Immunology Flashcards
What are the functions of a lymph node? What occurs in the primary and secondary follicles of a lymph node? Where are they located? The medulla? The paracortex?
nonspecific filtration by macrophages
B and T cell storage
immune response activation
Follicle is located in the outer cortex. It is the site of b cell storage and proliferation. The primary follicles are dense and dormant. Secondary follicles are acives and have pale germinal centers
The medulla has medullary cords and sinuses. Sinuses communicate with efferent lymphatics and contain reticular cells and macrophages
The paracortex is between the medulla and the follicles and houses T cells. It contains venules which T and B cells enter from the blood. It is not well developed in pts iwth Digeorge.
What do the mediastinal LNs drain? Internal iliac? Para-aortic? Superficial inguinal? Popliteal? What dos the right lymphatic duct drain? Thoracic duct? To where?
Mediastinal=trachea and esophagus
internal iliac=lower rectum to anal canal, bladder, vagina, prostate
Para-aortic=uterus, testes, ovaries, kidneys
superficial inguinal=anal canal, skin below umbilicus, scrotum
Popliteal=dorsolateral foott, posterior calf
What are the sinusoids of the spleen? Where are t cells found in spleen? B cells? Where is the marginal zone and what is located there? Function? What is the function of macrophages in the spleen?
Sinusoids are long vascular channels in red pulp with fenestrated barrel hoop BM.
T cells are in periarteriolar lymph sheath (PALS) in white pulp
B cells in follicles in white pulp
Marginal zone is right b/w red and white pulp. Where APCs capture blood born antigens for recognition by lymphocytes.
Macrophages in spleen remove encapsulated bacteria.
Explain how splenic dysfnction can lead to susceptibility to encapsulated organisms? What are some organisms? What are some heme/lymph results post splenectomy?
It leads to decr. IgM leading to decr. complement activation leading to decr. C3b opsonization lead to incr. susc. to encaps. organisms
SHiNE SKiS
Strep pneumoniae H. influenzae Neisseria meningitidis E. coli Salmonella spp. Klebsiella pneumo Group B Strep
Howell-Jolly bodies (nuclear remnants)
Target cells
Thrombocytosis
Lymphocytosis
What is the function of the thymus? From what is it derived? What is the cortex like? What occurs there? medulla? What occurs there?
T cell differentiation and maturation.
third pharyngeal pouch
Cortex is dense with immature T cells (positive selection)
Medulla is pale wiht mature t cells and hassall corpuscles (negative selection).
Compare and contrast innate immunity and adaptive immunity concerning components, mechanism, resistance, response to pathogens, physical barriers, secreted proteins, and key features in pathogen recognition.
INNATE
Complement, neutrophils, NK cells, Macrophages, monocytes, dendritic cells
Germline encoded
Resistance persists through generations
Nonspecific and rapid response
Skin, cilia
Lysozyme, complement, CRP, and Defensins are secreted
TLRs recognize PAMPs such as LPS, flagellin, and ssRNA
ADAPTIVE
B cells and T cells
Variation through V(D)J recombination
Resistance not heritable
Highly specific response, refined over time. Memory response.
No physical barriers
Immunoglobulins secreted
Memory cells: activated T and B cells—>subsequent exposure leads to stronger, quicker response
What genes encode MHC? Compare and contrast the two MHC molecules concerning Loci, binding proteins, cellular location, function, antigen loading mechanism, structure, and associated proteins
HLA genes
MHC I
HLA-A,B,C
TCR AND CD-8
all nucleated cells
present endogenously synth. proteins to CD8+ cytotoxic t cells
antigen peptides loaded onto MHC I in RER after delivery via TAP
Beta 2 microglobulin
An alpha chain associated with a beta 2 microglobulin
MHC II
HLA-P,Q,R
TCR AND CD-4
APCs
Present exogenously synth antigens to helper T cells
Antigen loaded following release of invariant chain in acidified endosome
invariant chain
an alpha and a beta chain
Which diseass are associated with HLA-A3, B27, DQ2/DQ8, DR2,DR3, DR4, DR5
A3=hemochromatosis
B27=seronegative arthropathies (psoriatic arthritis, ankylosing spondylitis, arthrithis of IBD, and Reactive Arthritis
DQ2/DQ8=celiac disease
DR2=MS, hay fever, SLE, Goodpasture
DR3=DM-I, SLE, Graves, Hashimoto
DR4=RA, DM-I
DR5=pernicious anemia, Hashimoto
What is the funciton of NK cells? What cytokines enhance their activity? What signals them to kill (2 mechanisms)?
Use perforin and granzyme to induce apoptosis of virally infected cells and tumor cells
IL-2, IL-12, IFN-alpha, IFN-beta
Exposure to nonspecific activation signal on target cell or absence of class I MHC
Antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound Ig, activates the NK cell)
What are the major funcitons of both B cells and T cells?
B CELLS
Recognize antigen-undergo somatic hypermutation to optimize antigen specificity
Produce antibody
Maintain immunologic memory
T CELLS
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 (IV)
Acute and chronic cellular organ rejection
What steps occur in the differentiation of T cells? Where do the steps occur? What cytokines determine what kind of helper T cell it will become?
T cell precursor formed in marrow
Double positive T cell in thymus cortex. Positive selection (T cells expressing TCRs capable of binding surface self-MHC molecules survive)
Medulla-Either CD4+ or CD8+. Negative selection (T celsl expressing TCRs with high affinity for self antigens undergo apoptosis)
CD4+ and CD8+ t cells migrate to LNs
In the lymph node, IL-12 converts a helper T cell into a TH-1 cell. IL-4 into a Th2 cell. IL-6 and TGF-beta into a Th17 cell.
Compare and contrast Th1 and Th2 cells concerning what they secrete, function, how they’re activated, and how they’re inhibited. How do macrophages interact with helper T cells?
TH1 CELL
IFN-gamma
Activates macrophages and cytotoxic T cells
IFN-gamma and IL-12
IL-4 and IL-10
macrophages release IL-12–>Th1 cells which release IFN-gamma to stimulate macrophages
TH2 CELL
IL-4, 5, 10, and 13
Recruits eosinophils for parasite defense and promotes IgE production by B cells
Activated by IL-4
Inhibited by IFN gamma
What is the function of cytotoxic T cells? Mechanism?
Kill virus infected neoplastic,, and donor graft cells by inducing apoptosis
Release cytotoxic granules containing preformed proteins (performin, granzyme B)
What is the function of regulatory T cells? Markers? mechanism?
Help maintain specific immune tolerance by suppressing CD4 and CD8 T cell effector fucntions
CD3, 4, 25, and FOXP3
Activated T regs produce anti inflmmatory cytokines (IL-10, TGF-beta
How are naive t cells activated? How does b cells activation and calss switching occur?
DC sampls and processes antigen, migrates to the draining LN
Presents antigen on MHCII or MHC I and presented to CD4 or CD8 pos. cels
Costimulation provided by interaction b/w B7 and CD28 for CD4 cells and by IL-2 (from CD4 Th1 type cells) for CD8 cells
B CELL
Th- cell activation as above
B cell acts as an APC, presents antigen on MHC II
CD40 receptor on B cells binds CD40L on Th cell
Th cell secretes cytokines that determine Ig class switching of B cell. Be cells activates and undergoes class switching, affinity maturation, and antibody production
What are the parts of an antibody? What are the functions of the different parts? What are 3 functions of antibodies? How is antibody diversity generated (4 things)?
Fab portion-binds antigen. determines idiotypes (which antigen it binds)-Heavy chain and light chain
Fc portion-constan. complement binding (closest to the Fab portion) and macrophage binding (furthest from Fab). Determines isotype
DIVERSITY
Random recombination of VJ (light) or V (D) J chains (heavy)
Random combination of heavy chains with light chains
Somatic hypermutation following antigen stimulation
Addition of NTs to DNA during recombination
FUNCTION
opsonization, neutralization, and complement activation
What antibodies to mature B cells express on their surface. Where does isotype switching occur? What are the functions/unique characteristics of IgG, IgA, IgM, IgD, and IgE?
Mature B cells express IgD and IgM. Isotype switching occurs in germinal centers
IgG is the main antibody in secondary delayed response to an antigen. Most abundant in serum. Crosses placent. Fixes complement. Opsonizes bacteria, neutralizes bacterial toxins and viruses
IgA prevents attachment of microbes to mucous membranes. Does not fix complement. It is a monomer in circulation but a dimer when secreted. It is produced in the GI tract (Peyers patches) and protects against gut infections (giardia). Released into secretions (tears, saliva, mucus) and breastmilk)
IgM is produced in the primary (immediate) response to antigen. It fixes complement. Does not cross the placenta. It is the antigen receptor on the surface of b cells. Monomer on B cell. Pentamer when secreted. Pentamer enables avid binding to antigen while humoral response evolves
IgD=unclear function
IgE=binds mast cells and basophils. Cross links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine. Mediates immunity to worms by activating eosinophils.