Diseases to Remember

Question 1

Leprosy

Answer 1

Clinical Features: Cutaneous lesions, neuropathic changes and deformities

M. Leprae colonizes macrophages and other host cells and multiplies within
Macrophages need to be activated in order to kill it
Grows best at 86 degrees, so likes to hang out at joints

IFN-y can help

Question 2

Mycobacteria

Answer 2

Evades the immune system by preventing the fusion go phagosome to lysosome, prevents degradation

Question 3

Herpes Simplex Virus (HSV)

Answer 3

Evades immune system by reducing the function of TAP

Question 4

Cytomegalovirus (CMV)

Answer 4

Evades immune system by preventing proteasomal activity and preventing Class 1 MHC from pinching off ER

Question 5

Epstein Barr Virus (EBV)

Answer 5

Evades immune system by prevent proteasomal activity and inhibiting macrophage activity by releasing IL-10

Question 6

Pox virus

Answer 6

Evades immune system by releasing soluble CXCRs

Question 7

Toxic Shock Syndrome

Answer 7

Associated with localized S. aureus (gram +) infection, food poisoning, local colonization
Tampons provide a good food source
Toxic Shock Protein = super antigen that binds to B chain of TCR and does not require antigen or co-stimulatory receptors to process response

Question 8

What are the consequences of super antigen?

Answer 8

Fever, rash, edema, hypotension, shock

TNF-a and IL-1 contribute to increase in vascular permeability that lead to leakage of fluid

Question 9

Hyper IgM Syndrome

Answer 9

5 types --> inability to class switch 
X-linked = defect in CD40L, autosomal = defect in CD40
X-linked --> probs with T-cell activation, suffers from opportunistic infections 
Syndrome with defect in AID --> probs with B-cells

Question 10

C3 Deficiencies (Alternative pathway)

Answer 10

Life threatening, severe, recurrent infections

Deficiencies in Factor H and I mimic C3 deficiencies, because exhausts C3 from system
Pyogenic infections, SLE

Alternative pathway - Factor D, Properdin Def = Nisserial

Question 11

MAC deficiencies

Answer 11

Generally healthy

Increase in infection by Nisseria gonorrhea and N. meningitis

Question 12

Deficiencies in early complement activation (Classical)

Answer 12

C1, C2, C4 –> C2 most common
With C2 def. pts have high degrees of SLE
May arise from failure to clean immune complexes which deposit on blood vessel walls and tissues
Produces local inflammation –> may lead to breakdown of tolerance to self –> autoimmunity

Question 13

C1inh Deficiency and Hereditary Angioneurotic Edema (HAE)

Answer 13

C1 not regulated properly –> C4/2 chronically low

Hereditary Angioneurotic Edema (HAE)
Pt have attacks with swelling involving extremities, GI tract, and Face
may affect upper respiratory tract leading to suffocation
Tx: Berinet, purifies human C1inh

Question 14

Paroxysomal Nocturnal Hemoglobinuria (PHN)

Answer 14

Hemolytic disorder with spontaneous episodes of complement-mediated RBC lysis (also leks and platelets)
Tx: erythropoietin, corticosteroids, eculizumab

Defect in phosphatidylinositol glycan class A gene (PIG-A)
It is required for synthesis of glycosyl phosphatidylinositol (GPI) anchor
Lack of CD59 and CD55 complement reg proteins
Leads to complement mediated intravascular hemolysis

Question 15

Class 1 HLA gene (HLA-B27) increases risk of…

Answer 15

Ankylosing Spondylitis (by 90)

Question 16

Class 2 HLA genes (HLA-DR4) increase risk of…

Answer 16

Type 1 DM (25), Pemphigus vulgaris (14), RA (4)

Question 17

Describe PTPN22 role in autoimmunity.

Answer 17

Abnormal TYROSINE PHOSPHATASE reg of T-cell selection and activation

Disease association: RA, T1D, autoimmune thyroid diseas

Question 18

Describe CTLA4 role in autoimmunity.

Answer 18

Impaired inhibitory checkpoint and Treg function - loss of B-cell, T-cell function

Diseases: T1D, RA, many autoimmune diseases

Question 19

Describe AIRE role in autoimmunity.

Answer 19

Reduced expression of peripheral tissue antigens in thymus, leading to defective elimination of self-reactive T - necessary for thymic expression of self-proteins

Diseases: Autoimmune Polyendocrine syndrome (APS-1), DM, adrenal, parathyroid

Question 20

Describe FAS role in autoimmunity.

Answer 20

Defective apoptosis of self-reactive T and B cells in periphery - splenomegaly, lymphadenopathy

Disease: Autoimmune lymphoproliferative syndrome (ALPS), adrenals

Question 21

Describe FOXP3 role in autoimmunity.

Answer 21

Deficiency of T-regs

Disease: Immune dysregulation X-linked polyendocrinopathy and enteropathy - IPEX - widespread autoimmunity

Question 22

Infection - Disease association to remember

Answer 22

Streptococcus - Rheumatic Fever
Chlamydia - Reiter’s Syndrome (HLA-B27)
Shigella, Salmonella - Reactive Arthritis (HLA-B27)
Coxsackie, echovirus, rubella - IDDM (HLA-DQ..)

Question 23

SLE

Answer 23

Polytrophic Immune Complex Disease
Defective apoptotic process leading to increased nucleic acid Ags available to stimulate immune response
Susceptible gene + UV radiation

Question 24

RA

Answer 24

Inflammation in synovium
Th1/17 cytokine release sustains inflammation
Ab production against rheumatoid factor (Fc portion of Ig)
Defective clearance of immune complexes; failure of B cell tolerance

Question 25

Immunodeficiencies associated with lymphocyte MATURATION of BOTH Ts and Bs

Answer 25

X-linked SCID ADA and PNP Def JAK3 Def RAG1/2 Def

Question 26

Immunodeficiencies associated with lymphocyte MATURATION of B-CELLS

Answer 26

X-linked Agammaglobulemia | Ig Heavy chain def

Question 27

Immunodeficiencies associated with lymphocyte MATURATION of T-CELLS

Answer 27

Di-George Syndrome

Question 28

Immunodeficiencies associated with lymphocyte ACTIVATION and FUNCTION of BOTH Ts and Bs

Answer 28

X-linked lymphoproliferative syndrome

Question 29

Immunodeficiencies associated with lymphocyte ACTIVATION and FUNCTION of B-CELLS

Answer 29

X-linked Hyper IgM syndrome Common Variable Immunodeficiency IgA Def Isolated IgG subclass def

Question 30

Immunodeficiencies associated with lymphocyte ACTIVATION and FUNCTION of T-CELLS

Answer 30

Bare Lymphocyte Syndrome MHC Class 1 Def Wiskott-Aldrich syndrome IPEX

Question 31

Immunodeficiencies in Innate Immunity

Answer 31

``` Chediak-Higashi disease Leukocyte Adhesion disease Chronic Granulomatous disease G6PD Def Myeloperoxidase def Severe Chronic Neutropenia ```

Question 32

Characteristics of Complement Deficiencies

Answer 32

Defects in Classical more common - Pt have high number of autoimmune disorder, including LUPUS-like syndrome Defects in Alternative - present with Nisserial infections

Question 33

Type 1 Hypersensitivity Diseases

Answer 33

Anaphylaxis - Tx with Epi Bronchial Asthma - Tx with corticosteroids, leukotriene antagonists, phosphodiesterase inhibitors Allergies - Tx with desensitization, Anti-IgE, Antihistamine

Question 34

Type 2 Hypersensitivity Diseases

Answer 34

``` Autoimmune Hemolytic anemia Autoimmune thrombocytopenia purpura Good pasture syndrome - C'/Fc receptor-mediated inflam Graves disease Myasthenia graves Pemphigus Vulgaris Pernicious anemia Rheumatic Fever ```

Question 35

Type 3 Hypersensitivity Diseases

Answer 35

``` SLE Polyartertitis nodosa Poststreptococcal glomerulonephritis Serum sickness Arthus reaction ```

Question 36

Type 4 Hypersensitivity Diseases

Answer 36

``` RA Multiple Sclerosis Type 1 DM Crohn's Contact sensitivity Chronic infection Viral Hepatitis Superag mediated diseases ```