Basics

Question 1

Henoch schonlein purpura ( IgA vasculitis)
Immune mediated type III hypersensitivity reaction IgA immune complex deposition, activation of complement
1. Palpable purpura on thighs buttocks ankles
2. Arthritis or arthralgia
3. Abd pain or intussuseption
4. Renal disease
5. Leucocytoclastic vasculitis
Histopathologic finding: damaged small vessels with fibrinoid necrosis, peri vascular neutrophilic inflammation
Deposition of IgA and C3

Question 2

Hereditary angioedema
C1 estrase inhibitor deficiency
C1 activated leads to consumption of C4
Decrease C4 level
C1 inhibitor also blocks kallikrein induce conversion of kininogen into bradykinin, results in increase Bradykinin activation cause vasodilation
ACEI are contraindicated in these pts bcoz ACE converts bradykinin into inactive products
Rx: supportive care, C1esterase inhibitor concentrate or kallikrein inhibitor

Question 3

Sjogren syndrome
Dry eyes (keratoconjunctivitis sicca)
Dry mouth ( xerostomia)
Dry skin (xerosis)
Complications: Recurent dental infections
Corneal damage
Salivary glands hypertrophy
Non-Hodgkin lymphoma
Vaginal dryness causes dysparunia
Biopsy: lymphocytic infiltrate with germinal centers
Positive anti-Ro(SSA) and anti-la(SSB)

Question 4

Inflammatory lymphadenopathy
Foreign antigens displayed by dendritic cells, processed by B cells displayed to naive T cells via MHC class II, naive T cells differentiate into helper T cells and activate B cells proliferation and secrete cytokines which causes pain and inflammation of lymph nodes and enlargement due to germinal centers.

Question 5

Hyper IgM syndrome
X-linked recessive disorder
Deficient CD40L or CD40 interaction
Defective class switching in B cells
Dec IgG , IgA, IgE, Inc IgMMM
Recurrent sinopulmonary, GI and opportunistic infections
Interaction of CD40 and CD40L is required for APCs and B cells co stimulation due to this reason cell-mediated immunity is also deficient in this condition

Question 6

Chronic Granulomatous Disease
Deficiency of NADPH oxidase
Unable to produce superoxide radical i.e oxidative burst to kill intracellular pathogen
Recurrent infection of catalase positive bacteria and fungi( bcoz catalase convert H2O2 into water)
Diffuse granuloma formation
Dx: NBT and DHR
Nitroblue tetrazolium test( no change in colour)
Dihydrorhodamine flow cytometry (no fluorescence)
E.g staph aureus, burkholderia, serratia, nocardia, aspergillus.

Question 7

Serum Sickness
Type III hypersensitivity reaction deposition of immune complexes in tissues followed by activation of complement ( dec C3 level)
Histology: small vessel vascuilitis with fibrinoid necrosis and neutrophil infiltration
Serum sickness like reaction often occurs following drugs like penicillin, cefaclor, TMP-SMX. Other triggers are non-human immunoglobulin and chimeric monoclonal antibodies
Symptoms: fever, pruritic skin rash, arthralgia, sometimes lymphadenopathy and proteinuria after 7-14 days post exposure

Question 8

SLE
Type II hypersensitivity mediated pancytopenia, autoantibodies against blood cell antigens
Symptoms:Pancytopenia, malar or discoid rash, photosensitivity, serositis, symmetric migratory arthritis, thromboembolic events due to vasculitis and antiphospholipid antibodies
Labs:positive ANA (sensitive but not specific), anti-DNA antibodies and anti-Smith ( specific but not sensitive)
Low complement level
Immune complex deposition
Elevated inflammatory markers ( ESR, CRP)

Question 9

Severe combined immunodeficiency disease (SCID)
Low CD3+ T cells and hypogammaglobulinemia
Common findings: mucocutaneous candidiasis(thrush), chronic diarrhoea, severe bacterial viral fungal and opportunistic infection in infancy, failure to thrive
Thymic aplasia due to severe T cell deficiency
Rx: stem cell transplant
Retroviral gene therapy
Make sure not to confuse with DiGeorge
Congenital HIV infection also presents similar cause severe recurrent infection and failure to thrive
Candidal skin test is delayed type IV hypersensitivity assess cell mediated immunity via recruiting macrophages, CD4 and CD8 T-cells

Question 10

Pneumococcal vaccines
Two types of vaccines
PPSV23 polysaccharide vaccine, generates humoral immunity which lasts for 05 years
PPSV23 is not immunogenic in children <2 years due to their immature humoral immunity
PCV13 conjugate vaccine contain protein and exhibit robust immune response through T cells, long lasting immunity due to memory B cells, strongly immunogenic recommended in children routine immunization where as PPSV23 is recommended for all adults age >65

Question 11

Lupus Nephritis
Type III hypersensitivity immune complex deposition in mesengium sub endothelium, sub epithelial spaces results in diffuse proliferative glomerulonephritis

Question 12

Asplenia
Splenic capillaries are open ended pour the whole blood into red pulp, there macrophges lining the pulp remove the dead and abnormal erythrocytes and any bacteria present in blood, will be displayed by macrophages to B and T cells in the white pulp.
Asplenic pts are prone to encapsulated bacterial infection and needs vaccination against strep pneumo, hemo influenza, neisseria.
Spleen is the most common injured organ in blunt abdominal trauma
Spleen is responsible for clearance of encapsulated bacteria

Question 13

Type I hypersensitivity reaction
Pt predispose to allergy, on first encounter to allergen will cause Ab class switching from IgM to IgE which is specific to allergen bound to Fc receptors of basophils and mast cells, upon subsequent exposure IgE cross links and activate the release of inflammatory mediators like histamine, PGs and cause vasodilation results in wheal(central pallor) and flare(peripheral erythema) reaction.
In severe cases, cause anaphylactic shock

Question 14

Monoclonal Antibodies
1) cytokine inhibitors: bind to free circulating cytokines or cytokine receptor e.g (infliximab and etanercept) bind TNF-a
IL-2 inhibitor (aldesleukin)
2) T cell costimulation inhibitor: e.g they block CD28 on cytotoxic T cells which binds to CD80/86 ligand (abatacept) block CD28
3) B-cell inhibition/depletion
Inhibit (belimumab) and deplet ( infliximab)
Rituximab block CD20

Question 15

Anaphylaxis
Type I hypersensitivity
Trigger ( foods like nuts) medication like beta lactam antibiotic and insect sting
Cause by widespread mast cell and basophils degranulation that result in increase histamine and tryptase
Tryptase is specific to mast cell and can be used as clinical indicator for anaphylaxis

Question 16

Lung Transplant Rejection
Hyperacute:within minutes to hrs due to preformed antibodies to donor ABO or HLA antigen, mechanism, neutorphilic infiltration with fibrinoid necrosis and ischemia (White Graft Rejection)
Acute: ( <6 months) due to cell mediated response to mismatched HLA antigens, mechanism: peri vascular and submucosal lymphocyte infiltrate
Chronic: within months to years due to mixed cell mediated and antibody response, mechanism, submucosal inflammation, granulation and scarring of small airways and BRONCHIOLITIS OBLILTERANS

Question 17

1st generation antihistamine vs 2nd generation antihistamine:-
1st have side effects like anti muscarinic, anti-alpha adrenergic and anti- serotonergic and they are lipophilic cross BBB and cause sedation. They are avoided in elderly population
2nd are less side effects less lipophilic so more preferable in old population

Question 18

T-regulatory cells
FOXP3 activates CD-4 T cells into regulatory T cells that inhibits immune system via:
IL-10:Decrease MHC-II expression, inhibits macrophages
TGF-beta: B-cell proliferation decrease and promotes T reg cells production
CTLA-4: binds CD-80/86 on APC and inhibits co-stimulation of T -cells
Mutation in FOXP3 results in “IPEX SYNDROME” marked by autoimmune enteritis, eczematous dermatitis and type 1 DM also increased immunoglobulin production and autoimmunity

Question 19

Contact Dermatitis
Type IV hypersensitivity reaction (delayed)
Poison ivy,oak,sumac contain urshiol, a small allergenic substance when attached to protein( hapten) cause immune response
Symptoms: highly pruritic rash with papules vesicles bullae that may show excoriation.
2 phases of contact dermatitis
Sensitization phase: creation of hapten senstive T- cells takes 14 days, cutaneous dendritic cells take up the hapten and express on MHC- I and MHC-II travel to draining lymph node and activate CD- 4 or CD- 8 cells
Elicitation phase: 2 to 3 days following re-exposure to same antigen, hapten is taken up by skin cells and activate hapten sensitive T cells in dermis and epidermis results in inflammation.
In urshiol- induced contact dermatitis CD-8 T cells are main mediators

Question 20

Leucocyte adhesion deficiency (LAD)
Results from absence of CD18 which lead to inability to synthesize beta-2 integrin, and affecting tight adhesion, crawling and transmigration
C/F : recurrent bacterial skin infection without pus formation , delayed separation of umbilical cord and poor wound healing
Three subtypes of this disease LAD type 1 mentioned above and LAD type 2 and 3

Question 21

Wegner granulomatosis (granulomatosis with polyangitis)
C-ANCA positive (antibodies against neutrophils)
Features: necrotizing vasculitis of upper and lower respiratory tract causing nasal ulcerations, sinusitis, hemoptysis. Rapidly proliferating glomerulonephritis.

Question 22

Immunosuppressants:-
1)Mycophenolate: inhibit conversion of IMP into GMP in purine de novo synthesis pathway via blocking IMPDH
It mainly affects lymphocytes bcoz they don’t have purine salvage pathway they mainly rely on de novo synthesis where as the other hematopoetic cell line have purine salvage pathway so they compensate
Its main side effects is lymphopenia and GI symptoms.

Question 23

Red Man Syndrome
Cause by rapid infusion of vancomycin which directly activates the mast cell leading to the release of potent vasoactive mediators
It is not true IgE mediated allergic reaction, discontinuation and diphenhydramine will resolve the symptoms and later vancomycin can be continued at a slower rate

Question 24

Glucocorticoids:-
Reduce inflammation and end organ damage in inflammatory disease
Dec macrophage and lymphocytes activation via decreasing transcription of pro-inflammatory cytokines( IL-1, INF-gamma)
Increase anti-inflammatory cytokines ( IL-10)
Impair migration of leucocytes towards site of inflammation
Reduce adhesion molecule expression on neutrophils and endothelial cells, also reduce chemokines which results in neutrophilia
Promote apoptosis of monocytes, lymphocytes and eosinophils.
Decrease production of prostaglandins and luekotrienes

Question 25

Complement pathway:-
Three ways to activate
Classical pathway: (antigen- antibody complex) Activated when IgM or IgG bind to antigen, bind with C1 complement via their Fc portion
Alternative pathway: Autoactivated C3b bind with Factor B or Factor D and cleaves C2 and C4 without C1
Lectin pathway: pattern recognition receptors recognize carbs on pathogen and activate proteases which cleaves C2 and C4
All three pathways terminate in producing C3convertase.
Most common cause of complement deficiency is “Autoantibodies” which activate classical pathway
Classical pathway activation is marked by low C3 and C4 and normal factor B
CH50: a functional measure of entire classical complement pathway (C1-C9) will also be low
This pattern is seen in SLE

Question 26

Wiskott Aldrich Syndrome:-
X-linked recessive disorder
Mutation in WAS gene, responsible for cytoskeleton protein required for cell structure and cell to cell interaction
Symptoms: eczema, thrombocytopenia, recurrent infections
Deficiency of B cells and T cells also cause opportunistic infection and infection with encapsulated organisms.
Rx: HLA matched bone marrow transplantation

Question 27

X-linked agammaglobulinemia
Deficiency of BTK gene ( Bruton tyrosine kinase) results in impair B-cell maturation and immunoglobulin production
C/F: recurrent sinopulmonary infection, gastrointestinal infections especially chronic giardiasis, chronic severe life threatening ENTEROVIRAL infection. Small lymphoid tissue
Infection mainly occur after 3-6 months
Labs: CD19 or CD20 count low
IGs low and no antibody response to vaccines
Rx: immunoglobulin replacement therapy

Question 28

Chediak- Higashi- Syndrome
Autosomal recessive disease
Defects in phagosome-lymsosome fusion
Features: 1)immunodeficiency, due to loss of functional neutrophils results in recurrent pyogenic infections
2) partial occulocutaneous albinism, due to abnormal melanin storage
3)neurological defects, range from nystagmus to central or peripheral neuropathies
Histology; “giant lysosomal inclusions”

Question 29

Hyperacute Rejection of transplant:-
Due to preformed antibodies in the recepient that attack donor/graft antigens ( type II hypersensitivity) mostly these are anti- ABO or anti-HLA
Rejection occur within min to hours
Antibody and complement mediated vascular injury and thrombotic occlusions lead to cyanosis and ischemic necrosis of graft
To minimize the risk cross match ABO and HLA antigen before transplantation

Question 30

Acute transplant rejection:-
Within 06 months, naive immune cells are made against donor antigens.
Primarily cell-mediated
Lymphocytic Interstitial infiltrate
Increasing dose of immunosuppressants help to prevent acute rejection episodes

Question 31

T helper cells
Without contact with antigen, T helper cell is a naive T helper cell and have TCR and CD4+
As a APC and antigen complex interacts with T cell via MHC-II, T cells differentiate into either TH1 or TH2 cells.
If antigen is presented via macrophages, they release IL-12 which differentiate T cell into TH1 cell which produce gamma-IFN required for intracelluar pathogen.

Question 32

Graft versus host disease
A condition usually occurs following transplantation of lymphocyte rich organs(bone marrow, liver)
Immunocompetent donor T cells from graft survive and migrate into host tissue and recognize host MHC antigens as foreign and become sensitized
Any organ can be a target of graft T cell but most common include skin , GIT and liver manifest as maculopapular rash of palms and soles, nausea vomiting diarrhoea intestinal bleeding and abnormal LFTs

Question 33

Rheumatoid Arthritis:-
Pathogenesis involves both humoral and cell mediated immunity. CD4+ T cells Th1 and Th17 activate macrophages which release proinflammatory cytokines IL-1 and TNF-alpha which indirectly activate osteoclast lead to bony erosions
Radiographical findings include joint space narrowing and marginal joint erosions
Treatment is TNF-alpha and IL-1 inhibitors i.e (adalimumab and etanercept) and ( anakinra)

Question 34

Diabetic Nephropathy:-
Earliest change in diabetic nephropathy is increase in filtered glucose load, this lead to increase sodium resorption which decrease delivery of sodium to macula densa and activates tubuloglomerular autoregulation causing afferent arteriole vasodilation and efferent arteriole vasoconstriction which increase intraglomerular capillary pressure and GFR and glomerular hypertorphy