Microbiology MBBS > Immunity > Flashcards

Immunity Flashcards

(57 cards)

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1
Q

Haptens

A

Not immunogenic
Can bind to to preformed antibodies (antigenicity +ve)
Hapten + carrier protein ➡️ immunogenicity

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2
Q

Determinants of immunogenicity

A
  1. Chemical nature
  2. Molecular weight (minimum: 5K - 10K Da)
  3. Foreignness
  4. Degradability by host (lysosomal) enzymes
    Directly proportional to the last 3 factors
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3
Q

Immunogenicity of chemicals

A

Proteins > polysaccharides > Nucleic acids > lipids

More complex, more immunogenic

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4
Q

Properties of T independent antigen

A
  1. B cell can independently form antibodies
  2. Polyclonal activation
  3. IgM class mainly- no class switching
  4. Low affinity antibodies- no affinity maturation
  5. No memory response
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5
Q

Examples of T independent antigens

A
  1. Polysaccharide
  2. Lipids
  3. Nucleic acid
  4. Lipopolysaccharide
  5. Simple proteins
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6
Q

T dependent antigen properties

A
  1. Th cells required for antibody formation by B cell
  2. Only antigen specific B cells are activated
  3. IgM ➡️ IgG,A,E - class switching positive
  4. Affinity increases from low to high: affinity maturation positive
  5. Memory response positive
    Example: complex proteins
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7
Q

Polyvalent immune response

A

Single antigen containing multiple epitopes against which an adaptive response is generated

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8
Q

Types of epitopes

A
  1. Linear/sequential:
    Formed by residues right next to each other in the primary structure of antigen
    Does not get destroyed on denaturation / digestion
  2. Conformational/ discontinuous:
    Formed by residues far apart in primary structure but brought close to form epitopes due to tertiary/quaternary foldings
    Gets destroyed on denaturation/digestion
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9
Q

Recognition of types of epitopes by cells

A

T cells recognise only linear epitopes

B cells recognise both types of epitopes

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10
Q

Special types of antigens

A
  1. Heterophile antigens
  2. Iso antigens
  3. Super antigens/T cell mitogens (5-20% Th cells instead of <0.0001% gets activated)
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11
Q

Heterophile antigens

A

Similar antigens which are shared by unrelated species

Eg., Forssman antigen: shared by all prokaryotes and eukaryotes (except rabbit)

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12
Q

Iso antigens

A

Present only in some members of same species

Eg., blood group antigens, Rh factor, MHC antigens

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13
Q

T cell mitogens/ Super antigens

A

Small/medium molecular weight proteins which activate large no. of T cells

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14
Q

When a foreign antigen enters the body

A
  1. Antigen entry
  2. Innate immunity fails to control infection
  3. Dendritic cell phagocytose the foreign antigen
  4. Processes it in lysosome
  5. Conjugation of the antigenic peptide
  6. Presented in groove of MHC-II
  7. Antigen migrates to lymph node
  8. Th cell recognises peptide with Vα and Vβ parts
  9. Immunological synapse is formed then activated
  10. Stimulates adaptive immunity
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15
Q

Super antigens activates immune system by the mechanism

A

Does not need processing by APCs

  1. Direct bond to MHC-II of APC at a site lateral to usual antigen presenting groove
  2. Need to be recognised just by Vβ part of receptor of Th cell
  3. 5-20% helper T cells (sharing same Vβ of T cell receptor) are activated, expanded
  4. Massive cytokine release
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16
Q

Antibodies basics

A 
Tetrameric glycoprotein (not polypeptides)
20-25% of total proteins in blood
Class determining domains: CH3/CH4
Antigen binding domains: Vl+Vh
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17
Q

Parts of an antibody in terms of chains

A 
1. 2 identical light (L) chains: 
 κ and λ (60:40 ratio in blood)
2. 2 identical heavy (H) chains:
 μ, ε, δ, γ(1-4), α(1-2)
 Class of H chain ➡️ class of antibodies
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18
Q

Properties of H chain of antibody

A

Molecular weight: 50K-75K Da
446-576 aa with carbohydrates substitutions
The 1st 110 aa from amino terminal ➡️ determine antigen binding ➡️ Vh (variable part)
Due to disulphide bonds each heavy chain gets folded into globular domains

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19
Q

Antibodies classified on the basis of domains

A 
1. Antibodies having CH4:
• Domains Vh, CH1, CH2, CH3 and CH4
• IgM, IgE
2. Antibodies not having CH4:
• Domains Vh, CH1, CH2 and CH3
• IgA, IgG, IgD
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20
Q

Properties of L chain of antibody

A

Molecular weight: 25K Da

211-217 with few carbohydrate substitutions

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21
Q

Parts of an antibody based on functionality

A
  1. 6 hyper variable loops which finally come in contact with antigens known as CDR (complementarity determining regions) or paratope:
    3 in Vl and 3 in Vh
  2. Part not taking part in antigen binding: frame work region
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22
Q

Action of enzymes on antibodies

A 
Papain:
 2 Fab + 1 Fc (crystallisable)
Pepsin:
 Cleaves below hinge region
•Mercaptoethanol breaks interchain disulphide bonds and forms 2 L chains + 2 H chains
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23
Q

Antigenic determinants of antibodies

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A
  1. Isotypic determinant
  2. Idiotypic determinants
  3. Allotypic determinants
24
Q

Isotypic determinants

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A

aa residues which determine the class or subclass of L chain or H chain or antibody
Eg.,
Of L chain: in Cl
Of H chain and antibody: CH3/ CH4

25
Idiotypic determinants
aa residues which determine antigen binding Of a L chain: Vl Of a H chain: Vh Of an antibody: in both
26
Allotypic determinants
``` Slight variations on aa sequences in the same class or subclass of a L/H chain in different individuals of the same species In the constant part ```
27
Examples of allotypic determinants
Only known for: 1. γ H chain: Gm markers 2. α2 H chain: Am markers 3. κ L chain: Km markers
28
Functions of antibodies
1. Neutralisation: IgG and IgA 2. Opsonisation 3. ADCC: non phagocytic killing 4. Complement fixation/ classical complement pathway activation: IgM> IgG3> G1> G2
29
Opsonisation mechanism
Macrophages, monocytes, neutrophils, dendritic cells have receptors for Fc part of IgG
30
ADCC
``` Antibody mediated cell cyto toxicity Non phagocytic killing of antibody coated cells/antigens by cytotoxic effector cells Effector cells: Neutrophil NK cells Eosinophils Macrophages ```
31
Complement system is constituted by
11 complement proteins and 9 regulatory proteins C1q, C1r, C1s, C2 to C9 proteins The 3 C1 proteins together form the C1 complex C1qr2s2
32
C3,C6,C9 complement proteins are formed in
Liver
33
Spleen produces the complement proteins
C5, C8
34
C2, C4 are produced by
Macrophages
35
C1 complement protein is formed in
Intestinal epithelium | C7 site of synthesis is unknown
36
Most abundant complement protein in blood
C3>> C4
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Role of C3b
Excess C3b deposits on antigen ➡️ binds to receptors on macrophages, neutrophil, monocytes ➡️ phagocytosis ➡️ opsonising the antigen
38
Anaphylatoxins and chemotactic complement proteins of classical pathway
Anaphylatoxins: C5a >C3a >C4a Parts which are produced as a byproducts of classical pathway Chemotactic: C5
39
Properdin pathway/ Alternate pathway activated by is activated by
1. Lipopolysaccharide 2. Viral envelopes 3. Fungal walls 4. Cobra venom 5. IgA/ IgD aggregates 6. Nephritic factor
40
Classical pathway of complement activation
``` Part of adaptive immunity Stimulated by binding of antigen to: IgM >IgG3 >IgG1 >IgG2 C3 convertase: C4b2b C5 convertase: C4b2b5b Membrane Attack Complex (MAC) ➡️ forms pores in antigen ➡️ osmotic lysis. ```
41
Mechanism of complement activation via classical pathway
1. Antibodies bind to antigen 2. Conformational change in Fc bond 3. Exposing site for C1q, binding 4. Spontaneous activation of C1r 5. Activation of C1s: Acts on C2 and C4 where both a parts are removed ➡️ C4b2b 6. This complex breakdowns multitude of C3 and C4b2b3b is produced 7. C5 is cleaved and C5b which deposits on the surface of antigen 8. Combines with others to form C5b6789 ➡️ membrane attack complex.
42
Properdin pathway/ alternate pathway
C3 convertase: C3bBb | C5 convertase: C3bBb3b
43
Activation of properdin pathway/ alternate pathway
1. C3b from tickover comes in contact with LPS,... 2. LPS-C3b binds to factor B to form LPS-C3bB which then binds to factor D which cleaves Ba off 3. C3bBb is stabilised by properdin 4. This then cleaves C3 to form C3b 5. C3bBb3b then continued as classical pathway
44
Tickover of properdin pathway of complement activation
Slow spontaneous hydrolysis of C3 to C3a and C3b which are immediately hydrolysed (but if C3b comes in contact with initiating factors, the alternate pathway is initiated)
45
Lectin pathway
1. Serum mannose binding lectin (MBL) encounters mannose residues of any antigen of cell 2. Bound MBL activates MASP-1 and 2 3. MBL-(MASP-1)2-(MASP-2)2 activates C4b and C2b 4. Rest continues as classical pathway
46
Regulation of complement activation
1. Activation of zymogen occurs only on pathogen, not on host cell. So some mechanisms are formed on host cells. 2. Activated complement proteins are later inactivated
48
Activation of zymogen is regulated on host cells by (part of regulation of complement activation)
1. DAF and CRI on host cell compete with Factor B for binding to C3b 2. Membrane Cofactor Protein on host cell acts as cofactor for hydrolysis of bound C3b by Factor I 3. CD59/ protectin: on host cells prevents the assembly of membrane attack complex MAC on host cells
48
Complement deficiencies
C1 C2 C4: SLE MBL and C3: severe pyogenic infections C5-C9: predisposition to Neisseria infections C1 esterase: hereditary angioneurotic edema DAF and CD59: paroxysmal nocturnal hemoglobinuria
49
Examples of inactivation of activated complement proteins
1. C1 esterase/ C1 inhibitor dissociates C1q from C1r-C1s | 2. Serum factor I(along with Factor H as cofactor) hydrolyses C3b into inactivated C3b and C3d
50
Properties of innate immunity
1. Acts in minutes: first line of defence 2. Prior microbial exposure not required 3. Limited diversity 4. Non-specific 5. No memory
51
MAMPs
``` They are repeating patterns of conserved molecules which are common to most microbial patterns (MAMPs). Examples are: 1. Peptidoglycan 2. Lipopolysaccharide LPS 3. Teichoic acid 4. Lipoproteins ```
52
Pattern recognition receptors PRRs
These are mobiles present on the bee of host cells that recognise MAMPs. They are generally conserved regions, encoded by germ line genes. • Toll-like receptors TLRs are classical examples of pattern recognition receptors, named after fruit fly; main receptor for inducing innate immunity • Signals generated following binding of TLRs to MAMPs
53
Components of innate immunity
1. Anatomical and physiological barriers 2. Phagocytes 3. NK cells 4. Other rare classes of lymphocytes 5. Mast cells 6. Dendritic cells 7. Complement pathways 8. Inflammatory response 9. Normal resident flora 10. Cytokines 11. Acute phase reactants proteins
54
Sites of synthesis of APRs Acute phase reactant proteins
1. Liver (major site) 2. Endothelial cells 3. Fibroblasts 4. Monocytes 5. Adipocytes
55
Positive APRs
1. Serum amyloid A 2. CRP 3. Complement proteins 4. Coagulation proteins 5. Proteinase inhibitors 6. α-1 acid glycoprotein 7. Mannose binding protein 8. Haptoglobin 9. Metal binding proteins
56
Negative APRs
Their levels decrease during acute inflammation, creating a negative feedback that stimulates the liver to produce positive APRs. Example: albumin 2. Transferrin 3. Antithrombin
57
Role of APRs
1. Various anti microbial and anti-inflammatory activities | 2. Metal binding proteins can chelate various metals such as
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