Lymphocytes Flashcards
Innate immunity components (6)
- Neutrophils
- Macrophages
- Monocytes
- Dendritic cells
- Natural Killer cells
- Complement
Adaptive immunity components
T cells
B cells
Circulating antibodies
Adaptive immunity mechanism
Variation through VDJ recombination during lymphocyte development
Germline encoded immunity
Innate
Resistance persists through generations and doesn’t change within an organisms lifetime: innate or adaptive immunity-?
Innate
Highly specific response to pathogens
Adaptive immunity
No memory response
Innate immunity
Fastest immunity
Innate
Secreted proteins implied in innate immunity
Lyzozyme
Complement
CRP
Defensins
Physical barriers implied in innate immunity
Epithelial tight junctions
Mucus
Pathogen recognition features in innate immunity
TLR: Toll-Like Receptors
PAMPs: pathogen-associated molecular patterns
PAMP in gram negative bacteria
Lipopolisaccarides
Encoded by HLA genes
MHC: major histocompatibility complex I and II
Function of MHC
Present antigen fragments to T cells and bind T cell receptors: TCRs
MHC I loci
HLA A
HLA B
HLA C
MHC 1 loci have 1 letter
MHC II loci
HLA DP
HLA DQ
HLA DR
MHC I and MHC II binding
8 rule:
HLA I x CD8
HLA II x CD4
Both TCR
MHC I structure
1 long chain
1 short chain
MHC II structure
2 equal length chains
MHC I expression
ALL nucleated cells (Not RBC), APCs and platelets
MHC II expression
APCs
MHC ___ presents exogenously synthesized antigens (eg bacterial proteins) to _____ T cells
II
CD4 (T helper)
MHC___ presents endogenously synthesized antigens (eg. viral or cytosolic proteins) to _____ T cells
I
CD8+ cytotoxic
Protein associated with MHC II
Invariant chain
Protein associated with MHC I
B2 microglobulin
Antigen loading in MHC I
Antigen peptides loaded onto MCH I in RER after delivery via TAP (transporter associated with antigen processing)
Antigen loading in MHC II
Antigen loaded following release of invariant chain in an acidified endosome
HLA associated to hemochromatosis
A3
HLA associated to Graves and myastenia gravis
B8
Diseases associated to HLA b27
Seronegative arthropathies: PAIR Psoriatic arthitis Ankylosing spondylitis IBD-associated arthitis Reactive arthritis: Reiter's syndrome
HLA associated to Celiac disease
DQ2, DQ8 I ate (8) too (2) much gluten at Dairy Queen
HLA associated to multiple sclerosis, hay fever, SLE, Goodpasture syndrome
DR2: DesgRacia2
HLA associated to SLE
DR3
DR2
HLA associated to DM1, Rheumatoid disease
DR4
HLA associated to Hashimoto tyroiditis and pernicious anemia
DR5
HLA associated to Addison disease
HLA B8, DR4
Lymphocyte member of innate immune system
Natural Killer cells
Function of natural killer cells
Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells
Enhances NK activity
IL2, IL12, IFN alpha and beta
Signals of NK cell activation
- Nonspecific activation signal on target cell
- MHC absence
- Antibody dependent cell mediated cytotoxicity
CD4+ function
Help B cell make antibodies and produce cytokines to recruit phagocytes and activate other leukocytes
Optimize antigen specifity in B cells
Somatic hypermutation
Responsable for accute and chronic cellular organ rejection
T cells
REsponsible for type IV hypersensitivity
Cell mediated: T cell
Positive selection of T cells takes place in
Thyme cortex
Negative selection of T cells takes place in
Thyme medulla
Deficiency of AIRE (autoinmune regulator)
Autoinmune polyendocrine syndrome 1 (chromosome 21)
T cells expressing TCRs capable of binding self-MHC on cortical epithelial cells survive
Positive selection: Cortex
T cells expressing TCRs with high affinity for self antigens undergo apoptosis
Negative selection: medulla
Helper T cell that secretes IFN gamma and IL-2
Th1 cell
Th1 cell function
Activates macrophages and cytotoxic T cells
Helper T cell that secretes IL-4,5,6,10,13
Th2 cell
Th2 cell function
Recruits eosinophils for parasite defense
Promotes IgE production by B cells
Th1 cell differentiation is induced by
IL-12 (macrophages, dendritic and other APC)
INF gamma
Th2 cell differentiation is induced by
IL-2
IL-4
Th2 cell is inhibited by
IFN gamma from Th1 cell
TH1 cell is inhibited by
IL-4 and IL-10 from Th2
Function of Cytotoxic T cells
Kill virus-infected/neoplastic/ donor graft cells
Inducing apopotosis by releasing cytotoxic granules containing preformed proteins (perforin, granzyme B)
Expression of CD3, CD4 and FOXP3
Regulatory T cells
Activated regulatory T cells (Tregs) produce…
Antiinflamatory cytokines (IL-10, TGF beta)
Tregs function
Mantain specific immune tolerance by supressing CD4 and CD8 T cell effector functions
Genetic defficiency of FOXP3
IPEX: immune dysregulation, polyendocrinopathy, entheropathy X linked syndrome
Diabetes in male infants
Antigen presenting cells
B cells
Dendritic cells
Langerhans cells
Macrophages
Signals required for T cell activation
- Antigen is presented on MHC II/I and recognised by TCR on CD4/8
- Proliferation and survival: B7 (cd80/86)protein on dentritic cell and CD28 on naïve T cell
Signals required for B cell activation and class switching
- Foreign Antigen is presented on MHC II to TCR on Th cell
- CD40 receptor on B cell binds to CD40L on Th cell
Th cell secretes cytokines that determine Ig class switching of B cell
Determines idiotype
Fab fragment: antigen binding
Fab fragment
Contains variable regions consisting of light (L) and heavy (H) chains: recognizes antigens
Region of antibody that fixes complement
FC
Characteristics of Fc fragment on an antobody
- Constant
- Carboxyl terminal
- Complement binding
- Carbohydrate side chains
Determines isotype of an antybody
Fc fragment: IgA, G, E,M
Generation of antibody diversity (antigen independent)
- Random combination of VJ (light chain) or VDJ (heavy chain) genes
- Random addition of nucleotides to DNA during recombination by terminal deoxynucleotide transferase (TdT)
- Random combination of heavy chains with light chains
Generation of antibody diversity (antigen dependent)
Somatic hypermutation and affinity maturation (variable region)
Isotype switching: constant region
Mature naïve B cells prior to activation express what types of Ig?
Ig M
Ig D
Main antibody in delayed response to an antigen
IgG
Most abundant Ig in serum
IgG
Ig that crosses placenta
IgG
Ig that doesnt fix complement
IgA
Ig that prevents attachment of bacteria and viruses to mucous membranes
IgA
IgA dimer
J chain binds
Most produced antibody overall
IgA (but IgG is the higher in serum)
Ig in breast milk and secretions
IgA
Produces in the immediate response to an antigen
IgM
Doesnt cross the placenta
IgM (pentamer)
Enables avid binding to antigen in IgM
Pentamer conformation
Ig that binds mast cells and basophils
IgE
Ig that mediates immediate hypersensitivity (type I)
IgE: cross links when exposed to allergen
Ig with lowest concentration in serum
IgE
Antigens lacking a peptide component
Thymus independent antigens: cannot be presented by MHC to T cells