Lymphocytes Flashcards
Innate vs adaptive immunity according to components
innate immunity –> neutrophils, macrophages, monocytes, demdritic cells, NK cells (lymphoid origin), complement
adaptive immunity –> T and B cells, circulating antiboides
Innate vs adaptive immunity according to origin
innate immunity –> germline encoded
adaptive immunity –> Variation through V(D)J recombination during lymphocytes development
Innate vs adaptive immunity according to resistance persistence
innate immunity –> resistance persists through generations. Does not change within an organisms lifetime
adaptive immunity –> Microbial resistance not heritable
Innate vs adaptive immunity according to type of response to pathogens (specificity)
innate immunity –> nonspecific,
adaptive immunity –> highly specific, refined over time
Innate vs adaptive immunity according to time of response to pathogens
innate immunity –> rapidly (minutes to hours)
adaptive immunity –> develops over long periods, memory response is faster and more rodust
Innate vs adaptive immunity according to physical barriers
innate immunity –> epithelial tight juctions, mucus
adaptive immunity –> no
Innate vs adaptive immunity according to secreted proteins
innate immunity –> Lysozyme, complement, C-reactive proteins, defensins
adaptive immunity –> immunoglobulins
Innate immunity - key features in pathogen recognition
TOLL-like receptors (TLRs): pattern recognition receptors that recognize pathogen associated molecular patterns (PAMPs)
Innate immunity - example of PAMPs
- LPS
- Flagellin
- ssRNA
adaptive immunity - key features in pathogen recognition
Memory cells: activated B and T cells –> subsequent exposure to a previously encountered antigen –> stronger, quicker immune response
MHC types / encoded by
MHC I and II / encoded by HLA genes
MHC function
present antigen fragments to T cells and bind T-cell receptors (TCRs)
TCR vs TLR according to meaning
TCR –> T-cell receptor
TLR –> Toll-like receptor
MCH I vs II according to loci
MCH I –> HLA-A. HLA-B, HLA-C
MCH II –> HLA-DR, HLA-DP, HLA-DQ
MCH I vs II according to binding
MCH I –> TCR and CD8
MCH II –> TCR and CD4
(mnemonic: 4x2=8, 8x1=8)
MCH I vs II according to expression (which cells express them)
MCH I –> all nucleated cells (not on RBCs)
MCH II –> antigen presenting cells (APCs)
MCH I vs II according to function
MCH I –> present ENDOGENOUSLY synthesised antigens (eg. viral or cytosolic proteins) to CD8 cytotoxic cells
MCH II –> present EXOGENOUSLY synthesised antigens (eg. bacterial proteins) to CD4 helper T cells
MCH I vs II according to antigen loading
MCH I –> Antigen peptides loaded onto MHC I in RER after delivery via TAP (transporter associated antigen processing)
MCH II –> antigen loaded following release of invariant chain in an acidified endosome
MCH I vs II according to associated proteins
MCH I –> β2-microglobulin
MCH II –> Invariant chains (CD74)
MCH I structure
a peptide, β2-microglobulin –> peptide-binding grove
MCH II structure
α peptide, β peptide, invariant chain
invariant chain (cd74) - function
- shape the peptide binding groove and prevent formation of a closed conformation
- prevent binding of peptides from the endogenous pathway to the groove
3 .facilitates MHC class II’s export from the ER in a vesicle
HLA subtypes are associated with (all types and diseases)
HLA-A3 –> hemochromotosis
HLA-B8 –> Addison disease, myasthenia gravis
HLA-B27 –> seronegative arthritis
HLA-DQ2/DQ8 –> celiac disease
HLA-DR2 –> Multiple sclerosis, Hay fever, SLE, Goodpasture syndrome
HLA-DR3 –> DM1, SLE, Graves disease, Hashimoto thyroditis, Addisson
HLA-DR4 –> RA, DM1, Addison disease
HLA-DR5 –> Pernicious anemia, Hashimoto
seronegative arthritis - types and genetics
genetics: B27
types 1. Psoriatic arhtritis 2. Ankylosing spondylitis
3. arthritis of Inflammatory bowel disease
4. Reactive arthritis (Reiter syndrome)
Hay fever - definition/causes/manifestations
an allergy caused by pollen or dust in which –> mucous membranes of the eyes and nose are inflamed
–> causing running at the nose and watery eyes
HLA - SLE
DR2
DR3
HLA - Hashimoto
DR3
DR5
HLA - diabetes mellitus
DM1 –> DR3, DR4
Natural Killer cells - type of cell and immunity
Lymphocyte member of innate immune system
Natural Killer cells - mechanism of action
- Use perforin and granzymes to induce apoptosus if virally infected cells and tumor cells
- Kills via antibody-depended cell-mediated cytotoxicity (CD16 binds FC region of bound IG, activating NK cells)
Their activity is enhanced by IL-2, IL12, INF-α, INF-β
Natural Killer cells - their activity is enhanced by
- IL-2
- IL-12
- INF-α
- INF-β
NK cells - antibody-depended cell-mediated cytotoxicity - mechanism
CD16 binds FC region of bound IG, activating NK cells
NK cells induced to kill when
- exposed to a nonspecific activation signal on target cell and/or 2. to an absence of class I MHC on target cell surface
Major B-cell functions (and mechanism)
- Recognize antigen –> undegro somatic hypermutation to optimize antigen specificity
- Produce antibody –> differentiate into plasma cells to secrete specific immunoglobins
- Maintain immunologic memory –> memory cells persists and accelerate future response to antigen
Major T-cell function (CD4 and CD8)
- CD4 help B cells make antibodies and produce cytokines to recruit phagocytes and activate other leukocytes
- CD8 directly kill virus-infected cells (and neoplastic)
- Delayed cell-mediated hypersensitivity
- Acute and chronic cellular organ rejection
Differentiation of T-cells (and location)
T cell precursor (no CD4,8, no T-cell receptor) in bone marrow –> T cell with CD4, CD8 (both) and T-cell receptor (cortex of thymus) –> T cells with T-cell receptor and either CD8 or CD4 (medulla of Thymus) –>:
CD8: Cytotoxic T cells (lymph node)
CD4: Helper T cells (lymph node) –> a. IL-12: Th1
b. il-4: Th2 c. TGF-β + IL-6: TH 17
CD4: Helper T cells (lymph node) –> ….(differentiate to, and how)
a. IL-12 + INF-γ: Th1
b. il-4: Th2 c. TGF-β + IL-6: Th17
Central tolerance is the
mechanism by which newly developing T cells and B cells are rendered non-reactive to self
Central tolerance - T cells - types (and location)
- positive selection –> thimic cortex
2. negative selection –> thimic medulla
T cells positive selection - location and mechanism
location: thymic cortex
T cells expressing TCRs capable of binding surface self-MHC molecules survive
T cells negative selection - location and mechanism
location: thymic medulla
T cells expressing TCRs with high affinity for self antigens undergo apoptosis –> Tissue restricted self antigens are expressed in thymus due to the action of autoimmune regulator (AIRE)
AIRE –> transcriptio factor –> major proteins from elsewhere in the body (tissue-restricted antigens)