Immunology- Immune responses Flashcards
Antibody structure
and function
Fab (containing the variable/hypervariable regions) consisting of light (L) and heavy (H) chains
recognizes antigens.
Fc region of IgM and IgG fixes complement. Heavy chain contributes to Fc and Fab regions. Light chain contributes only to Fab region.
Generation of antibody diversity (antigen
independent)
- Random recombination of VJ (light-chain)
or V(D)J (heavy-chain) genes. - Random addition of nucleotides to
DNA during recombination by terminal
deoxynucleotidyl transferase (TdT). - Random combination of heavy chains with
light chains.
Generation of antibody specificity (antigen
dependent)
- Somatic hypermutation and affinity
maturation (variable region). - Isotype switching (constant region).
Mature, naive B cells prior to activation express…
IgM and IgD
IgG
Fixes complement, opsonizes bacteria, neutralizes bacterial toxins and viruses. Only isotype that crosses the placenta
IgA
Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement.
Monomer (in circulation) or dimer (with J chain when secreted).
Released into secretions (tears, saliva, mucus) and breast milk.
IgM
Antigen receptor on the surface of B cells. Monomer on B cell, pentamer with J chain when secreted.
Pentamer enables avid binding to antigen while humoral response evolves.
IgD
Unclear function. Found on surface of many B cells and in serum.
IgE
Binds mast cells and basophils; cross-links when exposed to allergen, mediating immediate (type I)
hypersensitivity
Thymus-independent
antigens
Antigens lacking a peptide component (eg, lipopolysaccharides from gram ⊝ bacteria); cannot
be presented by MHC to T cells. Weakly immunogenic
Complement activation pathways
Classic—IgG or IgM mediated.
Alternative—microbe surface molecules.
Lectin—mannose or other sugars on microbe
surface
Complement function
C3b—opsonization.
C3a, C4a, C5a—anaphylaxis.
C5a—neutrophil chemotaxis.
C5b-9—cytolysis by MAC
Complement inhibitors
Inhibitors—decay-accelerating factor (DAF, aka CD55) and C1 esterase inhibitor help prevent complement activation on self cells (eg, RBCs).
Early complement deficiencies (C1-C4)
Increased risk of severe, recurrent pyogenic sinus and respiratory tract infections. Increased risk of SLE.
Terminal complement deficiencies (C5–C9)
Increased susceptibility to recurrent Neisseria bacteremia.
C1 esterase inhibitor
deficiency
Hereditary angioedema due to unregulated activation of kallikrein..
Characterized by Lower C4 levels. ACE inhibitors are contraindicated.
Paroxysmal nocturnal
hemoglobinuria
PIGA gene preventing the formation of anchors for complement inhibitors, such as (DAF/CD55) and (MIRL/CD59).
Causes complement-mediated lysis of RBCs.
Important cytokines
IL1, 2, 3, 4, 5, 6
“Hot T-bone stEAK”: IL-1: fever (hot). IL-2: stimulates T cells. IL-3: stimulates bone marrow. IL-4: stimulates IgE production. IL-5: stimulates IgA production. IL-6: stimulates aKute-phase protein production.
Important cytokines Il-8 IL-12 INF gamma IL-10
Major chemotactic factor for neutrophils
Induces differentiation of T cells into Th1 cells.
stimulates macrophages to kill phagocytosed pathogens.
Attenuates inflammatory response. Decreases expression of MHC class II and Th1 cytokines.
Respiratory burst
oxidative burst
- NADPH oxidase (deficiency = chronic granulomatous disease).
- Superoxide dismutase
- Myeloperoxidase
- Glutathione peroxidase (requires selenium)
- Glutathione reductase (requires riboflavin)
- G6PD
Pyocianin
of P aeruginosa generates ROS to kill competing pathogens.
Lactoferrin
is a protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation.
Interferon-α and -β
A part of innate host defense against both RNA and DNA viruses. Are glycoproteins synthesized by virus-infected cells.
Cell surface proteins T cells - Helper t cells - Cytotoxic T cells - Regulatory T cells
TCR (binds antigen-MHC complex)
CD3 (associated with TCR for signal transduction)
CD28 (binds B7 on APC)
- Helper T cells CD4, CD40L, CXCR4/CCR5 (co-receptor for HIV)
- CD8
- CD4, CD25
Cell surface proteins
B cells
Ig (binds antigen)
CD19, CD20, CD21 (receptor for EBV), CD40
MHC II, B7
Cell surface proteins
Macrophages
CD14 (receptor for PAMPs, eg, LPS), CD40 CCR5
MHC II, B7 (CD80/86)
Fc and C3b receptors (enhanced phagocytosis)
Cell surface proteins
NK
CD16, CD56 (suggestive marker for NK)
Cell surface proteins
Hematopoietic stem cells
CD34
After exposure to… unvaccinated patients are given preformed antibodies (passive immunity).
“To Be Healed Very Rapidly”
Tetanus toxin, Botulinum toxin, HBV, Varicella, Rabies virus, or diphtheria toxin.
Live attenuated vaccine
cellular and humoral responses
“Attention! Please Vaccinate Small, Beautiful Young
Infants with MMR Regularly!”
Adenovirus (nonattenuated, given to military recruits),
Polio (sabin), Varicella (chickenpox), Smallpox, BCG, Yellow fever, Influenza (intranasal), MMR, Rotavirus.
Killed or inactivated vaccine
humoral responses
SalK = Kille RIP Always
Rabies, Influenza (injection), Polio (Salk), hepatitis A.
Subunit vaccine
(only the antigens that best stimulate the immune
system)
HBV (antigen = HBsAg), HPV (types 6, 11, 16, and 18), acellular pertussis (aP), Neisseria meningitidis (various strains), Streptococcus pneumoniae Haemophilus influenzae type b.
Toxoid vaccine
Denatured bacterial toxin
Denatured bacterial toxin
Hypersensitivity types
(ABCD): Anaphylactic and Atopic (type I), antiBody-mediated (type II), Immune Complex (type III), Delayed (cell-mediated, type IV).
Direct Coombs test
Indirect Coombs test
detects antibodies attached directly to the RBC surface.
detects presence of unbound antibodies in the serum
Serum sickness—
the prototype immune complex disease.
Antibodies to foreign proteins are produced and 1–2 weeks later, antibodyantigen complexes form and deposit in tissues, complement activation, inflammation and tissue damage.
Arthus reaction
A local subacute immune complex-mediated hypersensitivity reaction.
Intradermal injection of antigen into a presensitized individual leads to immune complex formation in the
skin.
IV hypersensitivity
4T’s: T cells, Transplant rejections, TB skin tests, Touching (contact dermatitis).
Fourth (type) and last (delayed).
Blood transfusion reactions
Allergic/anaphylactic reaction.
Febrile nonhemolytic transfusion reaction
Acute hemolytic transfusion reaction
Transfusion-related acute lung injury
Autoantibodies
pag. 115 usmle first aid
X-linked (Bruton) agammaglobulinemia
Defect
presentation
finding
Defect in BTK,no B-cell maturation. X-linked recessive.
Recurrent bacterial and enteroviral infections after 6
months.
Absent B cells in peripheral blood, low Ig of all classes. Absent/scanty lymph nodes and tonsils.
Selective IgA deficiency
Defect
presentation
finding
Cause Unknown. Most common 1° immunodeficiency.
majority Asymptomatic. can see Airway and GI infections, Autoimmune disease, Atopy, Anaphylaxis to
IgA-containing products.
low IgA with normal IgG, IgM levels
Common variable immunodeficiency
Defect
presentation
finding
Defect in B-cell differentiation. Cause is unknown.
Presents after age 2 and may be considerably delayed;
Risk of autoimmune disease, bronchiectasis, lymphoma,
sinopulmonary infections.
Low plasma cells, low immunoglobulins.
IL-12 receptor deficiency
Defect
presentation
finding
low Th1 response. Autosomal recessive.
Disseminated mycobacterial and fungal infections.
Low INF gamma
Autosomal dominant hyper-IgE syndrome
(Job syndrome)
Defect
presentation
finding
Deficiency of Th17 cells due to STAT3 mutation.
FATED: coarse Facies, cold (noninflamed) staphylococcal Abscesses, retained primary Teeth, high IgE, Dermatologic problems (eczema). Bone fracture
Chronic mucocutaneous candidiasis
Defect
presentation
finding
T-cell dysfunction. Can result from congenital genetic
defects in IL-17 or IL-17 receptors.
Noninvasive Candida albicans infections of skin and mucous membranes.
Absent in vitro T-cell proliferation in response to
Candida antigens. Absent cutaneous reaction to
Candida antigens.
Severe combined immunodeficiency
Defect
presentation
finding
Defective IL-2R gamma chain (most common, X-linked recessive), adenosine deaminase deficiency
(autosomal recessive).
Failure to thrive, chronic diarrhea, thrush. Recurrent
viral, bacterial, fungal, and protozoal infections.
Absence of thymic shadow (CXR), germinal centers
(lymph node biopsy), and T cells (flow cytometry).
Ataxia-telangiectasia
Defect
presentation
finding
Defects in ATM gene, failure to detect DNA damage. AR.
Triad: cerebellar defects (Ataxia), spider Angiomas
(telangiectasia A ), IgA deficiency.
high AFP.
low IgA, IgG, and IgE.
Lymphopenia, cerebellar atrophy.
Hyper-IgM syndrome
Defect
presentation
finding
Most commonly due to defective CD40L on Th cells, class switching defect. XR
Severe pyogenic infections early in life; opportunistic
infection Pneumocystis, Cryptosporidium, CMV.
Normal or high IgM.
low IgG, IgA, IgE.
Wiskott-Aldrich syndrome
Defect
presentation
finding
Mutation in WASp gene; leukocytes and platelets
unable to reorganize actin cytoskeleton. XR
WATER: Wiskott-Aldrich: Thrombocytopenia, Eczema,
Recurrent (pyogenic) infections.
low to normal IgG, IgM.
High IgE, IgA.
Fewer and smaller platelets.
Leukocyte adhesion deficiency (type 1)
Defect
presentation
finding
Defect in LFA-1 integrin (CD18) protein on
phagocytes; impaired migration and chemotaxis. AR
Recurrent skin and mucosal bacterial infections, absent
pus, impaired wound healing, delayed (> 30 days) separation of umbilical cord.
high neutrophils in blood. Absence of neutrophils at
infection sites.
Chédiak-Higashi syndrome
Defect
presentation
finding
Defect in lysosomal trafficking regulator gene (LYST). AR
PLAIN: Progressive neurodegeneration,
Lymphohistiocytosis, Albinism (partial), recurrent
pyogenic Infections by staphylococci and
streptococci, peripheral Neuropathy.
Giant granules in granulocytes and platelets.
Pancytopenia. Mild coagulation defects.
Chronic granulomatous disease
Defect
presentation
finding
Defect of NADPH oxidase. X linked
susceptibility to catalase ⊕ organisms.
Abnormal dihydrorhodamine (flow cytometry) test (low green fluorescence). Nitroblue tetrazolium dye reduction test (obsolete) fails to turn blue.
Encapsulated bacteria
Encapsulated (Please SHINE my SKiS): Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus Influenzae type b, Neisseria meningitidis, Escherichia coli, Salmonella, Klebsiella pneumoniae, Group B Streptococcus.
Bacterias and micotic suceptibility when low granulocytes
Staphylococcus, Burkholderia cepacia, Pseudomonas
aeruginosa, Serratia, Nocardia
Candida (systemic), Aspergillus, Mucor
Virus that present with deficences of B cells
Enteroviral encephalitis,
poliovirus
Types of Transplant rejection
Hyperacute
acute
chronic
Graft vs Host disease
