midterm revision part 1 Flashcards by Elyaa Saleh

Explain how the 4 hallmarks of inflammation come about

1) Cytokines produced by macrophages cause vasodilation of blood vessles (Close to the site of infection) hense so heat and redness–> reduced velocity of blood flow
2) Activation of endothelial cells lining the blood vessel → expression of cell adhesion molecules → binding and extravasation of circulating leukocytes into tissues
3) Increased vascular permeability → plasma (+plasma proteins e.g. complement) invade the tissue at the point of infection (hence swelling (edema) and pain)
4) Clotting in microvessels in the site of infection prevents the spread of pathogen

* the 4 hallmarks: heat, redness, pain, swelling

How well did you know this?

Not at all

Perfectly

which cell surface proteins are found on macropahges, neutrophils and DCs?

DCs: DENTRITIC CELLS

CD14

How well did you know this?

Not at all

Perfectly

Which cell surface proteins are found on NK cells?

CD16,CD56

How well did you know this?

Not at all

Perfectly

Which cell surface proteins are found on B cells?

BCR, CD19, CD20, CD21

How well did you know this?

Not at all

Perfectly

Which cell surface protein is found on TH cells

TH : t-helper cells

TCR, CD3,CD4

How well did you know this?

Not at all

Perfectly

Which cell surface proteins are found of TC cells

TC: cytotoxic T cells

TCR, CD3,CD8

How well did you know this?

Not at all

Perfectly

Cells that act as APCs (antigen presenting cells)

Macrophages, DCs , B cells, monocytes

positive for CD14 marker

How well did you know this?

Not at all

Perfectly

What are the key elements of innate immunity?

1) Physical barrier –> epithelial layer of the skin and mucosal/glandular tissues , which prevent pathogen entery into the body’s interior
2) Chemical barrier –> acidic pH, anti-microbial proteins and peptides

How well did you know this?

Not at all

Perfectly

immune cells that are part of Adaptive immunity

T (CD 4+ ,CD8+) and B cells ; antibodies

How well did you know this?

Not at all

Perfectly

Immune cells that are part of Innate immunity

phagocytes, NKs, DCs, Mast cells, Complement proteins, macrophages, Antimicrobial molecules (AMPs)

How well did you know this?

Not at all

Perfectly

MoA of AMPs in innate immunity

*AMPs: antimicrobial peptides

provide a first line defense against pathogens (bacteria, viruses,fungi etc) -> DNA, RNA, protein synthesis inhibition –> Apoptosis

the cellular bridge btw innate and adaptive immunity

How well did you know this?

Not at all

Perfectly

(Innate/Adaptive) immunity : immediate defence against by a pathogen (Response T: min/hr)

Innate

How well did you know this?

Not at all

Perfectly

(Innate/Adaptive) immunity: response takes days/weeks to arise following exposure to Ag

Adaptive

How well did you know this?

Not at all

Perfectly

Innate vs Adaptive Immunity

How well did you know this?

Not at all

Perfectly

How does a phagocytic cell recognize microbes, triggering their phagocytosis?

PRRs recognizing PAMPs
Opsonin receptors recognizing opsonins (MBL, Ficolins, C1)
```
   Not all PRRs trigger phagocytosis
```

* PAMPs : found on the cell components of pathogens

How well did you know this?

Not at all

Perfectly

explain what causes Opsonization of bacteria

Fc receptors and complement receptors (CR1) on phagocytes connect opsonin-tagged pathogens (IgG/ C3b) to phagocytes –> Phagocytosis

How well did you know this?

Not at all

Perfectly

what are the 2 primary opsonins used to defend against bacteria?

C3b (also C4b) and Immunoglobulin G (IgG)

How well did you know this?

Not at all

Perfectly

In the complement system, what is the fxn of the plasma protein C3b?

Opsonization
(C4b too)

How well did you know this?

Not at all

Perfectly

NADPH oxidase deficiency resulting in reduced ROS production during phagocytosis, reduced ability to kill ingested microbes
Most often X-linked recessive disorder
Increased susceptibility to catalase positive microorganisms
Treatment with IFNγ
Diagnosis: negative nitroblue tetrazolium test and dihydrorhodamine assay

Type of innate immune deficiency?

Chronic granulomatous disease

sos
History : necrotic skin lesions, recurrent and prolonged infections forming pus (pyogenic bacteria)
complications: Lymphaedenopathy
LAB: marked neutrophilia, nomral no. of lymphocytes

How well did you know this?

Not at all

Perfectly

pateints w/ defects in NADPH oxidase subunits resulting in No ——— production during
phagocytosis –> reduced ability to kill ingested microbes

ROS
* No reactive oxygen species –> increases susceptibility to catalase +ve microorganisms

How well did you know this?

Not at all

Perfectly

Phagocytes employ an array of killing mechanisms to kill microbes. How?

By producing ROS , RNS and antimicrobial peptides –> which are highly toxic to phagocytosed microbes

How well did you know this?

Not at all

Perfectly

———– : Components of the dead/dying cells & damaged tissues recognized by PRRs leading to cell clearance

DAMPs (Damage (Danger)- associated molecular patterns)

How well did you know this?

Not at all

Perfectly

PRRs are expressed on?

Innate immune cells (macropahges, NKs, DCs, neutrophils)

PAMP recognition by PRRs induces the production of ————- that mediate the effector functions of the innate immune responses

Cytokines

Cytokines/ chemokines —> trigger inflammation

* Autosomal recessive disorder * Caused by **deficiency of CD18** which is the common β2 chain of a number of integrins including **LFA-1** * **First indication: delayed separation of umbilical cord stump and omphalitis** (infection of the umbilicus) * **Recurrent bacterial and fungal infections** * **Neutrophilia, no pus formation, necrotic lesions** * Diagnosis: evaluation of expression of CD18 by flow cytometry Type of Deficiency ?

**LAD** - Leukocyte adhesion deficiency

* **Autosomal recessive** disorder caused by **mutations in CHS1** which encodes for **LYST** (lysosomal trafficking regulator) protein: which regulates lysosome size, movement and function * **Partial oculocutaneous albinism**(partial absence of pigment in skin, hair and eyes (metallic **silver colour of hair**, abnormal retinal pigment cells cause **poor vision**) * **Large intracellular granules in leukocytes** are typical of CHS with H&E staining **Diagnosis : * neutropenia and detection of giant granules in neutrophils** * **impairment in T cells, Nk cells and grnaulocytes** Type of Disorder?

**Chediak-Higashi syndrome (CHS)**

The 3 pathways of the complement system

1) Lectin pathway 2) classical pathway 3) Alternative pathway

What are the functions of the complement system?

1) **Lysis** of pathogens through the **MAC**(membrane attack complex) 2) **Opsonization**, which promotes phagocytosis (**C3b** mainly but also C4b) 3) **Clearnace** which of immune complexes from the circulation, **deposits them to the spleen and liver** 4) Release of **Anaphylatoxins (C3a, C5a, C4a)** , that induce **inflammation**

# * Complement system Cleavage of -------- is the critical step in complement activation and **leads directly or indirectly to all the effector activities of the complement system**

**C3**

In the complement system, the activation of what two plasma proteins can cause anaphylaxis?

**C3a**, C4a, **C5a** (induce inflammation) * C5a has the highest biological activity then C3a --> C4a (C5a> C3a> C4a)

What triggers the activation of Complement via the Lectin pathway?

Microbial surfaces Notes: soluble protein **MBL** (lectines) binds to microbial surfaces --> **MASPs** attach to lectine --> cleaves **C4** and **C2** to form ---> **C3 converatse (C4b2a)**--> deposition of **C3b** on the surface of the pathogen

What triggers the activation of Complement via the Classical pathway?

Antigen-antibody complexes Notes: **C1 complex** recognizes **IgG &IgM** antibodies bound to antigens --> Cleavage of **C4 ,then C2**--> **C3 convertase (C4b2a)**

What triggers the activation of Complement via the Alternative pathway?

Microbial surfaces (esp. **Properdin** aka factor P and factor D)

Exaplain how the Alternative pathway works

* **1st way of activation --> acts as an amplification step for the classical and lectin pathways** [Once C3b has been formed by whichever pathway, the alternative pathway can act as an amplification to increase C3b production rapidly] * **2nd way of activation -> spontaneous hydrolysis 'tickiver' of C3 to form C3(H2O)** [Properdin binds to C3(H2O) or C3b which stabilizes the C3 converatse (C3bBb) in the alternative pathway]

MoA of Properdin | *factor P

1) Can act as a PRRs 2) facilitates pahgocytosis on cells undergoing apoptosis ( through the alternative pathyway)

The 3 pathways of complement activation (Classical, lectin & Alternative), **involve diffrent initiators** but all converge in the generation of the **same enzyme** --------------- , which **cleaves C3 into ------- &---------**

C3 convertase **C3a & C3b**

which two types of immunoglobulins activate complement via the **classic pathway**?

**IgG & IgM** (recongnized by C1 antibodies)

C1 complex consists of?

C1q , C1r & C1s | *initiators of the classical pathway

After the generation of C3 converatse, all three pathways cluminate in the fromation of ----------- ?

**C5 convertase** --> **C5** (by the addition of C3b to C3 converatse) -> **C5a and C5b**

what is the fxn of C5a vs C5b

**C5a** --> Anaphylatoxin so **inflammation** **C5b** --> provides a binding site on the surface of the target cell for the **generation of MAC**

The membrane attack complex (**MAC**) is composed of which complement proteins?

C5b, C6, C7, C8, and C9

The membrane attack complex of complement is esp important in the defence against what type of bacteria?

Gram -ve bacteria

what is the fxn of MAC in the complement system?

Lysis of target antigen

In the complement system, the deficinecy of which plasma proteins can predispose someone to *** recurrent meningococcal and gonococcal infections w/ Neisseria spp*?**

C5-C9 [MAC components]

SLE is related to a deficinecy is what type of complement protein?

**C4 deficiency** --> leads to a reduction of C3b deposited on immune complexes

which complement protein is responsible for neutrophil chemotaxis ?

C5a

the deficeincy of what plasma protein leads to overactive complement and hereditary angioedmea?

C1 esterase inhibitor (**C1INH**)

What are the clinical sequelae of hereditary complement **C3 deficiency**?

Recurrent pyogenic sinus, Neisseria spp. sometimes immune-complex disease

In the complement system, the deficinecy of which plasma proteins can predispose someone to ***bacterial infections, mainly in childhood*?** *bacterial infections: pyogenic infections/ recurrent respiratory tract infections

**MBL** (MBL pathway- lectine)

In the complement system, the deficinecy of which plasma proteins can predispose someone to ***immune complex disease (e.g., SLE, Glomerulonephritis, vasculitis*?**

C1, C2, C4 (Classical pathway)

In the complement system, the deficinecy of which plasma proteins can predispose someone to ***pyogenic bacterai and Neisseria spp. but no immune complex disease*?**

Factor D , Factor P [Properdin] (Alternative pathway)

* Dominant autosomal inheritance * **Defective or absent C1INH (C1 esterase inhibitor)** which results in increased levels of edema-factors C2-kinin and bradykinin * Recurrent attacks of skin, laryngeal or intestinal oedema * Diagnosis when disease is active: **reduced C4 and C2 levels, normal C3** * Treatment Danazol Syndrome?

Hereditary angioedema (HAE)

* **Mutations in PIG-A gene** result in lack of GPI-anchor * Presents with **lack of complement regulatory proteins DAF (CD55) and CD59** --> affect RBCs, platelets and granulocytes * symptoms: Abdominal pain, **drak-coloured urine in the morning**, Jaundice, Hemoglobinuria (25% of patients), Thromboembolic events, Fatigue, SOB * Treatment: Eculizumab Syndrome?

Paroxysmal nocturnal hemoglobinuria (PNH)

Deficiency in what molecule would lead to resistance to septic shock?

TNF-α

Deficiency in any of the components of MAC causes?

Fatal meningitis caused by bacterial species (Neisseria Meningitudis)