Immunology 1s - Introduction Flashcards by Leila Aval

Skin - how does it act as a barrier to infection?

Physical barrier: tightly packed keratinised cells
Physiological factors: low pH and low oxygen tension
Sebaceous glands: produce hydrophobic oils and lysozymes

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Mucosal surface - 5 ways it acts as a barrier to infection

Physical barrier - traps invading pathogens
Mucus contains secretory IgA - binds to pathogens
Lysozyme
Lactoferrin (Starves bacteria of iron)
Cilia

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Commensal bacteria - how does it act as a barrier to infection?

100tn bacteria, competes with pathogens for resources

Produce fatty acids and bactericides which inhibit pathogen growth

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Polymorphonuclear cells include?

Neutrophils
Basophils/mast cells
eosinophils

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Soluble component of innate immune system

Complement
Acute phase proteins
Cytokines/chemokines

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How do cells of the innate immune system identify pathogens?

PRRs

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What receptors do polymorphonuclear cells express?

Receptors for cytokines/chemokines to detect inflammation
PRRs
Fc receptors for Ig (Detect immune complexes)

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Actions of PMNCs

Migrate rapidly to site of injury
Express cytokine/chemokine receptors, Fc for Ig, PRRs
Phagocytosis, oxidative and non-oxidative killing
Release enzymes, histamine, lipid mediators of inflammation from granuels
Release cytokines and chemokines to regulate inflammation

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Mononuclear cells include?

monocytes, macrophages, lymphocytes

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What do monocytes differentiate in to and where does this happen?

Differentiate in to macrophages in tissues

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How do monocytes differ from PMNCs?

They are able to express processed antigen to T cells

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Difference between cytokines and chemokines

CYtokines –> activate vascular endothelium and enhance vascular permeability
Chemokines –> Attract phagocytes

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What do PRRs recognise?

PAMPs e.g. bacterial sugars, DNA, RNA

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What process is endocytosis facilitated by?

Opsonisation

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2 ways in which microorganisms are recognised by innate immune response?

PRRs e.g. TLRs and mannose receptors

2. Fc receptors for Fc portion of Ig to recognise immune complexes

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3 examples of opsonins

Antibodies - bind to Fc receptor
APPs (CRP)
Complement (bind to complement receptors

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2 killing methods by PMNCs

Oxidative killing - NADPH oxidase complex converts oxygen to reactive oxygen species (superoxide and hydrogen peroxide). Myeloperoxidases: production of hydrochlorous acid (an antimicrobial) from hydrogen peroxide and chloride

Non-oxidative killing - Release of lysozyme/lactoferrin from granules into phagolysosome

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What happens to neutrophils after they phagocytose a lot?

Phagocytosis depletes the glycogen reserves of the neutrophil –> die. As they die, residual enzymes are released which causes liquefaction of adjacent tissue. Accumulation of dead neutrophils in infected tissue –> pus , accumulation of pus –> abscess

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What are NK cells?

A type of lymphocyte. They are cytotoxic and kill altered-self cells or virus-infected cells

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What do NK cells have on their surface which allows them to recognise non-self cells?

They have an activating and inhibitory receptor. The inhibitory receptor is for self-HLA molecules to prevent mal-activation by normal self. If inhibitory receptor not activated –> lysis

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What do dendritic cells represent?

INNATE-ADAPTIVE transformation

Following phagocytosis, dendritic cells will…

Upregulate expression of HLA molecules
Express co-stimulatory molecules
Migrate via lymphatics to LNs (mediated by CCR7)
Present antigens to T cells in LNs to prime adaptive immune response

Soluble components of adaptive immune system

Chemokines and cytokines

Primary lymphoid organs

bone marrow (T and B cells derived, B cells mature)
Thymus (T cells mature)

Adaptive immune system, why is the receptor repertoire not entirely genetically encoded?

VDJ recombination means that a vast array of specificities can be generated

Secondary lympoid organ examplesq

Spleen MALT Lymph nodes

What process occurs to T cells in the thymus?

Positive and negative selection

Which CD marker is found on ALL T-cells?

CD3

Which cells are selected for in the thymus and what % is this?

Cells with intermediate affinity ~10% of T-cells

What kind of peptides to CD4+ T helper cells recognise?

peptides derived from extracellular proteins presented on HLA Class II (HLA DR DP DQ)

Which cells have MHC-1 and which have MHC-II?

MHC-1 (HLA-A HLA-B HLA-C) - all cells | mHC II - APCs

Functions of CD4+ T-helper cells

Provide help for developing full B-cell response | Provide help for developing some CD8+ T-cell responses

Funciton of CD8+ Cytotoxic killer T-cells?

Kill cells directly: perforin and granzymes, expression of Fas ligand Particularly importnat in defence against viruses and tumours

What markers do Tregs express?

FOXP3 and CD25

What do Th1 cells secret?

IFN gamma and IL-2 (subset of CD4 T cell)

Which CD4+ T-cell plays an important role in Ig class switching?

T follicular helper (Tfh) cells

Central toelrance of B cells

No recognition of self in BM --> Survive | Recognition of self in BM --> negative selection

B cell maturation

They originally exist in the periphery as IgM but then can undergo a germinal centre reaction to differentiate in to IgG, igE, IgA

Germinal centre reaction

1. Dendritic cell primes CD4+ T cells 2. cD4+ T helper cell (TFh) help for B cell differentiation (required CD40L:CD40) 3. B cell proliferation (somatic hypermutation and isotype switching)

In which condition is there an absence of CD40L:CD40?

Hyper igM syndrome

Which part of an immunoglobulin determines its class?

Heavy chain

Which immunoglobulin predominates the B cell memory response?

Response is dominated by IgG antibodies of high affinity (AS opposed to primary response where you get big IgM)

What is another difference between primary and secondary B cell response?

The memory response may be independent of help from CD4+ T cells

What activates the classical complement pathway?

Immune complexes. Binding of antigen to antibody results in a conformational change in anitbody shape which exposes binding site for C1. Binding of C1 to immune complex --> activation of cascade.

Which complement proteins are involved in the classical pathway?

C1,C2,C4

Which complement proteins are involved in MBL pathway?

C2,C4

What activates the MBL pathway?

Direct binding of MBL to microbial cell surface carbohydrates. Directly stimulates the classical pathway involving C2 and C4 but NOT C1. NOt dependent on adaptive immune response.

What activates the alternative pathway?

Direct binding of C3 to bacterial cell wall components e.g. LPS (gram-ve) or teichoic acid (gram+ve).

Which factors invovled in alternative complement pathway??

BIP

Which complement protiens does the final common pathway include?

C5-C9 --> MAC (punches holes in bacterial cell walls)

Which chemokines are important in dendritic cell homing to LN?

CCL19 and CCL21 are important ligands for CCR7 on DCs