Lymphocytes Flashcards
Components of innate immunity
- Neutrophils
- macrophages
- monocytes
- dendritic cells
- natural killer (NK) cells (lymphoid origin)
- complement
Components of Adaptive Immunity
- T cells
- B cells
- circulating antibodies
Innate immunity genetic mechanism
Germline encoded
Adaptive immunity genetic mechanism
Variation through V(D)J recombination during lymphocyte development
Innate immunity resistance
Does not change within a lifetime
Persists through generations
Adaptive Immunity resistance
Microbial resistance is not heritable
Innate immunity response to pathogens
Nonspecific Occurs rapidly (minutes to hours)
Adaptive immunity response to pathogens
Highly specific, refined over time
Develops over long periods; memory response is faster and more robust
Innate immunity physical barriers
- Epithelial tight junctions
- mucus
Adaptive immunity phyiscal barriers
N/A
Innate immunity secreted proteins
- Lysozyme
- Complement
- C-reactive protein (CRP)
- Defensins
Adaptive immunity secreted proteins
Immunoglobulins
Innate immunity 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)
Adaptive immunity pathogen recognition
Memory cells: activated B and T cells;
subsequent exposure to a previously encountered antigen → stronger, quicker immune response
MHC (I and II)
MHC encoded by HLA genes.
- Present antigen fragments to T cells
- and bind T-cell receptors (TCRs).
MHC I loci
- HLA-A
- HLA-B
- HLA-C
MHC II loci
- HLA-DR
- HLA-DP
- HLA-DQ
MHC I binding
TCR and CD8
MHC II binding
TCR and CD4
MHC I expression
Expressed on all nucleated cells
Not expressed on RBCs
MHC II expression
Expressed on APCs
MHC I function
Present endogenously synthesized antigens (e.g., viral or cytosolic proteins) to CD8+ cytotoxic T cells
MHC II function
Present exogenously synthesized antigens (e.g., bacterial proteins) to **CD4+ helper T cells **
MHC I antigen loading
Proteasome breaks down protein (could be viral) in the cytoplasm. It enters the RER via TAP (transporter associated with antigen processing), Tapasin links MHC I to TAP so it can pick up protein pieces and continue folding. The complex can then move to the cell surface.
Associated with beta 2 microglobulin protein.
Note that the alpha subunit of MHC I has three subunits.
MHC II antigen loading
The exogenous antigen is taken up and loaded into an endosome. MHC II αβ and Ii (invariant chain) move from the ER (targeted by Ii) to the golgi and then move to combine with the endosome. As the endesome becomes more acidic, proteasomes break down the protein. As the MHC II endosome becomes more acidic and combined with the endosome, Ii is degraded to CLIP. Acidic conditions and HLA-DM MHCII → binds protein.
Note that MHC I only has an α chain but MHC II has an α and β chain.
MHC I associated proteins
β2-microglobulin
MHC II associated proteins
Invariant chain (Ii chain) & CLIP
HLA-A, HLA-B, HLA-C are the loci for
MHC I
HLA-DR, HLA-DP, HLA-DQ are the loci for
MHC II
TCR and CD8 bind
MHC I
TCR and CD4 bind
MHC II
Expressed on all nucleated cells
Not expressed on RBCs
MHC I
Expressed on APCs
MHC II
Present endogenously synthesized antigens (e.g., viral or cytosolic proteins) to CD8+ cytotoxic T cells
MHC I
Present exogenously synthesized antigens (e.g., bacterial proteins) to CD4+ helper T cells
MHC II
What is β2-microglobulin associated with?
MHC I
What is the invariant chain (Ii chain) protein associated with?
MHC II
Has an alpha and beta chain
MHC II
Has an alpha chain with three subunits
MHC I
HLA subtype A3 is associated with
Hemochromatosis (MHCI?)
Hemochromatosis is associated with this HLA subtype
A3
HLA subtype B27 is associated with this disease
- Psoriatic arthritis
- Ankylosing spondylitis
- arthritis of Inflammatory bowel disease
- Reactive arthritis (formerly Reiter syndrome)
PAIR. Also known as seronegative arthropathies.
(MHCI?)
- Psoriatic arthritis
- Ankylosing spondylitis
- arthritis of Inflammatory bowel disease
- Reactive arthritis (formerly Reiter syndrome)
Are associated with which HLA subtype?
B27
HLA subtype DQ2/DQ8 is associated with this disease
Celiac disease.
HLA subtype DR2 is associated with this disease
- Multiple sclerosis
- hay fever
- SLE
- Goodpasture syndrome.
HLA subtype DR3 is associated with this disease
- Diabetes mellitus type 1
- SLE
- Graves disease
- Hashimoto thyroiditis
HLA subtype DR4 is associated with this disease
- Rheumatoid arthritis
- diabetes mellitus type 1
[There are 4 walls in a “rheum” (room)]
HLA subtype DR5 is associated with this disease
- Pernicious anemia → vitamin B12 deficiency
- Hashimoto thyroiditis
Celiac disease is associated with which HLA subtype?
DQ2/DQ8
- Multiple sclerosis
- hay fever
- SLE
- Goodpasture syndrome
are associated with which HLA subtype?
DR2
- Diabetes mellitus type 1
- SLE
- Graves disease
- Hashimoto thyroiditis
Are associated with which HLA subtype?
DR3
- Rheumatoid arthritis
- diabetes mellitus type 1
Are associated with which HLA subtype?
DR4
- Pernicious anemia → vitamin B12 deficiency,
- Hashimoto thyroiditis.
Are associated with which HLA subtype?
DR5
Hay fever
Gross pollens causing allergic rhinitis
Goodpasture
Anti-GBM disease (kidney and lung)
Pernicious anemia
Autoimmune destruction of gastric parietal cells → lost IF → B12 deficiency
How are natural killer cells unique components of innate immunity?
They don’t need an MHC I complex (mostly viral)
How does the adaptive immunity mechanism work?
Heavy chain- DNA: first DJ then V. RNA removes space between that and the constant region.
Light chain- DNA: VJ only. RNA removes extra in between the constant
Kappa light chain
Lambda heavy chain
What are the seronegative arthropathies?
(involves joints)
- Psoriatic arthritis
- Ankylosing spondylitis
- arthritis of Inflammatory bowel disease
- Reactive arthritis (formerly Reiter syndrome)
Natural killer cells
- Lymphocyte member of innate immune system
- Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells
- Induced to kill when exposed to a
- nonspecific activation signal on a 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).
Natural killer cells activity enhanced by
- IL-2
- IL-12
- IFN-α
- IFN-β
B-Cell functions
- Recognize antigen—undergo somatic hypermutation (→ as it replicates) to optimize antigen specificity (→ also isotype / class switching, see later…)ץ
- 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 antibodies and produce cytokines to recruit phagocytes and activate other leukocytes.
- CD8+ T cells directly kill virus-infected cells.
- Delayed cell-mediated hypersensitivity (type IV).
- Acute and chronic cellular organ rejection.
CD4 TH1 → CD8
