SAS/Review Flashcards
A patient receives a 10/10 HLA matched kidney from a relative. After 8 months the kidney function starts to decline and biopsy demonstrates chronic inflammation and arteriosclerosis (thickening/hardening of the vessels). Which cells mediate this process?
CD4+ helper T-cells, macrophages
This is chronic rejection; it takes months to years, and is associated wtih hardening and thickening of vessels and arteriosclerosis
Central CD4+ T-cell tolerance occurs in which of the following tissues?
E - the thymus
Central tolerance occurs in thymus through negative selection; T-cells with high affinity for self peptides presented by MHC undergo apoptosis or become TRegs
26-year-old woman returns from a safari vacation in Tanzania with fever and body aches. She received no vaccines prior to her trip and did not take malaria prophylaxis. Her blood smear is shown. What infection does she have?
A. Plasmodium falciparum
B. Plasmodium vivax
C. Trypanosoma cruzi
D. Leishmania donovani
A. Plasmodium falciparum
Infects many RBCs, causes clumping of RBCs
- P. vivax* does not cause clumping, infects <2% of RBCs (reticulocytes only)
- Trypanosoma* would be in its wiggly form (trypomastigote) in the blood
- Leishmania* don’t live in the blood
Which complement protein is good at opsonizing bacteria?
C3b
You are treating a 35 year old patient with shingles.
What illness did this patient likely have as a child?
What is unusual or concerning about this presentation?
The patient likely had chicken pox (Varicella zoster virus) as a child; shingles is a reactivation of VZV
The presentation of shingles in this patient is concerning because they are young; VZV usually re-activates when the patient’s T-cell function is less than optimal, which happens naturally with age.
Because the patient is young, we might suspect a pathology that is suppressing the function of T-cells
What does it mean if an organism is oxidase positive?
Which organisms are oxidase positive?
Oxidase positive = has cytochrome C in cell membrane = all are aerobic (either strict or facultative)
- Pasteurella
- Pseudomonas Aeruginosa
- Campylobacter
- Vibrio
- Helicobacter
- Neisseria
List some of the relevant encapsulated organisms
SCHENK-PB
- Streptococcus pneumoniae
- Cryptococcus neoformans
- Haemophilus influenzae
- E. coli (some)
- Neisseria meningitidis
- Klebsiella pneumoniae
- Pseudomonas aeruginosa
- Bacillus antrhacis
Which cytokines induce Th2 T cells?
What are the major cytokines produced by Th2 T cells?
What does this trigger?
What is the result?
Th2 cells are induced by IL-4
Th2 cells produce IL-4, IL-5, IL-13
This triggers stimulation of IgE, production/activation of mast cells and eosinophils
-> Host defense against helminthic parasites
~but may cause~
-> Allergies; allergic rhinitis, anaphylaxis, asthma (mediates class switching to IgE)
Which immune component mediates chronic organ rejection?
What is the time scale?
Which antigens are causing problems?
CD4+ helper T cells, macrophages
Months/years
MHC minor proteins
(Characterized by hardening/thickening of vessels, arteriosclerosis)
Which cells express CTLA-4?
What does CTLA-4 do in the body?
TRegs express CTLA-4
B7 on APCs binds CTLA-4
- This blocks costimulation by blocking CD-28 on T-cells from binding to B7
- This dampens the Th2 CD4+ T cell response, thus inhibiting IL-2 secretion
Which component of the immune system is particularly important in fighting fungal infections?
- Th17 CD4+ helper T cells
- Secrete IL-17 -> Promote neutrophilic inflammation
- Respond to extracellular pathogens (like fungus)
- IgA
- Can dimerize and cross epithelium of the gut; fight the organism before it even enters the cells of the body
Which fungus is most likely to cause meningitis?
Cryptococcus
A patient has a history of recurrent infections, many of which are pyogenic and/or granulomatous
Notable organisms include serratia marcescens and staph. aureus
Defects in which immune cells are suspected?
Neutrophils;
This pattern is indicative of a failure to kill organisms that have been phagocytosed;
- A defect in NAPDH oxidase would result in persistent, abscess forming infections, especially from catalase (+) organisms
- Catalase breaks down hydrogen peroxide, preventing the formation of hypochlorite ion; an oxidative burst is needed to kill them
Which antibodies, prescribed in cancer treatment, would enhance T-cell activation?
What are the possible consequences?
Anti-PD-1, anti-CTLA-4 antibodies enhance T-cell activation
Potential problem = loss of peripheral tolerance -> autoimmune response
List the relevant obligate intracellular pathogens
- Viruses
Bacteria: Really, Check your Cox My People (it’s an obligation)
- Chlamydia
- Rickettsia
- Coxiella
- Mycobacterium leprae
- Plasmodium
Parasites - Toxic Toilet Paper = LeManiacsCrying
(they can’t stop, they have to cry)
- Toxoplasma
- Trypanosoma
- Pneumocystis
- Cryptosporidium
- Leishmania
What does IFN-gamma do?
Stimulates phagocytosis by macrophages
Increases expression of MHC I and MHC II
Promotes Th1 response
Inhibits Th2 response
What are the symptoms of antibody deficiency?
Infection with pyogenic bacteria (Staphylococcus aureus, streptococcus pneumoniae)
Which fungi are associated with pneumonia?
* = Fungi that can infect healthy people (others typically infect immunocompromised)
- Histoplasma*
- Blastomyces*
- Coccidioides*
- Aspergillus
- Pneumocystis
- agents of mucormycosis
Increased susceptibility to Neisseria is asosciated with deficiencies in which components of the immune system?
Complement proteins from C5-C9; deficiencies of these complement proteins prevent the formation of the membrane-attack complex (MAC) (via the classic pathway) that is required to kill neisseria
Deficiencies in Factor D and properdin, required for the alternate complement pathway, also result in increased risk of Neisserial infections
Infections are likely to be recurrent and invasive
What are the major risk factors for Clostridium botulium infection?
Home-canned foods (everyone; spores germinate in the can)
Honey (babies; the spores can germinate in the baby)
Causes flaccid paralysis
What does TNF-alpha do?
Proinflammatory cytokine
Many effects!
What is the clinical presentation of a neutrophil defect?
Abscesses of skin, soft tissue lymph nodes, bone, and liver
(S. aureus, Klebsiella spp)
Which agent is used to treat pneumocystis?
Trimethoprim-sulfamethoxazole
Although pneumocystis is a fungus, it must be treated wtih trimethoprim-sulfamethoxazole; other anti-fungal agents won’t work
A patient presents with 3 days of painful rash (shown below) that is isolated on his right buttock and thigh
He is not taking any medications and reports no allergies
What is the most likely cause of this rash?
Varicella Zoster Virus
- Isolated; does not cross midline
- Painful
What kind of hemolysis is this?
Which organisms exhibit this pattern?
Beta hemolysis (complete lysis of RBCs)
Group A strep = S. pyogenes
Group B strep = S. agalactiae
List the waterborne parasites
GEN-CS (General Seas… even though some are from freshwater)
- Giardia
- Entamoeba histolytica
- Naegleria fowleri
- Cryptosporidium
- Schistosomiasis
Which cells express CD19?
All B cells
What does TGF-beta do?
Anti-inflammatory cytokine
Turns off imune response
What does IL-1 do?
Pyrogenic
Pro-inflammatory
(Similar to IL-6)
What is the vector of yersinia pestis transmission?
Oriental rat flea
(yersinia pestis causes the plague)
Which T-cell subset is most important in driving the increased production of IgG and IgA antibodies in response to a pertussis infection?
CD4+ Th2 Helper T-cells
A virus is translated immediately upon entry into the host cell.
What can you deduce about its nucleic acid?
It is ss(+) RNA
What does IL-2 do?
Promotes T-cell growth and activation
Can act in an autocrine fashion
What is the clinical presentation of a defect in T cells?
- Persistent thrush
- Sinopulmonary infections
- Skin or soft tissue infections
- Chronic diarrhea
(Candida albicans, S. aureus, Pneumocystis, Herpes simplex viruses)
Which cells express CD40?
B cells, other APCs
(Bind CD40L on CD4+ helper T-cell to induce cytokine production, form germinal center)
How can retroviruses be distinguished from other RNA viruses?
They are transcribed by a RNA-dependent DNA polymerase
The carry their own viral integrase to insert the DNA into the human genome
Which rashe is typically only found in patients with advanced HIV/AIDS?
HHV-8 (Kaposi sarcoma)
52 year old Hatian immigrant presents with fever, profuse sweating, labile hypertension, tachycardia, and facial spasms. Loud noises cause him to contrort his body in muscle spasms.
What is the likely causative agent of his symptoms?
Clostridium tetani
He has tetanus
A new patient in your clinic presents with the following rash. He is a 43 year old male who reports unprotected sexual contact with other men since he became sexually active 20 years ago. He has not seen a doctor in the last 15 years.
What is the most concerning diagnosis for this rash?
How would you confirm your diagnosis?
How would you evaluate progression of the diagnosis?
Kaposi Sarcoma (HHV-8); this is concerning because it typically only appears in patients with advanced HIV/AIDS
Confirm diagnosis with HIV antibody/antigen ELISA
Evaluate progression with T-cell count using flow cytometry
Which complement proteins are involved in the MAC?
C5b - C9
Any deficiencies in the above will result in problems with formation of the MAC -> increased suseptibility to encapsulated bactera (like nesseria meningitidis), and other gram negative bacteria
What is the major risk factor for contracting Vibrio?
Contaminated water, raw shellfish
Vibrio cholerae -> Cholera
(Watery diarrhea, rice-water stools)
Which cytokines induce Th1 T cells?
What are the major cytokines produced by Th1 T cells?
What does this trigger?
What is the result?
Th1 cells are induced by IFN-gamma and IL-12
Th1 cells produce IFN-gamma
This triggers macrophage activation, stimulation of IgG, and antibody production
-> Host defense against intracellular microbes
~but may cause~
-> Autoimmune and other chronic inflammatory diseases (IBD, psoriasis, granulomatous inflammation)
What is the main cell type involved in Type IV hypersensitivity?
What are the major antibodies?
CD4+ Th1 helper T-cells, macrophages
No antibodies!
(Type IV = delayed-type hypersensitivity)
Which disease can be acquired from Triatoma aka Reduviid aka the kissing bug?
American trypanosomiasis (T. cruzi)
Which cells are most critical in controlling the growth of M. tuberculosis?
CD4+ Th1 Helper T-cells
(Combat intracellular pathogens; in the case of MTB, they mediate the granulomatous response)
What tissue is this?
Lymph node
How do capsules contriubute to the virulence of some bacteria?
Block phagocytosis
Prevent against dessication
Which cell subsets are typically inhibited in the treatment of Crohn’s disease?
Why?
Th1 and Th17 CD4+ helper T-cells
- These cells are involved in IBD and psoriasis
- Downregulating these cells helps to control these conditions
What is the major risk factor for contracting a Treponema infection?
Close contact with an infected person
(Syphillis)
Which gram-negative bacilli can tolerate oxygen, but cannot ferment glucose or lactose?
Pseudomonas aeruginosa (Oxidase +)
Acinetobacter (Oxidase -)
Which components of the immune system mediate Type II allergic reactions?
Cells: CD8+ T cells, NK cells, neutrophils
Antibodies: preformed IgG, IgM (attached to cells or ECM)
Which cells express CD56?
NK cells
What is Cell C?
A neutrophil
A patient presents with blurry vision, trouble swallowing and speaking, and labored breathing.
Which of the following toxins might be causing her symptoms?
A. Staphylococcal enterotoxin
B. Botulinum toxin
C. Tetanus toxin
D. Diphtheria toxin
B. Botulinum toxin
Symptoms are associated with flaccid paralysis
(Would be an even stronger connection if people who had eaten the same poorly canned food all presented together)
What is the major risk factor for contracting MRSA?
Close contact with an infected person
For which clinical diseases would you prescribe CTLA-4?
Why?
Rheumatoid arthritis (or other diseases in which you want to suppress the Th2 CD4+ T cell response)
CTLA-4 binds B7 (CD80/CD86); this prevents the T-cell’s CD28 from binding to B7, blocking the costimulatory signal
This decreases the Th2 T-cell response
What tissue is this?
Colon
(The cirles are Peyer’s patches?)
Rheumatoid arthritis may have a hereditary basis due to the inheritance of MHC class II alleles.
The involvement of MHC class II suggests that ___________ cells are involved in the pathogenesis of rheumatoid arthritis
The involvement of MHC class II suggests that CD4+ helper T-cells cells are involved in the pathogenesis of rheumatoid arthritis
CD4+ helper T-cells recognize antigen on MHC II
Describe the structure and action of diphtheria toxin
A/B toxin
Blocks protein synthesis, induces cell lysis
-> Thick pseudomembrane that covers the back of the throat
What type of hypersensitivity reaction involves the fomation of immune complexes?
Type III
What tissue is this?
Spleen
Which antibiotics inhibit protein synthesis?
- Macrolides (50S)
- Lincosamides (50S)
- Oxazolidinones (23S RNA of 50S Ribosome)
- Tetracyclines (30S)
- Aminoglycosides (30S)
Which cells in the body does botulinum toxin bind to?
What is the effect?
Botulinum toxin binds to presynaptic motor end plates, preventing ACh release
The result is flaccid paralysis (Blurry vision, impaired swallowing/speaking, may lead to difficulty breathing)
Your body has lots of IgA floating around in it right now
Compare the affinity of IgA for B. pertussis produced by a plasma cell after infection with the affinity of IgM on a naive B-cell before infection
Explain.
The IgA produced by the plasma cells after a B. pertussis infection is most likely has a higher affinity than the original IgM produced by a naive B cell
The original IgM has some affinity for B. pertussis.
Upon infection, Th2 CD4+ helper T-cells are activated by APCs (Bind antigen on MHC II, CD40:CD40L interaction) to form a germinal center and release cytokines
- This promotes both class switching from IgM -> IgA and somatic hypermutation
- Somatic hypermutation and selection by folicular dendritic cells will select for the IgA antibodies with the highest affinity for B. pertussis antigen
Which enzyme catalyzies the formation of the hypochlorite ion?
Myeloperoxidase
Which test tube represents the growth of Neisseria meningitidis?
Test tube 1
Neisseria meningitidis is an obligate aerobe; will need oxygen, which is located near the surface of the liquid
What kind of animal causes this characteristic bulls-eye?
What disese is it associated with?
Ticks
Lyme disease (specifically Ixodes, the black-legged tick)
Peripheral CD4+ T-cell tolerance occurs in which of the following tissues?
A - Colon
B - Lymph node
C - Tonsil
D - Spleen
Peripheral tolerance occurs in secondary lymphoid tissues; T-cells that react with antigen in the absence of co-stimulation (ex: self antigen) in the peripheral immune tissues become anergic to that specific antigen
What is the major risk factor for contracting Leptospirosis?
Leptosporisis is caused by Leptospira interrogans
Transmitted in urine from infected animals (rats and mice)
Causes fever, jaundice, vomiting, general sickness. May cause meningitis
What is the major risk factor for contracting Borrelia?
Tick bite -> Lyme disease
Louse bite -> Relapsing fever
Intracellular Trypanosoma cruzi parasites in myocardium are called…
Amastigotes
- Trophomastigotes are in human blood
- Epimastigotes and promastigotes are in the reduviid bug (kissing bug)
Ixodes, the black legged tick, is the vector for which diseases?
Lyme disease
Anaplasmosis
What is thWhat is the human intracellular life cycle form of Malaria?
Trophozoite and Schiznot
What is the major risk factor for contracting Clostridium tetani?
Soil-contaminated wound
(Tetanus: stiff/rigid paralysis)
What is the main cell type involved in Type I hypersensitivity?
What are the major antibodies?
Mast cells
IgE
(Type I = immediate/anaphylactic reaction)
What is the intracellular life cycle form of Trypanosoma?
Amastigote
Imbalance in which immune cells leads to allergies and asthma?
Skew towards Th2 CD4+ helper T-cells
(and away from TRegs)
List the waterborne bacterial pathogens
SEALS are Very Cute Mammal Leopards
(Seals live in water and leopard seals are a thing)
- Shigella
- E. coli
- Aeromonas
- Legionella
-
Salmonella
- Vibrio
- Campylobacter
- Mycobacterium marinum
- Leptospirosis
What is the major risk factor for Tularemia?
Rabbit exposure or tick bite -> transmission of Francisella tularensis
Causes skin ulcer (granuloma) at site of bite; swollen lymph nodes, fever, headache, fatigue