29 Immune responses Flashcards

1
Q

Innate vs adaptive immunity

A

Innate: first line of defense, nonspecific, fast acting, kills all non-self
Adaptive: acquired, specific, memory, antibodies and antigen (HUMORAL IMMUNITY)

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2
Q

Innate immunity: barriers

A

1 Epithelial cell layer: tight junctions, antimicrobial peptides (sebaceous gland, eccrine and paracrine)
2 Mucous membranes: mucins, proteins, proteases, protease inhibitors
3 Chemical environment: GI tract (hydrolytic and proteolytic enzymes), skin (pH, salt, fatty acids), GU tract (pH of vagina)

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3
Q

Phagocytes

A

1 Monocytes/macrophage
2 Granulocytes; neutrophils (intracellular vesicles), eosinophils/basophils (release granules)
3 Dendritic cells: activate T cells (APC function), regulatory cytokines

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4
Q

NK cells

A

Look for cells with specific receptors (MHC Class I) and kill with perforins and granzymes

ADCC: CD16 bind to Fc portion of antibodies

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5
Q

Microbial sensors

A

Toll-like receptors: recognize PAMPS on surface of pathogens
NOD-like receptors: intracellular (cytoplasm) receptor, activated NF-kB pathway
RIG-1 like helicases and MDA 5: cytoplasmic sensors of viral ssRNA -> IFN-1 -> inhibit viral replication

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6
Q

Complement system

A

Classical: antigen-antibody complex
Alternative: absence of antibody
Lectin: bypasses antibody (mannose binding lectin)

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7
Q

Complement system processes

A

Cytolysis (MAC: C5b, 6, 7, 8, 9)
Chemotaxis: C5a(attraction)
Opsonization: C3b
Vasodilation + vascular permeability: Anaphylatoxins (C3a, C5a) -> release histamine

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8
Q

Cytokines

A

Synthesis: macrophage, DCs, NK cells, T cells, B cells

Applications: biomarkers, immune status monitoring, therapeutic agents, targets of therapy

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9
Q

Other proteins

A

Defensins: form pore-like membrane
Collectins: garbage bags for macrophages

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10
Q

B lymphocytes

A

Plasma cells: produce antibodies
Memory B cells: proliferate in second infection
CD21: complement component
CD40: for maturation and antibody production

T-dependent: creates IgG; phagocytosed by macrophage -> APC (antigen + MHC II) -> CD4 Th cell
T-independent: creates IgM; B cell + antigen

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11
Q

CD4 T cells

A

T-helper cells
Th1: IL-2, IL-12; macrophage; B cells -> IgG
Th2: IL-4; mast cells and eosinophils; Bcells -> IgE
Th17: TGFB, IL-6,23,27,8; recruitment
Treg: TGFB, suppress responses

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12
Q

CD8 T cells

A

Effector cytotoxic cells (ETC)
Perforin
Granzyme: activate cellular caspase (apoptosis)

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13
Q

T cell receptor

A

B cell: light and heavy chain

T cell: a and B chain

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14
Q

MHC

A

Bind antigens + present to T cells
Binds to specific antigens only
HLA complex

MHC Class I: all nucleated cells, CD8
MHC Class II: B lymph, macrophage, DCs; CD4
MHC Class III

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15
Q

Clonal selection

A

Specific Bcell/Tcell proliferates after infection = immune response

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16
Q

Antibody (Ig)

A

Polyclonal: different antigenic determinants
Monoclonal: single clone, homogenous

Enhance phagocytosis (opsonization)
Neutralizes viruses 
Neutralizes toxins
Complement-mediated lysis
ADCC (killer cell-Fc -> lysis)
17
Q

Structure of antibodies

A

L and H chain: variable (antigen-binding) + constant

Fragments: Fab (antigen-binding) + Fc (complement fixation)

18
Q

Classes of Ig

A

IgG: 2L+2H; cross placenta; opsonization; 1=most abundant, 2=against encapsulated bacteria, 3=complement, 4=no complement

IgM: first produced; 5H2L2, no cross placenta, intracellular

IgA: serum (mono) and secretions(dimer)

IgE: allergic responses

IgD: mature B lymph with no antigen

19
Q

Antibody responses

A

1º: produces within days/weeks

2º: more rapid and higher levels; IgG, longer

20
Q

Active vs passive immunity

A

Active: produce antibodies; infection, immunization, exposure, transplant; long-lasting, delayed
Passive: pre-formed antibodies; short-term, immediate

21
Q

Methods of acquisition

A

Natural: no intervention; naturally acquired active (exposure), naturally acquired passive (breastfeeding)
Artificial: artificially acquired active (vaccine = live, attenuated or killed vaccine), passive (Ig/anti-toxin)

22
Q

Type I hypersensitivity

A

IMMEDIATE HYPERSENSITIVITY

Allergy: seconds after antigen -> IgE
First exposure: form IgE antibodies
Second exposure: cross-linking -> release mediators
Atopy: have pre-existing HLA haplotypes to predispose; already high IgE

Histamine: primary mediator
Prostaglandins and leukotrienes: from arachidonic acid, LB4 (recruits leukocytes) LC4/D4 (vasodilation and vascular permeability)

23
Q

Type II hypersensitivity

A

ANTIBODY-MEDIATED (+cell)

IgG-cells: complement mediated lysis (ABO rxns, Rh)
Antibody directed at cell (cell-cell interaction)

Penicillin: antibody-surface proteins, hemolysis
Goodpasture syndrome: antibody-BM, complement activation
Graves’ disease: antibody-TSH -> hyperthyroidism

24
Q

Type III hypersensitivity

A

IMMUNE COMPLEX

antibody-immune complex -> damage -> inflammation and complement activation
Autoimmune disorders

Local rxn (arthus reaction): wheal formation, IgG antibodies + complement activation
Systemic (post strep glomerulonephritis)
25
Q

Type IV

A

CELL-MEDIATED (DELAYED)

T cell-mediated: sensitized by antigen -> release inflammatory cytokines + macrophage
Prolonged eruption and inflammation in skin

Contact hypersensitivity: molecules = haptens = antigens -> cell-mediate hypersensitivity
Tuberculin-type: mononuclear cells accumulate in tissue

26
Q

Primary immunodeficiency diseases

A

Genetically determined
Increase susceptibility to infections (low/LOF B cells/Tcells/etc)

Chronic granulomatous disease: impaired phagocytosis, metabolic defect (no peroxide/superoxide); normal Ig/T/B/phago
Severe combined immunodeficiency: defect in B and T cell

27
Q

Secondary immunodeficiency

A

Induced by external factors

Infections: depressed T cell (HIV -> CD4 T cell)
Malignancy: low neutrophil = no phagocytosis; inc TGFB = suppress Th1
Drugs

28
Q

Autoimmunity

A

Hypersensitivity rxns

Type 2: GD, HA, MG, RF
Type 3: Glomerulonephritis, SLE/lupus, RA
Type 4: DM1

29
Q

Lab tests

A
Lab: Antibody evaluation assays
ELISA
Immunofluorescence (direct vs indirect)
Immunoblot/western blot 
Protein electrophoresis
Immunofixation electrophoresis

Lab: Evaluation of cellular responses
Flow cytometry
Functional cellular assays