Immunology - Lymphocytes Flashcards
1
Q
Innate immunity
- Components
- Resistance
- Response to pathogens
- Physical barriers
- Secreted proteins
- Key features in pathogen recognition
A
- Components
- Neutrophils, macrophages, monocytes, dendritic cells, NK cells (lymphoid origin), complement
- Resistance
- Germline encoded
- Resistance persists through generations, does not change within an organism’s lifetime
- Response to pathogens
- Nonspecific
- Occurs rapidly (minutes to hours)
- Physical barriers
- Epithelial tight junctions, mucus
- Secreted proteins
- Lysozyme, complement, CRP, defensins
- Key features in pathogen recognition
- Toll-like receptors (TLRs): pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs).
- Examples of PAMPs include LPS (gram-negative bacteria), flagellin (bacteria), ssRNA (viruses)
2
Q
Adaptive immunity
- Components
- Resistance
- Response to pathogens
- Secreted proteins
- Key features in pathogen recognition
A
- Components
- T cells, B cells, circulating antibodies
- Resistance
- Variation through V(D)J recombination during lymphocyte development
- Microbial resistance not heritable
- Response to pathogens
- Highly specific, refined over time
- Develops over long periods
- Memory response is faster and more robust
- Secreted proteins
- Immunoglobulins
- Key features in pathogen recognition
- Memory cells: activated B and T cells
- Subsequent exposure to a previously encountered antigen –> stronger, quicker immune response
3
Q
MHC I vs. II
- Both
- Loci
- Binding
- Expression
- Function
- Antigen loading
- Mode of transport to cell surface
A
- Both
- MHC encoded by HLA genes.
- Present antigen fragments to T cells and bind TCRs.
- Loci
- I: HLA-A, HLA-B, HLA-C
- II: HLA-DR, HLA-DP, HLA-DQ
- Binding
- I: TCR and CD8
- II: TCR and CD4
- Expression
- I: Expressed on all nucleated cells; Not expressed on RBCs
- II: Expressed only on APCs
- Function
- I: Present endogenously synthesized antigens (e.g., viral) to CD8+ cytotoxic T cells
- II: Present exogenously synthesized proteins (e.g., bacterial proteins, viral capsid proteins) to T-helper cells
- Antigen loading
- I: Antigen peptides loaded onto MHC I in RER after delivery via TAP peptide transporter
- II: Antigen loaded following release of invariant chain in an acidified endosome
- Mode of transport to cell surface
- I: β2-microglobulin
- II: Unknown
4
Q
HLA subtypes associated with diseases
- A3
- B27
- DQ2/DQ8
- DR2
- DR3
- DR4
- DR5
A
- A3
- Hemochromatosis.
- B27
-
Psoriatic arthritis, Ankylosing spondylitis, arthritis of Inflammatory bowel disease, Reactive arthritis (formerly Reiter syndrome).
- PAIR.
- Also known as seronegative arthropathies.
-
Psoriatic arthritis, Ankylosing spondylitis, arthritis of Inflammatory bowel disease, Reactive arthritis (formerly Reiter syndrome).
- DQ2/DQ8
- Celiac disease.
- DR2
- Multiple sclerosis, hay fever, SLE, Goodpasture syndrome.
- DR3
- Diabetes mellitus type 1, SLE, Graves disease.
- DR4
- Rheumatoid arthritis, diabetes mellitus type 1.
- There are 4 walls in a “rheum” (room).
- DR5
- Pernicious anemia –> vitamin B12 deficiency, Hashimoto thyroiditis.
5
Q
Natural killer cells
A
- Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells.
- Only lymphocyte member of innate immune system.
- Activity enhanced by IL-2, IL-12, IFN-β, and IFN-α.
- Induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface.
- Also kills via antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound Ig, activating the NK cell).
6
Q
Major functions of B and T cells
- B cell functions
- T cell functions
A
- B cell functions
- Recognize antigen—undergo somatic hypermutation to optimize antigen specificity.
- Produce antibody—differentiate into plasma cells to secrete specific immunoglobulins.
- Maintain immunologic memory—memory B cells persist and accelerate future response to antigen.
- T cell functions
- CD4+ T cells help B cells make antibody and produce cytokines to activate other cells of immune system.
- CD8+ T cells kill virus-infected cells directly.
- Delayed cell-mediated hypersensitivity (type IV).
- Acute and chronic cellular organ rejection.
- Rule of 8: MHC II × CD4 = 8; MHC I × CD8 = 8.
7
Q
Differentiation of T cells
- Positive selection
- Negative selection
A
- Positive selection
- Thymic cortex.
- T cells expressing TCRs capable of binding surface self MHC molecules survive.
- Negative selection
- Medulla.
- T cells expressing TCRs with high affinity for self antigens undergo apoptosis.
8
Q
T and B cell activation
- Antigen-presenting cells (APCs)
- Two signals are required for T cell activation
A
- Antigen-presenting cells (APCs):
- B cells
- Macrophages
- Dendritic cells.
- Two signals are required for T cell activation:
- B cell activation
- Class switching.
9
Q
Naive T cell activation
A
- Foreign body is phagocytosed by dendritic cell.
- Foreign antigen is presented on MHC II and recognized by TCR on Th (helper) cell.
Antigen is presented on MHC I to Tc (cytotoxic) cells (signal 1). - “Costimulatory signal” is given by interaction of B7 and CD28 (signal 2).
- Th cell activates and produces cytokines.
Tc cell activates and is able to recognize and kill virus-infected cell.
10
Q
B cell activation and class switching
A
- Helper T cell activation.
- B cell receptor-mediated endocytosis
- Foreign antigen is presented on MHC II and recognized by TCR on Th cell (signal 1).
- CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2).
- Th cell secretes cytokines that determine Ig class switching of B cell.
- B cell activates and undergoes class switching, affinity maturation, and antibody production.
11
Q
Helper T cells
- Th1 cell
- Secretes…
- Function
- Inhibited by…
- Th2 cell
- Secretes…
- Function
- Inhibited by…
- Macrophage-lymphocyte interaction
- CD4
A
- Th1 cell
- Secretes IFN-γ
- Activates macrophages and cytotoxic T lymphocytes (CTLs)
- Inhibited by IL-4 and IL-10 (from Th2 cell)
- Th2 cell
- Secretes IL-4, IL-5, IL-6, IL-13
- Recruits eosinophils for parasite defense and promotes IgE production by B cells
- Inhibited by IFN-γ (from Th1 cell)
- Macrophage-lymphocyte interaction
- Macrophages release IL-12, which stimulates T cells to differentiate into Th1 cells.
- Th1 cells release IFN-γ to stimulate macrophages.
- CD4
- Helper T cells have CD4, which binds to MHC II on APCs.
12
Q
Cytotoxic T cells
A
- Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis.
- Release cytotoxic granules containing preformed proteins
- Perforin—helps to deliver the content of granules into target cell
- Granzyme B—a serine protease, activates apoptosis inside target cell
- Granulysin—antimicrobial, induces apoptosis
- Cytotoxic T cells have CD8, which binds to MHC I on virus-infected cells.
13
Q
Regulatory T cells
A
- Help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions.
- Identified by expression of cell surface markers CD3, CD4, CD25 (a chain of IL-2 receptor), and transcription factor FOXP3.
- Activated regulatory T cells produce anti-inflammatory cytokines like IL-10 and TGF-β.
14
Q
Antibody structure and function
- Variable part
- Heavy chain
- Light chain
- Fab
- Fc
- Antibody diversity is generated by:
A
- Variable part of L and H chains recognizes antigens.
- Heavy chain contributes to Fc and Fab fractions.
- Light chain contributes only to Fab fraction.
- Fab
- Antigen-binding fragment
- Determines idiotype
- Unique antigen-binding pocket
- Only 1 antigenic specificity expressed per B cell
- Fc
- Constant
- Carboxy terminal
- Complement binding
- Carbohydrate side chains
- Determines isotype (IgM, IgD, etc.)
- Fc portion of IgM and IgG fixes complement
- Antibody diversity is generated by:
- Random “recombination” of VJ (light-chain) or V(D)J (heavy-chain) genes
- Random combination of heavy chains with light chains
- Somatic hypermutation (following antigen stimulation)
- Addition of nucleotides to DNA during recombination (see 1st entry in this list) by terminal deoxynucleotidyl transferase
15
Q
Immunoglobulin isotypes
A
- Mature B lymphocytes express IgM and IgD on their surfaces.
- They may differentiate in germinal centers of lymph nodes by isotype switching (gene rearrangement; mediated by cytokines and CD40 ligand) into plasma cells that secrete IgA, IgE, or IgG.
