasite defense & promotes IgE production by B cells
What are Th2 cells inhibited by?
IFN-gamma (from Th1 cell)
What is Macrophage-lymphocyte interaction?
Activated lymphocytes (release INF-gamma) & macrophages (release IL-1, TNF-alpha) stim one another
Helper T cells have ____ which binds to ____ on ___
CD4, MHCII, APCs
What do Cytotoxic T cells do?
Kill virus-infected, neoplastic & donor graft cells by inducing apoptosis
What do Cytotoxic T cells release?
Cytotoxic granules containing performed proteins
What is perforin?
Helps to deliver the content of granules into target cell
What is granzyme?
A serine protease, activates apoptosis inside target cell
What is granulysin?
Antimicrobial, induces apoptosis
What does CD8 on cytotoxic T cells bind to?
MHC I on virus-infected cells
What do Regulatory T cells do?
Help maintain specific immune tolerance by suppressing CD4 & CD8 T-cell effector functions
What do regulatory T cells express?
CD3, CD4, CD25 (alpha chain of IL-2 receptor) cell surface makers
What do activated regulatory T cells produce?
Anti-inflammatory cytokines like IL-10 & TGF-ß
What do the variable part of L & H chains on Ab recognize?
Antigens
What does the Fc portion of IgM & IgG do?
Fixes complement
What does the Heavy chain of Ab do?
Contributes to Fc & Fab fractions
What does the Light chain of Ab do?
Contributes only to Fab fraction
What is the Fab fraction of an Ab?
- Ag-binding fragment
- Determines idiotype: unique Ag-binding pocket; only 1 antigenic specificity expressed per B cell
What is the Fc fraction of an Ab?
- Constant
- Carboxy terminal
- Compliment binding at CH2 (IgG + IgM only)
- Carbohydrate side chains
- Determines isotype (IgM, IgD, etc)
What is Ab diversity generated by?
- Random “recombination” of VJ (light-chain) of V(D)J (heavy-chain) genes
- Random combo of heavy chains w/ light chains
- Somatic hypermutation (following Ag stim)
- Add of nucleotides to DNA during recombination by terminal deoxynucelotidyl transferase
What do mature B lymphocytes express?
IgM & IgD on their surfaces
How can mature B lymphocytes differentiate?
Isotype switching into plasma cells that secrete IgA, IgE or IgG
What is isotype switching?
Gene rearrangement mediate by cytokines & CD40 ligand
What is IgG?
Main Ab in 2° (delayed) response to an Ag
What is the most abundant Ig isotype?
IgG
What does IgG do?
- Fixes complement
- Crosses the placenta
- Opsonizes bacteria
- Neutralizes bacterial toxins & viruses
What does IgG do when it crosses the placenta?
Provides infants w/ passive immunity
What does IgA do?
Prevents attachment of bacteria & viruses to mucous membranes; does not fix complement
Is IgA a monomer or a dimer?
Monomer in circulation
Dimer when secreted
How does IgA cross epithelial cells?
Transcytosis
Where is IgA found?
Secretions (tears, saliva, mucus) & early breast milk (colostrum)
What does IgA pick up?
Secretory component from epithelial cells before secretion
What does IgM do?
Fixes complement but does not cross the placenta
When is IgM produced?
In 1° (immediate) reponse to an Ag
Where is the Ag receptor for IgM?
Surface of B cells
What is the structure of IgM?
Monomer on B cell or pentamer
What does the shape of an IgM pentamer allow?
Efficiently trap free Ags out of tissue while humoral response evolves
What is the function of IgD?
Unclear
Where is IgD found?
Surface of many B cells & in serum
What does IgE do?
- Binds mast cells & basophils
- Cross-links when exposed to allergen
- Mediating immediate (type I) hypersensitivity through release of inflam mediators suchs as histamine
What does IgE mediate?
Immunity to worms by activating esinophils
Where is the lowest concentration of IgE?
In serum
What are Thymus-independent Ags?
Ags lacking a peptide component; cannot be presented by MHC to T cells
What do Thymus-independent Ags do?
Stim release of Abs & do not result in immunologic memory
What are Thymus-independent Ags?
Ags containing a protein component
How does class switching & immunologic memory w/ Thymus-dependent Ags occur?
Result of direct contact of B cells w/ Th cells
