Immuno Flashcards
A 20-year-old man steps into an elevator full of people with influenza who are coughing and sneezing. The influenza viral particles that he inhales attach to respiratory epithelium, and viral infection reduces MHC class I molecules displayed on these epithelial cells. Which of the following immune cells is most likely to rapidly destroy the virally infected cells? A. CD4+ cell B. Dendritic cell C. Macrophage D. Natural killer cell E. Neutrophil
Natural killer cells are one of the first steps.
The lymph node
- Cortex- B-cell localization and proliferation. In outer cortex. 1° follicles are dense and dormant. 2° follicles have pale central germinal centers and are active.
- Paracortex- Houses T cells. Region of cortex between follicles and medulla. Contains high endothelial venules (HEV) through which T and B cells enter from blood. Look around, see if any pathogen is around and go right back out in lymph. You’re entire blood with circulating lymphocytes are traveling throughout the lymph nodes. I’ve got a receptor and I see something there on the APCs that I like, I stay and do my business. Underdeveloped in DiGeorge syndrome; enlarged in viral infection
- Medulla- Lymphocytes and plasma cells and medullary sinuses. Medullary sinuses communicate with efferent lymphatics. Where plasma cells develop.
- Naïve B and T cells enter T cell zone via holes in venules (HEV)
- Antigen from lymph drainage presented to receptive B and T cells. All other lymphocytes return to circulation via efferent lymph drainage
- B cells activate to make IgM localize to medullary cords (primary focus *this is where IgM is produced)
- Other activated B cells localize to follicle, expand and change antibody class (germinal center, IgG) - localization of complex to the germinal center to jack up things, the main antibody is IgG - class switching and lots of plasma cells are made.
- Plasma cells from germinal center leave lymph node via efferent lymph and travel back to bone marrow.
The spleen (immuno)
Only monitors the blood
- Red pulp (80% of spleen) with fenestrated sinusoids to filter out impurities and old RBCs. (just standard housekeeping process)
- White Pulp - T cells are found in the periarteriolar lymphatic sheath (PALS) and B cells are found in follicles. (antibodies against antigens, that has T cells. The T cells then present with the B cells in the are in between.
- Marginal zone - Between the red and white pulp, contains macrophages and specialized B cells, and is where antigen presenting cells (APCs) capture blood-borne antigens for recognition by lymphocytes. (it is like the paracortex) you will have internal production of antibodies
Splenic Dysfunction – Increased infections with encapsulated bacteria and lack of filtration of bad RBCs resulting in target cells and Howell-Jolly bodies: that is DNA remnant within the RBC that shouldn’t be there. When a nucleated RBC goes into the spleen and plucks it out, if it doesn’t work you will see nucleated RBCs which are Howell-Jolly body. Why is it important to vaccinate someone before you take out their spleen? Because you can die with encapsulated bacteria.
Adaptive immunity
Adaptive Immunity – Develops over time, and is highly-specific. Mediated by B, T and antibodies. Memory to a first exposure and subsequent exposure more robust. B cells develop in bone marrow; T cells develop in the thymus
Located in the anterior mediastinum, the thymus is derived from the 3rd pharyngeal pouch. Lymphocytes are of mesoderm origin.
Cortex (C) is dense with immature T cells; medulla (M) is pale with mature T cells and Hassall corpuscles containing epithelial reticular cells.
The thymus is hypoplastic in DiGeorge syndrome (no thymus) and severe combined immunodeficiency (SCID) - no T cells and thymus may be very small and enlarged in myasthenia gravis. Part of the treatment for MG is remove the thymus
Positive selection in the thymus occurs when thymocytes express functional versions of which critical molecule? A. CD28 B. Fc receptor C. MHC class I D. MHC class II E. T-cell receptor (TCR)
TCR
Immature T cells (double-psotive or CD4+ CD8+) interact with MHC class I and II-positive thymic epithelial cells. Following this interactio nthe T cells assume single postiive status either CD4 or CD8 expression. CD28 is a T cell surfae molecule involved in costimulation signals; however, it is not relevant for positive selection. Fc receptors and MHC class I molecules are expressed by T cells, but Fc receptors serve as a means to interact with antibodies and MHC to present antigens to other T cells. T cells do not express MHC class II molecules
MHC 1 vs MHC II
MHC1
HLA-A, B, C
TCR and CD8 binding
Expressed on all nucleated cells (not RBCs)
-presents endogenously synthesized antigens to cytotoxic T cells
-antigen peptides loaded onto MHC I in RER
-B2-microglobulin
HLA-DP, DQ, DR
TCR and CD4 binding
Expressed on APCs
-presents exogenous antigens to helper T cells
-antigen loaded following release of invariant chain in an acidified endosome
-invariant chain
The acidification of lysosomes within antigen-presenting cells is prevented in experimental settings. The affected cells show impaired interaction with T lymphocytes upon antigen exposure. The observed effect most likely results from a low cell surface expression of which of the following molecules?
A. MHC Class I B. MHC Class II C. T-cell receptor D. Integrins E. Cytokine receptors
MHC II is used to present environmental antigens on APCs. Material such as bacteria, viruses or freely circulating antigenic protein is taken up by APCs and degraded by acidification after endosome-lysosome fusion. Concurrently, MHC II molecules are synthesized in the rough ER and routed to the endosomes by the golgi apparatus. Each MHC class II has an invariant chain bound to its antigen binding site. This peptide fragment acts to guide the MHC class II molecule during sorting and removed by acid when fused to phagolysosome. The endogenous MHCI pathway has no invariant chain and acidification is not necessary.
The 4 Helper T cells starting with TH0 and their functions
Th0 > induced by… You need to memorize these
- IL-12 > Th1 > (IL-2, IFN-gamma) > cellular immunity, intracellular pathogens, autoimmunity
- IL-4,10 > Th2 > (IL-4,5,10,13) > humoral immunity, allergy, parasites
- IL-6, TGF-beta > Th17 > IL-17, 21,22 > innate immunity, autoimmunity
- TGF-beta > Treg > TGF-beta, IL-10 > immunosuppression
Macrophage- lymphocyte interaction
Macrophages and other APCs release IL-12, which stimulates T cells to differentiate into Th1 cells.
Th1 cells release IFN-γ to stimulate macrophages and CTLs.
IFN-γ also suppresses the Th2 response.
Macrophages also secrete IL-6 that activates Th17 T helper cells (chronic inflammation link to autoimmunity).
Macrophage-Lymphocyte Interaction is Important for Chronic Inflammation
When you have TH1 you don’t have Th2
There is also a feedback loop, IFN-gamma stimulates macrophage which makes more IL-12 and more TH1 cell, cycle of activation and suppressing humoral immunity
A 3-month-old girl is brought to the emergency department with fever, irritability, and vomiting for the past 2 days. On examination, she is ill-looking, lethargic, and febrile. Blood cultures grow Mycobacterium tuberculosis. One of her brothers died from disseminated M. tuberculosis during infancy. Impairment of which of the following protective mechanisms is most likely contributing to this patient’s infection
A. Antibody production B. Complement production C. IL-12 signaling D. lsotype switching E. Leukocyte adhesion
IL-12 deficiency. Host defense against mycobacterial infections depends on the interactions between macrophages and T cells. Macrophages infected with mycobacteria produce IL-12 which in turn stimulates T cells and NK cells to produce IFN-gamma. IFN-gamma then binds to its receptor on macrophages and promotes mycobacterial killing by phagocytes.
If this was not Mtb then you can’t exclude antibody things.
Th2 response to type 1 hypersensitivity
Classic Th2 Response is the Type I Hypersensitivity Reaction
Dendritic cells present antigen to naïve T cells and in the presence of local IL-4, differentiate into Th2 cells. IL-4 from Th2 cells acts on B cells to stimulate class switching to IgE (and IgG).
IL-5 activates eosinophils and IL-13 enhances IgE production and stimulates mucus secretion (not shown).
IL-10 from Th2 cells blocks macrophages and the Th1 response
Sensitization of Naive B cells
- B-cell receptor–mediated endocytosis (IgM).
- Foreign antigen is presented on MHC II and recognized by TCR on Th2 cell.
- CD40 receptor on B cell binds CD40 ligand (CD40L) on Th2 cell.
- Th2 cell secretes cytokines that determine Ig class switching of B cell. Make IL’s to make B cells that make circulating antibodies. IgG, IgE, IgA
- B cell activates and undergoes class switching, affinity maturation, and antibody production.
A 10-month-old male with a history of recurrent, serious extracellular bacterial infections is hospitalized with a new pneumonia. An immunologic workup reveals neutropenia, normal numbers of T and B cells, normal complement levels and activity, elevated IgM and very low IgG and IgA. What immunologic function is impaired in the child and best explains the infection in the above case?
A) B cell development in the bone marrow
B) B-cell migration to follicles in secondary lymphoid tissue
C) T cell development in the thymus D) Expression of functional antigen receptors on T cells
E) T-cell mediated class switching in B cells
Answer is E.
This case is descriptive of hyper-IgM syndrome, a disease whose molecular defect is caused by mutations in the gene for CD40 ligand. The fact that the patient has elevated IgM and very low levels of IgG and IgA suggests that the T cells cannot interact adequately with B cells to induce class switching. In addition to cytokine stimuli the interaction of CD40 on the B cell with CD40 ligand on the T cell is essential to stimulate class switching in B cells. The neutropenia may be due to the increased phagocytic activity to compensate for the lack of antibodies
Response to viral infection
1. Endogenously synthesized antigen is presented by infected cells to cytotoxic CD8+ T precursor lymphocytes (pCTLs) 2. Exogenous antigen is presented by dendritic cells or by B cells (surface IgM is the antigen receptor). • A Th1 response produces IL-2, and IFN- γ, which activate pCTLs into memory or effector CTLs. Effector CTLs directly kill infected cells by the production of perforins and granzymes. • A Th2 response produces B cell stimulating cytokines (IL-4,5,6,10, and TGF−β) that differentiate naive B cells into memory B cells and plasma cells. The latter produces large amounts antibodies that prevent further virus infection.
In an experiment, antigen is used to induce an immediate (type I) hypersensitivity response. Cytokines are secreted that are observed to stimulate IgE production by B cells, promote mast cell growth, and recruit and activate eosinophils in this response. Which of the following cells is most likely to be the source of these cytokines?
A. CD4+ lymphocytes B. Dendritic cells C. Macrophages D. Natural killer cells E. Neutrophils
Answer is A
CD4+ lymphocytes of the Th2 type are essential to the induction of type I hypersensitivity because they can secrete cytokines such as IL-4, 5 which are required for the growth, recruitment and activation of mast cells and eosinophils.
Antibody
Fab Region- antigen binding Fc Region- C-terminal, Complement binding (on IgM and IgG), Constant, Carbohydrate, Classifies isotype (IgG, IgA etc.)
Diversity and Specificity
- Variable recombinant of VJ (light) and VDJ (heavy) genes.
- Variable combinations of light and heavy chain.
- Somatic hypermutation in variable region to increase antigen affinity and specificity - the lymph node - germinal centers (make IgM in the paracortex, makes some antibody. But to make better antibody, hypermutation takes that B cell and starts to make FaB region, when someone bind even better to the antigen continue to survive)
- Isotype switching - also in germinal center
Functions of Ab: opsonization, neutralization, complement activation.
All the antibodies
IgG, IgA, IgM, IgD, IgE
IgG- Most abundant isotype in serum and in 2° (delayed) responses. Fixes complement, crosses the placenta (passive immunity for infant), opsonizes bacteria, neutralizes bacterial toxins and viruses.
IgA- Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement. Monomer (in circulation) or dimer when secreted with J chain (made in epithelium and protects Fc region against gut proteases). Produced in Peyer patches and protects against gut infections (e.g., Giardia). Most produced antibody overall, but has lower serum concentrations because released into secretions and breast milk.
IgM- Produced in the 1° (immediate) response to an antigen. Fixes complement but does not cross the placenta. Monomer on B cell, pentamer with J chain when secreted. Pentamer enables avid binding to antigen while humoral response evolves. IgD- Found on surface of many B cells and in serum. Function?
IgE- Binds mast cells and basophils; cross-links when exposed to allergen, mediates immediate (type I) hypersensitivity and immunity to worms by activating eosinophils. Lowest concentration in serum.
A person is experiencing a primary infection with the virus. B cells activated in a primary infection secrete which class of antibody first? A. IgA B. IgD C. IgE D. IgG E. IgM
IgM - the first antibody isotype produced by B cells, is IgM. That is the first type of B cell antigen receptor. IgA is the isotype of antibody synthesized and secreted primarily in the mucosa. IgD is an isotype of antibody found in the blood in low levels and its exact function is unknown. IgE is an isotype produced to mediate antibody-dependent cell cytotoxicity of parasites. it binds to Fc receptor on eosinophils, basophils, and mast cells and upon antigen binding results in granule release. IgG is the highest concentration of antibody in the serum, mediates complement activation, opsonization and can cross placenta to protect fetus
A person develops a viral infection and both T and B cells become activated to fight the infection. In which way is antigen recognition by B cells different from antigen recognition by T cells? A. B cells first travel to the lymph node follicle where they recognize the antigens trapped
by helper T cells B. B cells undergo receptor editing to change receptors that fail to bind to an antigen C. B cells utilize membrane immunoglobulin molecules to bind to antigen in its natural
state D. The antigen receptors on a single B cell have a broad specificity, and are able to
recognize several chemically unrelated antigens
C. CD4+ and CD8+ T cells can only respond to antigens once they have been processed and loaded onto MHC and displayed by antigen presenting cells. B cells recongize antigens directly. B cells traffic to the paracortex of the lymph nodes to interact with helper T cells. This interaction involves CD40 ligand CD40 which promote B cell expansion as plasma cells. Once receiving the CD40 signal the B cells traffic back into the lymphoid follicle and form a germinal center
A is true but B cell and T cells both do this so it is not a difference
Complement
C3a, C5a - anaphylaxis; C5a - neutrophil chemotaxis; C5b-9 -cytolysis by MAC.
Opsonins—C3b and IgG are the two 1° opsonins in bacterial defense to enhance phagocytosis. C3b also helps clear immune complexes.
Inhibitors—decay-accelerating factor (DAF, aka CD55) and C1 esterase inhibitor help prevent complement activation on self cells such as RBCs
A workup on an ill child revealed low levels of complement C3 in her blood. Which one of the following presentations did this child most likely manifest?
A. Immune hemolytic anemia B. Incomplete recovery from viral infections C. Poor response to vaccination D. Recurrent infections with extracellular bacteria
D
Complement proteins function in innate immunity through enzymatic cleavage of C3 to liberate C3b which directly binds to the pathogen surfaces. Following C3b insertion, enzyme cascade events result in lysis of the target cell by the membrane attack complex (complement protein scaffold C5-C9) and recruitment of phagocytes by C3a and C5a cleavage products
An 18-year-old female college student is hospitalized because of high fever, headache, and skin rash. She has a history of recurrent infections, including bacterial meningitis 6 months ago that was successfully treated with ceftriaxone. She takes no medications at home and denies recent travel. Her temperature is 39.1° C (102.4° F), blood pressure is 104/70 mm Hg, and pulse is 110/min and regular. Physical examination reveals a petechial rash on the trunk and extremities, including the palms and soles. Neurologic examination shows lethargy but an ability to follow commands. She has evidence of neck stiffness and photophobia. Which of the following immune system impairments is the most likely explanation for her symptoms?
A. Pure T-cell dysfunction B. Ineffective intracellular killing C. Selective lgA deficiency D. Inability to form the membrane attack complex
D. inability to form the membrane attack complex - meningitis - (**recurrent meningitis)
A. pure T cell dysfunction - DiGeorge
B. ineffective intracellular killing - CGD infections with catalase positive organisms
C. selective IgA deficiency - infection of sinuses and lungs, meningitis not found
A 26 year old female with a history of epistaxis and menorrhagia. She takes no medications or herbal substances. Her mother reports similar complaints. She most likely suffers from a defect in
A. Platelet aggregation B. Coagulation C. Antithrombin D. Fibrinolysis
A)
this patient most likley suffers from von Willebrands disease which affect 1-2 percent of general population
A 8 year old male presents with knee pain and has a history of hemarthoses. He has one uncle with a similar condition. He most likely suffers from a defect in
A. Platelet aggregation B. Coagulation C. Antithrombin D. Fibrinolysis
B. This patient most likely suffers from Hemophilia A, a X linked recessive condition resulting from factor VIII deficiency. Coag diseases tend to cause deep bleeding like into a joint space
