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Immunology FirstAid > Lymphocytes > Flashcards

Lymphocytes Flashcards

1
Q

Innate Immunity

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)

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2
Q

Adaptive immunity

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

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3
Q

MHC I

A

MHC encoded by HLA genes. Present antigen fragments to T cells and bind TCRs.
LOCI HLA-A, HLA-B, HLA-C
BINDING TCR and CD8
EXPRESSION
Expressed on all nucleated cells.
Not expressed on RBCs.
FUNCTION Present endogenously synthesized antigens
(e.g., viral) to CD8+ cytotoxic T cells
ANTIGEN LOADING Antigen peptides loaded onto MHC I in RER after delivery via TAP peptide transporter
MODE OF TRANSPORT TO CELL SURFACE
β2-microglobulin

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4
Q

MHC II

A

LOCI HLA-DR, HLA-DP, HLA-DQ
BINDING TCR and CD4
EXPRESSION Expressed only on APCs
FUNCTION
Present exogenously synthesized proteins (e.g., bacterial proteins, viral capsid proteins) to T-helper cells
ANTIGEN LOADING Antigen loaded following release of invariant chain in an acidified endosome.

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5
Q

HLA A3 subtype associated disease

A

Hemochromatosis

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6
Q

HLA B27 subtype associated disease

A

Psoriatic arthritis, Ankylosing spondylitis, arthritis of Inflammatory bowel disease, Reactive arthritis (formerly Reiter syndrome).
PAIR. Also known as seronegative arthropathies.

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7
Q

HLA DQ2/DQ8 subtype associated disease

A

Celiac disease

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8
Q

HLA DR2 subtype associated disease

A

Multiple sclerosis, hay fever, SLE, Goodpasture syndrome.

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9
Q

HLA DR3 subtype associated disease

A

Diabetes mellitus type 1, SLE, Graves disease.

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10
Q

HLA DR4 subtype associated disease

A

Rheumatoid arthritis, diabetes mellitus type 1.

There are 4 walls in a “rheum” (room).

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11
Q

HLA DR5 subtype associated disease

A

Pernicious anemia –> vitamin B12 deficiency

Hashimoto thyroiditis.

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12
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).

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13
Q

Major B cell functions

A

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.

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14
Q

Major T cell functions

A

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.

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15
Q

Differentiation of T cells

A

T-cell precursor (bone marrow)–>
CD4+,CD8+ T cell (thymus cortex)–>
1. CD8+ T cell (thymus medulla)–> Cytotoxic T cell (LN)
2. CD4+ T cell (thymus medulla)–> Helper T cell (LN) –>

via IL-12 –> Th1 cell
via IL-4 –> Th2 cell
via TGF-b + IL-6 –> Th17 cell
via TGF-b –> Treg cell

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.

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16
Q

T and B cell activation general

A 
Antigen-presenting cells (APCs): B cells, macrophages, dendritic cells.
Two signals are required for T cell activation, B cell activation, and class switching.
17
Q

Naive T cell activation

A
  1. Foreign body is phagocytosed by dendritic cell.
  2. 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).
  3. “Costimulatory signal” is given by interaction of B7 and CD28 (signal 2).
  4. Th cell activates and produces cytokines. Tc cell activates and is able to recognize and kill virus infected cell.
18
Q

B cell activation and class switching

A
  1. Helper T cell activation.
  2. B cell receptor-mediated endocytosis; foreign antigen is presented on MHC II and recognized by TCR on Th cell (signal 1).
  3. CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2).
  4. Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and antibody production.
19
Q

Th1 cell

A

Secretes IFN-γ
Activates macrophages and cytotoxic T lymphocytes (CTLs)
Inhibited by IL-4 and IL-10 (from Th2 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. Helper T cells have CD4, which binds to MHC II on APCs.

20
Q

Th2 cell

A

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. Helper T cells have CD4, which binds to MHC II on APCs.

21
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.

22
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 (α chain of IL-2 receptor), and transcription factor FOXP3.
Activated regulatory T cells produce anti-inflammatory cytokines like IL-10 and TGF-β.

23
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 (α chain of IL-2 receptor), and transcription factor FOXP3.
Activated regulatory T cells produce anti-inflammatory cytokines like IL-10 and TGF-β.

24
Q

Antibody structure and function

A

Variable part of L and H chains recognizes antigens.
Fc portion of IgM and IgG fixes complement.
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.)

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
25
Q

Opsonization

A

Antibody binding promotes phagocytosis

26
Q

Neutralization

A

Antibody prevents bacterial adherance

27
Q

Complement activation

A

Antibody activates complement, enhancing opsonization and lysis –> membrane attack complex (MAC)

Immunology FirstAid (4 decks)

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