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USMLE Step 1 Immunology

Subjects : health-sciences, usmle-step-1

Instructions:

Answer 50 questions in 15 minutes.
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Match each statement with the correct term.
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This is a study tool. The 3 wrong answers for each question are randomly chosen from answers to other questions. So, you might find at times the answers obvious, but you will see it re-enforces your understanding as you take the test each time.

1. Which MHC presents intracellular peptides? how so?
Isotype switching (activated by Th2 cell signals and cytokines) - somatic hypermutation
Periarteriolar lymphatic sheath in the white pulp that surround that dead end of the capillaries in the red pulp - contain T cells
MHC I; from RER with help of the B2 microglobulin
Severe recurrent pyogenic sinus and resp tract And increased susceptibility to type III hypersensitivity like SLE

2. So antibodies are the effectors for the humoral response. List some of their functions.
pale central germinal centers
Cross link antigens which increases their phagocytability; activate complement for MAC attack; opsonization; neutralization
Make antibody - allergy type 1 (igE) - Cytotoxic and immunecomplex hypersensitivity type II and III (igG); hyperacute organ rejection is Ab mediated
Anticentromere; anti Scl -70 (anti DNA topoisomerase I)

3. What is a type I hypersensitivity reaction? What is atopic?
An anaphylactic immediate reaction; atopy refers to the inherited propensity to develop asthmatic or allergic reactions
Defect in CD40L results in inability to class switch; a lot of IgM and no IgG - A - E
In IgE AIHA- it results in MAC attack (remember IgE is not an opsonin!) - in IgG AIHA C3b (and IgG) opsonization results in phagocytosis by fixed macrophages in the spleen
Anticentromere; anti Scl -70 (anti DNA topoisomerase I)

4. Describe the Mannose Lectin pathway
Found in the red pulp; contains the cords of billroth or the splenic parenchyma that have APCs/Macrophages that closely interact with the basement membrane of the vasculature and where RBCs squeeze through into the parenchyma and interact with Macrop
Negative!
Some microbial surfaces (only) have mannan binding lectin which activates a protease that cleaves C2 and C4 which combine to make C3. the rest follows the alternative pathway
Anti SS- A (anti RO) and Anti SS- B

5. What is the common variable immunodeficiency ? How is it different from Brutons?
Basophils! THey want IG E class switch!
Steroid responsive nephrotic syndrome
Defect in B cell maturation; idiopathic - presents at older age and normal number of B cells and hyperplastic germinal centers because B cells can be activated but can not produce Abs
Suppresses immune response (also specifically Th1 cells) and activates Th2; regulatory T cells

6. what cell surface proteins are on all APCs?
CROSS LINK Beta region on TCR of CD4 cells to the MHC class II on APCs this results in uncoordinated release of Interferon gamma from CD4 Th1 cells and subsequent release of IL1 - IL6 and TNF alpha from Macrophages --> toxic shock syndrome; s. pyogen
MHC II - B7
Delayed type hypersensitivity
Glycoproteins; HLA

7. To what disease do the autoantibodies to IgG (rheumatoid factor)?
Rheumatic arthritis
Cell mediated due to T cell cytotoxicity reacting to foreign MHCs; few weeks after
Recurrent infections to every type of antigen; bone marrow transplant (be weary of GVH disease!)
A B and T cell disorder; X linked recessive; progressive deletion of B and T cells; thrombocytopenic purpura - infections - eczema; high IgE and IgA but low IgM

8. What is the late phase reaction of anaphylaxis allergy? what mediates it?
IL 3; supports growth and differentiation of bone marrow stem cells
Hours later (instead of minutes); instead of release of preformed mediators - mast cells synthesize PGs and LTs that mediate the late phase reaction (edema - inflammation - decreased airflow)
Wiskott Aldrich syndrome
IgM or IgG antibodies coat the antigen and result in activation of MAC complex via the classical pathway OR fixed macrophages in the spleen phagoctyose the opsonized (C3b or igG) antigens - ex penicillin reaction; IgM AIHA - anti B IgMs in a group A

9. What is the clinical use for sirolimus? what should you combine it with?
IL 4
Internal iliac
Immunosuppression after kidney transplantation in combination with cyclosporine and corticosteroids
Since cant cross placenta most likely means that child was forced early to produce due to an infection (most likely CMV)

10. To what portion of the Antibody do the complements bind?
Fc
MHC I; from RER with help of the B2 microglobulin
Coarse Faces - cold (noninflamed d/t inability to attract neutrophils) staph abscesses - retained primary teeth - high igE - dermatologic problems (eczema)
Closed circuit where go directly to veins and open where squeeze out of capillary sinusoids and interact with either PALS or with macrophages in the cords of Billroth (for antigen immune function or for blood cleaning or for both) and squeeze back in

11. What is the defect in Leukocyte adhesion defect? What is the presentation? What are the labs?
MHC class molecules bind to KIRS or CD94 to prevent killing
1) VJ light chain random creation 2) VDJ (heavy chain) random creation 3) random combination of light with heavy 4) somatic hypermutation (high frequency mutating that occurs on activation) 5) terminal deoxynucleotidyl transferase (TDT) random additi
Defect in LFA 1 integrin (CD 18) protein on phagocytes (neutrophils!); recurrent bacterial infections - severe gingivitis - poor wound healing - absent pus formation - and delayed separation of the umbilicus; neutrophilia
Viral neutralization of igM and IgG!

12. Give three examples of bacteria that use antigenic variation and how.
Salmonella - 2 flagellar variants; Borrelia (relapsing fever); and Neisseria gonorrhoaea - pilus protein
Anti smooth muscle
NK cells
Severe recurrent pyogenic sinus and resp tract And increased susceptibility to type III hypersensitivity like SLE

13. ________ regulate the cell mediated response.
Proteins; IgG - IgM - endotoxin (microbial surfaces in general - nonspecific ones also) - mannose binding Lectin; classic - alternative - MB pathway (resp)
Antimicrosomal and antithyroglobulin
Humoral
MHC class molecules bind to KIRS or CD94 to prevent killing

14. Type IV hypersensitivity is i...
not Ab mediated
acute phase reactants
Paracortex; viral infection
Antihistone

15. What are the autoantibodies for wegeners granulomatosis?
In IgE AIHA- it results in MAC attack (remember IgE is not an opsonin!) - in IgG AIHA C3b (and IgG) opsonization results in phagocytosis by fixed macrophages in the spleen
C - ANCA (antiproteinase); in neutrophil; c= cytoplasmic
IL 1 - IL 6 - IL 12 - TNF alpha; IL 6- Th2 cells; IL 12- B cells
Axillary

16. What are the two signals required for T cells? what happens after?
MHC I/CD8 and IL2/IL 2 Receptor (IL 2 is from Th1!); cytoxicity!
Periarteriolar lymphatic sheath in the white pulp that surround that dead end of the capillaries in the red pulp - contain T cells
Delayed type hypersensitivity
When you select for which MHC it will have; take out the lymphs that self react

17. Often bacteria are associated with being killed by humoral immunity. Name some bugs that require cell mediated immunity because they evade humoral response
By transcytosis
Legionella - N. gonorrhea - L. monocytogenes - viruses - protozoa (leismaniasis)
Recurrent infections to every type of antigen; bone marrow transplant (be weary of GVH disease!)
Activates Th1 helper cells; Macrophages

18. A lymph node is a ________ lymphoid organ.
Alternative splicing of mRNA
mesenchymal
CGD; Jobs syndrome (defect in Neutrophil chemotactic response)
secondary

19. The ______ in the BM are DN - the DP are in the cortex of thymus
Maculopapular rash (palm - soles - back - neck) - jaundice with bile duct necrosis - hepatosplenomegaly - diarrhea; bone marrow and liver transplants (rich with lymphocytes); SCID patient receiving whole blood transfusion
T cell precursor
It is a localized type III hypersensitivity reaction to an external antigen; localized instead of systemic; ?; intradermal injection of the antigen results in antibody production and antigen antibody complexes deposit in the skin
Psoriasis - Ankylosis Spondylitis - IBD - Reiters; all seronegative spondylopathies

20. which cells have more complete tolerance - B or T cells?
C - ANCA (antiproteinase); in neutrophil; c= cytoplasmic
When you select for which MHC it will have; take out the lymphs that self react
T
Make antibody - allergy type 1 (igE) - Cytotoxic and immunecomplex hypersensitivity type II and III (igG); hyperacute organ rejection is Ab mediated

21. What is the marginal zone of the spleen? what happens there?
Recurrent infections to every type of antigen; bone marrow transplant (be weary of GVH disease!)
mesenchymal
Found in the red pulp; contains the cords of billroth or the splenic parenchyma that have APCs/Macrophages that closely interact with the basement membrane of the vasculature and where RBCs squeeze through into the parenchyma and interact with Macrop
Leukocyte adhesion defect; ataxia telangietasia; ataxia telangiectasia; chediak higashi syndrome; IgA def; Digeorge syndrome; Jobs; Chediak Higashi

22. What is the symptoms involved in graft versus host disease? it What transplant cases does it usually occur? give an example
Since it is a comp dependent type II hypersensitivity reaction; C3a brings anaphylotoxins that bring in mediators of shock
A j chain
Maculopapular rash (palm - soles - back - neck) - jaundice with bile duct necrosis - hepatosplenomegaly - diarrhea; bone marrow and liver transplants (rich with lymphocytes); SCID patient receiving whole blood transfusion
Recurrent sinopulmonary bacterial infections after 6 months (d/t mothers igGs transplacental) due to opsonization defect

23. What is the main function of IL 12? other than macrophages who else can release IL 12?
By transcytosis
carboxy terminal
Induce differentiation of T cells into Th1 helper cells and activates NK cells also; B cells
Negative selection

24. For which toxins are preformed antibodies (passive) given?
Histamine; post capillary venules - vasodilation
Tetanus - Botulinum - HBV - Rabies
Axillary
No! That is why they are different from T cells - they can recognize antigens in free solution; if a bug has a peptide fragment that a mature naive B cell recognizes it will bind to it and cause activation - it then gets activated into a plasma cell!

25. other than eat and bite RBCs what else do Macrophages of spleen do>
Severe pyogenic infections early in life
An alpha chain and a B2 microglobulin; on all nucleated cells; TCR and CD8; intracellular antigens
...
Remove encapsulated bacateria

26. What lymph node drains the scrotum?
No! That is why they are different from T cells - they can recognize antigens in free solution; if a bug has a peptide fragment that a mature naive B cell recognizes it will bind to it and cause activation - it then gets activated into a plasma cell!
B - T - and NK cells
Its main effect is a defect in Ab opsonization for killing
Superficial inguinal

27. Which disease is associated with HLA A3?
T cell and antibody mediated vascular damage due to MHC non self being recognized as self by self lymphocytes and resulting in attack of the foreign antigens it presents (all of them); months to years after; no :(
Hemochromatosis
A B and T cell disorder; defect in DNA repair enzymes; ataxia - telangactasia and IgA def; igA def. and increased AFP
Bind FcG for antibody dependent cellular cytotoxicity

28. Which disease is associated with DR3?
Thrombocytopenia
P - ANCA (antimyeloperoxidase); in neutrophil; p= perinuclear
not Ab mediated
DM type I

29. From where do cytokines come from?
DAF and C1 esterase inhibitor on cells prevent complement activation on their surfaces (microbial surfaces lack this)
Adenosine deaminase deficiency (AR) - defective IL 2 receptor (X linked) - and failure to synthesize MHC II; both humoral and cell mediated deficiency
T cell and antibody mediated vascular damage due to MHC non self being recognized as self by self lymphocytes and resulting in attack of the foreign antigens it presents (all of them); months to years after; no :(
Lymphocytes

30. What cytokines do macrophages release? who else can secrete IL 6? IL 12?
The antibodies (igM or IgG) either neutralize the target directly (cytoxic!) or recruit leukocytes (Neutrophils and Macrophages!) to incite tissue damage
Hereditary angioedema; PNH
Cell mediated due to T cell cytotoxicity reacting to foreign MHCs; few weeks after
IL 1 - IL 6 - IL 12 - TNF alpha; IL 6- Th2 cells; IL 12- B cells

31. What are the four steps in phagocytosis? What are the four disease that correspond to each step?
Opsonization (Brutons agammaglobulinemia) - adhesion (Leukocyte adhesion defect) - phagocytosis (chediak higashi syndrome) - respiratory burst (chronic granulomatous disease)
Defect in BTK a tyrosine kinase gene; failed maturation of B cells; X linked recessive
TNF alpha and IL1
Local infection/inflammation; infection of the ln itself; metastasis

32. What are some catalase positive organisms?
Fab portion
Superficial inguinal
S. aureus - E. Coli - aspergillus
Mediates septic shock; activates the endothelium for adhesion and dilation and leukocyte recruitment results in vascular leak

33. What is the pathogenesis of acute transplant rejection? When does it occur?
RNA segment reassortment
HBV - HBC - Kaposis - leukemias - malignant melanoma - hairy cell leukemia and condyluma accuminata
Cell mediated due to T cell cytotoxicity reacting to foreign MHCs; few weeks after
isotype

34. What are the three types of lymphocytes?
B - T - and NK cells
IgM and IgA
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate; yes! with immunosuppressants
cannot cross placenta

35. What is the main function of TNF alpha? How does it do this?
Anti TSh receptor
Digeorge syndrome - 22q11 deletion resulting in failure to develop 3rd and 4th pharyngeal pouches; cardiac and great vessel congenital defects - tetany from hypocalcemia - recurrent viral/fungal infections from T cell deficiency; hypoPTH - hypoCa - a
...
Mediates septic shock; activates the endothelium for adhesion and dilation and leukocyte recruitment results in vascular leak

36. How does igA cross the epithelium?
Lack of response from lymphocytes when activated; because they are self reactive - this is a form of tolerance
Cyclosporine and tacrolimus; sirolimus (as well as hyperlipidemia)
Edema and necrosis in that region
By transcytosis

37. What is serum sickness? give an example.
Salmonella - 2 flagellar variants; Borrelia (relapsing fever); and Neisseria gonorrhoaea - pilus protein
Antidote for digoxin intoxication
Type III hypersensitivity where an exogenous antigen results in a systemic antigen antibody complex disease (takes around 5 days after exposure for the Abs to develop); immune complexes then fix in tissue and activate complement resulting in tissue d
type four

38. what ensure that a memory response is generated?
An anaphylactic immediate reaction; atopy refers to the inherited propensity to develop asthmatic or allergic reactions
If there is class switching and plasma cell production (that is when memory cells are produced)
CROSS LINK Beta region on TCR of CD4 cells to the MHC class II on APCs this results in uncoordinated release of Interferon gamma from CD4 Th1 cells and subsequent release of IL1 - IL6 and TNF alpha from Macrophages --> toxic shock syndrome; s. pyogen
Since it is a comp dependent type II hypersensitivity reaction; C3a brings anaphylotoxins that bring in mediators of shock

39. What is the presentation of common variable immunodef? and What are the labs?
DM type I and RA
Viral neutralization of igM and IgG!
Can be acquired in 20s -30s; increased risk of autoimmune disease - lymphoma - Sp infections; normal number of B cells and no plasma cells and immunoglobulin
IL 5

40. What are complements in the complement system? What activates them? there seems to be different ones - What are these pathways called?
Glycoproteins; HLA
IgA; sinus and lung infections from lack of secretory defense - milk allergies and diarrhea from giardiasis; Anaphylasix on exposure to blood products with igA
Mycobacterium Tuberculosis - Mycobacterium Avium Intracellulare; Toxoplasmosis Gondii
Proteins; IgG - IgM - endotoxin (microbial surfaces in general - nonspecific ones also) - mannose binding Lectin; classic - alternative - MB pathway (resp)

41. What lymph node drains the thigh?
P - ANCA (antimyeloperoxidase); in neutrophil; p= perinuclear
Superficial inguinal
Severe recurrent pyogenic sinus and resp tract And increased susceptibility to type III hypersensitivity like SLE
Axillary

42. What does interferon gamma do? What two type of cells does it attack mostly?
Activates Macrophages and Th1 cells; suppresses Th2 cells; antiviral and antitumor
Immunosuppression after kidney transplantation in combination with cyclosporine and corticosteroids
Cytokine release syndrome due to initial release from initial binding (fever etc) and hypersensitivity reaction
HBV - HBC - Kaposis - leukemias - malignant melanoma - hairy cell leukemia and condyluma accuminata

43. What are the main symptoms of T cell immunodeficiencies?
not Ab mediated
IgE; by activating eosinophils
Intracellular pathogens (acute and chronic viruses and virally induced cancers)
C5a

44. What is the main function of IL 8?
A chemotactic factor for neutrophils
Thrombocytopenia
Normal pro B (CD 19 +) - no mature B cells results in decreased total B cell level - and decreased amount of immunoglobulins in each class
Its main effect is a defect in Ab opsonization for killing

45. What is a factor that is a predictor for a bad transplantation?
dimer
If there is class switching and plasma cell production (that is when memory cells are produced)
Capsule of lymph node is made up of type III collagen (made by reticulin fibers!) - extension of this collagen extends into the splenic tissue as trabeculae; nonspecific filtration of lymph by Macrophages - Antibody production (via activation) - stor
Patient has had previous exposure to blood products which result in presence of preformed anti HLA cytotoxic Abs

46. Name 5 ways Antibody diversity is generated?
Receiving preformed Antibodies
Daclizumab; prevent ACUTE rejection of renal transplant
1) VJ light chain random creation 2) VDJ (heavy chain) random creation 3) random combination of light with heavy 4) somatic hypermutation (high frequency mutating that occurs on activation) 5) terminal deoxynucleotidyl transferase (TDT) random additi
It is a localized type III hypersensitivity reaction to an external antigen; localized instead of systemic; ?; intradermal injection of the antigen results in antibody production and antigen antibody complexes deposit in the skin

47. What does granzyme do? who secretes it?
Soluble C3 spontaneously hydrolyzes spontaneously to C3b and opsonizes microbial and host cell surfaces and accumulates on surfaces; C3b activates C5 convertase which leads to MAC activation
Pernicious Anemia and Hashimotos
IgG
Its a serine protease that activates apoptosis; NK and CD8

48. What is the defect in hyper IgM syndrome? What are the lab results?
Legionella - N. gonorrhea - L. monocytogenes - viruses - protozoa (leismaniasis)
Defect in CD40L results in inability to class switch; a lot of IgM and no IgG - A - E
type four
Scratch test - histamine mediated wheal; radioimmunosorbent assay (detects specific IgEs in serum)

49. What are the PALS?
Periarteriolar lymphatic sheath in the white pulp that surround that dead end of the capillaries in the red pulp - contain T cells
Both decrease cd8 tcell prolif but one through mtor and the other through calcineurin (resp)
Cell mediated due to T cell cytotoxicity reacting to foreign MHCs; few weeks after
Adenosine deaminase deficiency (AR) - defective IL 2 receptor (X linked) - and failure to synthesize MHC II; both humoral and cell mediated deficiency

50. where do NK cells develop?
Not thymus - BM
They directly stimulate Macrophages by binding CD14; also the alternative complement pathway binds to these host surfaces and induces MAC complex; also TLRs exist for endotoxins; also IgM though not an opsonin can act as a pentamer and trap the antig
Yes
Anti U1 RNP (ribonucleoprotein)